Insecticidal proteins and methods of use thereof

Abstract

The invention is entitled "Insecticidal Proteins and Methods of Use Thereof." The invention provides compositions and methods for controlling pests. The methods involve transforming organisms with nucleic acid sequences that encode insecticidal proteins. In particular, the nucleic acid sequences are useful for making plants and microorganisms that have insecticidal activity. Thus, the invention provides transformed bacteria, plants, plant cells, plant tissues, and seeds. Compositions are insecticidal nucleic acids and proteins of bacterial species. The sequences are useful for constructing expression vectors for subsequent transformation into organisms of interest, including plants, as probes for isolating other homologous (or partially homologous) genes. The pesticidal proteins are useful for controlling, inhibiting the growth of, or killing Lepidoptera, Coleoptera, Diptera, fungal, Hemipteran, and nematode pest populations, as well as for producing compositions having insecticidal activity.

Description

[0001] Cross-references

[0002] This application claims the benefit of U.S. Provisional Application 61 / 937,295, filed February 7, 2014, and U.S. Provisional Application 62 / 051,720, filed September 17, 2014, the entire contents of which are incorporated herein by reference.

[0003] References to sequence lists submitted electronically

[0004] The official text of the sequence list was submitted electronically via EFS-Web as an ASCII format sequence list, named "6054PCT_Sequence_Listing", created on January 26, 2015, with a file size of 3,705 kilobytes, and submitted along with this specification. The sequence list contained in this ASCII format document is part of this specification and is incorporated herein by reference in its entirety. Technical Field

[0005] This disclosure relates to the field of molecular biology. Novel genes encoding insecticidal proteins are provided. These insecticidal proteins, along with the nucleic acid sequences encoding them, can be used to prepare insecticides and to produce transgenic insect-resistant plants. Background Technology

[0006] Biological control of agriculturally significant insect pests using microbial agents such as fungi, bacteria, or other insects offers an environmentally friendly and commercially attractive alternative to synthetic chemical pesticides. Generally, the use of biopesticides poses a lower risk of pollution and environmental harm, and they provide higher target specificity than traditional broad-spectrum chemical insecticides. Furthermore, biopesticides are often cheaper to produce, thus increasing the economic yield of many crops.

[0007] Certain species of Bacillus microorganisms are known to possess insecticidal activity against a range of insect pests, including Lepidoptera, Diptera, Coleoptera, Hemiptera, and others. Bacillus thuringiensis (Bt) and Bacillus popilliae are representative of the most successful biocontrol agents discovered to date. Insect pathogenicity is also thought to be caused by strains of Bacillus larvae, Bacillus lentimorbus, Bacillus sphaericus, and Bacillus cereus. Microbial insecticides, especially those derived from Bacillus strains, have played an important role in agriculture as an alternative to chemical pest control.

[0008] Recently, crops with enhanced insect resistance have been developed through genetic engineering to produce insecticidal proteins derived from Bacillus subtilis. For example, maize and cotton plants have been genetically engineered to produce insecticidal proteins isolated from Bt strains. These genetically engineered crops are now widely used in agriculture, providing farmers with an environmentally friendly alternative to traditional insect control methods. While these genetically engineered insect-resistant crops have proven commercially successful, they are resistant only to a narrow range of economically important insect pests. In some cases, insects can develop resistance to different insecticidal compounds, necessitating the search for alternative biological control agents for pest management.

[0009] Therefore, there is still a need for new insecticidal proteins with different ranges of insecticidal activity against insect pests, such as insecticidal proteins that are active against a variety of insects in the Lepidoptera and / or Coleoptera orders, including but not limited to insect pests that have developed resistance to existing insecticides. Summary of the Invention

[0010] Compositions and methods for conferring insecticidal activity to bacteria, plants, plant cells, tissues, and seeds are provided. The compositions comprise nucleic acid molecules encoding sequences of insecticidal and insecticidal polypeptides, a vector containing those nucleic acid molecules, and a host cell containing said vector. The compositions also comprise insecticidal polypeptide sequences and antibodies against those polypeptides. The nucleic acid sequences can be used in DNA constructs or expression cassettes for transformation and expression in organisms, including microorganisms and plants. The nucleotide or amino acid sequences can be synthetic sequences designed for expression in organisms, including but not limited to microorganisms or plants. The compositions also comprise transformed bacteria, plants, plant cells, tissues, and seeds.

[0011] Specifically, isolated or recombinant nucleic acid molecules are provided that encode a Pteridophyta insecticidal protein-83 (PtIP-83) polypeptide, the polypeptide comprising amino acid substitutions, deletions, insertions, or fragments thereof. Furthermore, the amino acid sequence corresponding to the PtIP-83 polypeptide is included. Isolated or recombinant nucleic acid molecules are provided, said nucleic acid molecules being capable of encoding SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 and SEQ ID NO: 769. The PtIP-83 polypeptide NO: 769, as well as amino acid substitutions, deletions, insertions, fragments thereof, and combinations thereof. Also included are nucleic acid sequences complementary to or hybridized to the sequence of the embodiment.Also provided are isolated or recombinant PtIP-83 peptides of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 and SEQ ID NO: 769, as well as amino acid substitutions, deletions, insertions, fragments thereof, and combinations thereof.

[0012] Methods for producing polypeptides and using those polypeptides to control or kill Lepidoptera, Coleoptera, nematodes, fungi, and / or Diptera pests are provided. The transgenic plants of the embodiments express one or more of the insecticidal sequences disclosed herein. In various embodiments, the transgenic plants also contain one or more additional genes for insect resistance, such as one or more additional genes for controlling Coleoptera, Lepidoptera, Hemiptera, or nematode pests. Those skilled in the art will understand that transgenic plants may contain any genes conferring the agronomic trait of interest.

[0013] It also includes methods for detecting nucleic acids and peptides in samples according to the implementation plan. Kits are provided for detecting the presence of the PtIP-83 peptide or the presence of polynucleotides encoding the PtIP-83 peptide in samples. The kits are provided together with all reagents and control samples required to perform the method for detecting the expected factor, as well as instructions for use.

[0014] The compositions and methods of the embodiments can be used to produce organisms with enhanced pest resistance or tolerance. These organisms and compositions containing said organisms are desirable for agricultural use. The compositions of the embodiments can also be used to produce modified or improved proteins with insecticidal activity, or to detect the presence of the PtIP-83 peptide. Attached Figure Description

[0015] Figure 1Phylogenetics of extant ferns based on the classification of ferns by ARSmith et al., TAXON, 55:705-731 (2006).

[0016] Figures 2a-2j The amino acid sequences of PtIP-83Aa (SEQ ID NO: 1), PtIP-83Ca (SEQ ID NO: 5), PtIP-83Cb (SEQ ID NO: 7), PtIP-83Cc (SEQ ID NO: 9), PtIP-83Cd (SEQ ID NO: 11), PtIP-83Ce (SEQ ID NO: 13), PtIP-83Cf (SEQ ID NO: 15), and PtIP-83Fa (SEQ ID NO: 3) are shown in comparison; the secondary structure predictions of PtIP-83Aa (SEQ ID NO: 1) and PtIP-83Fa (SEQ ID NO: 3) are compared using the PSIPRED method, i.e., high-order secondary structure prediction; and the position of the amino acid sequence motif relative to PtIP-83Aa (SEQ ID NO: 1) as predicted by MEME motif analysis are shown. “H” indicates the predicted helical structure, “E” indicates the PtIP-β chain structure, and “C” indicates the predicted coil structure.

[0017] Figures 3a-3b The sequence alignment between PtIP-83Aa (SEQ ID NO: 1) and PtIP-50Aa (SEQ ID NO: 34) is shown. The crossover points in the PtIP-83 Aa / PtIP-50Aa chimeras shown in Table 13 are indicated by arrows (↓) above the amino acids.

[0018] Figure 4a -4d shows the amino acid sequence alignments of PtIP-83Aa (SEQ ID NO: 1), PtIP-83Fa (SEQ ID NO: 3), PtIP-50Aa (SEQ ID NO: 34), PtIP-50Ba (SEQ ID NO: 35), and PtIP-50Bb (SEQ ID NO: 36). The identified conserved sequence motifs are indicated, and the amino acid sequence motif in PtIP-83Aa (SEQ ID NO: 1) is underlined.

[0019] Figures 5a-5eThe amino acid sequences of PtIP-83Aa (SEQ ID NO: 1), PtIP-83Ca (SEQ ID NO: 5), PtIP-83Cb (SEQ ID NO: 7), PtIP-83Cc (SEQ ID NO: 9), PtIP-83Cd (SEQ ID NO: 11), PtIP-83Ce (SEQ ID NO: 13), PtIP-83Cf (SEQ ID NO: 15), PtIP-83Cg (SEQ ID NO: 17), and PtIP-83Da (SEQ ID NO: 19) are shown in the diagram. Sequence differences are highlighted. Detailed Implementation

[0020] It should be understood that this disclosure is not limited to the specific methods, protocols, cell lines, genera, and reagents described, as these can vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of this disclosure.

[0021] Unless the context clearly specifies otherwise, the singular forms “a,” “an,” and “the” used herein include multiple referents. Thus, for example, reference to “a cell” includes multiple such cells, and reference to “the protein” includes reference to one or more proteins and their equivalents known to those skilled in the art, and so on. Unless otherwise expressly stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0022] This disclosure relates to compositions and methods for controlling pests. The method involves transforming organisms with a nucleic acid sequence encoding a PtIP-83 polypeptide. Specifically, the nucleic acid sequence of the embodiments can be used to prepare plants and microorganisms with insecticidal activity. Therefore, the present invention provides transformed bacteria, plants, plant cells, plant tissues, and seeds. The compositions are insecticidal nucleic acids and proteins of bacterial species. The nucleic acid sequences can be used to construct expression vectors for subsequent transformation into organisms of interest, as probes for isolating other homologous (or partially homologous) genes, and for producing altered PtIP-83 polypeptides by methods known in the art, such as site-directed mutagenesis, domain exchange, or DNA shuffling. PtIP-83 can be used to control or kill populations of Lepidoptera, Coleoptera, Diptera, fungi, Hemiptera, and nematodes, and for producing compositions with insecticidal activity. The insect pests of concern include, but are not limited to, Lepidoptera species, including but not limited to: corn ear borer (CEW) (Helicoverpa zea), European corn borer (ECB) (Ostrinia nubilalis), diamondback moths such as American cotton bollworm (Helicoverpa zea Boddie); soybean looper moths such as soybean looper moth (Pseudoplusia includens Walker); and soybean hairy moths such as soybean looper moth (Anticarsia gemmatalis Hübner), as well as Coleoptera species, including but not limited to western corn rootworm (Diabrotica virgifera)-WCRW, southern corn rootworm (Diabrotica undecimpunctata howardi)-SCRW, and northern corn rootworm (Diabrotica barberi)-NCRW.

[0023] The term "insecticide toxin" or "insecticide protein" as used herein refers to a toxin or protein homologous to one or more pests (including, but not limited to, members of the orders Lepidoptera, Diptera, Hemiptera, and Coleoptera or Nematoda). Insecticide proteins have been purified from organisms including, for example, species of Bacillus, Pseudomonas, Photorhabdus sp., Xenorhabdus sp., Clostridium bifermentans, and Paenibacillus popilliae. Insecticidal proteins include, but are not limited to: insecticidal proteins from Pseudomonas species, such as PSEEN3174 (Monalysin; (2011) PLoS Pathogens 7: 1-13); insecticidal proteins from biocontrol Pseudomonas protegens strains CHA0 and Pf-5 (formerly fluorescein Pseudomonas) (Pechy-Tarr, (2008) Environmental Microbiology 10: 2368-2386; GenBank accession number EU400157); insecticidal proteins from Pseudomonas Taiwanensis (Liu et al., (2010) J. Agric. Food Chem., 58: 12343-12349); and insecticidal proteins from Pseudomonas pseudoalcligenes (Zhang et al., (2009) Annals of Microbiology). 59:45-50 and Li et al., (2007) Plant Cell Tiss. Organ Cult. 89:159-168); insecticidal proteins from species of the genera *Photorhabdus* and *Xenorhabdus* (Hinchliffe et al., (2010) The Open Toxinology Journal, 3:101-118 and Morgan et al., (2001) Applied and Envir.Micro.67:2062-2069); US Patent 6,048,838 and US Patent 6,379,946; US Patent 20140007292 discloses the PIP-1 peptide; US Patent 20140033361 discloses the AfIP-1A and / or AfIP-1B peptides; US Patent 20140274885 and PCT Patent WO2014 / 150914 disclose the PHI-4 peptide;PIP-47 peptide (PCT sequence number PCT / US14 / 51063), PIP-72 peptide (PCT sequence number PCT / US14 / 55128), and delta-endotoxins, including but not limited to Cry1, Cry2, Cry3, Cry4, Cry5, Cry6, Cry7, Cry8, Cry9, Cry10, Cry11, Cry12, Cry13, Cry14, Cry15, Cry16, Cry17, Cry18, Cry19, Cry20, Cry21, Cry22, Cry23, Cry24, Cry25, Cry26, Cry27, Cry28, Cry29, Cry30, Cry31, Cry32, and Cry33. The following genes were identified: Cry34, Cry35, Cry36, Cry37, Cry38, Cry39, Cry40, Cry41, Cry42, Cry43, Cry44, Cry45, Cry46, Cry47, Cry49, Cry50, Cry51, Cry52, Cry53, Cry54, Cry55, Cry56, Cry57, Cry58, Cry59, Cry60, Cry61, Cry62, Cry63, Cry64, Cry65, Cry66, Cry67, Cry68, Cry69, Cry70, Cry71, and Cry72, as well as the Bacillus thuringiensis cyt1 and cyt2 genes. Members of these categories of Bacillus thuringiensis insecticidal proteins include, but are not limited to, Cry1Aa1 (accession number AAA22353); Cry1Aa2 (accession number AAA22552); Cry1Aa3 (accession number BAA00257); Cry1Aa4 (accession number CAA31886); Cry1Aa5 (accession number BAA04468); Cry1Aa6 (accession number AAA86265); Cry1Aa7 (accession number AAD46139); Cry1Aa8 (accession number I26149); Cry1Aa9 (accession number BAA77213); Cry1Aa10 (accession number AAD55382); Cry 1Aa11 (Login ID CAA70856); Cry1Aa12 (Login ID AAP80146); Cry1Aa13 (Login ID AAM44305); Cry1Aa14 (Login ID AAP40639); Cry1Aa15 (Login ID AAY66993); Cry1Aa16 (Login ID HQ439776); Cry1Aa17 (Login ID HQ439788); Cry1Aa18 (Login ID HQ439790); Cry1Aa19 (Login ID HQ685121); Cry1Aa20 (Login ID JF340156); Cry1Aa21 (Login ID JN651496);Cry1Aa22 (Login ID KC158223); Cry1Ab1 (Login ID AAA22330); Cry1Ab2 (Login ID AAA22613); Cry1Ab3 (Login ID AAA22561); Cry1Ab4 (Login ID BAA00071); Cry1Ab5 (Login ID CAA28405); Cry1Ab6 (Login ID AAA22420); Cry1Ab7 (Login ID CAA31620); Cry1Ab8 (Login ID AAA22551); Cry1Ab9 (Login ID CAA38701); Cry1Ab10 (Login ID A29125); Cry1Ab11 (Login ID I124) 19); Cry1Ab12 (Login ID AAC64003); Cry1Ab13 (Login ID AAN76494); Cry1Ab14 (Login ID AAG16877); Cry1Ab15 (Login ID AAO13302); Cry1Ab16 (Login ID AAK55546); Cry1Ab17 (Login ID AAT46415); Cry1Ab18 (Login ID AAQ88259); Cry1Ab19 (Login ID AAW31761); Cry1Ab20 (Login ID ABB72460); Cry1Ab21 (Login ID ABS18384); Cry1Ab22 (Login ID ABW87320); C Cry1Ab23 (Login ID HQ439777); Cry1Ab24 (Login ID HQ439778); Cry1Ab25 (Login ID HQ685122); Cry1Ab26 (Login ID HQ847729); Cry1Ab27 (Login ID JN135249); Cry1Ab28 (Login ID JN135250); Cry1Ab29 (Login ID JN135251); Cry1Ab30 (Login ID JN135252); Cry1Ab31 (Login ID JN135253); Cry1Ab32 (Login ID JN135254); Cry1Ab33 (Login ID AAS93798); Cry1Ab 34 (Login ID KC156668); Cry1Ab sample (Login ID AAK14336); Cry1Ab sample (Login ID AAK14337); Cry1Ab sample (Login ID AAK14338); Cry1Ab sample (Login ID ABG88858); Cry1Ac1 (Login ID AAA22331); Cry1Ac2 (Login ID AAA22338); Cry1Ac3 (Login ID CAA38098); Cry1Ac4 (Login ID AAA73077); Cry1Ac5 (Login ID AAA22339); Cry1Ac6 (Login ID AAA86266); Cry1Ac7 (Login ID AAB46989);Cry1Ac8 (Accession number AAC44841); Cry1Ac9 (Accession number AAB49768); Cry1Ac10 (Accession number CAA05505); Cry1Ac11 (Accession number CAA10270); Cry1Ac12 (Accession number I12418); Cry1Ac13 (Accession number AAD38701); Cry1Ac14 (Accession number AAQ06607); Cry1Ac15 (Accession number AAN07788); Cry1Ac16 (Accession number AAU87037); Cry1Ac17 (Accession number AAX18704); Cry1Ac18 (Accession number AAY88347); Cry1Ac19 (Accession number ABD37053); Cry1Ac20 (Accession number ABB89046); Cry1Ac21 (Accession number AAY66992); Cry1Ac22 (Accession number ABZ01836); Cry1Ac23 (Accession number CAQ30431); Cry1Ac24 (Accession number ABL01535); Cry1Ac25 (Accession number FJ513324); Cry1Ac26 (Accession number FJ617446); Cry1Ac27 (Accession number FJ617447); Cry1Ac28 (Accession number ACM90319); Cry1Ac29 (Accession number DQ438941); Cry1Ac30 (Accession number GQ227507); Cry1Ac31 (Accession number GU446674); Cry1Ac32 (Accession number HM061081); Cry1Ac33 (Accession number GQ866913); Cry1Ac34 (Accession number HQ230364); Cry1Ac35 (Accession number JF340157); Cry1Ac36 (Accession number JN387137); Cry1Ac37 (Accession number JQ317685); Cry1Ad1 (Accession number AAA22340); Cry1Ad2 (Accession number CAA01880); Cry1Ae1 (Accession number AAA22410); Cry1Af1 (Accession number AAB82749); Cry1Ag1 (Accession number AAD46137); Cry1Ah1 (Accession number AAQ14326); Cry1Ah2 (Accession number ABB76664); Cry1Ah3 (Accession number HQ439779); Cry1Ai1 (Accession number AAO39719); Cry1Ai2 (Accession number HQ439780); Cry1A-like (Accession number AAK14339); Cry1Ba1 (Accession number CAA29898); Cry1Ba2 (Accession number CAA65003); Cry1Ba3 (Accession number AAK63251); Cry1Ba4 (Accession number AAK51084); Cry1Ba5 (Accession number ABO20894);Cry1Ba6 (Login ID ABL60921); Cry1Ba7 (Login ID HQ439781); Cry1Bb1 (Login ID AAA22344); Cry1Bb2 (Login ID HQ439782); Cry1Bc1 (Login ID CAA86568); Cry1Bd1 (Login ID AAD10292); Cry1Bd2 (Login ID AAM93496); Cry1Be1 (Login ID AAC32850); Cry1Be2 (Login ID AAQ52387); Cry1Be3 (Login ID ACV96720); Cry1Be4 (Login ID HM070026); Cry1Bf1 (Login ID CAC50) 778); Cry1Bf2 (login number AAQ52380); Cry1Bg1 (login number AAO39720); Cry1Bh1 (login number HQ589331); Cry1Bi1 (login number KC156700); Cry1Ca1 (login number CAA30396); Cry1Ca2 (login number CAA31951); Cry1Ca3 (login number AAA22343); Cry1Ca4 (login number CAA01886); Cry1Ca5 (login number CAA65457); Cry1Ca6[1] (login number AAF37224); Cry1Ca7 (login number AAG50438); Cry1Ca8 ( Login ID AAM00264); Cry1Ca9 (Login ID AAL79362); Cry1Ca10 (Login ID AAN16462); Cry1Ca11 (Login ID AAX53094); Cry1Ca12 (Login ID HM070027); Cry1Ca13 (Login ID HQ412621); Cry1Ca14 (Login ID JN651493); Cry1Cb1 (Login ID M97880); Cry1Cb2 (Login ID AAG35409); Cry1Cb3 (Login ID ACD50894); Cry1Cb sample (Login ID AAX63901); Cry1Da1 (Login ID CAA38099); Cry1Da2 (Login ID I76415); Cry1Da3 (Login ID HQ439784); Cry1Db1 (Login ID CAA80234); Cry1Db2 (Login ID AAK48937); Cry1Dc1 (Login ID ABK35074); Cry1Ea1 (Login ID CAA37933); Cry1Ea2 (Login ID CAA39609); Cry1Ea3 (Login ID AAA22345); Cry1Ea4 (Login ID AAD04732); Cry1Ea5 (Login ID A15535); Cry1Ea6 (Login ID AAL50330); Cry1Ea7 (Login ID AAW72936);Cry1Ea8 (Login ID ABX11258); Cry1Ea9 (Login ID HQ439785); Cry1Ea10 (Login ID ADR00398); Cry1Ea11 (Login ID JQ652456); Cry1Eb1 (Login ID AAA22346); Cry1Fa1 (Login ID AAA22348); Cry1Fa2 (Login ID AAA22347); Cry1Fa3 (Login ID HM070028); Cry1Fa4 (Login ID HM439638); Cry1Fb1 (Login ID CAA80235); Cry1Fb2 (Login ID BAA25298); Cry1Fb3 (Login ID AAF217) 67); Cry1Fb4 (Login ID AAC10641); Cry1Fb5 (Login ID AAO13295); Cry1Fb6 (Login ID ACD50892); Cry1Fb7 (Login ID ACD50893); Cry1Ga1 (Login ID CAA80233); Cry1Ga2 (Login ID CAA70506); Cry1Gb1 (Login ID AAD10291); Cry1Gb2 (Login ID AAO13756); Cry1Gc1 (Login ID AAQ52381); Cry1Ha1 (Login ID CAA80236); Cry1Hb1 (Login ID AAA79694); Cry1Hb2 (Login ID HQ43) 9786); Cry1H sample (logo AAF01213); Cry1Ia1 (logo CAA44633); Cry1Ia2 (logo AAA22354); Cry1Ia3 (logo AAC36999); Cry1Ia4 (logo AAB00958); Cry1Ia5 (logo CAA70124); Cry1Ia6 (logo AAC26910); Cry1Ia7 (logo AAM73516); Cry1Ia8 (logo AAK66742); Cry1Ia9 (logo AAQ08616); Cry1Ia10 (logo AAP86782); Cry1Ia11 (logo C AC85964); Cry1Ia12 (Grant No. AAV53390); Cry1Ia13 (Grant No. ABF83202); Cry1Ia14 (Grant No. ACG63871); Cry1Ia15 (Grant No. FJ617445); Cry1Ia16 (Grant No. FJ617448); Cry1Ia17 (Grant No. GU989199); Cry1Ia18 (Grant No. ADK23801); Cry1Ia19 (Grant No. HQ439787); Cry1Ia20 (Grant No. JQ228426); Cry1Ia21 (Grant No. JQ228424); Cry1Ia22 (Grant No. JQ228427);Cry1Ia23 (Accession No. JQ228428); Cry1Ia24 (Accession No. JQ228429); Cry1Ia25 (Accession No. JQ228430); Cry1Ia26 (Accession No. JQ228431); Cry1Ia27 (Accession No. JQ228432); Cry1Ia28 (Accession No. JQ228433); Cry1Ia29 (Accession No. JQ228434); Cry1Ia30 (Accession No. JQ317686); Cry1Ia31 (Accession No. JX944038); Cry1Ia32 (Accession No. JX944039); Cry1Ia33 (Accession No. JX944040); Cry1Ib1 (Accession No. AAA82114); Cry1Ib2 (Accession No. ABW88019); Cry1Ib3 (Accession No. ACD75515); Cry1Ib4 (Accession No. HM051227); Cry1Ib5 (Accession No. HM070028); Cry1Ib6 (Accession No. ADK38579); Cry1Ib7 (Accession No. JN571740); Cry1Ib8 (Accession No. JN675714); Cry1Ib9 (Accession No. JN675715); Cry1Ib10 (Accession No. JN675716); Cry1Ib11 (Accession No. JQ228423); Cry1Ic1 (Accession No. AAC62933); Cry1Ic2 (Accession No. AAE71691); Cry1Id1 (Accession No. AAD44366); Cry1Id2 (Accession No. JQ228422); Cry1Ie1 (Accession No. AAG43526); Cry1Ie2 (Accession No. HM439636); Cry1Ie3 (Accession No. KC156647); Cry1Ie4 (Accession No. KC156681); Cry1If1 (Accession No. AAQ52382); Cry1Ig1 (Accession No. KC156701); Cry1I-like (Accession No. AAC31094); Cry1I-like (Accession No. ABG88859); Cry1Ja1 (Accession No. AAA22341); Cry1Ja2 (Accession No. HM070030); Cry1Ja3 (Accession No. JQ228425); Cry1Jb1 (Accession No. AAA98959); Cry1Jc1 (Accession No. AAC31092); Cry1Jc2 (Accession No. AAQ52372); Cry1Jd1 (Accession No. CAC50779); Cry1Ka1 (Accession No. AAB00376); Cry1Ka2 (Accession No. HQ439783); Cry1La1 (Accession No. AAS60191); Cry1La2 (Accession No. HM070031); Cry1Ma1 (Accession No. FJ884067); Cry1Ma2 (Accession No. KC156659);Cry1Na1 (Accession number KC156648); Cry1Nb1 (Accession number KC156678); Cry1-like (Accession number AAC31091); Cry2Aa1 (Accession number AAA22335); Cry2Aa2 (Accession number AAA83516); Cry2Aa3 (Accession number D86064); Cry2Aa4 (Accession number AAC04867); Cry2Aa5 (Accession number CAA10671); Cry2Aa6 (Accession number CAA10672); Cry2Aa7 (Accession number CAA10670); Cry2Aa8 (Accession number AAO13734); Cry2Aa9 (Accession number AAO13750); Cry2Aa10 (Accession number AAQ04263); Cry2Aa11 (Accession number AAQ52384); Cry2Aa12 (Accession number ABI83671); Cry2Aa13 (Accession number ABL01536); Cry2Aa14 (Accession number ACF04939); Cry2Aa15 (Accession number JN426947); Cry2Ab1 (Accession number AAA22342); Cry2Ab2 (Accession number CAA39075); Cry2Ab3 (Accession number AAG36762); Cry2Ab4 (Accession number AAO13296); Cry2Ab5 (Accession number AAQ04609); Cry2Ab6 (Accession number AAP59457); Cry2Ab7 (Accession number AAZ66347); Cry2Ab8 (Accession number ABC95996); Cry2Ab9 (Accession number ABC74968); Cry2Ab10 (Accession number EF157306); Cry2Ab11 (Accession number CAM84575); Cry2Ab12 (Accession number ABM21764); Cry2Ab13 (Accession number ACG76120); Cry2Ab14 (Accession number ACG76121); Cry2Ab15 (Accession number HM037126); Cry2Ab16 (Accession number GQ866914); Cry2Ab17 (Accession number HQ439789); Cry2Ab18 (Accession number JN135255); Cry2Ab19 (Accession number JN135256); Cry2Ab20 (Accession number JN135257); Cry2Ab21 (Accession number JN135258); Cry2Ab22 (Accession number JN135259); Cry2Ab23 (Accession number JN135260); Cry2Ab24 (Accession number JN135261); Cry2Ab25 (Accession number JN415485); Cry2Ab26 (Accession number JN426946); Cry2Ab27 (Accession number JN415764); Cry2Ab28 (Accession number JN651494);Cry2Ac1 (Grant No. CAA40536); Cry2Ac2 (Grant No. AAG35410); Cry2Ac3 (Grant No. AAQ52385); Cry2Ac4 (Grant No. ABC95997); Cry2Ac5 (Grant No. ABC74969); Cry2Ac6 (Grant No. ABC74793); Cry2Ac7 (Grant No. CAL18690); Cry2Ac8 (Grant No. CAM09325); Cry2Ac9 (Grant No. CAM09326); Cry2Ac10 (Grant No. ABN15104); Cry2Ac11 (Grant No. CAM83895); Cry2Ac12 (Grant No. CAM83896); Cry2Ad1 (GROUP ID AAF09583); Cry2Ad2 (GROUP ID ABC86927); Cry2Ad3 (GROUP ID CAK29504); Cry2Ad4 (GROUP ID CAM32331); Cry2Ad5 (GROUP ID CAO78739); Cry2Ae1 (GROUP ID AAQ52362); Cry2Af1 (GROUP ID ABO30519); Cry2Af2 (GROUP ID GQ866915); Cry2Ag1 (GROUP ID ACH91610); Cry2Ah1 (GROUP ID EU939453); Cry2Ah2 (GROUP ID ACL80665); Cry2A h3 (Login ID GU073380); Cry2Ah4 (Login ID KC156702); Cry2Ai1 (Login ID FJ788388); Cry2Aj (Login ID); Cry2Ak1 (Login ID KC156660); Cry2Ba1 (Login ID KC156658); Cry3Aa1 (Login ID AAA22336); Cry3Aa2 (Login ID AAA22541); Cry3Aa3 (Login ID CAA68482); Cry3Aa4 (Login ID AAA22542); Cry3Aa5 (Login ID AAA50255); Cry3Aa6 (Login ID AAC43266); Cry3Aa7 (Login ID CAB41411); Cry3Aa8 (Login ID AAS79487); Cry3Aa9 (Login ID AAW05659); Cry3Aa10 (Login ID AAU29411); Cry3Aa11 (Login ID AAW82872); Cry3Aa12 (Login ID ABY49136); Cry3Ba1 (Login ID CAA34983); Cry3Ba2 (Login ID CAA00645); Cry3Ba3 (Login ID JQ397327); Cry3Bb1 (Login ID AAA22334); Cry3Bb2 (Login ID AAA74198); Cry3Bb3 (Login ID I15475);Cry3Ca1 (Registration No. CAA42469); Cry4Aa1 (Registration No. CAA68485); Cry4Aa2 (Registration No. BAA00179); Cry4Aa3 (Registration No. CAD30148); Cry4Aa4 (Registration No. AFB18317); Cry4A sample (Registration No. AAY96321); Cry4Ba1 (Registration No. CAA30312); Cry4Ba2 (Registration No. CAA30114); Cry4Ba3 (Registration No. AAA22337); Cry4Ba4 (Registration No. BAA00178); Cry4Ba5 (Registration No. CAD30095); Cry4Ba sample (Registration No. ABC4768) 6); Cry4Ca1 (logo EU646202); Cry4Cb1 (logo FJ403208); Cry4Cb2 (logo FJ597622); Cry4Cc1 (logo FJ403207); Cry5Aa1 (logo AAA67694); Cry5Ab1 (logo AAA67693); Cry5Ac1 (logo I34543); Cry5Ad1 (logo ABQ82087); Cry5Ba1 (logo AAA68598); Cry5Ba2 (logo ABW88931); Cry5Ba3 (logo AFJ04417); Cry5Ca1 (logo HM461) 869); Cry5Ca2 (Login ID ZP_04123426); Cry5Da1 (Login ID HM461870); Cry5Da2 (Login ID ZP_04123980); Cry5Ea1 (Login ID HM485580); Cry5Ea2 (Login ID ZP_04124038); Cry6Aa1 (Login ID AAA22357); Cry6Aa2 (Login ID AAM46849); Cry6Aa3 (Login ID ABH03377); Cry6Ba1 (Login ID AAA22358); Cry7Aa1 (Login ID AAA22351); Cry7Ab1 (Login ID AAA21120); Cry 7Ab2 (Login ID AAA21121); Cry7Ab3 (Login ID ABX24522); Cry7Ab4 (Login ID EU380678); Cry7Ab5 (Login ID ABX79555); Cry7Ab6 (Login ID ACI44005); Cry7Ab7 (Login ID ADB89216); Cry7Ab8 (Login ID GU145299); Cry7Ab9 (Login ID ADD92572); Cry7Ba1 (Login ID ABB70817); Cry7Bb1 (Login ID KC156653); Cry7Ca1 (Login ID ABR67863); Cry7Cb1 (Login ID KC156698);Cry7Da1 (Login ID ACQ99547); Cry7Da2 (Login ID HM572236); Cry7Da3 (Login ID KC156679); Cry7Ea1 (Login ID HM035086); Cry7Ea2 (Login ID HM132124); Cry7Ea3 (Login ID EEM19403); Cry7Fa1 (Login ID HM035088); Cry7Fa2 (Login ID EEM19090); Cry7Fb1 (Login ID HM572235); Cry7Fb2 (Login ID KC156682); Cry7Ga1 (Login ID HM572237); Cry7Ga2 (Login ID KC15 6669); Cry7Gb1 (KC156650); Cry7Gc1 (KC156654); Cry7Gd1 (KC156697); Cry7Ha1 (KC156651); Cry7Ia1 (KC156665); Cry7Ja1 (KC156671); Cry7Ka1 (KC156680); Cry7Kb1 (BAM99306); Cry7La1 (BAM99307); Cry8Aa1 (AAA21117); Cry8Ab1 (EU044830); Cry8Ac1 (KC156697); Cry7Gb1 (KC156651); Cry7Gc1 (KC156654); Cry7Gd1 (KC156697); Cry7Ha1 (KC156651); Cry7Ia1 (KC156665); Cry7Ja1 (KC156671); Cry7Ka1 (KC156680); Cry7Ka1 (KC156680); Cry7Ka1 (KC15665 ... Cry8Ad1 (KC156662); Cry8Ba1 (AAA21118); Cry8Bb1 (CAD57542); Cry8Bc1 (CAD57543); Cry8Ca1 (AAA21119); Cry8Ca2 (AAR98783); Cry8Ca3 (EU625349); Cry8Ca4 (ADB54826); Cry8Da1 (BAC07226); Cry8Da2 (BD133574); Cry8Da3 (BD133575); Cry8D b1 (Login ID BAF93483); Cry8Ea1 (Login ID AAQ73470); Cry8Ea2 (Login ID EU047597); Cry8Ea3 (Login ID KC855216); Cry8Fa1 (Login ID AAT48690); Cry8Fa2 (Login ID HQ174208); Cry8Fa3 (Login ID AFH78109); Cry8Ga1 (Login ID AAT46073); Cry8Ga2 (Login ID ABC42043); Cry8Ga3 (Login ID FJ198072); Cry8Ha1 (Login ID AAW81032); Cry8Ia1 (Login ID EU381044);Cry8Ia2 (login number GU073381); Cry8Ia3 (login number HM044664); Cry8Ia4 (login number KC156674); Cry8Ib1 (login number GU325772); Cry8Ib2 (login number KC156677); Cry8Ja1 (login number EU625348); Cry8Ka1 (login number FJ422558); Cry8Ka2 (login number ACN87262); Cry8Kb1 (login number HM123758); Cry8Kb2 (login number KC156675); Cry8La1 (login number GU325771); Cry8Ma1 (login number HM0 44665); Cry8Ma2 (Grant No. EEM86551); Cry8Ma3 (Grant No. HM210574); Cry8Na1 (Grant No. HM640939); Cry8Pa1 (Grant No. HQ388415); Cry8Qa1 (Grant No. HQ441166); Cry8Qa2 (Grant No. KC152468); Cry8Ra1 (Grant No. AFP87548); Cry8Sa1 (Grant No. JQ740599); Cry8Ta1 (Grant No. KC156673); Cry8sample (Grant No. FJ770571); Cry8sample (Grant No. ABS53003); Cry9Aa1 (Grant No. C AA41122); Cry9Aa2 (GROUP NO: CAA41425); Cry9Aa3 (GROUP NO: GQ249293); Cry9Aa4 (GROUP NO: GQ249294); Cry9Aa5 (GROUP NO: JX174110); Cry9Aa (GROUP NO: AAQ52376); Cry9Ba1 (GROUP NO: CAA52927); Cry9Ba2 (GROUP NO: GU299522); Cry9Bb1 (GROUP NO: AAV28716); Cry9Ca1 (GROUP NO: CAA85764); Cry9Ca2 (GROUP NO: AAQ52375); Cry9Da1 (GROUP NO: BAA19948); Cry9Da 2 (Login ID AAB97923); Cry9Da3 (Login ID GQ249293); Cry9Da4 (Login ID GQ249297); Cry9Db1 (Login ID AAX78439); Cry9Dc1 (Login ID KC156683); Cry9Ea1 (Login ID BAA34908); Cry9Ea2 (Login ID AAO12908); Cry9Ea3 (Login ID ABM21765); Cry9Ea4 (Login ID ACE88267); Cry9Ea5 (Login ID ACF04743); Cry9Ea6 (Login ID ACG63872); Cry9Ea7 (Login ID FJ380927);Cry9Ea8 (Accession number: GQ249292); Cry9Ea9 (Accession number: JN651495); Cry9Eb1 (Accession number: CAC50780); Cry9Eb2 (Accession number: GQ249298); Cry9Eb3 (Accession number: KC156646); Cry9Ec1 (Accession number: AAC63366); Cry9Ed1 (Accession number: AAX78440); Cry9Ee1 (Accession number: GQ249296); Cry9Ee2 (Accession number: KC156664); Cry9Fa1 (Accession number: KC156692); Cry9Ga1 (Accession number: KC156699); Cry9-like (Accession number: AAC63366); Cry10Aa1 (Accession number: AAA22614); Cry10Aa2 (Accession number: E00614); Cry10Aa3 (Accession number: CAD30098); Cry10Aa4 (Accession number: AFB18318); Cry10A-like (Accession number: DQ167578); Cry11Aa1 (Accession number: AAA22352); Cry11Aa2 (Accession number: AAA22611); Cry11Aa3 (Accession number: CAD30081); Cry11Aa4 (Accession number: AFB18319); Cry11Aa-like (Accession number: DQ166531); Cry11Ba1 (Accession number: CAA60504); Cry11Bb1 (Accession number: AAC97162); Cry11Bb2 (Accession number: HM068615); Cry12Aa1 (Accession number: AAA22355); Cry13Aa1 (Accession number: AAA22356); Cry14Aa1 (Accession number: AAA21516); Cry14Ab1 (Accession number: KC156652); Cry15Aa1 (Accession number: AAA22333); Cry16Aa1 (Accession number: CAA63860); Cry17Aa1 (Accession number: CAA67841); Cry18Aa1 (Accession number: CAA67506); Cry18Ba1 (Accession number: AAF89667); Cry18Ca1 (Accession number: AAF89668); Cry19Aa1 (Accession number: CAA68875); Cry19Ba1 (Accession number: BAA32397); Cry19Ca1 (Accession number: AFM37572); Cry20Aa1 (Accession number: AAB93476); Cry20Ba1 (Accession number: ACS93601); Cry20Ba2 (Accession number: KC156694); Cry20-like (Accession number: GQ144333); Cry21Aa1 (Accession number: I32932); Cry21Aa2 (Accession number: I66477); Cry21Ba1 (Accession number: BAC06484); Cry21Ca1 (Accession number: JF521577);Cry21Ca2 (Grant No. KC156687); Cry21Da1 (Grant No. JF521578); Cry22Aa1 (Grant No. I34547); Cry22Aa2 (Grant No. CAD43579); Cry22Aa3 (Grant No. ACD93211); Cry22Ab1 (Grant No. AAK50456); Cry22Ab2 (Grant No. CAD43577); Cry22Ba1 (Grant No. CAD43578); Cry22Bb1 (Grant No. KC156672); Cry23Aa1 (Grant No. AAF76375); Cry24Aa1 (Grant No. AAC61891); Cry24Ba 1 (Login ID BAD32657); Cry24Ca1 (Login ID CAJ43600); Cry25Aa1 (Login ID AAC61892); Cry26Aa1 (Login ID AAD25075); Cry27Aa1 (Login ID BAA82796); Cry28Aa1 (Login ID AAD24189); Cry28Aa2 (Login ID AAG00235); Cry29Aa1 (Login ID CAC80985); Cry30Aa1 (Login ID CAC80986); Cry30Ba1 (Login ID BAD00052); Cry30Ca1 (Login ID BAD67157); Cry30Ca2 (Login ID BAD32657); Cry24Ca1 (Login ID BAD6 ... ACU24781); Cry30Da1 (Grant No. EF095955); Cry30Db1 (Grant No. BAE80088); Cry30Ea1 (Grant No. ACC95445); Cry30Ea2 (Grant No. FJ499389); Cry30Fa1 (Grant No. ACI22625); Cry30Ga1 (Grant No. ACG60020); Cry30Ga2 (Grant No. HQ638217); Cry31Aa1 (Grant No. BAB11757); Cry31Aa2 (Grant No. AAL87458); Cry31Aa3 (Grant No. BAE79808); Cry31Aa4 (Grant No. BAF32) 571); Cry31Aa5 (login number BAF32572); Cry31Aa6 (login number BAI44026); Cry31Ab1 (login number BAE79809); Cry31Ab2 (login number BAF32570); Cry31Ac1 (login number BAF34368); Cry31Ac2 (login number AB731600); Cry31Ad1 (login number BAI44022); Cry32Aa1 (login number AAG36711); Cry32Aa2 (login number GU063849); Cry32Ab1 (login number GU063850); Cry32Ba1 (login number BAB78601);Cry32Ca1 (login ID BAB78602); Cry32Cb1 (login ID KC156708); Cry32Da1 (login ID BAB78603); Cry32Ea1 (login ID GU324274); Cry32Ea2 (login ID KC156686); Cry32Eb1 (login ID KC156663); Cry32Fa1 (login ID KC156656); Cry32Ga1 (login ID KC156657); Cry32Ha1 (login ID KC156661); Cry32Hb1 (login ID KC156666); Cry32Ia1 (login ID KC156667); Cry32 Ja1 (KC156685); Cry32Ka1 (KC156688); Cry32La1 (KC156689); Cry32Ma1 (KC156690); Cry32Mb1 (KC156704); Cry32Na1 (KC156691); Cry32Oa1 (KC156703); Cry32Pa1 (KC156705); Cry32Qa1 (KC156706); Cry32Ra1 (KC156707); Cry32Sa1 (KC156709); Cry32Ta1 (KC156685); Cry32Ka1 (KC156688); Cry32Ra1 (KC156707); Cry32Sa1 (KC156709); Cry32Ta1 (KC156685); Cry32Ka1 (KC156688); Cry32Ra1 (KC156707); Cry32Ta1 (KC156689); Cry32Ra1 (KC156688); Cry32Ra1 (KC156689 ... Cry32Ua1 (KC156655); Cry33Aa1 (AAL26871); Cry34Aa1 (AAG50341); Cry34Aa2 (AAK64560); Cry34Aa3 (AAT29032); Cry34Aa4 (AAT29030); Cry34Ab1 (AAG41671); Cry34Ac1 (AAG50118); Cry34Ac2 (AAK64562); Cry34Ac3 (AAT29029); Cry34Ba1 (AAK6) 4565); Cry34Ba2 (logo AAT29033); Cry34Ba3 (logo AAT29031); Cry35Aa1 (logo AAG50342); Cry35Aa2 (logo AAK64561); Cry35Aa3 (logo AAT29028); Cry35Aa4 (logo AAT29025); Cry35Ab1 (logo AAG41672); Cry35Ab2 (logo AAK64563); Cry35Ab3 (logo AY536891); Cry35Ac1 (logo AAG50117); Cry35Ba1 (logo AAK64566);Cry35Ba2 (Accession number AAT29027); Cry35Ba3 (Accession number AAT29026); Cry36Aa1 (Accession number AAK64558); Cry37Aa1 (Accession number AAF76376); Cry38Aa1 (Accession number AAK64559); Cry39Aa1 (Accession number BAB72016); Cry40Aa1 (Accession number BAB72018); Cry40Ba1 (Accession number BAC77648); Cry40Ca1 (Accession number EU381045); Cry40Da1 (Accession number ACF15199); Cry41Aa1 (Accession number BAD35157); Cry41Ab1 (Accession number BAD35163); Cry41Ba1 (Accession number HM461871); Cry41Ba2 (Accession number ZP_04099652); Cry42Aa1 (Accession number BAD35166); Cry43Aa1 (Accession number BAD15301); Cry43Aa2 (Accession number BAD95474); Cry43Ba1 (Accession number BAD15303); Cry43Ca1 (Accession number KC156676); Cry43Cb1 (Accession number KC156695); Cry43Cc1 (Accession number KC156696); Cry43-like (Accession number BAD15305); Cry44Aa (Accession number BAD08532); Cry45Aa (Accession number BAD22577); Cry46Aa (Accession number BAC79010); Cry46Aa2 (Accession number BAG68906); Cry46Ab (Accession number BAD35170); Cry47Aa (Accession number AAY24695); Cry48Aa (Accession number CAJ18351); Cry48Aa2 (Accession number CAJ86545); Cry48Aa3 (Accession number CAJ86546); Cry48Ab (Accession number CAJ86548); Cry48Ab2 (Accession number CAJ86549); Cry49Aa (Accession number CAH56541); Cry49Aa2 (Accession number CAJ86541); Cry49Aa3 (Accession number CAJ86543); Cry49Aa4 (Accession number CAJ86544); Cry49Ab1 (Accession number CAJ86542); Cry50Aa1 (Accession number BAE86999); Cry50Ba1 (Accession number GU446675); Cry50Ba2 (Accession number GU446676); Cry51Aa1 (Accession number ABI14444); Cry51Aa2 (Accession number GU570697); Cry52Aa1 (Accession number EF613489); Cry52Ba1 (Accession number FJ361760);Cry53Aa1 (Login ID EF633476); Cry53Ab1 (Login ID FJ361759); Cry54Aa1 (Login ID ACA52194); Cry54Aa2 (Login ID GQ140349); Cry54Ba1 (Login ID GU446677); Cry55Aa1 (Login ID ABW88932); Cry54Ab1 (Login ID JQ916908); Cry55Aa2 (Login ID AAE33526); Cry56Aa1 (Login ID ACU57499); Cry56Aa2 (Login ID GQ483512); Cry56Aa3 (Login ID JX025567); Cry 57Aa1 (Login ID ANC87261); Cry58Aa1 (Login ID ANC87260); Cry59Ba1 (Login ID JN790647); Cry59Aa1 (Login ID ACR43758); Cry60Aa1 (Login ID ACU24782); Cry60Aa2 (Login ID EAO57254); Cry60Aa3 (Login ID EEM99278); Cry60Ba1 (Login ID GU810818); Cry60Ba2 (Login ID EAO57253); Cry60Ba3 (Login ID EEM99279); Cry61Aa1 (Login ID HM035087); Cry61Aa 2 (Login ID HM132125); Cry61Aa3 (Login ID EEM19308); Cry62Aa1 (Login ID HM054509); Cry63Aa1 (Login ID BAI44028); Cry64Aa1 (Login ID BAJ05397); Cry65Aa1 (Login ID HM461868); Cry65Aa2 (Login ID ZP_04123838); Cry66Aa1 (Login ID HM485581); Cry66Aa2 (Login ID ZP_04099945); Cry67Aa1 (Login ID HM485582); Cry67Aa2 (Login ID ZP_04148882); Cr y68Aa1 (Login ID HQ113114); Cry69Aa1 (Login ID HQ401006); Cry69Aa2 (Login ID JQ821388); Cry69Ab1 (Login ID JN209957); Cry70Aa1 (Login ID JN646781); Cry70Ba1 (Login ID ADO51070); Cry70Bb1 (Login ID EEL67276); Cry71Aa1 (Login ID JX025568); Cry72Aa1 (Login ID JX025569); Cyt1Aa (GenBank Login ID X03182); Cyt1Ab (GenBank Login ID X98793);Cyt1B (GenBank login number U37196); Cyt2A (GenBank login number Z14147); and Cyt2B (GenBank login number U52043).

[0024] Examples of delta-endotoxins include, but are not limited to, the Cry1A protein of U.S. Patents 5,880,275 and 7,858,849; the DIG-3 or DIG-11 toxins (with N-terminal deletions of α-helix 1 and / or α-helix 2 variants of cry proteins such as Cry1A and Cry3A) of U.S. Patent Application Serial No. 10 / 525,318; the Cry1C of U.S. Patent 6,033,874; the Cry1F of U.S. Patents 5,188,960 and 6,218,188; the Cry1A / F chimera of U.S. Patents 7,070,982, 6,962,705 and 6,713,063; and Cry2 proteins, such as those of U.S. Patent 7,064. Cry2Ab protein (249); Cry3A protein, including but not limited to engineered hybrid insecticidal protein (eHIP) formed by a unique combination of variable and conserved blocks of at least two different Cry proteins (US Patent Application Publication 2010 / 0017914); Cry4 protein; Cry5 protein; Cry6 protein; Cry8 protein of US Patents 7,329,736, 7,449,552, 7,803,943, 7,476,781, 7,105,332, 7,378,499 and 7,462,760; Cry9 protein, such as members of the Cry9A, Cry9B, Cry9C, Cry9D, Cry9E and Cry9F families; Naimov et al., (2008) Applied Cry15 protein (published in *Environmental Microbiology*, 74: 7145-7151); Cry22 and Cry34Ab1 proteins (published in US patents 6,127,180, 6,624,145, and 6,340,593); CryET33 and CryET34 proteins (published in US patents 6,248,535, 6,326,351, 6,399,330, 6,949,626, 7,385,107, and 7,504,229); US patent publications 2006 / 0191034, 2012 / 0278954, and PCT publication WO Homologs of CryET33 and CryET34 (US Patent 2012 / 139004); Cry35Ab1 protein (US Patents 6,083,499, 6,548,291, and 6,340,593); Cry46 protein, Cry51 protein, and Cry binary toxin; TIC901 or related toxins; TIC807 (US Patent Application Publication 2008 / 0295207); ET29, ET37, TIC809, TIC810, TIC812, TIC127, and TIC128 (US Patent Application 2006 / 033867).AXMI-027, AXMI-036, and AXMI-038 of U.S. Patent 8,236,757; AXMI-031, AXMI-039, AXMI-040, and AXMI-049 of U.S. Patent 7,923,602; AXMI-018, AXMI-020, and AXMI-021 of WO 2006 / 083891; AXMI-010 of WO 2005 / 038032; WO AXMI-003 of 2005 / 021585; AXMI-008 of U.S. Patent Application Publication 2004 / 0250311; AXMI-006 of U.S. Patent Application Publication 2004 / 0216186; AXMI-007 of U.S. Patent Application Publication 2004 / 0210965; AXMI-009 of U.S. Patent Application Publication 2004 / 0210964; AXMI-014 of U.S. Patent Application Publication 2004 / 0197917; AXMI-004 of U.S. Patent Application Publication 2004 / 0197916; AXMI-028 and AXMI-029 of WO 2006 / 119457; WO AXMI-007, AXMI-008, AXMI-0080rf2, AXMI-009, AXMI-014, and AXMI-004 of U.S. Patent No. 8,084,416; AXMI-150 of U.S. Patent Application Publication No. 2011 / 0023184; and AXMI-011 and AXMI-004 of U.S. Patent Application Publication No. 2011 / 0263488. -012, AXMI-013, AXMI-015, AXMI-019, AXMI-044, AXMI-037, AXMI-043, AXMI-033, AXMI-034, AXMI-022, AXMI-023, AXMI-041, AXMI-063, and AXMI-064; AXMI-R1 and related proteins as disclosed in U.S. Patent Application Publication 2010 / 0197592; WO AXMI221Z, AXMI222z, AXMI223z, AXMI224z, and AXMI225z of WO 2011 / 103248; AXMI218, AXMI219, AXMI220, AXMI226, AXMI227, AXMI228, AXMI229, AXMI230, and AXMI231 of WO 2011 / 103247; AXMI-115, AXMI-113, AXMI-005, AXMI-163, and AXMI-184 of U.S. Patent 8,334,431; and AXMI-001, AXMI-002, AXMI-030, AXMI-035, and AXMI-045 of U.S. Patent Application Publication 2010 / 0298211.U.S. Patent Application Publication 2009 / 0144852: AXMI-066 and AXMI-076; U.S. Patent 8,318,900: AXMI128, AXMI130, AXMI131, AXMI133, AXMI140, AXMI141, AXMI142, AXMI143, AXMI144, AXMI146, AXMI148, AXMI149, AXMI152, AXMI153, AXMI154, AXMI155, AXMI156, AXMI157, AXMI... US Patents: I158, AXMI162, AXMI165, AXMI166, AXMI167, AXMI168, AXMI169, AXMI170, AXMI171, AXMI172, AXMI173, AXMI174, AXMI175, AXMI176, AXMI177, AXMI178, AXMI179, AXMI180, AXMI181, AXMI182, AXMI185, AXMI186, AXMI187, AXMI188, AXMI189; Application for publication of AXMI079, AXMI080, AXMI081, AXMI082, AXMI091, AXMI092, AXMI096, AXMI097, AXMI098, AXMI099, AXMI100, AXMI101, AXMI102, AXMI103, AXMI104, AXMI107, AXMI108, AXMI109, AXMI110, AXMI111, AXMI112, AXMI114, and AXMI116 under application number 2010 / 0005543. AXMI117, AXMI118, AXMI119, AXMI120, AXMI121, AXMI122, AXMI123, AXMI124, AXMI1257, AXMI1268, AXMI127, AXMI129, AXMI164, AXMI151, AXMI161, AXMI183, AXMI132, AXMI138, AXMI137, and the cry proteins of U.S. Patent 8,319,019, such as Cry1A and Cry3A with modified proteolytic sites;U.S. Patent Application Publication 2011 / 0064710 discloses Cry1Ac, Cry2Aa, and Cry1Ca toxin proteins from Bacillus thuringiensis strain VBTS 2528. Other Cry proteins are well known to those skilled in the art (see Crickmore et al., "Bacillus thuringiensis toxinnomenclature" (2011), lifesci.sussex.ac.uk / home / Neil_Crickmore / Bt / (accessible via the "www" prefix on the World Wide Web)). The insecticidal activity of Cry proteins is well known to those skilled in the art (for a review, see van Frannkenhuyzen, (2009) J. Invert. Path. 101: 1-16). The use of Cry proteins as traits in transgenic plants is well known to those skilled in the art, and Cry transgenic plants (including, but not limited to, plants expressing Cry1Ac, Cry1Ac+Cry2Ab, Cry1Ab, Cry1A.105, Cry1F, Cry1Fa2, Cry1F+Cry1Ac, Cry2Ab, Cry3A, mCry3A, Cry3Bb1, Cry34Ab1, Cry35Ab1, Vip3A, mCry3A, Cry9c, and CBI-Bt) have received regulatory approval (see, Sanahuja, (2011) Plant Biotech Journal 9: 283-300 and cera-gmc.org / index.php?action=gm_crop_database (accessible on the World Wide Web with the prefix "www") CERA. (2010) GM CropDatabase Center for Environmental Risk Assessment (CERA), ILSI Research Foundation, Washington. DC (CERA. (2010) Transgenic Crops Database, Center for Environmental Risk Assessment (CERA), International Academy of Life Sciences Research Grant, Washington). More than one insecticidal protein well known to those skilled in the art can also be expressed in plants, such as Vip3Ab & Cry1Fa (US2012 / 0317682); Cry1BE & Cry1F (US2012 / 0311746); Cry1CA & Cry1AB (US2012 / 0311745); Cry1F & CryCa (US2012 / 0317681); Cry1DA & Cry1BE (US2012 / 0331590); Cry1DA & Cry1Fa (US2012 / 0331589).Cry1AB & Cry1BE (US2012 / 0324606); Cry1Fa & Cry2Aa and Cry1I & Cry1E (US2012 / 0324605); Cry34Ab / 35Ab and Cry6Aa (US20130167269); Cry34Ab / VCry35Ab & Cry3Aa (US20130167268); and Cry3A and Cry1Ab or Vip3Aa (US20130116170). Insecticidal proteins also include insecticidal lipases, including acyl hydrolases as described in US Patent 7,491,869 and cholesterol oxidases such as those from Streptomyces (Purcell et al. (1993) Biochem Biophys Res Commun 15: 1406-1413). Insecticidal proteins also include VIP (plant-derived insecticidal protein) toxins, as specified in U.S. Patent Nos. 5,877,012, 6,107,279, 6,137,033, 7,244,820, 7,615,686, and 8,237,020. Other VIP proteins are well known to those skilled in the art (see lifesci.sussex.ac.uk / home / Neil_Crickmore / Bt / vip.html (accessible via the World Wide Web with the prefix "www")). Insecticidal proteins also include toxin complex (TC) proteins, which are derived from organisms such as those of the genera *Pathogenic Bacillus*, *Luminobacterium*, and *Paenibacillus* (see U.S. Patents 7,491,698 and 8,084,418). Some TC proteins have "independent" insecticidal activity, while others enhance the activity of independent toxins produced by the same given organism. The toxicity of “independent” TC proteins (derived from, for example, *Proteobacterium*, *Pathobacterium*, or *Bacillus* species) can be enhanced by one or more TC protein “synergists” from organisms of different genera. There are three main types of TC proteins. As mentioned herein, type A proteins (“protein A”) are independent toxins. Type B proteins (“protein B”) and type C proteins (“protein C”) enhance the toxicity of type A proteins. Examples of type A proteins are TcbA, TcdA, XptA1, and XptA2. Examples of type B proteins are TcaC, TcdB, XptB1Xb, and XptC1Wi. Examples of type C proteins are TccC, XptC1Xb, and XptB1Wi. Insecticidal proteins also include spider, snake, and scorpion venom proteins. Examples of spider venom peptides include, but are not limited to, lycotoxin-1 peptide and its mutants (US Patent 8,334,366).

[0025] In some embodiments, the PtIP-83 polypeptide comprises an amino acid sequence deduced from the full-length nucleic acid sequence disclosed herein, as well as an amino acid sequence shorter than the full-length sequence due to the use of an alternative downstream starting site or due to processing to produce a shorter protein with insecticidal activity. Processing can occur in the organism expressing the protein or in the pest after protein ingestion.

[0026] Therefore, this paper provides novel isolated or recombinant nucleic acid sequences conferring insecticidal activity. The amino acid sequence of the PtIP-83 polypeptide is also provided. Proteins translated from these PtIP-83 polypeptide genes allow for cellular control or killing of pests that feed on them.

[0027] Nucleic acid molecules and their variants and fragments

[0028] One aspect relates to isolated or recombinant nucleic acid molecules comprising a nucleic acid sequence encoding a PtIP-83 polypeptide or its biologically active portion, and nucleic acid molecules sufficient to serve as hybridization probes for recognizing nucleic acid molecules encoding proteins having regions of sequence homology. As used herein, the term "nucleic acid molecule" refers to DNA molecules (e.g., recombinant DNA, cDNA, genomic DNA, plastid DNA, mitochondrial DNA) and RNA molecules (e.g., mRNA), as well as analogs of DNA or RNA produced using nucleotide analogs. Nucleic acid molecules can be single-stranded or double-stranded, but double-stranded DNA is preferred.

[0029] "Isolated" nucleic acid molecule (or DNA) is used herein to refer to a nucleic acid sequence (or DNA) that is no longer in its natural environment, such as in vitro. "Recombinant" nucleic acid molecule (or DNA) is used herein to refer to a nucleic acid sequence (or DNA) in a recombinant bacterial or plant host cell. In some embodiments, the "isolated" or "recombinant" nucleic acid does not contain a sequence naturally flanking the nucleic acid in the genomic DNA of the source organism (i.e., the sequence located at the 5′ and 3′ ends of the nucleic acid) (preferably a protein-coding sequence). For the purposes of this disclosure, "isolated" or "recombinant" excludes isolated chromosomes when used to refer to nucleic acid molecules. For example, in various embodiments, a recombinant nucleic acid molecule encoding the PtIP-83 polypeptide may contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb, or 0.1 kb of a nucleic acid sequence naturally flanking the nucleic acid molecule in the genomic DNA of the source cell of the nucleic acid.

[0030] In some embodiments, the isolated nucleic acid molecule encoding the PtIP-83 polypeptide has one or more alterations in its nucleic acid sequence compared to the natural or genomic nucleic acid sequence. In some embodiments, the alterations to the natural or genomic nucleic acid sequence include, but are not limited to: alterations to the nucleic acid sequence due to the degeneracy of the genetic code; alterations to the nucleic acid sequence due to amino acid substitutions, insertions, deletions, and / or additions compared to the natural or genomic sequence; removal of one or more introns; deletion of one or more upstream or downstream regulatory regions; and deletion of 5' and / or 3' untranslated regions associated with the genomic nucleic acid sequence. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is a non-genomic sequence.

[0031] Various polynucleotides encoding the PtIP-83 polypeptide or related proteins have been envisioned. These polynucleotides, when operatively linked to suitable promoters, transcription terminators, and / or polyadenylated sequences, can be used to generate the PtIP-83 polypeptide in host cells. These polynucleotides can also be used as probes to isolate homologous or substantially homologous polynucleotides encoding the PtIP-83 polypeptide or related proteins.

[0032] Polynucleotide encoding PtIP-83 polypeptide

[0033] The polynucleotide source encoding the PtIP-83 polypeptide or related protein is a fern or other primitive plant species comprising SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 752 or SEQ ID NO: 752. PtIP-83 polynucleotide NO: 753, which encodes the PtIP-83 polypeptide of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769.SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO:752 and SEQ ID The polynucleotide NO: 753 can be used to express the PtIP-83 polypeptide in bacterial hosts including, but not limited to, those of Agrobacterium, Bacillus, Escherichia, Salmonella, Pseudomonas, and Rhizobium. The polynucleotide can also be used as a probe to isolate homologous or substantially homologous polynucleotides encoding the PtIP-83 polypeptide or related proteins. Such probes can be used to identify homologous or substantially homologous polynucleotides derived from fern species.

[0034] The polynucleotide encoding the PtIP-83 polypeptide can also be synthesized de novo from the PtIP-83 polypeptide sequence. The sequence of the polynucleotide gene can be deduced from the PtIP-83 polypeptide sequence using the genetic code. Computer programs such as "BackTranslate" (GCG) can be used to do this. TMThe software package (Acclerys, Inc., San Diego, Calif) can be used to convert peptide sequences into the corresponding nucleotide sequences encoding that peptide. Examples of PtIP-83 polypeptide sequences that can be used to obtain the corresponding nucleotide coding sequences include, but are not limited to, the PtIP-83 polypeptides of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 and SEQ ID NO: 769. Furthermore, the synthetic PtIP-83 polynucleotide sequences disclosed herein can be engineered to be expressed in plants. U.S. Patent 5,500,365 describes a method for synthesizing plant genes to improve the expression level of proteins encoded by the synthetic gene. This method involves modifying the structural gene sequence of a foreign transgene to make it more efficiently transcribed, processed, translated, and expressed by the plant. Genes that are adequately expressed in plants are characterized by the elimination of sequences that could cause undesirable intron splicing or polyadenylation in the coding region of the gene transcript, while substantially preserving the amino acid sequence of the toxic portion of the insecticidal protein. A similar method for obtaining enhanced expression of transgenes in monocotyledonous plants is disclosed in U.S. Patent 5,689,052.

[0035] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is a nucleic acid molecule having the following characteristics: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 752, SEQ ID NO: 753. NO: 753 shows the sequence of polynucleotides, as well as its variants, fragments, and complementary sequences. "Complementary sequence" is used herein to refer to a nucleic acid sequence that is sufficiently complementary to a given nucleic acid sequence so that it can hybridize to that given nucleic acid sequence to form a stable double strand. "Polynucleotide sequence variant" is used herein to refer to a nucleic acid sequence that encodes the same polypeptide except for the degeneracy of the genetic code.

[0036] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is a non-genomic nucleic acid sequence. As used herein, "non-genomic nucleic acid sequence," "non-genomic nucleic acid molecule," or "non-genomic polynucleotide" refers to a nucleic acid molecule that has one or more alterations in its nucleic acid sequence compared to a native or genomic nucleic acid sequence. In some embodiments, alterations to a native or genomic nucleic acid molecule include, but are not limited to: changes in the nucleic acid sequence due to degeneracy of the genetic code; codon optimization of the nucleic acid sequence for expression in plants; changes in the nucleic acid sequence compared to a native or genomic sequence to introduce at least one amino acid substitution, insertion, deletion, and / or addition; removal of one or more introns associated with a genomic nucleic acid sequence; insertion of one or more heterologous introns; deletion of one or more upstream or downstream regulatory regions associated with a genomic nucleic acid sequence; insertion of one or more heterologous upstream or downstream regulatory regions; deletion of 5' and / or 3' untranslated regions associated with a genomic nucleic acid sequence; insertion of heterologous 5' and / or 3' untranslated regions; and modification of polyadenylation sites. In some embodiments, the non-genomic nucleic acid molecule is cDNA. In some embodiments, the non-genomic nucleic acid molecule is a synthetic nucleic acid sequence.

[0037] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is a non-genomic polynucleotide having a nucleotide sequence having at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the following nucleic acid sequences: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5. SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 752 or SEQ ID NO: 753, wherein the PtIP-83 peptide has insecticidal activity.

[0038] In some implementations, the non-genomic polynucleotide is not a nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 752, or SEQ ID NO: 753.

[0039] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence having at least 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the following amino acid sequence: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769, wherein the PtIP-83 polypeptide has insecticidal activity.

[0040] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769.Compared with natural amino acids in 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO:768 or SEQ ID NO: 769 has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 or more amino acid substitutions at the corresponding position.

[0041] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising any one of the amino acid sequences of SEQ ID NO: 236-299, SEQ ID NO: 334-367, SEQ ID NO: 398-427, SEQ ID NO: 518-607, SEQ ID NO: 640-645, and SEQ ID NO: 728-737.

[0042] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is any of the following: SEQ ID NO: 172-235, SEQ ID NO: 300-333, SEQ ID NO: 368-397, SEQ ID NO: 428-517, SEQ ID NO: 634-639 and SEQ ID NO: 718-727.

[0043] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide variant of SEQ ID NO: 1, wherein the amino acid at position 53 is Val, Ala, Cys, or Thr; the amino acid at position 54 is Lys, Ala, Cys, Asp, Glu, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, or Thr; the amino acid at position 55 is Arg, Ala, Asp, Glu, Phe, Gly, Is, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; and the amino acid at position 56 is Leu, Glu, Phe, Ile, Met, or Thr. Or Val; the amino acid at position 57 is Tyr, Cys, Ile, Leu, Met, Thr, or Val; the amino acid at position 58 is Val, Cys, Ile, or Leu; the amino acid at position 59 is Phe, Leu, Met, Val, or Tyr; the amino acid at position 60 is Ala, Cys, Gly, Ser, Thr, or Val; the amino acid at position 61 is Asp, Glu, His, or Ser; the amino acid at position 62 is Val, Ala, Cys, Ile, Leu, or Thr; the amino acid at position 63 is Val, Ala, Cys, Ile, Leu, or Met. Or Thr; the amino acid at position 64 is Glu, Ala, Cys, Phe, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 65 is Leu, Ala, Cys, Phe, His, Ile, Met, Asn, Gln, Thr, Val, or Trp; the amino acid at position 66 is Pro, Asp, Gly, Met, Gln, or Arg; the amino acid at position 363 is Gln, Ala, Cys, Glu, Phe, Gly, His, Lys, Leu, or Asn. The amino acid at position 364 is Ile, Ala, Cys, Glu, Phe, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 365 is Leu, Ala, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Arg, Val, Trp, or Tyr; the amino acid at position 366 is Gly, Ala, Cys, Phe, His, Ile, Lys, Leu, Met, Asn, Ser, Thr, or Val.The amino acid at position 367 is Ser, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Pro, Gln, Arg, Thr, Val, or Trp; the amino acid at position 368 is Tyr, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Trp; the amino acid at position 369 is Leu, Ala, Cys, Asp, Phe, Gly, Ile, Met, Thr, or Val; the amino acid at position 370 is Leu, Al a, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 371 is Gln, Ala, Cys, Asp, Glu, Phe, Gly, Ile, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp; the amino acid at position 372 is Gln, Ala, Cys, Asp, Phe, Gly, His, Ile, Leu, Asn, Arg, Ser, Val, or Tyr; the amino acid at position 373 is Asn, Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Gln, Ser, Thr, Val, or Trp; the amino acid at position 556 is Trp, Phe, Thr, or Tyr; the amino acid at position 557 is Arg, Cys, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 558 is Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Leu, Asn, Pro, Gln, Arg, Ser, Val, Trp, or Tyr; the amino acid at position 559 is Lys, Ala, Cys, Ph The amino acid at position 560 is Cys, Ala, Phe, Gly, Ile, Met, Asn, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 561 is Lys, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 562 is Asn, Cys, Asp, Glu, Gly, His, Leu, Met, Arg, Ser, Thr, Val, or Tyr.The amino acid at position 563 is Val, Ala, Cys, Asp, Phe, His, Ile, Leu, Met, Asn, Gln, Thr, or Trp; the amino acid at position 564 is Ala, Cys, Gly, Met, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 646 is Leu, Ala, Cys, Gly, Ile, Met, Asn, Gln, Ser, Thr, or Val; the amino acid at position 647 is Leu, Asp, Gly, Met, Asn, Gln, or Thr; the amino acid at position 648 is Met, Ala, Cys, Asp, Glu, Phe, Gly, H The amino acid at position 649 is Pro, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Met, Asn, Gln, Arg, Ser, Thr, Thr, Trp, or Tyr; the amino acid at position 650 is Thr, Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Arg, Ser, Val, or Tyr; the amino acid at position 651 is Glu, Ala, Cys, Asp, Gly, His, Ile, Leu. Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 652 is Leu, Cys, Phe, Ile, Lys, Met, Pro, Arg, Ser, Thr, or Val; the amino acid at position 653 is Thr, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Pro, Arg, Ser, Val, or Trp; the amino acid at position 654 is Thr, Ala, Cys, Phe, Ile, Lys, Leu, Met, Pro, Arg, Ser, Val, Trp, or Tyr; the amino acid at position 655 is Trp, Phe, or Tyr; the amino acid at position 771 is Arg, Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Asn, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 772 is Arg, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 773 is Asp, Ala, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr;The amino acid at position 774 is Gln, Ala, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 775 is Val, Ala, Cys, Asp, Glu, Gly, His, Ile, Asn, Pro, Gln, Arg, Ser, Thr, or Tyr; the amino acid at position 776 is Leu, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Asn, Pro, Gln, Arg, Ser, T hr, Val, or Tyr; the amino acid at position 777 is Pro, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 778 is Phe, Ala, His, Ile, Leu, Met, Asn, Gln, Ser, Val, Trp, or Tyr; the amino acid at position 779 is Gln, Ala, Cys, Asp, Glu, Gly, His, Lys, Leu, Asn, Pro, Arg, Ser, Thr, or Va. The amino acid at position 780 is Ala, Cys, Asn, Pro, Gln, or Ser; the amino acid at position 781 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 782 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 783 is Pro, Ala, Cys, Asp, The amino acid at position 784 is Glu, Gly, His, Asn, Gln, Arg, Ser, Thr, or Val; the amino acid at position 784 is Leu, Ala, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Val, or Trp; the amino acid at position 785 is Asn, Ala, Cys, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; and the amino acid at position 786 is Tyr, Phe, Ile, Leu, or Trp.

[0044] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide variant of SEQ ID NO: 1, wherein the amino acid at position 1 is Met or deleted; the amino acid at position 2 is Ala or deleted; the amino acid at position 3 is Leu, Val, or deleted; the amino acid at position 4 is Val, Met, or Leu; the amino acid at position 7 is Gly or Ser; the amino acid at position 8 is Lys or Thr; the amino acid at position 10 is Phe or Tyr; the amino acid at position 11 is Glu or Arg; the amino acid at position 18 is Met or Ile; the amino acid at position 19 is Gly, Pro, or Ala; the amino acid at position 20 is Val or deleted; the amino acid at position 21 is Leu or Val; and the amino acid at position 23 is... The amino acid at position 37 is Arg or Gln; the amino acid at position 38 is Arg or Asn; the amino acid at position 40 is Ala or Ser; the amino acid at position 43 is Asn or Asp; the amino acid at position 45 is Gly or Ala; the amino acid at position 46 is Gln or Glu; the amino acid at position 48 is Glu, Pro, or Val; the amino acid at position 51 is Glu or Gly; the amino acid at position 52 is Lys, Arg, or Thr; the amino acid at position 56 is Leu or Val; the amino acid at position 59 is Phe or Leu; the amino acid at position 66 is Pro or Ala; the amino acid at position 67 is... Val, Pro, or Thr; the amino acid at position 68 is Val, Arg, Phe, or Gly; the amino acid at position 69 is Glu, Ala, or Lys; the amino acid at position 70 is Trp, Thr, His, Tyr, or Arg; the amino acid at position 71 is Arg, Pro, or deleted; the amino acid at position 72 is Trp, Asp, Leu, or deleted; the amino acid at position 73 is Pro, Gln, Asn, His, or deleted; the amino acid at position 74 is Pro, Met, or Thr; the amino acid at position 75 is Gln, His, or Arg; the amino acid at position 76 is Ile, Met, or Leu; the amino acid at position 84 is Ile or... Val; the amino acid at position 91 is Trp or Phe; the amino acid at position 93 is Thr or Ile; the amino acid at position 94 is Asp or Gly; the amino acid at position 96 is Arg or Ser; the amino acid at position 97 is Gln, Phe, or Arg; the amino acid at position 98 is Ser or missing; the amino acid at position 99 is Asp or Ala; the amino acid at position 100 is Thr or Ala; the amino acid at position 101 is Glu, Thr, or Trp; the amino acid at position 103 is His, Arg, Glu, or Gln; the amino acid at position 105 is Thr or Pro; the amino acid at position 108 is Lys, Gln, or Glu.The amino acid at position 109 is Leu or Val; the amino acid at position 111 is Ala or Thr; the amino acid at position 112 is Ile, Arg, Thr, or is missing; the amino acid at position 113 is Gln, Ala, Gly, or is missing; the amino acid at position 114 is Arg, Glu, or Ile; the amino acid at position 115 is Glu or Gln; the amino acid at position 116 is Glu, Asn, Gln, or Arg; the amino acid at position 117 is Asn, Val, Tyr, or Phe; the amino acid at position 118 is Arg or Lys; the amino acid at position 119 is Trp or Ser; the amino acid at position 122 is Thr, Lys, or A The amino acid at position 124 is Ala or Thr; the amino acid at position 126 is Gly or Asp; the amino acid at position 127 is Met or Ala; the amino acid at position 128 is Asn or Lys; the amino acid at position 131 is Val, Ile, or Thr; the amino acid at position 133 is Ile or Val; the amino acid at position 134 is His or Tyr; the amino acid at position 135 is Ala or Gly; the amino acid at position 137 is Glu or Lys; the amino acid at position 139 is Gln or Glu; the amino acid at position 140 is Val, Arg, or Leu; the amino acid at position 141 is Gly or Ser; the amino acid at position 142... The amino acid at position 144 is Val or Pro; the amino acid at position 145 is Thr, Leu, Phe, or Tyr; the amino acid at position 146 is Met, Pro, or Asn; the amino acid at position 147 is Serp or Asn; the amino acid at position 148 is Ser, Ala, or Pro; the amino acid at position 149 is Ser or missing; the amino acid at position 150 is Val, Ile, or Tyr; the amino acid at position 152 is Arg, Ala, Val, or Gly; the amino acid at position 154 is Ser, Trp, or Glu; the amino acid at position 156 is Leu, Asp, or Gln; The amino acid at position 158 is Ser or Cys; the amino acid at position 159 is Val, Thr, or Ile; the amino acid at position 162 is Ser or Ala; the amino acid at position 163 is Gly or is missing; the amino acid at position 164 is Phe or is missing; the amino acid at position 165 is Arg or Ala; the amino acid at position 166 is Ala, Arg, Met, or Phe; the amino acid at position 167 is Val or His; the amino acid at position 168 is Ser or Asn; the amino acid at position 169 is Val, His, or Thr; the amino acid at position 170 is Phe or Val; the amino acid at position 171 is Glu, Asn, or Asp.The amino acid at position 172 is Val, Ala, Arg, or Glu; the amino acid at position 175 is Ser, Arg, or Trp; the amino acid at position 176 is Val or Ile; the amino acid at position 177 is Arg or Ile; the amino acid at position 179 is Thr, Ile, Val, or Ser; the amino acid at position 180 is Leu, Phe, or Thr; the amino acid at position 181 is Gly, Thr, Gln, or Ser; the amino acid at position 182 is Ala, Leu, Phe, or Ile; the amino acid at position 183 is Thr or Gly; the amino acid at position 184 is Leu, Thr, Ser, or Arg; the amino acid at position 185... The amino acid at position 186 is Arg, Gly, Asp, or Ala; the amino acid at position 187 is Asp, Thr, or Ser; the amino acid at position 188 is His, Gly, or Ala; the amino acid at position 189 is Ala, Arg, Pro, or is missing; the amino acid at position 190 is Leu, Asn, or is missing; the amino acid at position 191 is Tyr or is missing; the amino acid at position 192 is Ser, Ile, Val, or Asn; the amino acid at position 193 is Thr or Asp; the amino acid at position 194 is Thr or Ser; the amino acid at position 195 is Met or Thr; the amino acid at position 196... The amino acid at position 197 is Gln, His, Leu, or Ser; the amino acid at position 198 is Thr, Glu, or Ala; the amino acid at position 199 is Pro or Arg; the amino acid at position 200 is Asn, Ser, Thr, or Gly; the amino acid at position 201 is Ala, Leu, Glu, or Trp; the amino acid at position 202 is Ser, Asp, Phe, or Leu; the amino acid at position 203 is His, Pro, Gly, or Ser; the amino acid at position 204 is Ile, Trp, His, or Gly; the amino acid at position 205 is Ser, Asn, or Ile; the amino acid at position 20... The amino acid at position 6 is Ala, Gly, Asp, Tyr, or Arg; the amino acid at position 207 is Phe, Val, or Leu; the amino acid at position 208 is Asn, Ser, Pro, or Leu; the amino acid at position 210 is Arg, Asp, Glu, or Tyr; the amino acid at position 211 is Ile, Ser, or Thr; the amino acid at position 212 is Val, Ala, or Asp; the amino acid at position 214 is Pro or Arg; the amino acid at position 215 is Ser or Thr; the amino acid at position 217 is Tyr or Phe; the amino acid at position 218 is Arg or Ser; and the amino acid at position 219 is Val or Ala.The amino acid at position 220 is Cys, Leu, or Ser; the amino acid at position 221 is Pro or His; the amino acid at position 222 is Leu, Arg, or Ser; the amino acid at position 224 is Asn or Ser; the amino acid at position 225 is Asp, Arg, or Thr; the amino acid at position 226 is Thr or Asn; the amino acid at position 227 is Asp, Leu, or is deleted; the amino acid at position 228 is Thr or is deleted; the amino acid at position 229 is Tyr or is deleted; the amino acid at position 230 is Leu or is deleted; the amino acid at position 231 is Gly or is deleted; the amino acid at position 232 is Ile or is deleted; the amino acid at position 233... The amino acid is Pro or missing; the amino acid at position 234 is Ala, Pro, or missing; the amino acid at position 235 is Asp, Ile, or Val; the amino acid at position 236 is Val, Ser, or Glu; the amino acid at position 237 is Ala, Phe, or Tyr; the amino acid at position 238 is Ala or Thr; the amino acid at position 239 is Val, Ser, or Gly; the amino acid at position 240 is Leu or Ile; the amino acid at position 243 is Asp or Glu; the amino acid at position 249 is Asn or Ser; the amino acid at position 252 is Leu or Met; the amino acid at position 257 is Thr or Ser; the amino acid at position 259 is... His or Leu; amino acid at position 266 is Ala or Val; amino acid at position 267 is Cys or Gly; amino acid at position 268 is His, Arg, or Tyr; amino acid at position 272 is Asp or Glu; amino acid at position 273 is Val, Met, Ile, or Leu; amino acid at position 274 is Val or Met; amino acid at position 278 is Gly or Ala; amino acid at position 279 is Glu or Val; amino acid at position 281 is Leu or Ala; amino acid at position 282 is Asn, Leu, or Ile; amino acid at position 285 is Asn or Ser; amino acid at position 286 is Lys. The amino acid at position 287 is either Asp or Glu; the amino acid at position 290 is either Pro, Gln, or Arg; the amino acid at position 291 is either Leu or Val; the amino acid at position 292 is either Lys or Val; the amino acid at position 293 is either Glu or Gln; the amino acid at position 294 is either Ser, Asn, or Lys; the amino acid at position 295 is either Thr or Ser; the amino acid at position 296 is either Gln or His; the amino acid at position 297 is either Leu or Met; the amino acid at position 300 is either Ser or Thr; the amino acid at position 301 is either Glu or Ala; the amino acid at position 302 is either Ser, Pro, or Ala.The amino acid at position 304 is Lys or Asn; the amino acid at position 313 is Val or Ile; the amino acid at position 314 is His, Glu, or Gln; the amino acid at position 315 is Ala, Cys, or Ser; the amino acid at position 316 is Ala or Val; the amino acid at position 317 is Met or Ile; the amino acid at position 319 is Met or Ile; the amino acid at position 320 is Val or Gly; the amino acid at position 321 is Arg or Pro; the amino acid at position 322 is Ile or Phe; the amino acid at position 323 is Gly or Val; the amino acid at position 324 is Leu or Ser; the amino acid at position 336... It is Ser or Asn; the amino acid at position 339 is Asn, Lys, or Arg; the amino acid at position 350 is Arg or Gln; the amino acid at position 351 is Glu or Asp; the amino acid at position 353 is Lys or Arg; the amino acid at position 354 is Gln or Arg; the amino acid at position 355 is Phe or Leu; the amino acid at position 356 is Lys or Arg; the amino acid at position 360 is Ile, Val, or Ala; the amino acid at position 365 is Leu or Phe; the amino acid at position 371 is or Glu; the amino acid at position 372 is or Lys; the amino acid at position 374 is Arg or Lys; the amino acid at position 376... The amino acid at position 378 is Phe or Leu; the amino acid at position 381 is Leu or Val; the amino acid at position 388 is Ala or Ser; the amino acid at position 395 is Arg or Lys; the amino acid at position 396 is Glu, Gln, or Gly; the amino acid at position 399 is Asp or Asn; the amino acid at position 400 is Asn, Thr, or Asp; the amino acid at position 401 is Thr or Ala; the amino acid at position 402 is Phe, Ile, or Leu; the amino acid at position 406 is Asp or Glu; the amino acid at position 408 is Leu or Met; the amino acid at position 410 is Gl. y or Leu; the amino acid at position 414 is Ala or Glu; the amino acid at position 416 is Ser, Asn, or Asp; the amino acid at position 417 is Ser, Arg, or Gly; the amino acid at position 423 is Lys or Gln; the amino acid at position 431 is Arg or Lys; the amino acid at position 432 is Gln or Glu; the amino acid at position 436 is Arg or Glu; the amino acid at position 440 is Asn or Arg; the amino acid at position 442 is Leu or Val; the amino acid at position 447 is Ser, Lys, or Arg; the amino acid at position 448 is Ala or Ser; the amino acid at position 451 is Gln or Met;The amino acid at position 453 is either Gly or Ala; the amino acid at position 455 is either Ala or Val; the amino acid at position 457 is either Leu or Val; the amino acid at position 467 is either Val or Ala; the amino acid at position 471 is either Gly or Ala; the amino acid at position 475 is either Ser or Asn; the amino acid at position 483 is either Gly or Ala; the amino acid at position 493 is either Gln or Gly; the amino acid at position 504 is either Val or Ile; the amino acid at position 506 is either Asp or His; the amino acid at position 509 is either Asp or Asn; the amino acid at position 510 is either Ser or Ala; the amino acid at position 512 is either Glu or Asp. The amino acid at position 515 is Gly or Ser; the amino acid at position 516 is Gln or His; the amino acid at position 517 is Ile or Leu; the amino acid at position 519 is Asp, Gly, or Gln; the amino acid at position 522 is Val, Glu, Pro, or Val; the amino acid at position 525 is Glu or Asp; the amino acid at position 526 is Leu or Met; the amino acid at position 539 is Val or Ile; the amino acid at position 555 is Val or Ala; the amino acid at position 557 is Arg or Lys; the amino acid at position 563 is Val or Met; the amino acid at position 571 is Ser or Cys; the amino acid at position 575... The amino acid at position 577 is Val or Glu; the amino acid at position 577 is Met or Ile; the amino acid at position 579 is Glu or Gln; the amino acid at position 583 is Asp or Glu; the amino acid at position 589 is Met or Leu; the amino acid at position 590 is Met or Leu; the amino acid at position 593 is Met or Ile; the amino acid at position 595 is Arg or Gln; the amino acid at position 596 is Ser or Thr; the amino acid at position 597 is Gln or His; the amino acid at position 607 is Ala or Val; the amino acid at position 608 is Asp or Asn; the amino acid at position 612 is Tyr, His, or Phe; the amino acid at position 61... The amino acid at position 7 is Thr or Ile; the amino acid at position 618 is Gln or His; the amino acid at position 625 is Arg or Ser; the amino acid at position 626 is Met or Ile; the amino acid at position 628 is Leu or Ile; the amino acid at position 633 is Ile or Met; the amino acid at position 634 is Leu or Met; the amino acid at position 642 is Arg or Met; the amino acid at position 648 is Met or Thr; the amino acid at position 651 is Glu or Gln; the amino acid at position 654 is Thr, Val, or Ala; the amino acid at position 658 is Gly or Arg; the amino acid at position 663 is Gly or Ala.The amino acid at position 664 is Asp or Asn; the amino acid at position 668 is Ala or Thr; the amino acid at position 669 is Gln or His; the amino acid at position 671 is Asn or Ser; the amino acid at position 675 is Ile, Val, or Ser; the amino acid at position 678 is Met, Ile, Ala, or Thr; the amino acid at position 682 is Pro or Gln; the amino acid at position 683 is Ser or Pro; the amino acid at position 685 is Asp or Asn; the amino acid at position 694 is Asp or Gly; the amino acid at position 697 is Asn or Ser; the amino acid at position 704 is Glu or Gly; the amino acid at position 714... The amino acid at position 721 is Ala or Gly; the amino acid at position 722 is Ser or Asn; the amino acid at position 724 is Ser or Thr; the amino acid at position 734 is His or Gln; the amino acid at position 736 is Val or Ala; the amino acid at position 737 is Lys or Gln; the amino acid at position 739 is Ala or Ser; the amino acid at position 740 is Ser or Met; the amino acid at position 741 is Gly or Asn; the amino acid at position 742 is Ile or Gly; the amino acid at position 743 is Gly or omitted; the amino acid at position 745 is Gly or Asp; the amino acid at position 751... The amino acid at position 753 is Thr, Ser, or Ala; the amino acid at position 754 is Thr or Ser; the amino acid at position 756 is Thr or Ile; the amino acid at position 757 is Val or Ile; the amino acid at position 766 is Ile or Val; the amino acid at position 773 is Asp or Glu; the amino acid at position 774 is Gln or Glu; the amino acid at position 776 is Leu or Met; the amino acid at position 777 is Pro or Thr; the amino acid at position 782 is Ala, Asp, or Val; the amino acid at position 786 is Tyr or Phe; the amino acid at position 787 is His or Gln. The amino acid at position 788 is Tyr or Met; the amino acid at position 789 is Ala or Arg; the amino acid at position 790 is Tyr or Thr; the amino acid at position 791 is Arg or Ala; the amino acid at position 792 is Leu or Ser; the amino acid at position 796 is Asp or Glu; the amino acid at position 797 is Ser, Thr, or Ala; the amino acid at position 802 is Glu or Gln; the amino acid at position 806 is Gln, Asp, Glu, or His; the amino acid at position 810 is Lys or Thr; the amino acid at position 819 is Arg or His; and the amino acid at position 829 is Lys, Ser, Ala, or Pro.The amino acid at position 832 is Ala, Lys, or Glu; the amino acid at position 833 is Gly or Glu; the amino acid at position 842 is Leu or Pro; the amino acid at position 847 is Gln or Glu; the amino acid at position 848 is Ile or Val; the amino acid at position 849 is Val or Ala; the amino acid at position 855 is Thr or Met; the amino acid at position 860 is Ile or Val; and the amino acid at position 864 is His or Gln.

[0045] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide variant of SEQ ID NO: 1, wherein the amino acid at position 1 is Met or deleted; the amino acid at position 2 is Ala or deleted; the amino acid at position 3 is Leu, Val, Ile or deleted; the amino acid at position 4 is Val, Met, Ile or Leu; the amino acid at position 7 is Gly, Thr or Ser; the amino acid at position 8 is Lys, Arg, Ser or Thr; the amino acid at position 10 is Phe, Trp or Tyr; the amino acid at position 11 is Glu, Asp, Lys or Arg; the amino acid at position 18 is Met, Val, Leu or Ile; and the amino acid at position 19 is Gly, Pro or Ala. The amino acid at position 20 is Val, Ile, Leu, or is missing; the amino acid at position 21 is Leu, Ile, or Val; the amino acid at position 23 is Arg, Lys, Asn, or Gln; the amino acid at position 37 is Val, Ile, or Leu; the amino acid at position 38 is Arg, Lys, Gln, or Asn; the amino acid at position 40 is Ala, Gly, Thr, or Ser; the amino acid at position 43 is Asn, Gln, Glu, or Asp; the amino acid at position 45 is Gly or Ala; the amino acid at position 46 is Gln, Asp, Asn, or Glu; the amino acid at position 48 is Glu, Asp, Pro, or Ile. The amino acid at position 51 is Glu, Asp, Ala, or Gly; the amino acid at position 52 is Lys, Arg, Ser, or Thr; the amino acid at position 56 is Leu, Ile, or Val; the amino acid at position 59 is Phe, Ile, Val, or Leu; the amino acid at position 66 is Pro, Gly, or Ala; the amino acid at position 67 is Val, Pro, Ile, Leu, Ser, or Thr; the amino acid at position 68 is Val, Arg, Phe, Ile, Leu, Lys, or Gly; the amino acid at position 69 is Glu, Ala, Asp, Gly, Arg, or Lys; the amino acid at position 70... The amino acid at position 71 is Trp, Thr, His, Tyr, Lys, or Arg; the amino acid at position 72 is Arg, Pro, Lys, or is missing; the amino acid at position 73 is Pro, Gln, Asn, His, or is missing; the amino acid at position 74 is Pro, Met, Ser, or Thr; the amino acid at position 75 is Gln, His, Asn, Lys, or Arg; the amino acid at position 76 is Ile, Met, Val, or Leu; the amino acid at position 84 is Ile, Leu, or Val; and the amino acid at position 91 is Trp or Phe.The amino acid at position 93 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 94 is Asp, Glu, Ala, or Gly; the amino acid at position 96 is Arg, Lys, Thr, or Ser; the amino acid at position 97 is Gln, Phe, Asn, Lys, or Arg; the amino acid at position 98 is Ser, Thr, or is missing; the amino acid at position 99 is Asp, Glu, Gly, or Ala; the amino acid at position 100 is Thr, Ser, Gly, or Ala; the amino acid at position 101 is Glu, Thr, Asp, Ser, or Trp; and the amino acid at position 103 is His, Arg, Lys, or Gly. u or Gln; the amino acid at position 105 is Thr, Ser, or Pro; the amino acid at position 108 is Lys, Arg, Asn, Asp, Gln, or Glu; the amino acid at position 109 is Leu, Ile, or Val; the amino acid at position 111 is Ala, Ser, or Thr; the amino acid at position 112 is Ile, Arg, Thr, Leu, Val, Lys, Ser, or is missing; the amino acid at position 113 is Gln, Ala, Gly, Asn, or is missing; the amino acid at position 114 is Arg, Glu, Lys, Asp, or Ile; the amino acid at position 115 is Glu, Asp, Asn, or Gln; the 1st The amino acid at position 16 is Glu, Asn, Gln, Asp, Lys, or Arg; the amino acid at position 117 is Asn, Val, Tyr, Ile, Leu, Gln, Trp, or Phe; the amino acid at position 118 is Arg or Lys; the amino acid at position 119 is Trp, Thr, or Ser; the amino acid at position 122 is Thr, Lys, Ser, Arg, or Ala; the amino acid at position 124 is Ala, Gly, Ser, or Thr; the amino acid at position 126 is Gly, Ala, Glu, or Asp; the amino acid at position 127 is Met, Gly, or Ala; and the amino acid at position 128 is Asn, Gly ... The amino acid at position 131 is ln, Arg, or Lys; the amino acid at position 131 is Val, Ile, Leu, Ser, or Thr; the amino acid at position 133 is Ile, Leu, or Val; the amino acid at position 134 is His or Tyr; the amino acid at position 135 is Ala or Gly; the amino acid at position 137 is Glu, Asp, Arg, or Lys; the amino acid at position 139 is Gln, Asn, Asp, or Glu; the amino acid at position 140 is Val, Arg, Ile, Lys, or Leu; the amino acid at position 141 is Gly, Ala, Thr, or Ser; the amino acid at position 142 is Val, Ile, Leu, or Pro.The amino acid at position 144 is Thr, Leu, Phe, Ile, Val, or Tyr; the amino acid at position 145 is Met, Pro, Gln, or Asn; the amino acid at position 146 is Ser, Gly, Thr, Ala, Gln, or Asn; the amino acid at position 147 is Trp, Gln, Tyr, or Asn; the amino acid at position 148 is Ser, Ala, Thr, Gly, or Pro; the amino acid at position 149 is Ser, Thr, or is missing; the amino acid at position 150 is Val, Ile, Leu, or Tyr; the amino acid at position 152 is Arg, Ala, Val, Ile, Leu, Lys, or Gly; the amino acid at position 154... The amino acid at position 156 is Ser, Trp, Thr, Asp, or Glu; the amino acid at position 157 is Leu, Asp, Ile, Val, Asn, Glu, or Gln; the amino acid at position 158 is Ser, Thr, or Cys; the amino acid at position 159 is Val, Thr, Leu, or Ile; the amino acid at position 162 is Ser, Thr, Gly, or Ala; the amino acid at position 163 is Gly, Ala, or is missing; the amino acid at position 164 is Phe or is missing; the amino acid at position 165 is Arg, Lys, Gly, or Ala; the amino acid at position 166 is Ala, Arg, Met, Lys, or Phe; the amino acid at position 167... The amino acid at position 168 is Val, Ile, Leu, or His; the amino acid at position 169 is Val, His, Ile, Leu, Ser, or Thr; the amino acid at position 170 is Phe, Ile, Leu, or Val; the amino acid at position 171 is Glu, Asn, Gln, or Asp; the amino acid at position 172 is Val, Ala, Arg, Ile, Leu, Gly, Lys, Asp, or Glu; the amino acid at position 175 is Ser, Arg, Thr, Lys, or Trp; the amino acid at position 176 is Val, Leu, or Ile; and the amino acid at position 177 is A. The amino acid at position 179 is Thr, Ile, Val, Leu, or Ser; the amino acid at position 180 is Leu, Phe, Ile, Val, Ser, or Thr; the amino acid at position 181 is Gly, Thr, Gln, Asn, or Ser; the amino acid at position 182 is Ala, Leu, Phe, Val, or Ile; the amino acid at position 183 is Thr, Ser, Ala, or Gly; the amino acid at position 184 is Leu, Thr, Ser, Ile, Val, Lys, or Arg; the amino acid at position 185 is Arg, Gly, Asp, Lys, Glu, or Ala.The amino acid at position 186 is Pro, Val, Ile, Leu, Asn, or Gln; the amino acid at position 187 is Asp, Thr, Glu, or Ser; the amino acid at position 188 is His, Gly, or Ala; the amino acid at position 189 is Ala, Arg, Pro, Lys, Gly, or is missing; the amino acid at position 190 is Leu, Asn, Ile, Val, Gln, or is missing; the amino acid at position 191 is Tyr or is missing; the amino acid at position 192 is Ser, Ile, Val, Leu, Thr, or Asn; the amino acid at position 193 is Thr, Ser, Glu, or Asp; the amino acid at position 194 is Thr or... Ser; the amino acid at position 195 is Met or Thr; the amino acid at position 196 is Gln, His, Leu, Asn, Ile, Val, Thr, or Ser; the amino acid at position 197 is Ala, Gly, Ile, Val, or Leu; the amino acid at position 198 is Thr, Glu, Ser, Asp, Gly, or Ala; the amino acid at position 199 is Pro, Lys, or Arg; the amino acid at position 200 is Asn, Ser, Thr, Gln, Ala, or Gly; the amino acid at position 201 is Ala, Leu, Glu, Ile, Asp, or Trp; the amino acid at position 202 is Ser, Asp, Phe, Ile, Val, Thr, Glu, or Leu; the amino acid at position 203 is His, Pro, Gly, Ala, Thr, or Ser; the amino acid at position 204 is Ile, Trp, His, Leu, Val, Ala, or Gly; the amino acid at position 205 is Ser, Asn, Leu, Val, Thr, Gln, or Ile; the amino acid at position 206 is Ala, Gly, Asp, Tyr, Glu, Lys, or Arg; the amino acid at position 207 is Phe, Val, Ile, or Leu; the amino acid at position 208 is Asn, Ser, Pro, Gln, Thr, Val, Ile, or Leu; the amino acid at position 210... The amino acid at position 211 is Arg, Asp, Glu, Lys, Ser, or Tyr; the amino acid at position 212 is Ile, Ser, Leu, Val, or Thr; the amino acid at position 213 is Val, Ala, Ile, Leu, Glu, Gly, or Asp; the amino acid at position 214 is Pro, Lys, or Arg; the amino acid at position 215 is Ser or Thr; the amino acid at position 217 is Tyr or Phe; the amino acid at position 218 is Arg, Lys, Thr, or Ser; the amino acid at position 219 is Val, Ile, Leu, or Ala; and the amino acid at position 220 is Cys, Leu, Ile, Val, Thr, or Ser.The amino acid at position 221 is Pro or His; the amino acid at position 222 is Leu, Arg, Lys, Ile, Val, Thr, or Ser; the amino acid at position 224 is Asn, Gln, Thr, or Ser; the amino acid at position 225 is Asp, Arg, Glu, Lys, Ser, or Thr; the amino acid at position 226 is Thr, Ser, Gln, or Asn; the amino acid at position 227 is Asp, Leu, Glu, Ile, Val, or is missing; the amino acid at position 228 is Thr, Ser, or is missing; the amino acid at position 229 is Tyr or is missing; the amino acid at position 230 is Leu, Ile, Val, or is missing; the 2 The amino acid at position 31 is Gly, Ala, or absent; the amino acid at position 232 is Ile, Leu, Val, or absent; the amino acid at position 233 is Pro or absent; the amino acid at position 234 is Ala, Pro, Gly, or absent; the amino acid at position 235 is Asp, Ile, Leu, Glu, or Val; the amino acid at position 236 is Val, Ser, Ile, Leu, Thr, Asp, or Glu; the amino acid at position 237 is Ala, Phe, or Tyr; the amino acid at position 238 is Ala, Gly, Ser, or Thr; the amino acid at position 239 is Val, Ser, Ile, Leu, Thr, Ala, or Gly; The amino acid at position 240 is Leu, Val, or Ile; the amino acid at position 243 is Asp or Glu; the amino acid at position 249 is Asn, Gln, Thr, or Ser; the amino acid at position 252 is Leu, Ile, Val, or Met; the amino acid at position 257 is Thr or Ser; the amino acid at position 259 is His, Ile, Val, or Leu; the amino acid at position 266 is Ala, Ile, Leu, or Val; the amino acid at position 267 is Cys, Ala, or Gly; the amino acid at position 268 is His, Arg, Lys, or Tyr; the amino acid at position 272 is Asp or Glu; and the amino acid at position 273 is V. The amino acid at position 274 is Val, Ile, Leu, or Met; the amino acid at position 278 is Gly or Ala; the amino acid at position 279 is Glu, Asp, Gly, or Val; the amino acid at position 281 is Leu, Ile, Val, Gly, or Ala; the amino acid at position 282 is Asn, Leu, or Ile; the amino acid at position 285 is Asn, Gln, Thr, or Ser; the amino acid at position 286 is Lys, Asp, Arg, or Glu; the amino acid at position 287 is Leu, Ile, or Val; and the amino acid at position 290 is Pro, Gln, Asn, Lys, or Arg.The amino acid at position 291 is Leu, Ile, or Val; the amino acid at position 292 is Lys, Arg, Ile, Leu, or Val; the amino acid at position 293 is Glu, Asp, Asn, or Gln; the amino acid at position 294 is Ser, Asn, Thr, Gln, Arg, or Lys; the amino acid at position 295 is Thr or Ser; the amino acid at position 296 is Gln, Asn, or His; the amino acid at position 297 is Leu, Ile, Val, or Met; the amino acid at position 300 is Ser or Thr; the amino acid at position 301 is Glu, Asp, Gly, or Ala; the amino acid at position 302 is Ser, Pro The amino acid at position 304 is Lys, Arg, Gln, or Asn; the amino acid at position 313 is Val, Leu, or Ile; the amino acid at position 314 is His, Glu, Asn, Asp, or Gln; the amino acid at position 315 is Ala, Cys, Gly, Thr, or Ser; the amino acid at position 316 is Ala, Ile, Leu, or Val; the amino acid at position 317 is Met, Leu, Val, or Ile; the amino acid at position 319 is Met, Leu, Val, or Ile; the amino acid at position 320 is Val, Ile, Leu, Ala, or Gly; the amino acid at position 321 is A rg, Lys, or Pro; amino acid at position 322 is Ile, Leu, Val, or Phe; amino acid at position 323 is Gly, Ile, Leu, or Val; amino acid at position 324 is Leu, Ile, Val, Thr, or Ser; amino acid at position 336 is Ser, Thr, Gln, or Asn; amino acid at position 339 is Asn, Lys, Gln, or Arg; amino acid at position 350 is Arg, Lys, Asn, or Gln; amino acid at position 351 is Glu or Asp; amino acid at position 353 is Lys or Arg; amino acid at position 354 is Gln, Asn, Lys, or Arg; amino acid at position 355... The amino acid is Phe, Ile, Leu, or Leu; the amino acid at position 356 is Lys or Arg; the amino acid at position 360 is Ile, Val, Leu, Gly, or Ala; the amino acid at position 365 is Leu, Ile, Val, or Phe; the amino acid at position 371 is Glu or Asp; the amino acid at position 372 is Lys or Arg; the amino acid at position 374 is Arg or Lys; the amino acid at position 376 is Phe, Ile, Val, or Leu; the amino acid at position 378 is Glu or Asp; the amino acid at position 381 is Leu, Ile, or Val; the amino acid at position 388 is Ala, Thr, Gly, or Ser.The amino acid at position 395 is Arg or Lys; the amino acid at position 396 is Glu, Gln, Asp, Asn, Ala, or Gly; the amino acid at position 399 is Asp, Gln, Glu, or Asn; the amino acid at position 400 is Asn, Thr, Ser, Glu, Gln, or Asp; the amino acid at position 401 is Thr, Ser, Gly, or Ala; the amino acid at position 402 is Phe, Ile, Val, or Leu; the amino acid at position 406 is Asp or Glu; the amino acid at position 408 is Leu, Ile, Val, or Met; and the amino acid at position 410 is Gly, Ile, Val, Ala, or Leu. u; The amino acid at position 414 is Ala, Gly, Asp, or Glu; The amino acid at position 416 is Ser, Asn, Thr, Gln, Glu, or Asp; The amino acid at position 417 is Ser, Arg, Lys, Thr, Ala, or Gly; The amino acid at position 423 is Lys, Arg, Asn, or Gln; The amino acid at position 431 is Arg or Lys; The amino acid at position 432 is Gln, Asn, Asp, or Glu; The amino acid at position 436 is Arg, Lys, Asp, or Glu; The amino acid at position 440 is Asn, Gln, Lys, or Arg; The amino acid at position 442 is Leu, Ile, or V al; the amino acid at position 447 is Ser, Lys, Thr, or Arg; the amino acid at position 448 is Ala, Gly, Thr, or Ser; the amino acid at position 451 is Gln, Asn, or Met; the amino acid at position 453 is Gly or Ala; the amino acid at position 455 is Ala, Leu, Ile, or Val; the amino acid at position 457 is Leu, Ile, or Val; the amino acid at position 467 is Val, Ile, Leu, Gly, or Ala; the amino acid at position 471 is Gly or Ala; the amino acid at position 475 is Ser, Thr, Gln, or Asn; the amino acid at position 483 is Gly or Ala; The amino acid at position 493 is Gln, Asn, or Gly; the amino acid at position 504 is Val, Leu, or Ile; the amino acid at position 506 is Asp, Glu, or His; the amino acid at position 509 is Asp, Glu, Gln, or Asn; the amino acid at position 510 is Ser, Thr, Gly, or Ala; the amino acid at position 512 is Glu or Asp; the amino acid at position 515 is Gly, Ala, Thr, or Ser; the amino acid at position 516 is Gln, Asn, or His; the amino acid at position 517 is Ile, Val, or Leu; and the amino acid at position 519 is Asp, Asn, Glu, Gly, or Gln.The amino acid at position 522 is Val, Glu, Pro, Ile, Leu, or Asp; the amino acid at position 525 is Glu or Asp; the amino acid at position 526 is Leu, Ile, Val, or Met; the amino acid at position 539 is Val, Leu, or Ile; the amino acid at position 555 is Val, Leu, Ile, or Ala; the amino acid at position 557 is Arg or Lys; the amino acid at position 563 is Val, Leu, Ile, or Met; the amino acid at position 571 is Ser, Thr, or Cys; the amino acid at position 575 is Val, Leu, Ile, Asp, or Glu; the amino acid at position 577 is Met. The amino acid at position 579 is Glu, Asp, Asn, or Gln; the amino acid at position 583 is Asp or Glu; the amino acid at position 589 is Met, Ile, Val, or Leu; the amino acid at position 590 is Met, Ile, Val, or Leu; the amino acid at position 593 is Met, Leu, Val, or Ile; the amino acid at position 595 is Arg, Lys, Asn, or Gln; the amino acid at position 596 is Ser or Thr; the amino acid at position 597 is Gln, Asn, or His; the amino acid at position 607 is Ala, Gly, Ile, Leu, or Val; the amino acid at position 608... The amino acid at position 612 is Asp, Glu, Gln, or Asn; the amino acid at position 612 is Tyr, His, or Phe; the amino acid at position 617 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 618 is Gln, Asn, or His; the amino acid at position 625 is Arg, Lys, Thr, or Ser; the amino acid at position 626 is Met, Leu, Val, or Ile; the amino acid at position 628 is Leu, Val, or Ile; the amino acid at position 633 is Ile, Leu, Val, or Met; the amino acid at position 634 is Leu, Ile, Val, or Met; and the amino acid at position 642 is Arg, L... The amino acid at position 648 is either ys or Met; the amino acid at position 651 is Met, Ser, or Thr; the amino acid at position 654 is Thr, Val, Ser, Ile, Leu, Gly, or Ala; the amino acid at position 658 is Gly, Lys, Ala, or Arg; the amino acid at position 663 is Gly or Ala; the amino acid at position 664 is Asp, Glu, Gln, or Asn; the amino acid at position 668 is Ala, Gly, Ser, or Thr; the amino acid at position 669 is Gln, Asn, or His; the amino acid at position 671 is Asn, Gln, Thr, or Ser.The amino acid at position 675 is Ile, Val, Ile, Thr, or Ser; the amino acid at position 678 is Met, Ile, Ala, Leu, Ser, or Thr; the amino acid at position 682 is Pro, Asn, or Gln; the amino acid at position 683 is Ser, Thr, or Pro; the amino acid at position 685 is Asp, Glu, Asp, or Asn; the amino acid at position 694 is Asp, Glu, Ala, or Gly; the amino acid at position 697 is Asn, Gln, Thr, or Ser; the amino acid at position 704 is Glu, Asp, Ala, or Gly; the amino acid at position 714 is Ala or Gly; the amino acid at position 721... The amino acid at position 722 is Ser, Thr, Gln, or Asn; the amino acid at position 724 is Ser or Thr; the amino acid at position 734 is His, Asn, or Gln; the amino acid at position 736 is Val, Leu, Ile, or Ala; the amino acid at position 737 is Lys, Arg, Asn, or Gln; the amino acid at position 739 is Ala, Gly, Thr, or Ser; the amino acid at position 740 is Ser, Thr, or Met; the amino acid at position 741 is Gly, Ala, Gln, or Asn; the amino acid at position 742 is Ile, Leu, Val, Ala, or Gly; the amino acid at position 743... The amino acid at position 745 is Gly or absent; the amino acid at position 745 is Gly, Ala, Glu, or Asp; the amino acid at position 751 is Thr, Ser, Gly, or Ala; the amino acid at position 753 is Gln, Asn, Lys, or Arg; the amino acid at position 754 is Thr or Ser; the amino acid at position 756 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 757 is Val, Leu, or Ile; the amino acid at position 766 is Ile, Leu, or Val; the amino acid at position 773 is Asp or Glu; the amino acid at position 774 is Gln, Asn, Asp, or Glu; the amino acid at position 776 is Leu, The amino acid at position 777 is Pro, Ser, or Thr; the amino acid at position 782 is Ala, Asp, Glu, Ile, Leu, or Val; the amino acid at position 786 is Tyr or Phe; the amino acid at position 787 is His, Asn, or Gln; the amino acid at position 788 is Tyr or Met; the amino acid at position 789 is Ala, Lys, or Arg; the amino acid at position 790 is Tyr or Thr; the amino acid at position 791 is Arg, Lys, Gly, or Ala; the amino acid at position 792 is Leu, Ile, Val, Thr, or Ser; the amino acid at position 796 is Asp or Glu.The amino acid at position 797 is Ser, Thr, or Ala; the amino acid at position 802 is Glu, Lys, Asp, Asn, or Gln; the amino acid at position 806 is Gln, Asp, Glu, Asn, or His; the amino acid at position 810 is Lys, Arg, or Thr; the amino acid at position 819 is Arg, Lys, or His; the amino acid at position 829 is Lys, Ser, Ala, or Pro; the amino acid at position 832 is Ala, Lys, Arg, Asp, or Glu; the amino acid at position 833... The amino acid is Gly, Ala, Asp, or Glu; the amino acid at position 842 is Leu, Ile, Val, or Pro; the amino acid at position 847 is Gln, Asn, Asp, or Glu; the amino acid at position 848 is Ile, Leu, or Val; the amino acid at position 849 is Val, Leu, Ile, Gly, or Ala; the amino acid at position 855 is Thr, Ser, or Met; the amino acid at position 860 is Ile, Leu, or Val; and the amino acid at position 864 is His, Asn, or Gln.

[0046] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide variant of SEQ ID NO: 1, wherein the amino acid at position 1 is Met or deleted; the amino acid at position 2 is Ala or deleted; the amino acid at position 3 is Leu, Val, Ile or deleted; the amino acid at position 4 is Val, Met, Ile or Leu; the amino acid at position 7 is Gly, Thr or Ser; the amino acid at position 8 is Lys, Arg, Ser or Thr; the amino acid at position 10 is Phe, Trp or Tyr; the amino acid at position 11 is Glu, Asp, Lys or Arg; the amino acid at position 18 is Met, Val, Leu or Ile; and the amino acid at position 19 is Gly, Pr The amino acid at position 20 is Val, Ile, Leu, or is missing; the amino acid at position 21 is Leu, Ile, or Val; the amino acid at position 23 is Arg, Lys, Asn, or Gln; the amino acid at position 37 is Val, Ile, or Leu; the amino acid at position 38 is Arg, Lys, Gln, or Asn; the amino acid at position 40 is Ala, Gly, Thr, or Ser; the amino acid at position 43 is Asn, Gln, Glu, or Asp; the amino acid at position 45 is Gly or Ala; the amino acid at position 46 is Gln, Asp, Asn, or Glu; the amino acid at position 48 is Glu. The amino acid at position 51 is Glu, Asp, Pro, Ile, Leu, or Val; the amino acid at position 52 is Lys, Arg, Ser, or Thr; the amino acid at position 53 is Val, Ala, Cys, or Thr; the amino acid at position 54 is Lys, Ala, Cys, Asp, Glu, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, or Thr; the amino acid at position 55 is Arg, Ala, Asp, Glu, Phe, Gly, Is, Lys, Leu, Met, Asn, Gln, Ser, Thr, Va. The amino acid at position 56 is Leu, Glu, Phe, Ile, Met, Thr, or Val; the amino acid at position 57 is Tyr, Cys, Ile, Leu, Met, Thr, or Val; the amino acid at position 58 is Val, Cys, Ile, or Leu; the amino acid at position 59 is Phe, Leu, Met, Val, or Tyr; the amino acid at position 60 is Ala, Cys, Gly, Ser, Thr, or Val; the amino acid at position 61 is Asp, Glu, His, or Ser; the amino acid at position 62 is Val, Ala, Cys, Ile, Leu, or Thr.The amino acid at position 63 is Val, Ala, Cys, Ile, Leu, Met, or Thr; the amino acid at position 64 is Glu, Ala, Cys, Phe, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 65 is Leu, Ala, Cys, Phe, His, Ile, Met, Asn, Gln, Thr, Val, or Trp; the amino acid at position 66 is Pro, Asp, Gly, Met, Gln, or Arg; the amino acid at position 67 is Val, Pro, Ile, Leu, Ser, or Thr; the amino acid at position 68... The amino acid at position 69 is Val, Arg, Phe, Ile, Leu, Lys, or Gly; the amino acid at position 70 is Trp, Thr, His, Tyr, Lys, or Arg; the amino acid at position 71 is Arg, Pro, Lys, or is missing; the amino acid at position 72 is Trp, Asp, Leu, Ile, Val, Glu, or is missing; the amino acid at position 73 is Pro, Gln, Asn, His, or is missing; the amino acid at position 74 is Pro, Met, Ser, or Thr; and the amino acid at position 75 is Gln, His, Asn, Lys, or A rg; the amino acid at position 76 is Ile, Met, Val, or Leu; the amino acid at position 84 is Ile, Leu, or Val; the amino acid at position 91 is Trp or Phe; the amino acid at position 93 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 94 is Asp, Glu, Ala, or Gly; the amino acid at position 96 is Arg, Lys, Thr, or Ser; the amino acid at position 97 is Gln, Phe, Asn, Lys, or Arg; the amino acid at position 98 is Ser, Thr, or is missing; the amino acid at position 99 is Asp, Glu, Gly, or Ala; the amino acid at position 100 is Thr or Ser. The amino acid at position 101 is Glu, Thr, Asp, Ser, or Trp; the amino acid at position 103 is His, Arg, Lys, Glu, or Gln; the amino acid at position 105 is Thr, Ser, or Pro; the amino acid at position 108 is Lys, Arg, Asn, Asp, Gln, or Glu; the amino acid at position 109 is Leu, Ile, or Val; the amino acid at position 111 is Ala, Ser, or Thr; the amino acid at position 112 is Ile, Arg, Thr, Leu, Val, Lys, Ser, or is missing; the amino acid at position 113 is Gln, Ala, Gly, Asn, or is missing.The amino acid at position 114 is Arg, Glu, Lys, Asp, or Ile; the amino acid at position 115 is Glu, Asp, Asn, or Gln; the amino acid at position 116 is Glu, Asn, Gln, Asp, Lys, or Arg; the amino acid at position 117 is Asn, Val, Tyr, Ile, Leu, Gln, Trp, or Phe; the amino acid at position 118 is Arg or Lys; the amino acid at position 119 is Trp, Thr, or Ser; the amino acid at position 122 is Thr, Lys, Ser, Arg, or Ala; the amino acid at position 124 is Ala, Gly, Ser, or Thr; and the amino acid at position 126 is Gly. The amino acid at position 127 is Met, Gly, or Ala; the amino acid at position 128 is Asn, Gln, Arg, or Lys; the amino acid at position 131 is Val, Ile, Leu, Ser, or Thr; the amino acid at position 133 is Ile, Leu, or Val; the amino acid at position 134 is His or Tyr; the amino acid at position 135 is Ala or Gly; the amino acid at position 137 is Glu, Asp, Arg, or Lys; the amino acid at position 139 is Gln, Asn, Asp, or Glu; the amino acid at position 140 is Val, Arg, Ile, Lys, or Leu; the amino acid at position 141... The amino acid at position 142 is Gly, Ala, Thr, or Ser; the amino acid at position 144 is Thr, Leu, Leu, or Pro; the amino acid at position 145 is Met, Pro, Gln, or Asn; the amino acid at position 146 is Ser, Gly, Thr, Ala, Gln, or Asn; the amino acid at position 147 is Trp, Gln, Tyr, or Asn; the amino acid at position 148 is Ser, Ala, Thr, Gly, or Pro; the amino acid at position 149 is Ser, Thr, or is missing; the amino acid at position 150 is Val, Ile, Leu, or Tyr; the amino acid at position 1... The amino acid at position 52 is Arg, Ala, Val, Ile, Leu, Lys, or Gly; the amino acid at position 154 is Ser, Trp, Thr, Asp, or Glu; the amino acid at position 156 is Leu, Asp, Ile, Val, Asn, Glu, or Gln; the amino acid at position 158 is Ser, Thr, or Cys; the amino acid at position 159 is Val, Thr, Leu, or Ile; the amino acid at position 162 is Ser, Thr, Gly, or Ala; the amino acid at position 163 is Gly, Ala, or is missing; the amino acid at position 164 is Phe or is missing; and the amino acid at position 165 is Arg, Lys, Gly, or Ala.The amino acid at position 166 is Ala, Arg, Met, Lys, or Phe; the amino acid at position 167 is Val, Ile, Leu, or His; the amino acid at position 168 is Ser, Thr, Gln, or Asn; the amino acid at position 169 is Val, His, Ile, Leu, Ser, or Thr; the amino acid at position 170 is Phe, Ile, Leu, or Val; the amino acid at position 171 is Glu, Asn, Gln, or Asp; the amino acid at position 172 is Val, Ala, Arg, Ile, Leu, Gly, Lys, Asp, or Glu; the amino acid at position 175 is Ser, Arg, Thr. The amino acid at position 176 is Val, Leu, or Ile; the amino acid at position 177 is Arg, Lys, Leu, Val, or Ile; the amino acid at position 179 is Thr, Ile, Val, Leu, or Ser; the amino acid at position 180 is Leu, Phe, Ile, Val, Ser, or Thr; the amino acid at position 181 is Gly, Thr, Gln, Asn, or Ser; the amino acid at position 182 is Ala, Leu, Phe, Val, or Ile; the amino acid at position 183 is Thr, Ser, Ala, or Gly; the amino acid at position 184 is Leu, Thr, Ser, or Il. The amino acid at position 185 is Arg, Gly, Asp, Lys, Glu, or Ala; the amino acid at position 186 is Pro, Val, Ile, Leu, Asn, or Gln; the amino acid at position 187 is Asp, Thr, Glu, or Ser; the amino acid at position 188 is His, Gly, or Ala; the amino acid at position 189 is Ala, Arg, Pro, Lys, Gly, or is missing; the amino acid at position 190 is Leu, Asn, Ile, Val, Gln, or is missing; the amino acid at position 191 is Tyr or is missing; the amino acid at position 192 is Ser, Ile, Val, ... Leu, Thr, or Asn; amino acid at position 193 is Thr, Ser, Glu, or Asp; amino acid at position 194 is Thr or Ser; amino acid at position 195 is Met or Thr; amino acid at position 196 is Gln, His, Leu, Asn, Ile, Val, Thr, or Ser; amino acid at position 197 is Ala, Gly, Ile, Val, or Leu; amino acid at position 198 is Thr, Glu, Ser, Asp, Gly, or Ala; amino acid at position 199 is Pro, Lys, or Arg; amino acid at position 200 is Asn, Ser, Thr, Gln, Ala, or Gly.The amino acid at position 201 is Ala, Leu, Glu, Ile, Asp, or Trp; the amino acid at position 202 is Ser, Asp, Phe, Ile, Val, Thr, Glu, or Leu; the amino acid at position 203 is His, Pro, Gly, Ala, Thr, or Ser; the amino acid at position 204 is Ile, Trp, His, Leu, Val, Ala, or Gly; the amino acid at position 205 is Ser, Asn, Leu, Val, Thr, Gln, or Ile; the amino acid at position 206 is Ala, Gly, Asp, Tyr, Glu, Lys, or Arg; the amino acid at position 207 is Phe, V... The amino acid at position 208 is Asn, Ser, Pro, Gln, Thr, Val, Ile, or Leu; the amino acid at position 210 is Arg, Asp, Glu, Lys, Ser, or Tyr; the amino acid at position 211 is Ile, Ser, Leu, Val, or Thr; the amino acid at position 212 is Val, Ala, Ile, Leu, Glu, Gly, or Asp; the amino acid at position 214 is Pro, Lys, or Arg; the amino acid at position 215 is Ser or Thr; the amino acid at position 217 is Tyr or Phe; the amino acid at position 218 is Arg, Lys, Thr, or Ser. The amino acid at position 219 is Val, Ile, Leu, or Ala; the amino acid at position 220 is Cys, Leu, Ile, Val, Thr, or Ser; the amino acid at position 221 is Pro or His; the amino acid at position 222 is Leu, Arg, Lys, Ile, Val, Thr, or Ser; the amino acid at position 224 is Asn, Gln, Thr, or Ser; the amino acid at position 225 is Asp, Arg, Glu, Lys, Ser, or Thr; the amino acid at position 226 is Thr, Ser, Gln, or Asn; the amino acid at position 227 is Asp, Leu, Glu, Ile, Val, or is missing; the amino acid at position 228... The amino acid at position 229 is Thr, Ser, or deleted; the amino acid at position 230 is Leu, Ile, Val, or deleted; the amino acid at position 231 is Gly, Ala, or deleted; the amino acid at position 232 is Ile, Leu, Val, or deleted; the amino acid at position 233 is Pro or deleted; the amino acid at position 234 is Ala, Pro, Gly, or deleted; the amino acid at position 235 is Asp, Ile, Leu, Glu, or Val; the amino acid at position 236 is Val, Ser, Ile, Leu, Thr, Asp, or Glu; the amino acid at position 237 is Ala, Phe, or Tyr.The amino acid at position 238 is Ala, Gly, Ser, or Thr; the amino acid at position 239 is Val, Ser, Ile, Leu, Thr, Ala, or Gly; the amino acid at position 240 is Leu, Val, or Ile; the amino acid at position 243 is Asp or Glu; the amino acid at position 249 is Asn, Gln, Thr, or Ser; the amino acid at position 252 is Leu, Ile, Val, or Met; the amino acid at position 257 is Thr or Ser; the amino acid at position 259 is His, Ile, Val, or Leu; the amino acid at position 266 is Ala, Ile, Leu, or Val; the amino acid at position 267 is Cy. The amino acid at position 268 is His, Arg, Lys, or Tyr; the amino acid at position 272 is Asp or Glu; the amino acid at position 273 is Val, Met, Ile, or Leu; the amino acid at position 274 is Val, Ile, Leu, or Met; the amino acid at position 278 is Gly or Ala; the amino acid at position 279 is Glu, Asp, Gly, or Val; the amino acid at position 281 is Leu, Ile, Val, Gly, or Ala; the amino acid at position 282 is Asn, Leu, or Ile; the amino acid at position 285 is Asn, Gln, Thr, or Ser; the amino acid at position 286 is L... The amino acid at position 287 is Leu, Ile, or Val; the amino acid at position 290 is Pro, Gln, Asn, Lys, or Arg; the amino acid at position 291 is Leu, Ile, or Val; the amino acid at position 292 is Lys, Arg, Ile, Leu, or Val; the amino acid at position 293 is Glu, Asp, Asn, or Gln; the amino acid at position 294 is Ser, Asn, Thr, Gln, Arg, or Lys; the amino acid at position 295 is Thr or Ser; the amino acid at position 296 is Gln, Asn, or His; the amino acid at position 297 is Leu, Ile, or Val. The amino acid at position 300 is either l or Met; the amino acid at position 301 is Glu, Asp, Gly, or Ala; the amino acid at position 302 is Ser, Pro, Thr, Gly, or Ala; the amino acid at position 304 is Lys, Arg, Gln, or Asn; the amino acid at position 313 is Val, Leu, or Ile; the amino acid at position 314 is His, Glu, Asn, Asp, or Gln; the amino acid at position 315 is Ala, Cys, Gly, Thr, or Ser; the amino acid at position 316 is Ala, Ile, Leu, or Val; and the amino acid at position 317 is Met, Leu, Val, or Ile.The amino acid at position 319 is Met, Leu, Val, or Ile; the amino acid at position 320 is Val, Ile, Leu, Ala, or Gly; the amino acid at position 321 is Arg, Lys, or Pro; the amino acid at position 322 is Ile, Leu, Val, or Phe; the amino acid at position 323 is Gly, Ile, Leu, or Val; the amino acid at position 324 is Leu, Ile, Val, Thr, or Ser; the amino acid at position 336 is Ser, Thr, Gln, or Asn; the amino acid at position 339 is Asn, Lys, Gln, or Arg; the amino acid at position 350 is Arg, Lys, Asn, or... Gln; the amino acid at position 351 is Glu or Asp; the amino acid at position 353 is Lys or Arg; the amino acid at position 354 is Gln, Asn, Lys, or Arg; the amino acid at position 355 is Phe, Ile, Leu, or Leu; the amino acid at position 356 is Lys or Arg; the amino acid at position 360 is Ile, Val, Leu, Gly, or Ala; the amino acid at position 363 is Gln, Ala, Cys, Glu, Phe, Gly, His, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp; the amino acid at position 364 is Ile, Ala, Cys, or Glu. The amino acid at position 365 is Leu, Ala, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 366 is Gly, Ala, Cys, Phe, His, Ile, Lys, Leu, Met, Asn, Ser, Thr, or Val; the amino acid at position 367 is Ser, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Pro, G ln, Arg, Thr, Val, or Trp; the amino acid at position 368 is Tyr, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Trp; the amino acid at position 369 is Leu, Ala, Cys, Asp, Phe, Gly, Ile, Met, Thr, or Val; the amino acid at position 370 is Leu, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr;The amino acid at position 371 is Gln, Ala, Cys, Asp, Glu, Phe, Gly, Ile, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp; the amino acid at position 372 is Gln, Ala, Cys, Asp, Phe, Gly, His, Ile, Leu, Asn, Arg, Ser, Val, or Tyr; the amino acid at position 373 is Asn, Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Gln, Ser, Thr, Val, or Trp; the amino acid at position 374 is Arg or Lys; the amino acid at position 376 is Phe, Ile, V... al or Leu; the amino acid at position 378 is Glu or Asp; the amino acid at position 381 is Leu, Ile, or Val; the amino acid at position 388 is Ala, Thr, Gly, or Ser; the amino acid at position 395 is Arg or Lys; the amino acid at position 396 is Glu, Gln, Asp, Asn, Ala, or Gly; the amino acid at position 399 is Asp, Gln, Glu, or Asn; the amino acid at position 400 is Asn, Thr, Ser, Glu, Gln, or Asp; the amino acid at position 401 is Thr, Ser, Gly, or Ala; the amino acid at position 402 is Phe, Ile, Val, or Leu; the amino acid at position 40... The amino acid at position 6 is Asp or Glu; the amino acid at position 408 is Leu, Ile, Val, or Met; the amino acid at position 410 is Gly, Ile, Val, Ala, or Leu; the amino acid at position 414 is Ala, Gly, Asp, or Glu; the amino acid at position 416 is Ser, Asn, Thr, Gln, Glu, or Asp; the amino acid at position 417 is Ser, Arg, Lys, Thr, Ala, or Gly; the amino acid at position 423 is Lys, Arg, Asn, or Gln; the amino acid at position 431 is Arg or Lys; the amino acid at position 432 is Gln, Asn, Asp, or Glu; the amino acid at position 436... The amino acid at position 440 is Arg, Lys, Asp, or Glu; the amino acid at position 440 is Asn, Gln, Lys, or Arg; the amino acid at position 442 is Leu, Ile, or Val; the amino acid at position 447 is Ser, Lys, Thr, or Arg; the amino acid at position 448 is Ala, Gly, Thr, or Ser; the amino acid at position 451 is Gln, Asn, or Met; the amino acid at position 453 is Gly or Ala; the amino acid at position 455 is Ala, Leu, Ile, or Val; the amino acid at position 457 is Leu, Ile, or Val; and the amino acid at position 467 is Val, Ile, Leu, Gly, or Ala.The amino acid at position 471 is Gly or Ala; the amino acid at position 475 is Ser, Thr, Gln, or Asn; the amino acid at position 483 is Gly or Ala; the amino acid at position 493 is Gln, Asn, or Gly; the amino acid at position 504 is Val, Leu, or Ile; the amino acid at position 506 is Asp, Glu, or His; the amino acid at position 509 is Asp, Glu, Gln, or Asn; the amino acid at position 510 is Ser, Thr, Gly, or Ala; the amino acid at position 512 is Glu or Asp; the amino acid at position 515 is Gly, Ala, Thr, or Ser; the amino acid at position 516... The amino acid at position 517 is Gln, Asn, or His; the amino acid at position 519 is Ile, Val, or Leu; the amino acid at position 519 is Asp, Asn, Glu, Gly, or Gln; the amino acid at position 522 is Val, Glu, Pro, Ile, Leu, or Asp; the amino acid at position 525 is Glu or Asp; the amino acid at position 526 is Leu, Ile, Val, or Met; the amino acid at position 539 is Val, Leu, or Ile; the amino acid at position 555 is Val, Leu, Ile, or Ala; the amino acid at position 556 is Trp, Phe, Thr, or Tyr; the amino acid at position 557... The amino acid at position 558 is Arg, Cys, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 559 is Lys, Ala, Cys, Phe, Gly, His, Ile, Lys, Leu, Asn, Gln, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 560 is Cys, Ala, P he, Gly, Ile, Met, Asn, Arg, Ser, Thr, or Val; the amino acid at position 561 is Lys, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 562 is Asn, Cys, Asp, Glu, Gly, His, Leu, Met, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 563 is Val, Ala, Cys, Asp, Phe, His, Ile, Leu, Met, Asn, Gln, Thr, or Trp;The amino acid at position 564 is Ala, Cys, Gly, Met, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 571 is Ser, Thr, or Cys; the amino acid at position 575 is Val, Leu, Ile, Asp, or Glu; the amino acid at position 577 is Met, Leu, Val, or Ile; the amino acid at position 579 is Glu, Asp, Asn, or Gln; the amino acid at position 583 is Asp or Glu; the amino acid at position 589 is Met, Ile, Val, or Leu; the amino acid at position 590 is Met, Ile, Val, or Leu; the amino acid at position 593... The amino acid at position 595 is Met, Leu, Val, or Ile; the amino acid at position 596 is Arg, Lys, Asn, or Gln; the amino acid at position 597 is Gln, Asn, or His; the amino acid at position 607 is Ala, Gly, Ile, Leu, or Val; the amino acid at position 608 is Asp, Glu, Gln, or Asn; the amino acid at position 612 is Tyr, His, or Phe; the amino acid at position 617 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 618 is Gln, Asn, or His; and the amino acid at position 625 is Arg, Lys, Thr, or Ser; the amino acid at position 626 is Met, Leu, Val, or Ile; the amino acid at position 628 is Leu, Val, or Ile; the amino acid at position 633 is Ile, Leu, Val, or Met; the amino acid at position 634 is Leu, Ile, Val, or Met; the amino acid at position 642 is Arg, Lys, or Met; the amino acid at position 646 is Leu, Ala, Cys, Gly, Ile, Met, Asn, Gln, Ser, Thr, or Val; the amino acid at position 647 is Leu, Asp, Gly, Met, Asn, Gln, or Thr; the amino acid at position 648... The amino acids at position 649 are Met, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 650 is Thr, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Met, Asn, Gln, Arg, Ser, Thr, Trp, or Tyr.The amino acid at position 651 is Glu, Ala, Cys, Asp, Gly, His, Ile, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 652 is Leu, Cys, Phe, Ile, Lys, Met, Pro, Arg, Ser, Thr, or Val; the amino acid at position 653 is Thr, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Pro, Arg, Ser, Val, or Trp; the amino acid at position 654 is Thr, Ala, Cys, Phe, Ile, Lys, Leu, M The amino acid at position 655 is Trp, Phe, or Tyr; the amino acid at position 658 is Gly, Lys, Ala, or Arg; the amino acid at position 663 is Gly or Ala; the amino acid at position 664 is Asp, Glu, Gln, or Asn; the amino acid at position 668 is Ala, Gly, Ser, or Thr; the amino acid at position 669 is Gln, Asn, or His; the amino acid at position 671 is Asn, Gln, Thr, or Ser; the amino acid at position 675 is Ile, Val, Ile, Thr, or Ser; the amino acid at position 678 is Met. Ile, Ala, Leu, Ser, or Thr; the amino acid at position 682 is Pro, Asn, or Gln; the amino acid at position 683 is Ser, Thr, or Pro; the amino acid at position 685 is Asp, Glu, Asp, or Asn; the amino acid at position 694 is Asp, Glu, Ala, or Gly; the amino acid at position 697 is Asn, Gln, Thr, or Ser; the amino acid at position 704 is Glu, Asp, Ala, or Gly; the amino acid at position 714 is Ala or Gly; the amino acid at position 721 is Ser, Thr, or Phe; the amino acid at position 722 is Ser, Thr, Gln, or Asn; the amino acid at position 72... The amino acid at position 4 is Ser or Thr; the amino acid at position 734 is His, Asn, or Gln; the amino acid at position 736 is Val, Leu, Ile, or Ala; the amino acid at position 737 is Lys, Arg, Asn, or Gln; the amino acid at position 739 is Ala, Gly, Thr, or Ser; the amino acid at position 740 is Ser, Thr, or Met; the amino acid at position 741 is Gly, Ala, Gln, or Asn; the amino acid at position 742 is Ile, Leu, Val, Ala, or Gly; the amino acid at position 743 is Gly or is missing; the amino acid at position 745 is Gly, Ala, Glu, or Asp.The amino acid at position 751 is Thr, Ser, Gly, or Ala; the amino acid at position 753 is Gln, Asn, Lys, or Arg; the amino acid at position 754 is Thr or Ser; the amino acid at position 756 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 757 is Val, Leu, or Ile; the amino acid at position 766 is Ile, Leu, or Val; the amino acid at position 771 is Arg, Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Asn, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 772 is A The amino acid at position 773 is Asp, Ala, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 774 is Gln, Ala, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; The amino acid at position 775 is Val, Ala, Cys, Asp, Glu, Gly, His, Ile, Asn, Pro, Gln, Arg, Ser, Thr, or Tyr; the amino acid at position 776 is Leu, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 777 is Pro, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 7... The amino acid at position 78 is Phe, Ala, His, Ile, Leu, Met, Asn, Gln, Ser, Val, Trp, or Tyr; the amino acid at position 779 is Gln, Ala, Cys, Asp, Glu, Gly, His, Lys, Leu, Asn, Pro, Arg, Ser, Thr, or Val; the amino acid at position 780 is Ala, Cys, Asn, Pro, Gln, or Ser; and the amino acid at position 781 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr.The amino acid at position 782 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 783 is Pro, Ala, Cys, Asp, Glu, Gly, His, Asn, Gln, Arg, Ser, Thr, or Val; the amino acid at position 784 is Leu, Ala, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Val, or Trp; the amino acid at position 785... The amino acid at position 786 is Asn, Ala, Cys, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 787 is His, Asn, or Gln; the amino acid at position 788 is Tyr or Met; the amino acid at position 789 is Ala, Lys, or Arg; the amino acid at position 790 is Tyr or Thr; the amino acid at position 791 is Arg, Lys, Gly, or Ala; The amino acid at position 792 is Leu, Ile, Val, Thr, or Ser; the amino acid at position 796 is Asp or Glu; the amino acid at position 797 is Ser, Thr, or Ala; the amino acid at position 802 is Glu, Lys, Asp, Asn, or Gln; the amino acid at position 806 is Gln, Asp, Glu, Asn, or His; the amino acid at position 810 is Lys, Arg, or Thr; the amino acid at position 819 is Arg, Lys, or His; the amino acid at position 829 is Lys, Ser, Ala, or Pro; the amino acid at position 832 is Ala, The amino acid at position 833 is Gly, Ala, Asp, or Glu; the amino acid at position 842 is Leu, Ile, Val, or Pro; the amino acid at position 847 is Gln, Asn, Asp, or Glu; the amino acid at position 848 is Ile, Leu, or Val; the amino acid at position 849 is Val, Leu, Ile, Gly, or Ala; the amino acid at position 855 is Thr, Ser, or Met; the amino acid at position 860 is Ile, Leu, or Val; and the amino acid at position 864 is His, Asn, or Gln.

[0047] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species within the phylum Pteridophyta. The phylogenetic analysis of ferns used herein is based on the classification of extant ferns by ARSmith et al., TAXON, 55:705-731 (2006). A shared phylogenetic analysis based on the ARSmith classification is shown in… Figure 1 Other phylogenetic classifications of extant ferns are known to those skilled in the art. Additional information on the phylogeny of ferns can be found at mobot.org / MOBOT / research / APweb / (accessible with the prefix "www") and Schuettpelz E. and Pryer KM, TAXON 56:1037-1050 (2007), based on three plastid genes. Other ferns and other primitive plant species can be found at homepages.caverock.net.nz / ~bj / fern / list.htm (accessible with the prefix http: / / ).

[0048] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the class Psilotopsida. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Psilotales within the class Psilotales. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Ophioglossales within the class Psilotales. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the family Psilotaceae within the order Ophioglossaceae within the class Psilotales. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the family Ophioglossaceae within the order Ophioglossaceae within the class Psilotales. In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species in the genera *Botrychium*, *Botrypus*, *Helminthostachys*, *Ophioderma*, *Cheiroglossa*, *Sceptridium*, or *Mankyua*.

[0049] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a species of the class Polypodiopsida / Pteridopsida. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Osmundales (Osmunda regalis); family Osmundaceae. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Hymenophyllales; family Hymenophyllaceae. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Gleicheniales; family Gleicheniaceae, Dipteridaceae or Matoniaceae. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the order Schizaeales; family Lygodiaceae, Anemiaceae or Schizaeaceae.In some implementations, the nucleic acid encoding the PtIP-83 polypeptide is derived from the order Cyperales; fern species of the genus *Lygodium* in the family Cyperaceae, selected from, but not limited to: *Lygodium artticulatum*, *Lygodium circinatum*, *Lygodium conforme*, *Lygodium cubense*, *Lygodium digitatum*, *Lygodium flexuosum*, *Lygodium heterodoxum*, *Lygodium japonicum*, *Lygodium kerstenii*, *Lygodium lanceolatum*, *Lygodium longifolium*, *Lygodium merrilii*, *Lygodium micans*, *Lygodium microphyllum*, and *Lygodium*. The species include *Lygodium microstachyum*, *Lygodium oligostachyum*, *Lygodium palmatum*, *Lygodium polystachyum*, *Lygodium radiatum*, *Lygodium reticulatum*, *Lygodium salicifolium*, *Lygodium scandens*, *Lygodium smithianum*, *Lygodium subareolatum*, *Lygodium trifurcatum*, *Lygodium venustum*, *Lygodium versteeghii*, *Lygodium volubile*, and *Lygodium yunnanense*. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the Order Salviniales; Family Marsileaceae or Family Salviniaceae.In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the Order Cyatheales; families Thyrsopteridaceae, Loxsomataceae, Culcitaceae, Plagiogyriaceae, Cibotiaceae, Cyatheaceae, Dicksoniaceae, or Metaxyaceae.

[0050] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the order Polypodiaceae; family Lindsaeaceae, Saccolomataceae, Cystodiaceae, Dennstaedtiaceae, Pteridaceae, Aspleniaceae, Thelypteridaceae, Woodsiaceae, Onocleaceae, Blechnaceae, Dryopteridaceae, Lomariopsidaceae, Tectariaceae, Oleandraceae, Davalliaceae, or Polypodiaceae.

[0051] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the genus *Adiantum* in the family Pteridaceae, order Polypodiales, selected from, but not limited to, *Adiantum ethiopicum*, *Adiantum aleuticum*, *Adiantum bonatianum*, *Adiantum cajennense*, *Adiantum capillus-junonis*, *Adiantum capillus-veneris*, *Adiantum caudatum*, *Adiantum chienii*, *Adiantum chilense*, *Adiantum cuneatum*, *Adiantum cunninghamii*, *Adiantum davidii*, *Adiantum diaphanum*, *Adiantum edentulum*, and *Adiantum davidii*. Adiantum edgeworthii, Adiantum excisum, Adiantum fengianum, Adiantum fimbriatum, Adiantum flabellulatum, Adiantum formosanum, Adiantum formosum, Adiantum fulvum, Adiantum gravesii, Adiantum hispidulum, Adiantum induratum, Adiantum jordanii, Adiantum juxtapositum, Adiantum latifolium, Adiantum leveillei, Adiantum lianxianense, Adiantum malesianum, Adiantum mariesii, Adiantum unifolium monochlamys, Adiantum myriosorum, Adiantum obliquum, Adiantum olgasaAdiantum pedatum, Adiantum pentadactylon, Adiantum peruvianum, Adiantum philippense, Adiantum princeps, Adiantum pubescens, Adiantum raddianum, Adiantum reniforme, Adiantum roborowskii, Adiantum serratodentatum, Adiantum sinicum, Adiantum soboliferum, Adiantum subcordatum, Adiantum tenerum, Adiantum terminatum, Adiantum tetraphyllum, Adiantum trapeziforme, Adiantum slender-leaved venustum), Adiantum viridescens, and Adiantum viridimontanum.

[0052] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus *Asplenium* in the family Aspleniaceae of the order Polypodiales.

[0053] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the genus *Asplenium* in the family Aspleniaceae, order Polypodiales, selected from, but not limited to, *Asplenium adiantum*, *Asplenium adulterinum*, *Asplenium aequibasis*, *Asplenium ethiopicum*, *Asplenium africanum*, *Asplenium × alternating-leaved*, *Asplenium angustum*, *Asplenium antiquum*, *Asplenium ascensionis*, *Asplenium attenuatum*, *Asplenium aureum*, *Asplenium auritum*, *Asplenium australasicum*, *Asplenium azoris*, *Asplenium bifrons*, and *Asplenium*. billottii, Asplenium bipinnatifidum, Asplenium brachycarpum, Asplenium bradleyi, Asplenium bulbiferum, Asplenium caudatum, Asplenium ceterach, Asplenium compressum, Asplenium congestum, Asplenium corderoanum, Asplenium crinicaule, Asplenium cristatum, Asplenium cuneifolium, Asplenium cymbifolium, Asplenium daghestanicum, Asplenium dalhousiae, Asplenium dareoides, Asplenium daghestanicum Asplenium daucifolium, Asplenium difforme, Asplenium fissum, Asplenium dimorphum, Asplenium divaricatum, Aspleniumdregeanum, Asplenium×ebenoides, Asplenium ecuadorense, Asplenium feei Kunze, Asplenium fissum, Aspleniumflabellifolium, Asplenium flaccidum, Asplenium fontanum, Asplenium forisiense, Asplenium formosum, Asplenium gemmiferum, Asplenium×germanicum, Asplenium gueinzii, Asplenium goudeyi, Asplenium hemionitis, Aspleniumhermannii-christii, Asplenium hookerianum, Asplenium hybridum, Asplenium incisum), Asplenium×jacksonii, Asplenium×kenzoi, Asplenium laciniatum, Asplenium lamprophyllum, Asplenium laserpitiifolium, Asplenium lepidum, Asplenium listeri, Asplenium longissimum, Asplenium lucidum, Asplenium lunulatum, Asplenium lyallii, Asplenium macedonicum, Asplenium majoricum, Asplenium marinum, Asplenium ×microdon, Asplenium milnei, Asplenium montanum, Asplenium musifolium, Asplenium nidus, Asplenium normale, Asplenium obliquum, Asplenium oblongifolium, Asplenium obovoidum obovatum, AspleniumAsplenium obtusatum, Asplenium oligolepidum, Asplenium oligophlebium, Asplenium onopteris, Asplenium pacificum, Asplenium palmeri, Asplenium petrarchae, Asplenium pinnatifidum, Asplenium planicaule, Asplenium platybasis, Asplenium platyneuron, Asplenium polyodon, Asplenium praemorsum, Asplenium prolongatum, Asplenium resiliens, Asplenium rhizophyllum, Asplenium richardii, Asplenium Asplenium rutamuraria, Asplenium rustifolium, Asplenium sagittatum, Asplenium sandersonii, Asplenium × sarniense, Asplenium schizotrichum, Asplenium schweinfurthii, Asplenium scleroprium, Asplenium scolopendrium (also known as Phylitis scolopendrium), Asplenium seelosii, Asplenium septentrionale, Asplenium × trichomonanes, Asplenium serra, Asplenium serratum, Asplenium sessilifolium, Asplenium shuttleworthianum, Asplenium simplicifrons, Asplenium splendens, Asplenium surrogatum, Aspleniumtenerum), Asplenium terrestre, Asplenium theciferum, Asplenium thunbergii, Asplenium trichomanes, Asplenium tutwilerae, Asplenium vespertinum, Aspleniumvieillardii, Asplenium virens, Asplenium viride), Aspleniumvittiforme and Asplenium viviparum.

[0054] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus *Blecnum* in the family Blechnaceae, order Polypodiales.

[0055] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from the genera *Acrophorus*, *Acrorumohra*, *Anapausia*, *Arachniodes*, *Bolbitis*, *Ctenitis*, *Cyclodium*, *Cyrtogonellum*, *Cyrtomidictyum*, *Cyrtomium*, *Diacalpe*, *Didymochlaena*, *Dryopsis*, *Dryopteris*, *Elaphoglossum*, *Hypodematium*, and *Lastreop* of the family Dryopteridaceae in the order Dryopteridaceae. Fern species of the genera *Leptorumohra*, *Leucostegia*, *Lithostegia*, *Lomagramma*, *Maxonia*, *Megalastrum*, *Olfersia*, *Peranema*, *Phanerophlebia*, *Phanerophlebiopsis*, *Polybotrya*, *Polystichopsis*, *Polystichum*, *Rumohra*, *Sorolepidium*, *Stigmatopteris*, or *Teratophyllum*.

[0056] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus *Polystichum* in the family Dryopteridaceae, order Polypodiaceae. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the genus *Polystichum* in the family Dryopteridaceae, order Polypodiaceae, selected from, but not limited to: *Polystichuma canthophyllum*, *Polystichum acrostichoides*, *Polystichuma culeatum*, *Polystichum acutidens*, *Polystichum cutipinnulum*, *Polystichum alcicorne*, *Polystichum aleuticum*, *Polystichum andersonii*, *Polystichum atkinsonii*, *Polystichum australiense*, *Polystichum bakerianum*, *Polystichum biaristatum*, *Polystichum bomiense*, *Polystichum bonseyi*, and *Polystichum simonii*. Polystichum braunii, Polystichum brachypterum, Polystichum calderonense, Polystichum californicum, Polystichum capillipes, Polystichum castaneum, Polystichum chilense, Polystichum christii Ching, Polystichum chunii Ching, Polystichum craspedosorum, Polystichum cyclolobum, Polystichum cystostegia, Polystichum deltodon, Polystichum dielsii, Polystichum discretum, Polystichum drepanum, Polystichumdudleyi, Polystichum duthiei, Polystichum echinatum, Polystichum erosum, Polystichum excellens, Polystichum eximium, Polystichum falcinipinnum, Polystichum falcinellum, Polystichum fallax, Polystichum formosanum, Polystichum gongboense, Polystichum grandifrons, Polystichum gymnocarpium, Polystichum haleakalense, Polystichum hancockii, Polystichum hecatopteron, Polystichum herbaceum, Polystichum imbricans, Polystichum Polystichum incongruum, Polystichum kruckebergii, Polystichum kwakiutlii, Polystichum lachenense, Polystichum lanceolatum, Polystichum lemmonii, Polystichum lentum, Polystichum lonchitis, Polystichum longidens, Polystichum longipaleatum, Polystichum longipes, Polystichum luctuosum, Polystichum macleae, Polystichum macrochlaenum, Polystichum makinoi, Polystichum martini, Polystichum mayebarae, Polystichum makinoi mediocre), Medog ear fern (Polystichum medogense), small ear fern (Polystichummicrochlamys), Polystichum mohrioides, Polystichum mmollissimum, Polystichum monticola, Polystichum moorei, Polystichum morii, Polystichum moupinense, Polystichum muricatum, Polystichum nakenense, Polystichum neolobatum, Polystichum nepalense, Polystichum ningshenense, Polystichum obliquum, Polystichum omeiense, Polystichum ordinatum, Polystichum orientalitibeticum, Polystichum paramoupinense, Polystichum The following are listed: parvipinnulum, Polystichumpiceopaleaceum, Polystichum polyblepharum, Polystichum prescottianum, Polystichum prionolepis, Polystichum proliferum, Polystichum pseudocastaneum, Polystichum pseudomakinoi, Polystichum punctiferum, Polystichum pungens, Polystichum qamdoense, Polystichum retrosopaleaceum, Polystichum rhombiforme, Polystichum rhomboidea, Polystichum richardii, Polystichum rigens, and Polystichum rigens. rotundilobum, Polystichum scopulinum, Polystichumsemifertile), spiny ear fern (Polystichum setiferum), Polystichum setigerum, Shaanxi ear fern (Polystichum shensiense), Polystichum silvaticum, single-winged ear fern (Polystichum simplicipinnum), Chinese ear fern (Polystichum sinense), dense-scaled ear fern (Polystichum squarrosum), budding ear fern (Polystichum stenophyllum), cat-like spiny ear fern (Polystichum stimulans), Qinling ear fern (Polystichum submite), South Asian ear fern (Polystichum tacticopterum), tail-leaved ear fern (Polystichum thomsoni), Tibetan ear fern (Polystichum tibeticum), Polystichum transvaalense, three-pronged ear fern (Polystichum tripteron), Tsus-simense (Polystichum tsus-simense), Polystichum vestitum, Polystichum wattii, Polystichum whiteleggei, Polystichum xiphophyllum, Polystichum yadongense, and Polystichum yunnanense.

[0057] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus *Rumohra* in the family Dryopteridaceae, order Polypodiales. Specifically, it is selected from, but is not limited to, *Rumohra adiantiformis*, *Rumohra aristata*, *Rumohra bartonae*, *Rumohra berteroana*, *Rumohra capuronii*, *Rumohra glandulosa*, *Rumohra humbertii*, *Rumohra linearisquamosa*, *Rumohra lokohensis*, *Rumohra madagascarica*, and *Rumohra quadrangularis*.

[0058] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species belonging to the genera *Campyloneurum*, *Drynaria*, *Lepisorus*, *Microgramma*, *Microsorum*, *Neurodium*, *Niphidium*, *Pecluma MG*, *Phlebodium*, *Phymatosorus*, *Platycerium*, *Pleopeltis*, and *Polypodium*.

[0059] In some implementations, the PtIP-83 peptide is derived from a fern species of the genus *Genus Microsorum* in the family Polypodiaceae.

[0060] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the genus *Microsorum* in the family Polypodiaceae, order Polypodiaceae, selected from, but not limited to: *Microsorum alatum*, *Microsorum angustifolium*, *Microsorum aurantiacum*, *Microsorum australiense*, *Microsorum baithoense*, *Microsorum basicordatum*, *Microsorum biseriatum*, *Microsorum brassii*, *Microsorum buergerianum*, *Microsorum chapaense*, *Microsorum cinctum*, *Microsorum commutatum*, *Microsorum congregatifolium*, *Microsorum cuneatum*, *Microsorum cuspidatum*, *Microsorum dengii*, *Microsorum egregium*, *Microsorum emeiensis*, *Microsorum ensatum*, and *Microsorum lanceolatum*. ensiforme), Microsorum excelsum, Microsorum fortunei, Microsorumgriseorhizoma, Microsorum grossum, Microsorum hemionitideum, Microsorumhenryi, Microsorum heterocarpum, Microsorum heterolobum, Microsorumhowense, Microsorum insigne), Microsorum intermedium, Microsorumkongtingense, Microsorum krayanense, Microsorum lanceolatum, Microsorum lancifolium, Microsorum lastii, Microsorum latilobatum, Microsorumleandrianum, Microsorumlineare), linguiforme, longissimum, longshengense, maculosum, maximum, membranaceum, membranifolium, microsorioides, minor, monstrosum, muliense, mutense, nanchuanense, ningpoense, normale, novae-zealandiae, ovalifolium, ovatum, palmatopedatum, Microsorum pappei, Papuan star fern (Microsorumpapuanum), Garden star fern (Microsorum parksii), Microsorum pentaphyllum, Hairy-tipped star fern (Microsorum piliferum), Pitcairn star fern (Microsorum pitcairnense), Microsorumpowellii, Winged star fern (Microsorum pteropodum), Winged star fern (Microsorum pteropus), Star fern (Microsorum punctatum), Bubble-faced star fern (Microsorum pustulatum), Creeping star fern (Microsorum rampans), Hairy-axis star fern (Microsorum revolutum), Microsorum rubidum, Microsorum samarense, Microsorum sapaense, Sarawak star fern (Microsorum sarawakense), Attached star fern (Microsorum scandens), Microsorumscolopendria, Microsorum sibomense, Microsorum sinense, Microsorum sopuense, Microsorum spectrum, Microsorum steerei, Microsorum subhemionitideum, Microsorum submarginale, Microsorum subnudum, Microsorum superficiale, Microsorum takhtajanii, Microsorum tenuipes, Microsorum tibeticum, Microsorum triglossum, Microsorum truncatum, Microsorum tsaii, Microsorum varians, Microsorum venosum, Microsorum vieillardii, Microsorum ×inaequibasis, Microsorum yiliang yiliangensis and Microsorum zippelii.

[0061] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus *Polypodium* L in the family Polypodiaceae. In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the genus *Polypodium* L in the family Polypodiaceae, order Polypodiaceae, selected from, but not limited to: *Polypodium absidatum*, *Polypodium acutifolium*, *Polypodium adiantiforme*, *Polypodium aequale*, *Polypodium affine*, *Polypodium albidopaleatum*, *Polypodium alcicorne*, *Polypodium alfarii*, *Polypodium alfredii*, *Polypodium alfredii var. curtii*, *Polypodium allosuroides*, *Polypodium alsophilicola*, *Polypodium amamianum*, *Polypodium amoenum*, *Polypodium amorphum*, *Polypodium anetioides*, *Polypodium anfractuosum*, and *Polypodium*. anguinum, Polypodium angustifolium f.remotifolia, Polypodium angustifolium var.amphostenon, Polypodium angustifoliumvar.heterolepis, Polypodium angustifolium var.monstrosa, Polypodium angustipaleatum, Polypodium angustissimum, Polypodium anisomeronvar.pectinatum, Polypodium antioquianum, Polypodium aoristisorum, Polypodium apagolepis, Polypodium apicidens, Polypodium apiculatum, Polypodium apoense, Polypodium appalachianum, Polypodium appressum, Polypodium arenarium, Polypodium argentinum, Polypodium argutum, Polypodium armatum, Polypodium aromaticum, Polypodium aspersum, Polypodium assurgens, Polypodium atrum, Polypodium auriculatum, Polypodium balaonense, Polypodium balliviani, Polypodium bamleri, Polypodium bangii, Polypodium bartlettii, Polypodium basale, Polypodium bernoullii, Polypodium biauritum, Polypodium bifrons, Polypodium blepharodes, Polypodium bolivari, Polypodium bolivianum, Polypodium bolobense, Polypodium bombycinum, Polypodium bombycinum var. insularum, Polypodium bradeorum, Polypodium bryophilum, Polypodium bryopodum, Polypodium buchtienii, Polypodium buesii, Polypodium bulbotrichum, Polypodium caceresii, Polypodium californicum f. brauscombii, Polypodium californicum f.parsonsiae, Polypodium californicum, Polypodium calophlebium, Polypodium calvum, Polypodium camptophyllarium var. abbreviatum, Polypodium capitellatum, Polypodium carpinterae, Polypodium chachapoyense, Polypodium chartaceum, Polypodium chimantense, Polypodium chiricanum, Polypodium choquetangense, Polypodium christensenii, Polypodium christii, Polypodium chrysotrichum, Polypodium ciliolepis, Polypodium cinerascens, Polypodium collinsii, Polypodium colysoides, Polypodium confluens, Polypodium conforme, Polypodium confusum, Polypodium congregatifolium, Polypodium connellii, Polypodium consimile var. bourgaeanum, Polypodium consimile var. minor, Polypodium conterminans, Polypodium contiguum, Polypodium cookii, Polypodium coriaceum, Polypodium coronans, Polypodium costaricense, Polypodium costatum, Polypodium crassifolium f. angustissimum, Polypodium crassifolium var.longipes, Polypodium crassulum, Polypodium craterisorum, Polypodium cryptum, Polypodium crystalloneuron, Polypodium cucullatum var. planum, Polypodium cuencanum, Polypodium cumingianum, Polypodium cupreolepis, Polypodium curranii, Polypodium curvans, Polypodium cyathicola, Polypodium cyathisorum, Polypodium cyclocolpon, Polypodium daguense, Polypodium damunense, Polypodium dareiformioides, Polypodium dasypleura, Polypodium decipiens, Polypodium decorum, Polypodium delicatulum, Polypodium deltoideum, Polypodium demeraranum, Polypodium denticulatum, Polypodium diaphanum, Polypodium dilatatum, Polypodium dispersum, Polypodium dissectum, Polypodium dissimulans, Polypodium dolichosorum, Polypodium dolorense, Polypodium donnell-smithii, Polypodium drymoglossoides, Polypodium ebeninum, Polypodium eggersii, Polypodium elmeri, Polypodium elongatum, Polypodium enterosoroides, Polypodium erubescens, Polypodium erythrolepis, Polypodium erythrotrichum, Polypodium eurybasis, Polypodium eurybasis var.villosum, Polypodium exornans, Polypodium falcoideum, Polypodiumfallacissimum, Polypodium farinosum, Polypodium faucium, Polypodium feei, Polypodium ferrugineum, Polypodium feuillei, Polypodium firmulum, Polypodium firmum, Polypodium flaccidum, Polypodium flagellare, Polypodium flexuosum, Polypodium flexuosum var.ekmanii, Polypodiumforbesii, Polypodium formosanum, Polypodium fraxinifoliumsubsp.articulatum, Polypodium fraxinifolium subsp.luridum、Polypodiumfructuosum、Polypodium fucoides、Polypodium fulvescens, Polypodium galeottii, Polypodium glaucum, Polypodium glycyrrhiza, Polypodium gracillimum, Polypodium gramineum, Polypodium grandifolium, Polypodium gratum, Polypodium gaveolens, Polypodium griseo-nigrum, Polypodium griseum, Polypodium guttatum, Polypodium haalilioanum, Polypodium hammatisorum, Polypodium hancockii, Polypodium haplophlebicum, Polypodium harrisii, Polypodium hastatumvar.simplex, Polypodium hawaiiense, Polypodium heanophyllum, Polypodium helleri, Polypodium hemionitidium, Polypodium henryi, Polypodium herzogii, Polypodium hesperium, Polypodium hessii, Polypodium hombersleyi, Polypodium hostmannii, Polypodium humile, Polypodium hyalinum, Polypodium iboense, Polypodium induens var. subdentatum, Polypodium insidiosum, Polypodium insigne, Polypodium intermedium subspecies masafueranum var. obtuseserratum, Polypodium intramarginale, Polypodium involutum, Polypodium itatiayense, Polypodium javanicum, Polypodium juglandifblium, Polypodium kaniense, Polypodium knowltoniorum, Polypodium kyimbilense, Polypodium l′herminieri var. costaricense, Polypodium lachniferum f. incurvata, Polypodium lachniferum var. glabrescens, Polypodium lachnopus, Polypodium lanceolatum var. complanatum, Polypodium lanceolatum var. trichophorum, Polypodium latevagans, Polypodium laxifrons, Polypodium laxifrons var.lividum, Polypodium lehmannianum, Polypodium leiorhizum, Polypodium leptopodon, Polypodium leuconeuron var. angustifolia, Polypodium leuconeuron var. latifolium, Polypodium leucosticta, Polypodium limulum, Polypodium lindigii, Polypodium lineatum, Polypodium lomarioides, Polypodium longifrons, Polypodium loretense, Polypodium loriceum var. umbraticum, Polypodium loriforme, Polypodium loxogramme f. gigas, Polypodium ludens, Polypodium luzonicum, Polypodium lycopodioides f. obtusum, Polypodium lycopodioides L., Polypodium macrolepis, Polypodium macrophyllum, Polypodium macrosorum, Polypodium macrosphaerum, Polypodium maculosum, Polypodium madrense, Polypodium manmeiense, Polypodium margaritiferum, Polypodium maritimum, Polypodium martensii, Polypodium mayoris, Polypodium megalolepis, Polypodium melanotrichum, Polypodium menisciifolium var.pubescens, Polypodium meniscioides, Polypodium merrillii, Polypodium mettenii, Polypodium mexiae, Polypodium microsorum, Polypodium militare, Polypodium minimum, Polypodium minusculum, Polypodium mixtum, Polypodium mollendense, Polypodium mollissimum, Polypodium moniliforme var. minus, Polypodium monoides, Polypodium monticola, Polypodium montigenum, Polypodium moritzianum, Polypodium moultonii, Polypodium multicaudatum, Polypodium multilineatum, Polypodium multisorum, Polypodium munchii, Polypodium muscoides, Polypodium myriolepis, Polypodium myriophyllum, Polypodium myriotrichum, Polypodium nematorhizon, Polypodium nemorale, Polypodium nesioticum, Polypodium nigrescentium, Polypodium nigripes, Polypodium nigrocinctum, Polypodium nimbatum, Polypodium nitidissimum, Polypodium nitidissimum var. latior, Polypodium nubrigenum, Polypodium oligolepis, Polypodium oligosorum, Polypodium oligosorum, Polypodium olivaceum, Polypodium olivaceum var.elatum, Polypodium oodes, Polypodium oosphaerum, Polypodium oreophilum, Polypodium ornatissimum, Polypodium ornatum, Polypodium ovatum, Polypodium oxylobum, Polypodium oxypholis, Polypodium pakkaense, Polypodium pallidum, Polypodium palmatopedatum, Polypodium palmeri, Polypodium panamense, Polypodium parvum, Polypodium patagonicum, Polypodium paucisorum, Polypodium pavonianum, Polypodium pectinatum var.caliense, Polypodium pectinatum var.hispidum, Polypodium pellucidum, Polypodium pendulum var.boliviense, Polypodium percrassum, Polypodium perpusillum, Polypodium peruvianum var.subgibbosum, Polypodium phyllitidis var.elongatum, Polypodium pichinchense, Polypodium pilosissimum, Polypodium pilosissimum var.glabriusculum, Polypodium pilossimum var.tunguraquensis, Polypodium pityrolepis, Polypodium platyphyllum, Polypodium playfairii, Polypodium plebeium var.cooperi, Polypodium plectolepidioides, Polypodium pleolepis, Polypodium plesiosorum var.i, Polypodium podobasis, Polypodiumpodocarpum, Polypodium poloense, Polypodium polydatylon, Polypodiumpolypodioides var.aciculare, Polypodium polypodioides var.michauxianum, Polypodium praetermissum, Polypodium preslianum var.immersum, Polypodiumprocerum, Polypodium procerum, Polypodium productum, Polypodium productum, Polypodium prolongilobum, Polypodium propinguum, Polypodium proteus, Polypodiumpruinatum, Polypodium pseudocapillare, Polypodium pseudofraternum, Polypodiumpseudonutans, Polypodium pseudoserratum, Polypodium pulcherrimum, Polypodiumpulogense, Polypodium pungens, Polypodium purpusii, Polypodium radicale, Polypodium randallii, Polypodium ratiborii, Polypodium reclinatum, Polypodiumrecreense, Polypodium repens var.abruptum, Polypodium revolvens, Polypodium rhachipterygium, Polypodium rhomboideum, Polypodium rigens, Polypodium robustum, Polypodium roraimense, Polypodium roraimense, Polypodium rosei, Polypodium rosenstockii, Polypodium rubidum, Polypodium rudimentum, Polypodium rusbyi, Polypodium sablanianum, Polypodium sarmentosum, Polypodium saxicola, Polypodiumschenckii, Polypodium schlechteri, Polypodium scolopendria, Polypodium scolopendria, Polypodium scolopendrium, Polypodium scouleri, Polypodium scutulatum, Polypodium segregatum, Polypodium semihirsutum, Polypodium semihirsutum var. fuscosetosum, Polypodium senile var. minor, Polypodium sericeolanatum, Polypodium serraeforme, Polypodium serricula, Polypodium sesquipedala, Polypodium sessilifolium, Polypodium setosum var.calvum, Polypodium setulosum, Polypodium shaferi, Polypodium sibomense, Polypodium siccum, Polypodium simacense, Polypodium simulans, Polypodiumsingeri, Polypodium sinicum, Polypodium sintenisii, Polypodium skutchii, Polypodium sloanei, Polypodium sodiroi, Polypodium sordidulum, Polypodiumsordidum, Polypodium sphaeropteroides, Polypodium sphenodes, Polypodium sprucei, Polypodium sprucei var.furcativenosa, Polypodium steirolepis, Polypodiumstenobasis, Polypodium stenolepis, Polypodium stenopterum, Polypodiumsubcapillare, Polypodium subflabelliforme, Polypodium subhemionitidium, Polypodium subinaequale, Polypodium subintegrum, Polypodium subspathulatum, Polypodium subtile, Polypodium subvestitum, Polypodium subviride, Polypodiumsuperficiale var.attenuatum, Polypodium superficiale var.chinensis, Polypodiumsursumcurrens, Polypodium tablazianum, Polypodium taenifolium, Polypodiumtamandarei, Polypodium tatei, Polypodium tenuiculum var. acrosora、Polypodium tenuiculum var.Brasiliense, Polypodium tenuilore, Polypodium tenuinerve, Polypodium tepuiense, Polypodium teresae, Polypodium tetragonum var. incompletum, Polypodium thysanolepis var. bipinnatifidum, Polypodium thyssanolepis, var. thyssanolepis, Polypodium thyssanolepsi, Polypodium tobagense, Polypodium trichophyllum, Polypodium tridactylum, Polypodium tridentatum, Polypodium trifurcatum var. brevipes, Polypodium triglossum (Three-leafed Polypodium), Polypodium truncatulum, Polypodium truncicola var. major, Polypodium truncicola var. minor, Polypodium tuberosum, Polypodium tunguraguae, Polypodium turquinum, Polypodium turrialbae, Polypodium ursipes, Polypodium vagans, Polypodium valdealatum, Polypodium versteegii, Polypodium villagranii, Polypodium virginianum f. cambroideum, Polypodium virginianum f. peraferens, Polypodium vittarioides, Polypodium vulgare (Common Polypodium), Polypodium vulgare L., Polypodium vulgare oreophilum subspecies, Polypodium vulgare var.acuminatum, Polypodium vulpinum, Polypodium williamsii, Polypodium wobbense, Polypodium×fallacissimum-guttatum, Polypodium xantholepis, Polypodium xiphopteris, Polypodium yarumalense, Polypodium yungense and Polypodium zosteriforme. .

[0062] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from a fern species of the genus Platycerium in the family Polypodiaceae.

[0063] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the phylum Lycophyta. The phylogeny of extant lycophytes used herein is based on the classification of N. Wikstrom, American Fern Journal, 91:150-156 (2001). Other phylogenetic classifications of extant lycophytes are known to those skilled in the art. Additional information on the phylogeny of ferns can be found at mobot.org / MOBOT / research / APweb / (accessible with the prefix "www") and based on three plastid genes in Schuettpelz E. and Pryer KM, TAXON 56:1037-1050 (2007). Other lycophyte species can be found on homepage s.caverock.net.nz / ~bj / fern / list.htm (accessible with the prefix http: / / ).

[0064] In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the class Isoetopsida or Lycopodiopsida.

[0065] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the order Selaginales (class Isoetes). In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the family Selaginellaceae (order Selaginellaceae). In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the genus Selaginella.

[0066] In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the Order Lycopodiales. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from fern species of the Family Lycopodiaceae or Family Huperziaceae within the Order Lycopodiaceae. In some embodiments, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the genera *Austrolycopodium*, *Dendrolycopodium*, *Diphasiastrum*, *Diphasium*, *Huperzia*, *Lateristachys*, *Lycopodiastrum*, *Lycopodiella*, *Lycopodium*, *Palhinhaea*, *Pseudodiphasium*, *Pseudolycopodiella*, *Pseudolycopodium*, or *Spinulum*. In some implementations, the nucleic acid molecule encoding the PtIP-83 polypeptide is derived from species of the genus *Genus Lycopodium*.

[0067] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence motif selected from the following: amino acid sequence motif 1 represented by the amino acid sequence of the formula MP[DE]MPSEADWSIFVNE[IV]EAVAEGMPTEVSEVP[AV]WKAKCKN[MV]AALGREM[SC]I (SEQ ID NO: 646); amino acid sequence motif 2 represented by the amino acid sequence of the formula PQLQYRMYG[NS]LI[KN]QMAQVAQNYDQ[ED]FKQ[FL]KLFI[IA]QNQI[LF]GSYLLQQN[KR]AF (SEQ ID NO: 647); amino acid sequence motif 2 represented by the amino acid sequence of the formula NTFMQMTPFTRWRLRLSASASENA[EG]LAFPTATA[PL]DSTT[EQ][IV]VITFHVTAIR (SEQ ID NO: 646). Amino acid sequence motif 3 represented by the amino acid sequence of formula [DN]FTSRHVVK[GD]IPVSLLLDGEDWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 649); amino acid sequence motif 4 represented by the amino acid sequence of formula IIHQP[SA]T[RQ][ST]G[IT]VYILLQGSTIFHDRRR[DE]EVMTFQAA[DA]PLN[FY][QH]YAYRLDTG (SEQ ID NO: 650); amino acid sequence motif 5 represented by the amino acid sequence of formula S[HQ]ADRLAAIQP[AV]DLTN[HY]LEMAT[HQ]MDMRTT[RS][MI]L[IL]GLLN[MI]LRIQNAALMYEY (SEQ ID NO: 649); Amino acid sequence motif 6 represented by the amino acid sequence of formula [VL]DRVEFSEVMVIHRMYVRL[SA]DL[ND]VGEL[PE]GA[EG][RK]VKR[VL]YV[FL]ADVVE (SEQ ID NO: 652) 7; Amino acid sequence motif 8 represented by the amino acid sequence of formula A[DE]RELQMESFHSAVISQRRQEL[ND]TA[IF]AKM[DE]R[LM]SLQMEEE[NS]RAMEQAQKEM (SEQ ID NO: 653) 8; Amino acid sequence motif 9 represented by the amino acid sequence of formula FVTAGATAPGA[AV]ASAGQAVSIAGQAAQ[AG]LRRVVEILE[GQ]LEAVMEVVAA[VI]K (SEQ ID NO: 654)Amino acid sequence motif 10 is represented by the amino acid sequence of formula DGMNWG[IT]YI[YH]GE[KE]V[EQ]RSPLLPSNAILAVWADRC[TI]ITSARHNH[VF]NAPGR[IV]I (SEQ ID NO: 655); amino acid sequence motif 11 is represented by the amino acid sequence of formula [KV][VK][CA]RPPSPDM[MV]SAVAEHALWLNDVLLQVVQ[KN]ESQ[LM]QGT[AE]PYNECLALLGR (SEQ ID NO: 656); amino acid sequence motif 12 is represented by the amino acid sequence of formula PTELT[VA]WPLGMDTV[AG]NLLIAQENAAL[VL]GLIQLGPSS (SEQ ID NO: 657); amino acid sequence motif 12 is represented by the amino acid sequence of formula RDQ[MT][HQ]MPGSVTVI[IV]LCRLLQFP[IT]DGSQA[TA]T (SEQ ID NO: 655). Amino acid sequence motif 13 represented by the amino acid sequence of formula TSIPVEVVTDP[SN]ILLGMQTTV[LH]IAEL (SEQ ID NO: 659); amino acid sequence motif 14 represented by the amino acid sequence of formula TSIPVEVVTDP[SN]ILLGMQTTV[LH]IAEL (SEQ ID NO: 659); amino acid sequence motif 15 represented by the amino acid sequence of formula EGLR[EQ]FQNRQVARA[VL]FAVLKAVA[MQ]I[AG] (SEQ ID NO: 660); amino acid sequence motif 16 represented by the amino acid sequence of formula W[TS]RVRIRHLEM[QH]F[AV]QEASG (SEQ ID NO: 661); amino acid sequence motif 17 represented by the amino acid sequence of formula QISELQY[ED]IWVQG[LM][ML]RDIA (SEQ ID NO: 662); amino acid sequence motif 18 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 659); amino acid sequence motif 19 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 659); amino acid sequence motif 10 represented by the amino acid sequence of formula EGLR[EQ]FQNRQVARA[VL]FAVLKAVA[MQ]I[AG] (SEQ ID NO: 660); amino acid sequence motif 11 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 659); amino acid sequence motif 12 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 659); amino acid sequence motif 13 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLD Amino acid sequence motif 18 represented by the amino acid sequence of formula MDYSTLYRDLNQIS (SEQ ID NO: 664); amino acid sequence motif 20 represented by the amino acid sequence of formula LRLPFM[QK]LHARVIEQN[VR]K[SE] (SEQ ID NO: 665); amino acid sequence motif 21 represented by the amino acid sequence of formula VDSLEQVG[QH][IL]V[GD]AP (SEQ ID NO: 666); amino acid sequence motif 22 represented by the amino acid sequence of formula [IV][EQ][CA]VMK[IM]GRF[VG][SL]VV (SEQ ID NO: 667);Amino acid sequence motif 23, represented by the amino acid sequence of formula TLTNEPSE[EQ]F (SEQ ID NO: 668); and amino acid sequence motif 24, represented by the amino acid sequence of formula LPRQSRNISF (SEQ ID NO: 669).

[0068] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence motif selected from the following: an amino acid sequence motif 1 having at least 90% sequence identity with an amino acid sequence represented by the formula MP[DE]MPSEADWSIFVNE[IV]EAVAEGMPTEVSEVP[AV]WKAKCKN[MV]AALGREM[SC]I (SEQ ID NO: 646); an amino acid sequence motif 2 having at least 90% sequence identity with an amino acid sequence represented by the formula PQLQYRMYG[NS]LI[KN]QMAQVAQNYDQ[ED]FKQ[FL]KLFI[IA]QNQI[LF]GSYLLQQN[KR]AF (SEQ ID NO: 647); and an amino acid sequence motif 2 having at least 90% sequence identity with an amino acid sequence represented by the formula NTFMQMTPFTRWRLRLSASASENA[EG]LAFPTATA[PL]DSTT[EQ][IV]VITFHVTAIR (SEQ ID NO: 646). Amino acid sequence motif 3 having at least 90% sequence identity with the amino acid sequence represented by NO: 648); amino acid sequence motif 4 having at least 90% sequence identity with the amino acid sequence represented by formula [DN]FTSRHVVK[GD]IPVSLLLDGEDWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 649); amino acid sequence motif 5 having at least 90% sequence identity with the amino acid sequence represented by formula IIHQP[SA]T[RQ][ST]G[IT]VYILLQGSTIFHDRRR[DE]EVMTFQAA[DA]PLN[FY][QH]YAYRLDTG (SEQ ID NO: 650); amino acid sequence motif 5 having at least 90% sequence identity with the amino acid sequence represented by formula S[HQ]ADRLAAIQP[AV]DLTN[HY]LEMAT[HQ]MDMRTT[RS][MI]L[IL]GLLN[MI]LRIQNAALMYEY (SEQ ID NO: 649) Amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by SEQ ID NO: 651; amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by formula [VL]DRVEFSEVMVIHRMYVRL[SA]DL[ND]VGEL[PE]GA[EG][RK]VKR[VL]YV[FL]ADVVE (SEQ ID NO: 652); amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by formula A[DE]RELQMESFHSAVISQRRQEL[ND]TA[IF]AKM[DE]R[LM]SLQMEEE[NS]RAMEQAQKEM (SEQ ID NO: 653);Amino acid sequence motif 9 having at least 90% sequence identity with the amino acid sequence represented by the formula FVTAGATAPGA[AV]ASAGQAVSIAGQAAQ[AG]LRRVVEILE[GQ]LEAVMEVVAA[VI]K (SEQ ID NO: 654); amino acid sequence motif 10 having at least 90% sequence identity with the amino acid sequence represented by the formula DGMNWG[IT]YI[YH]GE[KE]V[EQ]RSPLLPSNAILAVWADRC[TI]ITSARHNH[VF]NAPGR[IV]I (SEQ ID NO: 655); amino acid sequence motif 10 having at least 90% sequence identity with the amino acid sequence represented by the formula [KV][VK][CA]RPPSPDM[MV]SAVAEHALWLNDVLLQVVQ[KN]ESQ[LM]QGT[AE]PYNECLALLGR (SEQ ID NO: 654) Amino acid sequence motifs 11 and 12 that have at least 90% sequence identity with the amino acid sequence represented by formula PTELT[VA]WPLGMDTV[AG]NLLIAQENAAL[VL]GLIQLGPSS (SEQ ID NO: 657); amino acid sequence motifs 13 and 14 that have at least 90% sequence identity with the amino acid sequence represented by formula RDQ[MT][HQ]MPGSVTVI[IV]LCRLLQFP[IT]DGSQA[TA]T (SEQ ID NO: 658); amino acid sequence motifs 15 and 16 that have at least 90% sequence identity with the amino acid sequence represented by formula TSIPVEVVTDP[SN]ILLGMQTTV[LH]IAEL (SEQ ID NO: 659); and amino acid sequence motifs 16 and 17 that have at least 90% sequence identity with the amino acid sequence represented by formula EGLR[EQ]FQNRQVARA[VL]FAVLKAVA[MQ]I[AG] (SEQ ID NO: 657). 15. Amino acid sequence motifs that have at least 90% sequence identity with the amino acid sequence represented by NO: 660; 16. Amino acid sequence motifs that have at least 90% sequence identity with the amino acid sequence represented by W[TS]RVRIRHLEM[QH]F[AV]QEASG (SEQ ID NO: 661); 17. Amino acid sequence motifs that have at least 90% sequence identity with the amino acid sequence represented by QISELQY[ED]IWVQG[LM][ML]RDIA (SEQ ID NO: 662); 18. Amino acid sequence motifs that have at least 90% sequence identity with the amino acid sequence represented by TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 663);Amino acid sequence motifs 19 having at least 90% sequence identity with the amino acid sequence represented by the formula MDYSTLYRDLNQIS (SEQ ID NO: 664); amino acid sequence motifs 20 having at least 90% sequence identity with the amino acid sequence represented by the formula LRLPFM[QK]LHARVIEQN[VR]K[SE] (SEQ ID NO: 665); amino acid sequence motifs 21 having at least 90% sequence identity with the amino acid sequence represented by the formula VDSLEQVG[QH][IL]V[GD]AP (SEQ ID NO: 666); amino acid sequence motifs 22 having at least 90% sequence identity with the amino acid sequence represented by the formula [IV][EQ][CA]VMK[IM]GRF[VG][SL]VV (SEQ ID NO: 667); and amino acid sequence motifs 23 and 44 having at least 90% sequence identity with the amino acid sequence represented by the formula TLTNEPSE[EQ]F (SEQ ID NO: 664). Amino acid sequence motif 23 having at least 90% sequence identity with the amino acid sequence represented by formula LPRQSRNISF (SEQ ID NO: 669); and amino acid sequence motif 24 having at least 90% sequence identity with the amino acid sequence represented by formula LPRQSRNISF (SEQ ID NO: 669).

[0069] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence motif selected from the following: such as amino acid sequence motif 1 represented by the amino acid sequence of the formula MP[DE]MP[ST][ED]ADWSIFVNE[IVL]EAVAEGMPTEVSEVP[AV]W[KR]AKCKN[MV]AALGREM[SC]I (SEQ ID NO: 670); such as amino acid sequence motif 1 represented by the formula PQLQYRMYG[NS]LI[KRN]QMAQVAQNYD[QR][ED]FK[QR][FL][KR]LFI[IAVL]QNQI[LF]GSYLL[QE]QN[KR]AF (SEQ ID NO: 670). Amino acid sequence motif 2 represented by the amino acid sequence of formula N[TK]FMQMTPFT[RH]WRLRLSASA[SPKA]EN[AK][EG]LAFPTATA[PL]DSTT[EQ][IV][VA]ITFHVTAIR (SEQ ID NO: 672) represents amino acid sequence motif 3; amino acid sequence motif 4 represented by the amino acid sequence of formula [DN]FTSRHVVK[GD]IPV[SN]LLLDG[EG]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 673) represents amino acid sequence motif 4; amino acid sequence motif 5 represented by formula IIHQP[SA]T[RQ][ST]G[IT][VI]YILLQGST[IV]FHDRRR[DE][EQ]V[ML]T[FP]QAA[DAV]PLN[FY][QH]YAYRLDTG (SEQ ID NO: 672) represents amino acid sequence motif 672; amino acid sequence motif 672 represented by amino acid sequence of formula [DN]FTSRHVVK[GD]IPV[SN]LLLDG[EG]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 673) represents amino acid sequence motif 672; amino acid sequence motif 772 represented by amino acid sequence of formula IIHQP[SA]T[RQ][ST]G[IT][VI]YILLQGST[IV]FHDRRR[DE][EQ]V[ML]T[FP]QAA[DAV]PLN[FY][QH]YAYRLDTG (SEQ ID NO: 672) represents amino acid sequence motif 772; amino acid sequence motif 872 represented by amino acid sequence of formula [DN]FTSRHVVK[GD]IPV[SN]LLLDG[EG]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 673) represents amino acid sequence motif 872; amino acid sequence Amino acid sequence motif 5 represented by the amino acid sequence of NO: 674; such as amino acid sequence motif 6 represented by the amino acid sequence of formula S[HQ]ADRLAAIQP[AV][DN]LTN[HYF]LEMAT[HQ]MDMRTT[RS][MI]L[IL]GLLN[MI][LM]RIQNAAL[MR]YEY (SEQ ID NO: 675); such as amino acid sequence motif 6 represented by the amino acid sequence of formula [VL]D[RQ]VEFSEVMVIHRMYV[N]RL[SA]DL[ND]V[GA][EQ]L[PE]GA[EG][RK]VKR[VL]YV[FL]ADVVE (SEQ ID NO: 675). The amino acid sequence motif 7 represented by the amino acid sequence of NO: 676; the amino acid sequence motif 8 represented by the amino acid sequence of formula A[DE]RELQMESFH[SA]AVISQ[RK]R[QGE]EL[ND][TD][AT][IF]AKM[DE]R[LM]SLQMEEE[NSD][RG]AMEQA[QR]KEM (SEQ ID NO: 677);Amino acid sequence motif 9 is represented by the amino acid sequence of formula F[VL]TAGATAPGA[AV]ASAGQAV[SN]IAGQAAQ[AG]LRRVVEILE[GQ]LEAVMEVVAA[VI]K (SEQ ID NO: 678); amino acid sequence motif 9 is represented by the amino acid sequence of formula D[GD][MA][NK]WG[IT]Y[IV][YH][GA]E[KE]V[EQ][RVL]SPL[LYF][PN][SNG][NW][ASP][IY]L[AGV]V[WE]A[DQ]R[CS][TI]IT[SA]A[RFM]HN[HVT][VF][ND][AER]PG[RW][IV][IR] (SEQ ID NO: 678). Amino acid sequence motif 10 represented by the amino acid sequence of NO: 679; such as amino acid sequence motif 11 represented by the amino acid sequence of formula [KV][VK][CA][RGC][PHY]PSP[DE][MIL][MV]SAV[AG][EV]HA[LIN]WL[NS][DK]VLL[QR]VVQ[KN]ES[QH][LM]QGT[AE][PSA]YNECLALLGR (SEQ ID NO: 680); such as amino acid sequence motif 11 represented by the amino acid sequence of formula [PN]T[EQ]LT[VAT]WPL[GR]MDTV[AG][ND]LLI[AT][QH]E[NS]AAL[VLS]GL[ITMA]QLG[PQ][SP]S (SEQ ID NO: 680). Amino acid sequence motif 12 represented by the amino acid sequence of NO: 681; amino acid sequence motif 13 represented by the amino acid sequence of formula [RLC][DLWK][QNPR][MTP][HQR][MIL]PGSVTVI[IV]LCRLLQFP[IT][DG]G[SR][QFR][AS][TAD][TW] (SEQ ID NO: 682); amino acid sequence motif 14 represented by the amino acid sequence of formula [TA][SGV][IL]PV[ED]VVTDP[SN]IL[LM]GMQT[TS]V[LH]IAEL (SEQ ID NO: 683); amino acid sequence motif 15 represented by the amino acid sequence of formula EGLR[EQ]FQN[RE]QVA[RN]A[VL]FAVL[KS][AS]VA[MQ]I[AG] (SEQ ID NO: 682); Amino acid sequence motif 15 represented by the amino acid sequence of NO: 684; and amino acid sequence motif 16 represented by the amino acid sequence of formula W[TS]RVRIRHLEM[QH]F[AV][QK]E[AS][SM][GN](SEQ ID NO: 685);Amino acid sequence motif 17, represented by the amino acid sequence of formula Q[IM]S[EQ]LQY[ED]IWVQG[LM][ML]RD[IM]A (SEQ ID NO: 686); amino acid sequence motif 18, represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 663); amino acid sequence motif 19, represented by the amino acid sequence of formula [MLV]DY[SK][TSK]L[YF][RE]DLNQIS (SEQ ID NO: 687); amino acid sequence motif 20, represented by the amino acid sequence of formula L[RHQ]L[PT]FM[QK]LHA[RIT][VQL][IR]E[QER][NF][VR][KWS][SE] (SEQ ID NO: 688); amino acid sequence motif 20, represented by the amino acid sequence of formula V[DN][SA]L[ED]QV[GS][QH][IL]V[GD]AP (SEQ ID NO: 688). Amino acid sequence motif 21 represented by the amino acid sequence of formula [IV][EQH][CAS][VA][MI]K[IM][GV][RP][FI][VG][SL]VV (SEQ ID NO: 690); amino acid sequence motif 22 represented by the amino acid sequence of formula [IV][EQH][CAS][VA][MI]K[IM][GV][RP][FI][VG][SL]VV (SEQ ID NO: 690); amino acid sequence motif 23 represented by the amino acid sequence of formula TLTN[EQ]PSE[EQDH]F (SEQ ID NO: 691); and amino acid sequence motif 24 represented by the amino acid sequence of formula LP[RS]QS[RT]N[IV]SF (SEQ ID NO: 692).

[0070] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence motif selected from the following: an amino acid sequence motif having at least 90% sequence identity with an amino acid sequence represented by the formula MP[DE]MP[ST][ED]ADWSIFVNE[IVL]EAVAEGMPTEVSEVP[AV]W[KR]AKCKN[MV]AALGREM[SC]I (SEQ ID NO: 670); an amino acid sequence motif 1 having at least 90% sequence identity with an amino acid sequence represented by the formula PQLQYRMYG[NS]LI[KRN]QMAQVAQNYD[QR][ED]FK[QR][FL][KR]LFI[IAVL]QNQI[LF]GSYLL[QE]QN[KR]AF (SEQ ID NO: 670). Amino acid sequence motif 2 having at least 90% sequence identity with the amino acid sequence represented by NO: 671); amino acid sequence motif 3 having at least 90% sequence identity with the amino acid sequence represented by N[TK]FMQMTPFT[RH]WRLRLSASA[SPKA]EN[AK][EG]LAFPTATA[PL]DSTT[EQ][IV][VA]ITFHVTAIR (SEQ ID NO: 672); amino acid sequence motif 4 having at least 90% sequence identity with the amino acid sequence represented by [DN]FTSRHVVK[GD]IPV[SN]LLLDG[EG]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 673); amino acid sequence motif 4 having at least 90% sequence identity with the amino acid sequence represented by IIHQP[SA]T[RQ][ST]G[IT][VI]YILLQGST[IV]FHDRRR[DE][EQ]V[ML]T[FP]QAA[DAV]PLN[FY][QH]YAYRLDTG (SEQ ID NO: 672); Amino acid sequence motifs 5 having at least 90% sequence identity with the amino acid sequence represented by NO: 674; amino acid sequence motifs 6 having at least 90% sequence identity with the amino acid sequence represented by formula S[HQ]ADRLAAIQP[AV][DN]LTN[HYF]LEMAT[HQ]MDMRTT[RS][MI]L[IL]GLLN[MI][LM]RIQNAAL[MR]YEY (SEQ ID NO: 675); amino acid sequence motifs 7 having at least 90% sequence identity with the amino acid sequence represented by formula [VL]D[RQ]VEFSEVMVIHRMYV[N]RL[SA]DL[ND]V[GA][EQ]L[PE]GA[EG][RK]VKR[VL]YV[FL]ADVVE (SEQ ID NO: 676);Amino acid sequence motif 8 having at least 90% sequence identity with the amino acid sequence represented by formula A[DE]RELQMESFH[SA]AVISQ[RK]R[QGE]EL[ND][TD][AT][IF]AKM[DE]R[LM]SLQMEEE[NSD][RG]AMEQA[QR]KEM (SEQ ID NO: 677); and amino acid sequence motif 8 having at least 90% sequence identity with the amino acid sequence represented by formula F[VL]TAGATAPGA[AV]ASAGQAV[SN]IAGQAAQ[AG]LRRVVEILE[GQ]LEAVMEVVAA[VI]K (SEQ ID NO: 677). Amino acid sequence motif 9, which has at least 90% sequence identity with the amino acid sequence represented by NO: 678; and amino acid sequence motif 10, which has at least 90% sequence identity with the amino acid sequence represented by the formula D[GD][MA][NK]WG[IT]Y[IV][YH][GA]E[KE]V[EQ][RVL]SPL[LYF][PN][SNG][NW][ASP][IY]L[AGV]V[WE]A[DQ]R[CS][TI]IT[SA]A[RFM]HN[HVT][VF][ND][AER]PG[RW][IV][IR] (SEQ ID NO: 679); and amino acid sequence motif 10, which has at least 90% sequence identity with the amino acid sequence represented by the formula [KV][VK][CA][RGC][PHY]PSP[DE][MIL][MV]SAV[AG][EV]HA[LIN]WL[NS][DK]VLL[QR]VVQ[KN]ES[QH][LM]QGT[AE][PSA]YNECLALLGR (SEQ ID NO: 679). Amino acid sequence motifs 11 having at least 90% sequence identity with the amino acid sequence represented by [PN]T[EQ]LT[VAT]WPL[GR]MDTV[AG][ND]LLI[AT][QH]E[NS]AAL[VLS]GL[ITMA]QLG[PQ][SP]S (SEQ ID NO: 681) ; amino acid sequence motifs 12 having at least 90% sequence identity with the amino acid sequence represented by [RLC][DLWK][QNPR][MTP][HQR][MIL]PGSVTVI[IV]LCRLLQFP[IT][DG]G[SR][QFR][AS][TAD][TW] (SEQ ID NO: 682) ; amino acid sequence motifs 13 having at least 90% sequence identity with the amino acid sequence represented by [TA][SGV][IL]PV[ED]VVTDP[SN]IL[LM]GMQT[TS]V[LH]IAEL (SEQ ID NO: 680) ; and amino acid sequence motifs 14 and 50% sequence identity with the amino acid sequence represented by [TA][SGV][IL]PV[ED]VVTDP[SN]IL[LM]GMQT[TS]V[LH]IAEL (SEQ ID NO: 681) . The amino acid sequence motif represented by NO: 683) has at least 90% sequence identity with the amino acid sequence motif 14;Amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by EEGLR[EQ]FQN[RE]QVA[RN]A[VL]FAVL[KS][AS]VA[MQ]I[AG] (SEQ ID NO: 684) 15; amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by W[TS]RVRIRHLEM[QH]F[AV][QK]E[AS][SM][GN] (SEQ ID NO: 685) 16; amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by Q[IM]S[EQ]LQY[ED]IWVQG[LM][ML]RD[IM]A (SEQ ID NO: 686) 17; amino acid sequence motifs having at least 90% sequence identity with the amino acid sequence represented by TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 684) Amino acid sequence motif 18 having at least 90% sequence identity with the amino acid sequence represented by NO: 663; amino acid sequence motif 19 having at least 90% sequence identity with the amino acid sequence represented by formula [MLV]DY[SK][TSK]L[YF][RE]DLNQIS (SEQ ID NO: 687); amino acid sequence motif 20 having at least 90% sequence identity with the amino acid sequence represented by formula L[RHQ]L[PT]FM[QK]LHA[RIT][VQL][IR]E[QER][NF][VR][KWS][SE] (SEQ ID NO: 688); amino acid sequence motif 20 having at least 90% sequence identity with the amino acid sequence represented by formula V[DN][SA]L[ED]QV[GS][QH][IL]V[GD]AP (SEQ ID NO: 687); Amino acid sequence motifs 21 having at least 90% sequence identity with the amino acid sequence represented by NO: 689; amino acid sequence motifs 22 having at least 90% sequence identity with the amino acid sequence represented by formula [IV][EQH][CAS][VA][MI]K[IM][GV][RP][FI][VG][SL]VV (SEQ ID NO: 690); amino acid sequence motifs 23 having at least 90% sequence identity with the amino acid sequence represented by formula TLTN[EQ]PSE[EQDH]F (SEQ ID NO: 691); and amino acid sequence motifs 24 having at least 90% sequence identity with the amino acid sequence represented by formula LP[RS]QS[RT]N[IV]SF (SEQ ID NO: 692).

[0071] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide containing an amino acid sequence motif selected from the following: such as the amino acid sequence motif 1 represented by the amino acid sequence of the formula MP[DE]MP[ST][ED]ADWSIFVNE[IVL]EAVAEGMPTEVSEVP[AVIL]W[KR]AKCKN[MVIL]AALGREM[SCT]I (SEQ ID NO: 693); such as the amino acid sequence motif 1 represented by the formula PQLQYRMYG[NS]LI[KRNQ]QMAQVAQNYD[QRNK][ED]FK[QRNK][FL][KR]LFI[IAVL]QNQI[LFIV]GSYLL[QEND]QN[KR]AF (SEQ ID NO: 693). Amino acid sequence motif 2 represented by the amino acid sequence of NO: 694; amino acid sequence motif 3 represented by the amino acid sequence of N[TKSR]FMQMTPFT[RHK]WRLRLSASA[SPKATR]EN[AKR][EG]LAFPTATA[PLIV]DSTT[EQND][IVL][VAIL]ITFHVTAIR (SEQ ID NO: 695); amino acid sequence motif 4 represented by the amino acid sequence of [DNQE]FTSRHVVK[GDE]IPV[SNTQ]LLLDG[EGD]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 696); amino acid sequence motif 4 represented by the amino acid sequence of IIHQP[SAT]T[RQKN][ST]G[ITLVS][VIL]YILLQGST[IVL]FHDRRR[DE][EQDN]V[MLIV]T[FP]QAA[DAVEIL]PLN[FY][QHN]YAYRLDTG (SEQ ID NO: 695); Amino acid sequence motif 5 represented by the amino acid sequence of formula S[HQN]ADRLAAIQP[AVIL][DN]LTN[HYF]LEMAT[HQN]MDMRTT[RSKT][MILV]L[ILV]GLLN[MILV][LMIV]RIQNAAL[MRILVK]YEY (SEQ ID NO: 698); amino acid sequence motif 6 represented by the amino acid sequence of formula [VLI]D[RQKN]VEFSEVMVIHRMYV[N]RL[SAT]DL[NDQE]V[GA][EQND]L[PED]GA[EGD][RK]VKR[VLI]YV[FLIV]ADVVE (SEQ ID NO: 699); amino acid sequence motif 7 represented by the amino acid sequence of formula [VLI]D[RQKN]VEFSEVMVIHRMYV[N]RL[SAT]DL[NDQE]V[GA][EQND]L[PED]GA[EGD][RK]VKR[VLI]YV[FLIV]ADVVE (SEQ ID NO: 699);The amino acid sequence motif represented by the amino acid sequence of formula A[DE]RELQMESFH[SAT]AVISQ[RK]R[QGEND]EL[NDQE][TDSE][ATS][IFLV]AKM[DE]R[LMIV]SLQMEEE[NSDQET][RGK]AMEQA[QRNK]KEM (SEQ ID NO: 700) is shown as motif 8; the amino acid sequence motif represented by the amino acid sequence of formula F[VLI]TAGATAPGA[AVIL]ASAGQAV[SNTQ]IAGQAAQ[AG]LRRVVEILE[GQN]LEAVMEVVAA[VIL]K (SEQ ID NO: 700) is also shown as motif 8. The amino acid sequence motif represented by the amino acid sequence of NO: 701) is 9; such as the amino acid sequence motif represented by the formula D[GDE][MA][NKQK]WG[ITLVS]Y[IVL][YH][GA]E[KERD]V[EQND][RVLKI]SPL[LYFIV][PNQ][SNGTQ][NWQ][ASPT][IYLV]L[AGVIL]V[WED]A[DQNE]R[CST][TISLV]IT[SAT]A[RFMK]HN[HVTILS][VFIL][NDQE][AERDK]PG[RWK][IVL][IRLVK](SEQ ID Amino acid sequence motif 10 represented by the amino acid sequence of NO: 702); such as amino acid sequence motif 11 represented by the amino acid sequence of formula [KVRIL][VKRIL][CA][RGCK][PHY]PSP[DE][MILV][MVIL]SAV[AG][EVDIL]HA[LINVQ]WL[NSQT][DKER]VLL[QRNK]VVQ[KNRQ]ES[QHN][LMIV]QGT[AED][PSAT]YNECLALLGR (SEQ ID NO: 703); such as amino acid sequence motif 11 represented by the amino acid sequence of formula [PNQ]T[EQDN]LT[VATILS]WPL[GRK]MDTV[AG][NDQE]LLI[ATS][QHN]E[NSQT]AAL[VLSIT]GL[ITMALVS]QLG[PQN][SPT]S (SEQ ID NO: 703). Amino acid sequence motif 12 represented by the amino acid sequence of NO: 704; and amino acid sequence motif 13 represented by the amino acid sequence of formula [RLCKIV][DLWKEIVR][QNPRK][MTP][HQR][MILV]PGSVTVI[IVL]LCRLLQFP[ITLVS][DGE]G[SRTK][QFRNK][AST][TADES][TWS](SEQ ID NO: 705);Amino acid sequence motif 14, represented by the amino acid sequence of formula [TA][SGVTIL][ILV]PV[ED]VVTDP[SNTQ]IL[LMIV]GMQT[TS]V[LHIV]IAEL (SEQ ID NO: 706); amino acid sequence motif 15, represented by the amino acid sequence of formula EGLR[EQND]FQN[REKD]QVA[RNKQ]A[VLI]FAVL[KSRT][AST]VA[MQN]I[AG] (SEQ ID NO: 707); amino acid sequence motif 16, represented by the amino acid sequence of formula W[TS]RVRIRHLEM[QHN]F[AVIL][QKNR]E[AST][SMT][GNQ] (SEQ ID NO: 708); amino acid sequence motif 17, represented by the amino acid sequence of formula Q[IMLV]S[EQND]LQY[ED]IWVQG[LMIV][MLIV]RD[IMLV]A (SEQ ID NO: 706). Amino acid sequence motif 17 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 709); amino acid sequence motif 18 represented by the amino acid sequence of formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 663); amino acid sequence motif 19 represented by the amino acid sequence of formula [MLVI]DY[SKTR][TSKR]L[YF][REKD]DLNQIS (SEQ ID NO: 710); amino acid sequence motif 20 represented by the amino acid sequence of formula L[RHQKN]L[PTS]FM[QKNR]LHA[RITKLVS][VQLIN][IRLVK]E[QERNDK][NFQ][VRILK][KWSRT][SETD] (SEQ ID NO: 711); amino acid sequence motif 20 represented by the amino acid sequence of formula V[DNQE][SAT]L[ED]QV[GST][QHN][ILV]V[GDE]AP (SEQ ID NO: 711). Amino acid sequence motif 21 represented by the amino acid sequence of formula [IVL][EQHND][CAST][VAIL][MILV]K[IMLV][GVIL][RPK][FILV][VGIL][SLTIV]VV (SEQ ID NO: 713); amino acid sequence motif 22 represented by the amino acid sequence of formula [IVL][EQHND][CAST][VAIL][MILV]K[IMLV][GVIL][RPK][FILV][VGIL][SLTIV]VV (SEQ ID NO: 713); amino acid sequence motif 23 represented by the amino acid sequence of formula TLTN[EQDN]PSE[EQDHN]F (SEQ ID NO: 714); and amino acid sequence motif 24 represented by the amino acid sequence of formula LP[RSKT]QS[RTKS]N[IVL]SF (SEQ ID NO: 715).

[0072] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide comprising an amino acid sequence motif selected from the following: an amino acid sequence motif having at least 90% sequence identity with an amino acid sequence represented by the formula MP[DE]MP[ST][ED]ADWSIFVNE[IVL]EAVAEGMPTEVSEVP[AVIL]W[KR]AKCKN[MVIL]AALGREM[SCT]I (SEQ ID NO: 693); an amino acid sequence motif 1 having at least 90% sequence identity with an amino acid sequence represented by the formula PQLQYRMYG[NS]LI[KRNQ]QMAQVAQNYD[QRNK][ED]FK[QRNK][FL][KR]LFI[IAVL]QNQI[LFIV]GSYLL[QEND]QN[KR]AF (SEQ ID NO: 693). Amino acid sequence motif 2 having at least 90% sequence identity with the amino acid sequence represented by NO: 694; and amino acid sequence motif 3 having at least 90% sequence identity with the amino acid sequence represented by N[TKSR]FMQMTPFT[RHK]WRLRLSASA[SPKATR]EN[AKR][EG]LAFPTATA[PLIV]DSTT[EQND][IVL][VAIL]ITFHVTAIR (SEQ ID NO: 695); and amino acid sequence motif 3 having at least 90% sequence identity with the amino acid sequence represented by [DNQE]FTSRHVVK[GDE]IPV[SNTQ]LLLDG[EGD]DWEFEIPVQ[AG]GMSSFP (SEQ ID NO: 695). Amino acid sequence motif 4 having at least 90% sequence identity with the amino acid sequence represented by formula IIHQP[SAT]T[RQKN][ST]G[ITLVS][VIL]YILLQGST[IVL]FHDRRR[DE][EQDN]V[MLIV]T[FP]QAA[DAVEIL]PLN[FY][QHN]YAYRLDTG (SEQ ID NO: 697) ; Amino acid sequence motif 5 having at least 90% sequence identity with the amino acid sequence represented by formula S[HQN]ADRLAAIQP[AVIL][DN]LTN[HYF]LEMAT[HQN]MDMRTT[RSKT][MILV]L[ILV]GLLN[MILV][LMIV]RIQNAAL[MRILVK]YEY (SEQ ID NO: 698) ;Amino acid sequence motif 7 having at least 90% sequence identity with the amino acid sequence represented by formula [VLI]D[RQKN]VEFSEVMVIHRMYV[N]RL[SAT]DL[NDQE]V[GA][EQND]L[PED]GA[EGD][RK]VKR[VLI]YV[FLIV]ADVVE (SEQ ID NO: 699); and amino acid sequence motif 7 having at least 90% sequence identity with the amino acid sequence represented by formula A[DE]RELQMESFH[SAT]AVISQ[RK]R[QGEND]EL[NDQE][TDSE][ATS][IFLV]AKM[DE]R[LMIV]SLQMEEE[NSDQET][RGK]AMEQA[QRNK]KEM (SEQ ID NO: 699). The amino acid sequence motif 8, which has at least 90% sequence identity with the amino acid sequence represented by NO: 700, is similar to the amino acid sequence motif 8 represented by the formula F[VLI]TAGATAPGA[AVIL]ASAGQAV[SNTQ]IAGQAAQ[AG]LRRVVEILE[GQN]LEAVMEVVAA[VIL]K (SEQ ID The amino acid sequence motif 9, which has at least 90% sequence identity with the amino acid sequence represented by NO: 701, is similar to the amino acid sequence motif 9 of the formula D[GDE][MA][NKQK]WG[ITLVS]Y[IVL][YH][GA]E[KERD]V[EQND][RVLKI]SPL[LYFIV][PNQ][SNGTQ][NWQ][ASPT][IYLV]L[AGVIL]V[WED]A[DQNE]R[CST][TISLV]IT[SAT]A[RFMK]HN[HVTILS][VFIL][NDQE][AERDK]PG[RWK][IVL][IRLVK](SEQ ID) The amino acid sequence motif 10, which has at least 90% sequence identity with the amino acid sequence represented by NO: 702, and the amino acid sequence motif 11, which has at least 90% sequence identity with the amino acid sequence represented by formula [KVRIL][VKRIL][CA][RGCK][PHY]PSP[DE][MILV][MVIL]SAV[AG][EVDIL]HA[LINVQ]WL[NSQT][DKER]VLL[QRNK]VVQ[KNRQ]ES[QHN][LMIV]QGT[AED][PSAT]YNECLALLGR (SEQ ID NO: 703);Amino acid sequence motif 12 having at least 90% sequence identity with the amino acid sequence represented by the formula [PNQ]T[EQDN]LT[VATILS]WPL[GRK]MDTV[AG][NDQE]LLI[ATS][QHN]E[NSQT]AAL[VLSIT]GL[ITMALVS]QLG[PQN][SPT]S (SEQ ID NO: 704); and amino acid sequence motif 12 having at least 90% sequence identity with the amino acid sequence represented by the formula [RLCKIV][DLWKEIVR][QNPRK][MTP][HQR][MILV]PGSVTVI[IVL]LCRLLQFP[ITLVS][DGE]G[SRTK][QFRNK][AST][TADES][TWS] (SEQ ID NO: 704). Amino acid sequence motif 13 having at least 90% sequence identity with the amino acid sequence represented by NO: 705; amino acid sequence motif 14 having at least 90% sequence identity with the amino acid sequence represented by formula [TA][SGVTIL][ILV]PV[ED]VVTDP[SNTQ]IL[LMIV]GMQT[TS]V[LHIV]IAEL (SEQ ID NO: 706); amino acid sequence motif 15 having at least 90% sequence identity with the amino acid sequence represented by formula EGLR[EQND]FQN[REKD]QVA[RNKQ]A[VLI]FAVL[KSRT][AST]VA[MQN]I[AG] (SEQ ID NO: 707); amino acid sequence motif 15 having at least 90% sequence identity with the amino acid sequence represented by formula W[TS]RVRIRHLEM[QHN]F[AVIL][QKNR]E[AST][SMT][GNQ] (SEQ ID NO: 705); 16. Amino acid sequence motifs with at least 90% sequence identity to the amino acid sequence represented by NO: 708; 17. Amino acid sequence motifs with at least 90% sequence identity to the amino acid sequence represented by formula Q[IMLV]S[EQND]LQY[ED]IWVQG[LMIV][MLIV]RD[IMLV]A (SEQ ID NO: 709); 18. Amino acid sequence motifs with at least 90% sequence identity to the amino acid sequence represented by formula TFTLGSGVTGITSMHGEPSLDPWNGVSLDSASPTAF (SEQ ID NO: 663); 19. Amino acid sequence motifs with at least 90% sequence identity to the amino acid sequence represented by formula [MLVI]DY[SKTR][TSKR]L[YF][REKD]DLNQIS (SEQ ID NO: 710);Amino acid sequence motif 20 having at least 90% sequence identity with the amino acid sequence represented by formula L[RHQKN]L[PTS]FM[QKNR]LHA[RITKLVS][VQLIN][IRLVK]E[QERNDK][NFQ][VRILK][KWSRT][SETD] (SEQ ID NO: 711); amino acid sequence motif 21 having at least 90% sequence identity with the amino acid sequence represented by formula V[DNQE][SAT]L[ED]QV[GST][QHN][ILV]V[GDE]AP (SEQ ID NO: 712); amino acid sequence motif 21 having at least 90% sequence identity with the amino acid sequence represented by formula [IVL][EQHND][CAST][VAIL][MILV]K[IMLV][GVIL][RPK][FILV][VGIL][SLTIV]VV (SEQ ID NO: 711). Amino acid sequence motif 22 having at least 90% sequence identity with the amino acid sequence represented by NO: 713; amino acid sequence motif 23 having at least 90% sequence identity with the amino acid sequence represented by formula TLTN[EQDN]PSE[EQDHN]F (SEQ ID NO: 714); and amino acid sequence motif 24 having at least 90% sequence identity with the amino acid sequence represented by formula LP[RSKT]QS[RTKS]N[IVL]SF (SEQ ID NO: 715).

[0073] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide, which sequentially comprises, from the N-terminus to the C-terminus, an amino acid sequence motif selected from the following: motif 19 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 7 (SEQ ID NO: 652, SEQ ID NO: 676 or SEQ ID NO: 699), motif 13 (SEQ ID NO: 658, SEQ ID NO: 682 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 10 (SEQ ID NO: 655, SEQ ID NO: 679 or SEQ ID NO: 702), motif 18 (SEQ ID NO: 663), motif 24 (SEQ ID NO: 669, SEQ ID NO: 692 or SEQ ID NO: 715), motif 14 (SEQ ID NO: 659, ...5 (SEQ ID NO: 659, SEQ ID NO: 663), motif 16 (SEQ ID NO: 669 Generic 11 (SEQ ID NO: 656, SEQ ID NO: 680 or SEQ ID NO: 703), Generic 22 (SEQ ID NO: 667, SEQ ID NO: 690 or SEQ ID NO: 713), Generic 2 (SEQ ID NO: 647, SEQ ID NO: 671 or SEQ ID NO: 694), Generic 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), Generic 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), Generic 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), Generic 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), Generic 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 694), Generic 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), Generic 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), Generic 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), Generic 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 694), Generic 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 706), Generic 11 (SEQ ID NO: 656, SEQ ID NO: 680 or SEQ ID NO: 703), Generic 12 (SEQ ID NO: 683 or SEQ ID NO: 706), Generic 1 NO: 693), motif 17 (SEQ ID NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 6 (SEQ ID NO: 651, SEQ ID NO: 675 or SEQ ID NO: 698), motif 12 (SEQ ID NO: 657, SEQ ID NO: 681 or SEQ ID NO: 704), motif 4 (SEQ ID NO: 649, SEQ ID NO: 673 or SEQ ID NO: 696), motif 16 (SEQ ID ...16 (SEQ ID NO: 693), motif 17 (SEQ ID NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 16 (SEQ ID NO: 693), motif 17 (SEQ ID NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 17 (SEQ ID NO: 651, SEQ ID NO: 675 or SEQ ID NO: 698), motif 16 (SEQ ID NO:NO: 661, SEQ ID NO: 685 or SEQ ID NO: 708), motif 5 (SEQ ID NO: 650, SEQ ID NO: 674 or SEQ ID NO: 697), motif 23 (SEQ ID NO: 668, SEQ ID NO: 691 or SEQ ID NO: 714) and motif 3 (SEQ ID NO: 648, SEQ ID NO: 672 or SEQ ID NO: 695).

[0074] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide, which sequentially comprises, from the N-terminus to the C-terminus, an amino acid sequence motif selected from the following: motif 19 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 7 (SEQ ID NO: 652, SEQ ID NO: 676 or SEQ ID NO: 699), motif 13 (SEQ ID NO: 658, SEQ ID NO: 682 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 14 (SEQ ID NO: 659, SEQ ID NO: 683 or SEQ ID NO: 706), motif 2 (SEQ ID NO: 647, SEQ ID NO: 671 or SEQ ID NO: 694), motif 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 710). SEQ ID NO: 700), motif 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), motif 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), motif 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), motif 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 693), motif 17 (SEQ ID NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 6 (SEQ ID NO: 651, SEQ ID NO: 675 or SEQ ID NO: 698), motif 12 (SEQ ID NO: 657, SEQ ID NO: 681 or SEQ ID NO: 704), motif 4 (SEQ ID NO: 649, SEQ ID NO: 673 or SEQ ID NO: 696), motif 16 (SEQ ID NO: 700), motif 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), motif 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), motif 12 (SEQ ID NO: 657, SEQ ID NO: 681 or SEQ ID NO: 704), motif 13 (SEQ ID NO: 649, SEQ ID NO: 673 or SEQ ID NO: 696), motif 16 (SEQ ID NO: 700), motif 14 (SEQ ID NO: 700), motif 15 (SEQ ID NO: 660, SEQ ID NO: 684 or NO: 661, SEQ ID NO: 685 or SEQ ID NO: 708), motif 5 (SEQ ID NO: 650, SEQ ID NO: 674 or SEQ ID NO: 697), motif 23 (SEQ ID NO: 668, SEQ ID NO: 691 or SEQ ID NO: 714) and motif 3 (SEQ ID NO: 648, SEQ ID NO: 672 or SEQ ID NO: 695).

[0075] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide, which sequentially comprises amino acid sequence motifs from the N-terminus to the C-terminus: motif 19 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 7 (SEQ ID NO: 652, SEQ ID NO: 676 or SEQ ID NO: 699), motif 13 (SEQ ID NO: 658, SEQ ID NO: 682 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 10 (SEQ ID NO: 655, SEQ ID NO: 679 or SEQ ID NO: 702), motif 18 (SEQ ID NO: 663), motif 24 (SEQ ID NO: 669, SEQ ID NO: 692 or SEQ ID NO: 715), motif 14 (SEQ ID NO: 659, SEQ ID NO: 683 or SEQ ID NO: 715), and motif 14 (SEQ ID NO: 659, SEQ ID NO: 683 or SEQ ID NO: 710). SEQ ID NO: 706), SEQ ID NO: 656, SEQ ID NO: 680 or SEQ ID NO: 703), SEQ ID NO: 667, SEQ ID NO: 690 or SEQ ID NO: 713), SEQ ID NO: 647, SEQ ID NO: 671 or SEQ ID NO: 694), SEQ ID NO: 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), SEQ ID NO: 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), SEQ ID NO: 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), SEQ ID NO: 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), SEQ ID NO: 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 693), SEQ ID NO: 17 (SEQ ID NO: 706), SEQ ID NO: 670 or SEQ ID NO: 693), SEQ ID NO: 706, SEQ ID NO: 676 or SEQ ID NO: 703), SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 693, ... NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 6 (SEQ ID NO: 651, SEQ ID NO: 675 or SEQ ID NO: 698), motif 12 (SEQ ID NO: 657, SEQ ID NO: 681 or SEQ ID NO: 704), motif 4 (SEQ ID NO: 649, SEQ ID NO: 673 or SEQ ID NO: 696), motif 16 (SEQ ID ...6 (SEQ ID NO: 657, SEQ ID NO: 6NO: 661, SEQ ID NO: 685 or SEQ ID NO: 708), motif 5 (SEQ ID NO: 650, SEQ ID NO: 674 or SEQ ID NO: 697), motif 23 (SEQ ID NO: 668, SEQ ID NO: 691 or SEQ ID NO: 714) and motif 3 (SEQ ID NO: 648, SEQ ID NO: 672 or SEQ ID NO: 695).

[0076] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide, which sequentially comprises amino acid sequence motifs from the N-terminus to the C-terminus: motif 19 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 7 (SEQ ID NO: 652, SEQ ID NO: 676 or SEQ ID NO: 699), motif 13 (SEQ ID NO: 658, SEQ ID NO: 682 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 14 (SEQ ID NO: 659, SEQ ID NO: 683 or SEQ ID NO: 706), motif 2 (SEQ ID NO: 647, SEQ ID NO: 671 or SEQ ID NO: 694), motif 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), motif 15 (SEQ ID NO: 664, SEQ ID NO: 677 or SEQ ID NO: 700), motif 15 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 704), motif 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), motif 15 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 16 ...00), Generic 9 (SEQ ID NO: 654, SEQ ID NO: 678, or SEQ ID NO: 701), Generic 21 (SEQ ID NO: 666, SEQ ID NO: 689, or SEQ ID NO: 712), Generic 1 (SEQ ID NO: 646, SEQ ID NO: 670, or SEQ ID NO: 693), Generic 17 (SEQ ID NO: 662, SEQ ID NO: 686, or SEQ ID NO: 709), Generic 6 (SEQ ID NO: 651, SEQ ID NO: 675, or SEQ ID NO: 698), Generic 12 (SEQ ID NO: 657, SEQ ID NO: 681, or SEQ ID NO: 704), Generic 4 (SEQ ID NO: 649, SEQ ID NO: 673, or SEQ ID NO: 696), Generic 16 (SEQ ID NO: 661, SEQ ID NO: 685, or SEQ ID NO: 707), Generic 9 (SEQ ID NO: 654, SEQ ID NO: 678, or SEQ ID NO: 701), Generic 21 (SEQ ID NO: 666, SEQ ID NO: 689, or SEQ ID NO: 712), Generic 1 (SEQ ID NO: 646, SEQ ID NO: 670, or SEQ ID NO: 693), Generic 17 (SEQ ID NO: 662, SEQ ID NO: 686, or SEQ ID NO: 709), Generic 6 (SEQ ID NO: 651, SEQ ID NO: 675, or SEQ ID NO: 698), Generic 12 (SEQ ID NO: 657, SEQ ID NO: 681, or SEQ ID NO: 704), Generic 4 (SEQ ID NO: 649, NO: 708), motif 5 (SEQ ID NO: 650, SEQ ID NO: 674 or SEQ ID NO: 697), motif 23 (SEQ ID NO: 668, SEQ ID NO: 691 or SEQ ID NO: 714) and motif 3 (SEQ ID NO: 648, SEQ ID NO: 672 or SEQ ID NO: 695).

[0077] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which sequentially comprises, from the N-terminus to the C-terminus, a region A of about 200 to about 300 amino acids in length, the region A containing the amino acid sequence motifs of the following: motif 19 (SEQ ID NO: 664, SEQ ID NO: 687 or SEQ ID NO: 710), motif 7 (SEQ ID NO: 652, SEQ ID NO: 676 or SEQ ID NO: 699), motif 13 (SEQ ID NO: 658, SEQ ID NO: 682 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 10 (SEQ ID NO: 655, SEQ ID NO: 679 or SEQ ID NO: 702), motif 18 (SEQ ID NO: 663), motif 24 (SEQ ID NO: 669, SEQ ID NO: 692 or SEQ ID NO: 705), motif 20 (SEQ ID NO: 665, SEQ ID NO: 688 or SEQ ID NO: 711), motif 10 (SEQ ID NO: 655, SEQ ID NO: 679 or SEQ ID NO: 702), motif 18 (SEQ ID NO: 663), motif 24 (SEQ ID NO: 669, SEQ ID NO: 692 or SEQ ID NO: 705), and motif 24 (SEQ ID NO: 669, SEQ ID NO: 692 or SEQ ID NO: 705). NO: 715) and / or motif 14, having a predominantly nonconserved secondary structure; a region B of about 380 to about 465 amino acids in length, comprising the amino acid sequence motifs of the following: motif 22 (SEQ ID NO: 667, SEQ ID NO: 690 or SEQ ID NO: 713), motif 2 (SEQ ID NO: 647, SEQ ID NO: 671 or SEQ ID NO: 694), motif 8 (SEQ ID NO: 653, SEQ ID NO: 677 or SEQ ID NO: 700), motif 15 (SEQ ID NO: 660, SEQ ID NO: 684 or SEQ ID NO: 707), motif 9 (SEQ ID NO: 654, SEQ ID NO: 678 or SEQ ID NO: 701), motif 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), motif 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 715), motif 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 715), motif 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), motif 1 (SEQ ID NO: 646, SEQ ID NO: 670 or SEQ ID NO: 713), motif 2 (SEQ ID NO: 647, SEQ ID NO: 678 or SEQ ID NO: 701), motif 21 (SEQ ID NO: 666, SEQ ID NO: 689 or SEQ ID NO: 712), motif 1 (SEQ ID NO: 646, SEQ ID NO: 6 NO: 693), motif 17 (SEQ ID NO: 662, SEQ ID NO: 686 or SEQ ID NO: 709), motif 6 (SEQ ID NO: 651, SEQ ID NO: 675 or SEQ ID NO: 698) and / or motif 12 and having a structure that is primarily α-helical;And a region C of approximately 150 to approximately 180 amino acids, comprising the amino acid sequence motifs of the following: motif 16 (SEQ ID NO: 661, SEQ ID NO: 685, or SEQ ID NO: 708), motif 5 (SEQ ID NO: 650, SEQ ID NO: 674, or SEQ ID NO: 697), motif 23 (SEQ ID NO: 668, SEQ ID NO: 691, or SEQ ID NO: 714) and / or motif 3 (SEQ ID NO: 648, SEQ ID NO: 672, or SEQ ID NO: 695), having a common secondary structure primarily comprising a β-chain structure.

[0078] In some embodiments, the PtIP-83 polypeptide contains an amino acid sequence motif at the positions shown in Table 2.

[0079] In some embodiments, the nucleic acid molecule encodes the PtIP-83 polypeptide, which, from its N-terminus to its C-terminus, sequentially comprises: a region A of about 200 to about 300 amino acids in length, having a predominantly non-conserved secondary structure; a region B of about 380 to about 465 amino acids in length, having a shared secondary structure comprising 8 to 10 segments predominantly α-helical structures; and a region C of about 150 to about 180 amino acids in length, having a shared secondary structure comprising 6 to 8 segments predominantly β-chain structures. As used herein, “predominantly non-conserved secondary structure” means that the secondary structure region does not align consistently within the PtIP polypeptide family. As used herein, “predominantly α-helical structure” means that the secondary structure predicts the presence of one or more vacancies between coils and / or β-chain structures intervening in the α-helical structure. As used herein, “predominantly β-chain structure” means that the secondary structure predicts the presence of one or more vacancies between coils and / or α-helical structures intervening in the β-chain structure. In some implementations, the secondary structure is generated by PSIPRED, a high-order secondary structure prediction method (Jones DT. (1999) J.Mol.Biol. 292: 195-202).

[0080] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which comprises, from the N-terminus to the C-terminus, sequentially: a region A of about 200 to about 300 amino acids in length, the region A having a predominantly non-conserved secondary structure; a region B of about 380 to about 465 amino acids in length, the region B having a shared secondary structure comprising nine segments predominantly α-helical structures; and a region C of about 150 to about 180 amino acids in length, the region C having a shared secondary structure comprising seven segments predominantly β-chain structures.

[0081] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide that, from its N-terminus to its C-terminus, sequentially comprises: a region A of about 200 to about 300 amino acids in length, having a predominantly non-conserved secondary structure, wherein within about 30 to about 130 amino acid residues from the N-terminus of the PtIP-83 polypeptide, region A includes a conserved β-chain 1 (β1a) of about 4 to about 12 amino acids in length; a region B of about 380 to about 465 amino acids in length, having a shared secondary structure comprising nine segments predominantly α-helical structures; and a region C of about 150 to about 180 amino acids in length, having a shared secondary structure comprising seven segments predominantly β-chain structures.

[0082] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which sequentially comprises, from the N-terminus to the C-terminus: a region A of about 200 to about 300 amino acids in length, having a flexible shared secondary structure, wherein within about 50 to about 165 amino acid residues from the N-terminus of the PtIP-83 polypeptide, region A includes a conserved β chain 1 (β1a) of about 4 to about 12 amino acids in length, a coil of about 3 to about 18 amino acids in length, and a β chain 2 (β1b) of about 4 to about 32 amino acids in length; a region B of about 380 to about 465 amino acids in length, having a shared secondary structure comprising nine segments predominantly α-helical structures; and a region C of about 150 to about 180 amino acids in length, having a shared secondary structure comprising seven segments predominantly β-chain structures.

[0083] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which, from its N-terminus to its C-terminus, sequentially comprises: a region A of about 200 to about 300 amino acids in length, the region A having a predominantly non-conserved secondary structure; and a region B of about 380 to about 465 amino acids in length having a shared secondary structure, the shared secondary structure sequentially comprising: i) an α-helix-1 of about 10 to about 26 amino acids in length; ii) a coil-1 of about 2 to about 8 amino acids in length, which is laterally attached to the α-helix-1 and... iii) An α-helix-2 of about 15 to about 24 amino acids in length; iv) A coil-2 of about 4 to about 14 amino acids in length, with α-helix-2 and α-helix-3 attached to its sides; v) An α-helix-3 of about 15 to about 27 amino acids in length; vi) A coil-3 of about 11 to about 13 amino acids in length, with α-helix-3 and α-helix-4 attached to its sides; vii) An α-helix-4 of about 24 to about 180 amino acids in length; viiii) A coil-4 of about 4 to about 5 amino acids in length, with α-helix-4 attached to its sides. And α-helix-5; ix) α-helix-5 with a length of about 50 to about 54 amino acids; x) coil-5 with a length of about 11 to about 17 amino acids, with α-helix-5 and α-helix-6 attached to its sides; xi) α-helix-6 with a length of about 15 to about 16 amino acids; xii) coil-6 with a length of about 6 to about 9 amino acids, with α-helix-6 and α-helix-7 attached to its sides; xiii) α-helix-7 with a length of about 49 to about 55 amino acids; xiv) coil-7 with a length of about 3 to about 8 amino acids, with α-helix-7 attached to its sides. And α-helix-8; xv) α-helix-8 of about 33 to about 36 amino acids in length; xvi) coil-8 of about 14 to about 16 amino acids in length, with α-helix-8 and α-helix-9 attached to its sides; xvii) α-helix-9 of about 16 to about 23 amino acids in length; xviii) coil-9 of about 21 to about 28 amino acids in length, with α-helix-9 and region C attached to its sides; and region C of about 150 to about 180 amino acids in length, which has a common secondary structure comprising seven segments that are predominantly β-chain structures.

[0084] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which, from its N-terminus to its C-terminus, sequentially comprises: a region A of about 200 to about 300 amino acids in length, having a predominantly non-conserved secondary structure; a region B of about 380 to about 465 amino acids in length, having a shared secondary structure comprising nine segments predominantly α-helical; and a region C of about 150 to about 180 amino acids in length having a shared secondary structure, the shared secondary structure sequentially comprising: i) a β-chain-1 (β1) of about 3 to about 5 amino acids in length; ii) a coil of about 13 to about 17 amino acids in length; iii) a β-chain-2 (β2) of about 7 to about 11 amino acids in length; iv) a long The following are described: a coil of about 17 to about 23 amino acids; v) a β-chain-3 (β3) of about 5 to about 7 amino acids; vi) a coil of about 12 to about 14 amino acids; vii) a β-chain-4 (β4) of about 5 to about 6 amino acids; viiii) a coil of about 2 to about 7 amino acids; ix) a β-chain-5 (β5) of about 5 to about 7 amino acids; x) a coil of about 26 to about 28 amino acids; xi) a β-chain-6 (β6) of about 5 to about 7 amino acids; xii) a coil of about 16 to about 20 amino acids; and xiii) a β-chain-1 (β7) of about 13 to about 17 amino acids.

[0085] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which, from its N-terminus to its C-terminus, sequentially comprises: a region A of about 200 to about 300 amino acids in length, having a predominantly non-conserved secondary structure; and a region B of about 380 to about 465 amino acids in length having a shared secondary structure, which sequentially comprises: i) an α-helix-1 of about 10 to about 26 amino acids in length; ii) a coil-1 of about 2 to about 8 amino acids in length, laterally attached to α-helix-1 and α-helix-2; iii) an α-helix-2 of about 15 to about 24 amino acids in length; and iv) a coil-2 of about 4 to about 14 amino acids in length, laterally attached to α-helix-1. 2 and α-helix-3; v) α-helix-3 with a length of about 15 to about 27 amino acids; vi) coil-3 with a length of about 11 to about 13 amino acids, with α-helix-3 and α-helix-4 attached to its sides; vii) α-helix-4 with a length of about 24 to about 180 amino acids; viiii) coil-4 with a length of about 4 to about 5 amino acids, with α-helix-4 and α-helix-5 attached to its sides; ix) α-helix-5 with a length of about 50 to about 54 amino acids; x) coil-5 with a length of about 11 to about 17 amino acids, with α-helix-5 and α-helix-6 attached to its sides; xi) α-helix-6 with a length of about 15 to about 16 amino acids; xii) coil-6 with a length of about 6 to about 9 amino acids, with α-helix-6 attached to its sides. -6 and α-helix-7; xiii) α-helix-7 of about 49 to about 55 amino acids in length; xiv) coil-7 of about 3 to about 8 amino acids in length, with α-helix-7 and α-helix-8 attached to its sides; xv) α-helix-8 of about 33 to about 36 amino acids in length; xvi) coil-8 of about 14 to about 16 amino acids in length, with α-helix-8 and α-helix-9 attached to its sides; xvii) α-helix-9 of about 16 to about 23 amino acids in length; xviii) coil-9 of about 21 to about 28 amino acids in length, with α-helix-9 and region C attached to its sides; and region C of about 150 to about 180 amino acids in length having a common secondary structure, which sequentially includes: i ii) a β-chain of about 3 to about 5 amino acids in length; iii) a coil of about 13 to about 17 amino acids in length; iv) a β-chain of about 7 to about 11 amino acids in length; v) a β-chain of about 17 to about 23 amino acids in length; vi) a β-chain of about 5 to about 7 amino acids in length; vii) a coil of about 12 to about 14 amino acids in length; vii) a β-chain of about 5 to about 6 amino acids in length; viiii) a coil of about 2 to about 7 amino acids in length; ix) a β-chain of about 5 to about 7 amino acids in length;x) a coil of about 26 to about 28 amino acids in length; xi) a β-chain-6 (β6) of about 5 to about 7 amino acids in length; xii) a coil of about 16 to about 20 amino acids in length; and xiii) a β-chain-1 (β7) of about 13 to about 17 amino acids in length.

[0086] In some embodiments, the nucleic acid molecule encodes a PtIP-83 polypeptide, which sequentially comprises, from its N-terminus to its C-terminus: a region A of about 200 to about 300 amino acids in length, having a flexible shared secondary structure, wherein within about 30 to about 130 amino acid residues from the N-terminus of the PtIP-83 polypeptide, region A includes a conserved β-chain 1 (β1a) of about 4 to about 12 amino acids in length; and a region B of about 380 to about 465 amino acids in length having a shared secondary structure, which sequentially includes: i) an α-helix-1 of about 10 to about 26 amino acids in length; and ii) a coil-1 of about 2 to about 8 amino acids in length, laterally attached to an α-helix. -1 and α-helix-2; iii) α-helix-2 with a length of about 15 to about 24 amino acids; iv) coil-2 with a length of about 4 to about 14 amino acids, with α-helix-2 and α-helix-3 attached to its sides; v) α-helix-3 with a length of about 15 to about 27 amino acids; vi) coil-3 with a length of about 11 to about 13 amino acids, with α-helix-3 and α-helix-4 attached to its sides; vii) α-helix-4 with a length of about 24 to about 180 amino acids; viiii) coil-4 with a length of about 4 to about 5 amino acids, with α-helix-4 and α-helix-5 attached to its sides; ix) α-helix-5 with a length of about 50 to about 54 amino acids; x) coil-5 with a length of about 11 to about 17 amino acids, with α-helix-1 attached to its sides. 5 and α-helix-6; xi) α-helix-6 with a length of about 15 to about 16 amino acids; xii) coil-6 with a length of about 6 to about 9 amino acids, with α-helix-6 and α-helix-7 attached to its sides; xiii) α-helix-7 with a length of about 49 to about 55 amino acids; xiv) coil-7 with a length of about 3 to about 8 amino acids, with α-helix-7 and α-helix-8 attached to its sides; xv) α-helix-8 with a length of about 33 to about 36 amino acids; xvi) coil-8 with a length of about 14 to about 16 amino acids, with α-helix-8 and α-helix-9 attached to its sides; xvii) α-helix-9 with a length of about 16 to about 23 amino acids; xviii) coil-9 with a length of about 21 to about 28 amino acids, whose... The α-helix-9 is laterally attached to region C; and region C has a shared secondary structure of about 150 to about 180 amino acids in length, the shared secondary structure sequentially comprising: i) a β-chain-1 (β1) of about 3 to about 5 amino acids in length; ii) a coil of about 13 to about 17 amino acids in length; iii) a β-chain-2 (β2) of about 7 to about 11 amino acids in length; iv) a coil of about 17 to about 23 amino acids in length; v) a β-chain-3 (β3) of about 5 to about 7 amino acids in length; vi) a coil of about 12 to about 14 amino acids in length; vii) a β-chain-4 (β4) of about 5 to about 6 amino acids in length;viii) a coil of about 2 to about 7 amino acids in length; ix) a β-chain-5 (β5) of about 5 to about 7 amino acids in length; x) a coil of about 26 to about 28 amino acids in length; xi) a β-chain-6 (β6) of about 5 to about 7 amino acids in length; xii) a coil of about 16 to about 20 amino acids in length; and xiii) a β-chain-1 (β7) of about 13 to about 17 amino acids in length.

[0087] Nucleic acid molecules encoding transcription and / or translation products are also provided, which are subsequently spliced ​​to ultimately produce a functional PtIP-83 polypeptide. Splicing can be performed in vitro or in vivo and can involve cis or trans splicing. The substrate for splicing can be a polynucleotide (e.g., RNA transcript) or a polypeptide. An example of polynucleotide cis splicing is the removal of introns from the inserted coding sequence and splicing of two flanking exon regions to produce the PtIP-83 polypeptide coding sequence. An example of trans splicing would be the encryption of polynucleotides by splitting the coding sequence into two or more fragments, which can be transcribed individually and then spliced ​​to form a full-length insecticidal coding sequence. The use of splicing enhancer sequences that can be introduced into the construct can facilitate cis or trans splicing of the polypeptide (US Patents 6,365,377 and 6,531,316). Therefore, in some embodiments, the polynucleotides do not directly encode the full-length PtIP-83 polypeptide, but rather encode one or more fragments of the PtIP-83 polypeptide. These polynucleotides can be used to express a functional PtIP-83 polypeptide via a mechanism involving splicing, where splicing can occur at the polynucleotide (e.g., intron / exon) and / or polypeptide (e.g., intepid / exon) level. This can be used, for example, to control the expression of insecticidal activity, since the functional insecticidal polypeptide will only be expressed if all the necessary fragments are expressed in an environment that allows for splicing to produce a functional product. Furthermore, the introduction of one or more insert sequences into the polynucleotide can facilitate recombination with low-homology polynucleotides; the use of introns or intepids in the insert sequences facilitates the removal of the intercalated sequences, thereby restoring the function of the encoded variant.

[0088] Nucleic acid molecules that are fragments of the nucleic acid sequences encoding these PtIP-83 polypeptides are also covered by the embodiments described herein. As used herein, "fragment" refers to a portion of the nucleic acid sequence encoding the PtIP-83 polypeptide. The fragment of the nucleic acid sequence may encode the biologically active portion of the PtIP-83 polypeptide, or may be a fragment that can be used as a hybridization probe or PCR primer when using the methods disclosed below. The nucleic acid molecule that is a fragment of the nucleic acid sequence encoding the PtIP-83 polypeptide contains at least about 150, 180, 210, 240, 270, 300, 330, or 360 consecutive nucleotides or up to the number of nucleotides present in the full-length nucleic acid sequence encoding the PtIP-83 polypeptide disclosed herein, depending on the intended application. "Consecutive nucleotides" herein refers to nucleotide residues that are adjacent to each other. The fragment of the nucleic acid sequence of the embodiments will encode a protein fragment that retains the biological activity of the PtIP-83 polypeptide and thus retains the insecticidal activity. "Retained insecticidal activity" is used herein to mean that the polypeptide has at least about 10%, at least about 30%, at least about 50%, at least about 70%, 80%, 90%, 95% or higher of the full-length PtIP-83Aa polypeptide (SEQ ID NO: 1). In some embodiments, the insecticidal activity is lepidopteran activity. In one embodiment, the insecticidal activity is for Coleoptera species. In some embodiments, the insecticidal activity is for one or more insect pests of the following maize rootworm complex: Western maize rootworm Diabrotica virgifera; Northern maize rootworm D. barberi; Southern maize rootworm or eleven-spotted cucumber leaf beetle; Cucumber eleven-spotted leaf beetle (Diabrotica undecimpunctata howardi) and Mexican maize rootworm D. virgifera zeae. In one embodiment, the insecticidal activity is for leaf beetle species.

[0089] In some embodiments, the fragment of the nucleic acid sequence encoding the PtIP-83 polypeptide that encodes the protein bioactive portion will encode at least about 15, 20, 30, 50, 75, 100, 125 consecutive amino acids or up to the total number of amino acids present in the full-length PtIP-83 polypeptide of the embodiments described. In some embodiments, the fragment is, for example, generated by proteolysis, insertion of a start codon, deletion of a codon encoding a missing amino acid accompanied by insertion of a stop codon, or insertion of a stop codon in the coding sequence, relative to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23 or SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769 or a variant thereof, truncated from the N-terminus and / or C-terminus of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or more amino acids.In some implementations, the fragments covered herein are, for example, obtained through proteolysis or through the insertion of a start codon in the coding sequence, relative to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, SEQ ID NO: 769 or a variant thereof, produced by removing 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids from the N-terminus.

[0090] In some implementations, the fragments covered herein are, for example, obtained through proteolysis or through the insertion of a start codon in the coding sequence, relative to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, SEQ ID NO: 769 or a variant thereof, produced by removing amino acids 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14 from the N-terminus.

[0091] In some embodiments, the PtIP-83 polypeptide is encoded by a nucleic acid sequence that is sufficiently homologous to the nucleic acid sequences of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 717, SEQ ID NO: 738, SEQ ID NO: 739, SEQ ID NO: 740, SEQ ID NO: 741, SEQ ID NO: 742, SEQ ID NO: 743, SEQ ID NO: 744, SEQ ID NO: 745, SEQ ID NO: 746, SEQ ID NO: 747, SEQ ID NO: 748, SEQ ID NO: 749, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 752, or SEQ ID NO: 753. "Sufficient homology" is used herein to mean that, when compared with a reference sequence using one of the alignment procedures described herein and with standard parameters, the amino acid or nucleic acid sequences have at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher sequence homology. Those skilled in the art will recognize that these values ​​can be appropriately adjusted to determine the corresponding homology of the proteins encoded by the two nucleic acid sequences, taking into account codon degeneracy, amino acid similarity, reading frame positioning, etc.

[0092] In some implementations, sequence homology refers to the full-length sequence of the polynucleotide encoding the PtIP-83 polypeptide or to the full-length sequence of the PtIP-83 polypeptide.

[0093] In some embodiments, the nucleic acid encoding the PtIP-83 polypeptide is selected from any one of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 172-235, any one of SEQ ID NO: 300-333, any one of SEQ ID NO: 368-397, any one of SEQ ID NO: 428-517, SEQ ID NO: 717, SEQ ID NO: 718-727, and any one of SEQ ID NO: 738-753.

[0094] In some implementations, the nucleic acid encodes a PtIP-83 polypeptide, which, compared to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 763. NO: 769 has a sequence identity of at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater. In some implementations, sequence identity is achieved using all default parameters. The package (Invitrogen Corporation, Carlsbad, Calif.) The ClustalW algorithm in the module is used for computation. In some implementations, sequence identity is calculated across the entire length of the peptide using the ClustalW algorithm in the ALIGNX module of the Vector NTI package (Invitrogen Corporation, Carlsbad, Calif.) with all default parameters.

[0095] To determine the percentage of identity between two amino acid sequences or two nucleic acid sequences, the sequences are aligned for optimal comparison purposes. The percentage of identity between the two sequences is a function of the number of common positions shared by the sequences (i.e., percentage of identity = number of common positions / total number of positions (e.g., overlapping positions) × 100). In one embodiment, the two sequences are of the same length. In another embodiment, the comparison spans the entire reference sequence (e.g., across the entire SEQ ID NO: 1). The percentage of identity between the two sequences can be determined using techniques similar to those described below, with or without gaps. In calculating the percentage of identity, exact matches are typically counted.

[0096] Mathematical algorithms can be used to determine the percentage of identity between two sequences. A non-restrictive example of a mathematical algorithm for comparing two sequences is the algorithm by Karlin and Altschul, (1990) Proc. Natl. Acad. Sci. USA 87:2264, improved by Karlin and Altschul, (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877. Such algorithms are incorporated into the BLASTN and BLASTX programs by Altschul et al., (1990) J. Mol. Biol. 215:403. BLAST nucleotide searches can be performed using the BLASTN program with a score of 100 and a word length of 12 to obtain nucleic acid sequences homologous to the insecticidal nucleic acid molecule of the embodiment. BLAST protein searches can be performed using the BLASTX program with a score of 50 and a word length of 3 to obtain amino acid sequences homologous to the insecticidal protein molecule of the embodiment. For comparative purposes, alignments with vacancies can be obtained using Gapped BLAST (in BLAST 2.0), as described by Altschul et al. (1997) Nucleic Acids Res. 25: 3389. Alternatively, an iterative search using PSI-Blast can be performed, which detects distant relationships between molecules. See Altschul et al. (1997) (ibid.). When using BLAST, Gapped BLAST, and PSI-Blast programs, the default parameters of each program (e.g., BLASTX and BLASTN) can be used. Alignments can also be performed manually by inspection.

[0097] Another non-limiting example of a mathematical algorithm for sequence comparison is the ClustalW algorithm (Higgins et al., (1994) Nucleic Acids Res. 22: 4673-4680). ClustalW compares sequences and aligns amino acid or DNA sequences as a whole, thus providing data on the sequence conservation of entire amino acid sequences. The ClustalW algorithm is used in several commercial DNA / amino acid analysis software packages, such as... The package (Invitrogen Corporation, Carlsbad, Calif.) Module. After aligning amino acid sequences using ClustalW, the percentage of amino acid identity can be assessed. A non-limiting example of a software program for analyzing ClustalW alignments is GENEDOC. TM GENEDOC TM(Karl Nicholas) allows for the assessment of amino acid (or DNA) similarity and identity between multiple proteins. Another non-limiting example of a mathematical algorithm for sequence comparison is the algorithm of Myers and Miller, (1988) CABIOS 4:11-17. Such an algorithm is incorporated into the ALIGN program (version 2.0), which is part of the GCG Wisconsin Genetics software package version 10 (from Accelrys, Inc., 9685 Scranton Rd., San Diego, Calif., USA). When comparing amino acid sequences using the ALIGN program, the PAM120 weighted residue table, vacancy length penalty 12, and vacancy penalty 4 can be used.

[0098] Another non-limiting example of a mathematical algorithm for sequence comparison is the algorithm of Needleman and Wunsch, (1970) J. Mol. Biol. 48(3): 443-453, which uses GAP version 10 software with the following default parameters to determine sequence identity or similarity: identity % and similarity % of nucleic acid sequences are determined using GAP weight 50 and length weight 3 and the nwsgapdna.cmpii scoring matrix; identity % or similarity % of amino acid sequences are determined using GAP weight 8 and length weight 2 and the BLOSUM62 scoring procedure. An equivalence procedure may also be used. “Equivalence procedure” is used herein to refer to any such sequence comparison procedure that, for any two sequences under consideration, produces alignments with the same nucleotide residue matches and the same percentage of sequence identity compared to the corresponding alignments produced by GAP version 10.

[0099] The embodiments also cover nucleic acid molecules encoding variants of the PtIP-83 polypeptide. "Variants" of the PtIP-83 polypeptide-encoding nucleic acid sequences include those sequences encoding the PtIP-83 polypeptide disclosed herein but which differ conservedly due to the degeneracy of the genetic code, as well as those sequences that are sufficiently identical to those discussed above. Naturally occurring allelic variants can be identified using known molecular biology techniques, such as polymerase chain reaction (PCR) and hybridization techniques described below. Variant nucleic acid sequences also include synthetically obtained nucleic acid sequences, for example, generated by site-directed mutagenesis, but still encoding the disclosed PtIP-83 polypeptide, as discussed below.

[0100] This disclosure provides isolated or recombinant polynucleotides encoding any of the PtIP-83 polypeptides disclosed herein. Those skilled in the art will readily understand that, due to the degeneracy of the genetic code, there are numerous nucleotide sequences encoding the PtIP-83 polypeptides of this disclosure. Table 1 is a codon table providing synonymous codons for each amino acid. For example, codons AGA, AGG, CGA, CGC, CGG, and CGU all encode the amino acid arginine. Therefore, at each position in the nucleic acid of this disclosure designated as arginine by a certain codon, that codon can be changed to any of the corresponding codons mentioned above without altering the encoded polypeptide. It should be understood that U in the RNA sequence corresponds to T in the DNA sequence.

[0101] Table 1

[0102]

[0103] Those skilled in the art will also understand that changes can be introduced through mutations in the nucleic acid sequence, thereby altering the amino acid sequence of the encoded PtIP-83 polypeptide without changing the protein's biological activity. Therefore, variant nucleic acid molecules can be formed by introducing one or more nucleotide substitutions, additions, and / or deletions into the corresponding nucleic acid sequences disclosed herein, such that one or more amino acid substitutions, additions, or deletions are introduced into the encoded protein. Mutations can be introduced using standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Such variant nucleic acid sequences are also covered by this disclosure.

[0104] Alternatively, mutant nucleic acid sequences can be obtained by randomly introducing mutations along all or part of the coding sequence, such as through saturation mutagenesis. The resulting mutants can then be screened for their insecticidal activity to identify those that retain the activity. After mutagenesis, the encoded protein can be expressed in a recombinant manner, and its activity can be determined using standard assay techniques.

[0105] In addition to the standard cloning methods described by Ausubel, Berger, and Sambrook, the polynucleotides and fragments thereof disclosed herein are optionally used as substrates for a variety of recombination and recurrent recombination reactions, i.e., to generate additional insecticidal polypeptide homologs and fragments thereof with desired properties. A variety of such reactions are known, including those developed by the inventors and colleagues. Methods for generating variants of any of the nucleic acids listed herein include recurrent recombination of such polynucleotides with a second (or more) polynucleotide to form a library of variant polynucleotides, as are embodiments of this disclosure, the resulting library, the cell containing the library, and any recombinant polynucleotides generated by such methods. Additionally, such methods optionally include selecting variant polynucleotides from such libraries based on insecticidal activity when such recurrent recombination is performed in vitro or in vivo.

[0106] A variety of diversity generation schemes (including nucleic acid recursive recombination schemes) are available and have been well described in the art. These procedures can be used alone and / or in combination to generate one or more variants of nucleic acids or nucleic acid sets, as well as variants of the proteins they encode. These procedures, individually and collectively, provide robust and widely applicable methods for generating diverse nucleic acids and nucleic acid sets (including, for example, nucleic acid libraries), which can be used for, for example, the engineering or rapid evolution of nucleic acids, proteins, pathways, cells, and / or organisms to acquire new and / or improved properties.

[0107] Although distinctions and classifications have been made in the subsequent discussion for clarity, it should be understood that these techniques are generally not mutually exclusive. In fact, the various methods described can be used alone or in combination, in parallel or sequentially, to obtain a wide variety of sequence variants.

[0108] The result of any diversification process described herein may be the production of one or more nucleic acids, which may be selected or screened to obtain nucleic acids having or conferring desired properties or nucleic acids encoding proteins having or conferring desired properties. After diversification by one or more methods described herein or other methods available to those skilled in the art, any of the produced nucleic acids may be selected for desired activities or properties, such as insecticidal activity or such activity at a desired pH, etc. This may include the identification of any activity, which may be detected by any assay in the art in, for example, an automated or automatable format, see, for example, the discussion of screening for insecticidal activity below. Multiple related (or even unrelated) properties may be evaluated, either continuously or in parallel, at the discretion of the operator.

[0109] Descriptions of diverse generation procedures for producing modified nucleic acid sequences (e.g., nucleic acid sequences encoding peptides or fragments thereof with insecticidal activity) can be found in the following publications and references cited therein: Soong et al., (2000) Nat Genet 25(4): 436-439; Stemmer et al., (1999) Tumor Targeting 4: 1-4; Ness et al., (1999) Nat Biotechnol 17: 893-896; Chang et al., (1999) Nat Biotechnol 17: 793-797; Minshull and Stemmer, (1999) Curr Opin Chem Biol 3: 284-290; Christians et al., (1999) Nat Biotechnol 17 259-264; Crameri et al., (1998) Nature 391:288-291; Crameri et al., (1997) Nat Biotechnol 15:436-438; Zhang et al., (1997) PNAS USA 94:4504-4509; Patten et al., (1997) Curr Opin Biotechnol 8:724-733; Crameri et al., (1996) Nat Med 2:100-103; Crameri et al., (1996) Nat Biotechnol 14:315-319; Gates et al., (1996) J Mol Biol 255:373-386; Stemmer, (1996) “Sexual PCR and Assembly PCR” In: The Encyclopedia of Molecular Biology. VCH Publishers, New York. pp. 447-457; Crameri and Stemmer, (1995) BioTechniques 18: 194-195; Stemmer et al., (1995) Gene, 164: 49-53; Stemmer, (1995) Science 270: 1510; Stemmer, (1995) Bio / Technology 13:549-553; Stemmer, (1994) Nature370:389-391 and Stemmer, (1994) PNAS USA 91:10747-10751.

[0110] Mutational methods that generate diversity include, for example, site-directed mutagenesis (Ling et al., (1997) Anal Biochem 254(2): 157-178; Dale et al., (1996) Methods Mol Biol 57: 369-374; Smith, (1985) Ann RevGenet 19: 423-462; Botstein and Shortle, (1985) Science 229: 1193-1201; Carter, (1986) Biochem J 237: 1-7 and Kunkel, (1987) “The efficiency of oligonucleotide directed mutagenesis”, in Nucleic Acids & Molecular Biology (edited by Eckstein and Lilley, Springer Verlag, Berlin)); and mutagenesis using uracil-containing templates (Kunkel, (1985) PNAS). USA 82: 488-492; Kunkel et al., (1987) Methods Enzymol 154: 367-382 and Bass et al., (1988) Science 242: 240-245); Oligonucleotide site-directed mutagenesis (Zoller and Smith, (1983) Methods Enzymol 100: 468-500; Zoller and Smith, (1987) Methods Enzymol 154: 329-350 (1987); Zoller and Smith, (1982) Nucleic Acids Res 10: 6487-6500); Phosphate-modified DNA mutagenesis (Taylor et al., (1985) Nucleic Acids Res 13: 8749-8764; Taylor et al., (1985) Nucleic Acids Res 13: 8765-8787 (1985); Nakamaye and Eckstein, (1986) Nucl Acids Res 14: 9679-9698; Sayers et al., (1988) Nucl Acids Res 16: 791-802 and Sayers et al., (1988) Nucl Acids Res 16: 803-814); Mutagenesis using double-stranded DNA with vacancy (Kramer et al., (1984) Nucl Acids Res 12: 9441-9456; Kramer and Fritz, (1987) Methods Enzymol 154: 350-367;Kramer et al., (1988) Nucl Acids Res 16:7207 and Fritz et al., (1988) Nucl Acids Res 166987-6999.

[0111] Other suitable methods include point mismatch repair (Kramer et al., (1984) Cell 38: 879-887), mutagenesis using repair-deficient host strains (Carter et al., (1985) Nucl Acids Res 13: 4431-4443 and Carter, (1987) Methods in Enzymol 154: 382-403), deletion mutagenesis (Eghtedarzadeh and Henikoff, (1986) Nucl Acids Res 14: 5115), restriction selection and restriction purification (Wells et al., (1986) Phil Trans R Soc Lond A 317: 415-423), and mutagenesis via whole-genome synthesis (Nambiar et al., (1984) Science 223: 1299-1301; Sakamar and Khorana, (1988) Nucl Acids Res 14:6361-6372; Wells et al., (1985) Gene 34:315-323 and (Mandek et al., (1985) Nucl Acids Res 13: 3305-3316), double-strand break repair (Mandecki, (1986) PNAS USA, 83: 7177-7181 and Arnold, (1993) Curr Opin Biotech 4: 450-455). Further details on many of the above methods can be found in Methods Enzymol, Vol. 154, which also describes a useful comparison of troubleshooting problems for various mutagenesis methods.

[0112] Further details regarding various methods of generating diversity can be found in the following U.S. patents, PCT publications and applications, and EPO publications: U.S. Patent 5,723,323, U.S. Patent 5,763,192, U.S. Patent 5,814,476, U.S. Patent 5,817,483, U.S. Patent 5,824,514, U.S. Patent 5,976,862, U.S. Patent 5,605,793, U.S. Patent 5,811,238, U.S. Patent 5,830,721, U.S. Patent 5,834,252, U.S. Patent 5,837,458, WO 1995 / 22625, WO 1996 / 33207, WO 1997 / 20078, WO 1997 / 35966, WO 1999 / 41402, WO 1999 / 41383, WO 1999 / 41369, WO 1999 / 41368、EP 752008、EP 0932670、WO 1999 / 23107、WO 1999 / 21979、WO 1998 / 31837、WO 1998 / 27230、WO 1998 / 27230、WO 2000 / 00632、WO 2000 / 09679、WO 1998 / 42832、WO1999 / 29902、WO 1998 / 41653、WO 1998 / 41622、WO 1998 / 42727、WO 2000 / 18906、WO 2000 / 04190、WO 2000 / 42561、WO 2000 / 42559、WO 2000 / 42560, WO 2001 / 23401 and PCT / US01 / 06775.

[0113] The nucleotide sequences of the implementation scheme can also be used to isolate corresponding sequences from ferns or other primitive plants, particularly species of the genera *Asplenium*, *Polypodium*, *Adiantum*, *Platycerium*, *Nephrolepis*, *Ophioglossum*, *Colysis*, *Bolbitis*, *Blechnum*, *Selaginella*, *Lycopodium*, and *Huperzia*. Thus, these sequences can be identified based on their sequence homology with the sequences presented herein using methods such as PCR and hybridization. The implementation scheme covers sequences selected based on their sequence identity with the complete sequences or fragments thereof described herein. These sequences include sequences that are orthologs of the disclosed sequences. The term "ortholog" refers to a gene derived from a common ancestral gene and present in different species due to speciation. Genes present in different species are considered orthologs when their nucleotide sequences and / or the sequences of the proteins they encode are substantially identical, as defined elsewhere in this document. The functions of orthologs are often highly conserved across species.

[0114] In PCR methods, oligonucleotide primers can be designed for PCR reactions to amplify corresponding DNA sequences from cDNA or genomic DNA extracted from any organism of interest. The methods for designing PCR primers and PCR cloning are well known in the art and are disclosed in Sambrook et al., (1989) *Molecular Cloning: A Laboratory Manual* (2nd edition, ColdSpring Harbor Laboratory Press, Plainview, New York), hereinafter referred to as "Sambrook". See also Innis et al., eds., (1990) *PCR Protocols: A Guide to Methods and Applications* (Academic Press, New York); Innis and Gelfand, eds., (1995) *PCR Strategies* (Academic Press, New York); and Innis and Gelfand, eds., (1999) *PCR Methods Manual* (Academic Press, New York). Known PCR methods include, but are not limited to, methods using paired primers, nested primers, single-specific primers, degenerate primers, gene-specific primers, vector-specific primers, and partially mismatched primers.

[0115] To identify potential PtIP-83 peptides from fern or moss aggregates, fern or moss cell lysates can be screened using Western blotting and / or ELISA methods with antibodies against and / or generated from the PtIP-83 peptide. This type of assay can be performed in high-throughput mode. Positive samples can be further analyzed using various techniques such as antibody-based protein purification and identification. Methods for generating antibodies are well known in the art and are discussed below.

[0116] Alternatively, mass spectrometry-based protein identification methods can be used to identify homologs of the PtIP-83 peptide, using the protocol described in the literature (Scott Patterson, (1998), 10.22, 1-24, Current Protocol in Molecular Biology, published by John Wiley & Son Inc). Specifically, using an LC-MS / MS-based protein identification method, the MS data of a given cell lysate or a sample rich in the desired molecular weight (dissected from an SDS-PAGE gel of the relevant molecular weight band of the PtIP-83 peptide) were compared with those of the PtIP-83 peptide SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766. Sequence information of SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769 and their homologs is associated. Any match in the peptide sequence indicates the potential presence of a homologous protein in the sample. Additional techniques (protein purification and molecular biology) can be used to isolate proteins and identify the sequences of homologs.

[0117] In hybridization methods, cDNA or genomic libraries can be screened using all or part of the insecticidal nucleic acid sequence. Methods for constructing such cDNA and genomic libraries are well known in the art and disclosed in Sambrook and Russell, (2001) (ibid.). Hybridization probes can be genomic DNA fragments, cDNA fragments, RNA fragments, or other oligonucleotides, and can be labeled with detectable groups such as 32P or any other detectable markers such as other radioisotopes, fluorescent compounds, enzymes, or enzyme cofactors. Probes for hybridization can be prepared by labeling synthetic oligonucleotides encoding nucleic acid sequences based on the known PtIP-83 polypeptide sequence disclosed herein. Alternatively, degenerate primers designed based on conserved nucleotides or amino acid residues in the nucleic acid sequence or the encoded amino acid sequence can be used. The probe typically contains a nucleic acid sequence region that, under stringent conditions, hybridizes to at least about 12, at least about 25, at least about 50, 75, 100, 125, 150, 175, or 200 consecutive nucleotides of a nucleic acid sequence or fragment or variant thereof encoding the disclosed PtIP-83 polypeptide. Methods for preparing probes for hybridization are well known in the art and disclosed in Sambrook and Russell, (2001), which is incorporated herein by reference.

[0118] For example, the entire nucleic acid sequence encoding the PtIP-83 polypeptide disclosed herein, or one or more portions thereof, can be used as a probe capable of specifically hybridizing to a corresponding nucleic acid sequence and messenger RNA encoding a PtIP-83 polypeptide-like sequence. To achieve specific hybridization under various conditions, such probes comprise unique sequences and are preferably at least about 10 nucleotides or at least about 20 nucleotides in length. This probe can be used to amplify the corresponding insecticidal sequence from selected organisms via PCR. This technique can be used to isolate additional coding sequences from desired organisms or as a diagnostic assay to determine the presence of coding sequences in organisms. Hybridization techniques involve screening for hybridization on plated DNA libraries (plaques or colonies; see, for example, Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual (2nd ed., ColdSpring Harbor Laboratory Press, ColdSpring Harbor, NY). Hybridization of such sequences can be performed under stringent conditions. "Stringent conditions" or "stringent hybridization conditions" are used herein to refer to conditions where the probe hybridizes to a detectably higher degree with its target sequence than it hybridizes to other sequences (e.g., at least 2-fold higher than background). Stringent conditions are sequence-dependent and will vary in different situations. By controlling the stringency of hybridization and / or washing conditions, target sequences that are 100% complementary to the probe can be identified (homologous detection). Alternatively, stringent conditions can be adjusted to allow some mismatches in the sequences, thereby detecting a lower degree of similarity (heterologous detection). Typically, the probe length is less than about 1000 nucleotides, preferably less than 500 nucleotides.

[0119] Typically, stringent conditions are those where the salt concentration is below about 1.5 M sodium ions, typically about 0.01 to 1.0 M sodium ion concentration (or other salts), the pH is 7.0 to 8.3, and the temperature is at least about 30 °C for short probes (e.g., 10 to 50 nucleotides) and at least about 60 °C for long probes (e.g., more than 50 nucleotides). Stringent conditions can also be achieved by adding a destabilizing agent such as formamide. Exemplary low-stringent conditions include hybridization at 37 °C with a buffer solution of 30-35% formamide, 1 M NaCl, and 1% SDS (sodium dodecyl sulfate), followed by washing at 50-55 °C in 1 to 2 times the amount of SSC (20 times SSC = 3.0 M NaCl / 0.3 M trisodium citrate). Exemplary moderate-stringent conditions include hybridization at 37 °C in 40-45% formamide, 1.0 M NaCl, and 1% SDS, followed by washing at 55-60 °C in 0.5 to 1 times the amount of SSC. Exemplary high-toughness conditions include hybridization at 37°C in 50% formamide, 1M NaCl, and 1% SDS, followed by washing at 60-65°C in 0.1x SSC. Optionally, the wash buffer may contain about 0.1% to about 1% SDS. The duration of hybridization is typically less than about 24 hours, generally about 4 to about 12 hours.

[0120] Specificity typically varies with washing after hybridization, with key factors being the ionic strength and temperature of the final wash solution. For DNA-DNA hybrids, Tm can be estimated using the formula Meinkoth and Wahl, (1984) Anal. Biochem. 138: 267-284: Tm = 81.5 °C + 16.6 (log M) + 0.41 (% GC) - 0.61 (% form) - 500 / L; where M is the molar concentration of monovalent cations, % GC is the percentage of guanine and cytosine nucleotides in the DNA, % form is the percentage of formamide in the hybridization solution, and L is the length of the hybrid (in base pairs). Tm is the temperature at which 50% of the complementary target sequence hybridizes with a perfectly matched probe (at a defined ionic strength and pH). For every 1% mismatch, Tm decreases by approximately 1 °C; therefore, Tm, hybridization, and / or washing conditions can be adjusted to hybridize with sequences having the desired identity. For example, if a sequence with ≥90% identity is sought, Tm can be reduced by 10°C. Typically, stringent conditions are chosen to be approximately 5°C lower than the thermal desorption temperature (Tm) of the specific sequence and its complementary sequence at a given ionic strength and pH. However, extremely stringent conditions can be achieved using hybridization and / or washing at 1, 2, 3, or 4°C lower than the thermal desorption temperature (Tm); moderately stringent conditions can be achieved using hybridization and / or washing at 6, 7, 8, 9, or 10°C lower than the thermal desorption temperature (Tm); and low stringent conditions can be achieved using hybridization and / or washing at 11, 12, 13, 14, 15, or 20°C lower than the thermal desorption temperature (Tm). Using the formulas described above, the hybridization and washing compositions, and the desired Tm, those skilled in the art will recognize that variations in the stringency of the hybridization and / or washing solutions are inherently described. If the desired degree of mismatch results in a Tm below 45°C (including aqueous solutions) or 32°C (formamide solutions), it is preferable to increase the SSC concentration, thereby allowing the use of higher temperatures. Detailed instructions on nucleic acid hybridization can be found in Tijssen, (1993) Laboratory Techniques in Biochemistry and Molecular Biology - Hybridization with Nucleic Acid Probes, Part I, Chapter 2 (Elsevier, NY); and Ausubel et al., eds., Current Protocols in Molecular Biology, Chapter 2 (Greene Publishing and Wiley-Interscience, New York).See Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual (2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY).

[0121] In some embodiments, a polynucleotide encoding a PtIP-83 polypeptide is provided, the PtIP-83 polypeptide comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with any of the sequences in SEQ ID NO: 786-888.

[0122] In some embodiments, a polynucleotide encoding a PtIP-83 polypeptide is provided, the PtIP-83 polypeptide comprising any of the amino acid sequences in SEQ ID NO: 786-888.

[0123] In some embodiments, the polynucleotide encoding the PtIP-83 polypeptide containing any of the amino acid sequences in SEQ ID NO: 786-888 is a non-genomic sequence.

[0124] In some embodiments, the polynucleotide encoding the PtIP-83 polypeptide containing any of the amino acid sequences in SEQ ID NO: 786-888 is cDNA.

[0125] Proteins and their variants and fragments

[0126] The PtIP-83 polypeptide is also covered by this disclosure. As used interchangeably herein, “fern insecticidal protein-83,” “PtIP-83 polypeptide,” and “PtIP-83 protein” refer to a polypeptide that has insecticidal activity, including but not limited to insecticidal activity against one or more insect pests of the Lepidoptera and / or Coleoptera orders, and is sufficiently homologous to the protein of SEQ ID NO: 1. Various PtIP-83 polypeptides are envisioned. The PtIP-83 polypeptide or related protein may be derived from, but is not limited to, fern species selected from, but not limited to, *Polypodium punctatum*, *Lygodiuum flexuosum*, *Microsorum musifolium*, *Adiantum peruvianum*, *Adiantum trapeziforme*, and *Adiantum pedatum*.

[0127] "Sufficient homology" is used herein to mean that when compared with a reference sequence using one of the alignment procedures described herein and with standard parameters, the amino acid sequence has at least about 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher sequence homology. In some implementations, sequence homology refers to the full-length sequence of the PtIP-83 peptide. In some embodiments, the PtIP-83 polypeptide has at least about 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity with respect to SEQ ID NO: 1. Those skilled in the art will recognize that these values ​​can be appropriately adjusted to determine the corresponding homology of proteins by taking into account amino acid similarity, etc. In some embodiments, sequence identity is determined using a Vector function with all default parameters. Package (Invitrogen Corporation, Carlsbad, Calif.) The ClustalW algorithm in the module is used for computation. In some implementations, sequence identity is calculated using a Vector with all default parameters. Package (Invitrogen Corporation, Carlsbad, Calif.) The ClustalW algorithm in the module performs calculations across the entire length of the polypeptide.

[0128] As used herein, the terms “protein,” “peptide molecule,” or “polypeptide” include any molecule comprising five or more amino acids. It is well known in the art that protein, peptide, or polypeptide molecules can be modified, including post-translational modifications such as, but not limited to, disulfide bond formation, glycosylation, phosphorylation, or oligomerization. Therefore, as used herein, the terms “protein,” “peptide molecule,” or “polypeptide” include any protein modified by any biological or non-biological process. The term “amino acid” refers to all naturally occurring L-amino acids.

[0129] “Recombinant protein” or “recombinant polypeptide” is used herein to refer to a protein that is no longer in its natural environment, such as in vitro or in the cells of a recombinant bacterial or plant host. “Purified protein” or “purified polypeptide” is used herein to refer to a protein that is substantially free of cellular material. PtIP-83 polypeptides that are substantially free of cellular material include protein preparations having less than about 30%, 20%, 10%, or 5% (by dry weight) of non-insecticidal protein (also referred to herein as “contaminating protein”).

[0130] A “fragment” or “bioactive portion” includes a polypeptide fragment containing an amino acid sequence that is fully identical to that of the PtIP-83 polypeptide and exhibiting insecticidal activity. The “fragment” or “bioactive portion” of the PtIP-83 peptide includes those containing, such as SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769. Fragments with fully identical amino acid sequences as shown in NO: 769, wherein the PtIP-83 polypeptide possesses insecticidal activity. Such bioactive motifs can be prepared using recombinant techniques and their insecticidal activity can be evaluated.In some embodiments, the PtIP-83 polypeptide fragment is, for example, obtained through proteolysis, through the insertion of a start codon, or through the deletion of a codon encoding a missing amino acid accompanied by the insertion of a start codon and / or the insertion of a stop codon, relative to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID (SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769) is truncated from the N-terminus and / or C-terminus of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or more amino acids.

[0131] In some embodiments, the PtP-83 polypeptide fragments covered herein are, for example, generated by proteolysis or by insertion of a start codon, or by deletion of a codon encoding a missing amino acid accompanied by insertion of a start codon, relative to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, SEQ ID NO: 769 or variants thereof, produced by removing 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more amino acids from the N-terminus.

[0132] As used herein, “variant” refers to a protein or polypeptide having an amino acid sequence that is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the parent amino acid sequence.

[0133] In some embodiments, the PtIP-83 polypeptide comprises an amino acid sequence having at least 40%, 45%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the amino acid sequence of the following: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4. NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769, wherein the PtIP-83 polypeptide has insecticidal activity.

[0134] In some embodiments, the PtIP-83 polypeptide comprises an amino acid sequence having at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity over the full length of the following amino acid sequences: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759 ... NO:759, SEQ ID NO:760, SEQ ID NO:761, SEQ ID NO:762, SEQ ID NO:763, SEQ ID NO:764, SEQ ID NO:765, SEQ ID NO:766, SEQ ID NO:767, SEQ ID NO:768 or SEQ ID NO:769.

[0135] In some embodiments, the PtIP-83 polypeptide comprises an amino acid sequence having at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity over the full length of the following amino acid sequences: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 750, SEQ ID NO: 751, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759 ... NO:759, SEQ ID NO:760, SEQ ID NO:761, SEQ ID NO:762, SEQ ID NO:763, SEQ ID NO:764, SEQ ID NO:765, SEQ ID NO:766, SEQ ID NO:767, SEQ ID NO:768 or SEQ ID NO:769, and compared to SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID The natural sequences of SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769 have at least one amino acid substitution, deletion, insertion and / or addition at the N-terminus or C-terminus.

[0136] In some embodiments, the PtIP-83 peptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769.Compared with natural amino acids in 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO:768 or SEQ ID NO: 769 has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 or more amino acid substitutions at the corresponding position.

[0137] In some implementations, sequence identity is achieved using a Vector with all default parameters. The package (Invitrogen Corporation, Carlsbad, CaliF.) The ClustalW algorithm in the module performs calculations across the entire length of the polypeptide.

[0138] In some embodiments, the PtIP-83 peptide comprises an amino acid sequence that, compared to the natural amino acid sequence, is in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769. NO: 769 has any combination of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 amino acid substitutions at the corresponding position.

[0139] In some embodiments, the PtIP-83 peptide comprises an amino acid sequence that, compared to the natural amino acid sequence, is in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769. NO: 769 has any combination of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 amino acid substitutions at the corresponding position.

[0140] In some embodiments, the PtIP-83 peptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769.

[0141] In some implementations, the PtIP-83 peptide comprises a non-naturally occurring amino acid sequence. As used herein, the term "non-naturally occurring amino acid sequence" means an amino acid sequence that does not exist in nature.

[0142] In some embodiments, the PtIP-83 peptide is not one of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769.

[0143] In some embodiments, the PtIP-83 peptide is a variant of the peptides SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, or SEQ ID NO: 769, wherein the PtIP-83 peptide variant is different from SEQ ID NO: 1. SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 716, SEQ ID NO: 754, SEQ ID NO: 755, SEQ ID NO: 756, SEQ ID NO: 757, SEQ ID NO: 758, SEQ ID NO: 759, SEQ ID NO: 760, SEQ ID NO: 761, SEQ ID NO: 762, SEQ ID NO: 763, SEQ ID NO: 764, SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768 or SEQ ID NO: 769, having at least one amino acid substitution, deletion, insertion and / or addition at the N-terminus or C-terminus.

[0144] In some embodiments, the PtIP-83 polypeptide comprises the amino acid sequence of any one of SEQ ID NO: 236-299, SEQ ID NO: 334-367, SEQ ID NO: 398-427, SEQ ID NO: 518-607, SEQ ID NO: 640-645 and SEQ ID NO: 728-737.

[0145] In some embodiments, the PtIP-83 polypeptide is a variant of SEQ ID NO: 1, wherein the amino acid at position 53 is Val, Ala, Cys, or Thr; the amino acid at position 54 is Lys, Ala, Cys, Asp, Glu, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, or Thr; the amino acid at position 55 is Arg, Ala, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; and the amino acid at position 56 is Leu, Glu, Phe, Ile, Met, Thr, or Val; The amino acid at position 57 is Tyr, Cys, Ile, Leu, Met, Thr, or Val; the amino acid at position 58 is Val, Cys, Ile, or Leu; the amino acid at position 59 is Phe, Leu, Met, Val, or Tyr; the amino acid at position 60 is Ala, Cys, Gly, Ser, Thr, or Val; the amino acid at position 61 is Asp, Glu, His, or Ser; the amino acid at position 62 is Val, Ala, Cys, Ile, Leu, or Thr; and the amino acid at position 63 is Val, Ala, Cys, Ile, Leu, Met, or Thr. The amino acid at position 64 is Glu, Ala, Cys, Phe, Gly, His, Ile, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 65 is Leu, Ala, Cys, Phe, His, Ile, Met, Asn, Gln, Thr, Val, or Trp; the amino acid at position 66 is Pro, Asp, Gly, Met, Gln, or Arg; the amino acid at position 363 is Gln, Ala, Cys, Glu, Phe, Gly, His, Lys, Leu, Asn, A rg, Ser, Thr, Val, or Trp; the amino acid at position 364 is Ile, Ala, Cys, Glu, Phe, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 365 is Leu, Ala, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Arg, Val, Trp, or Tyr; the amino acid at position 366 is Gly, Ala, Cys, Phe, His, Ile, Lys, Leu, Met, Asn, Ser, Thr, or Val;The amino acid at position 367 is Ser, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Pro, Gln, Arg, Thr, Val, or Trp; the amino acid at position 368 is Tyr, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Trp; the amino acid at position 369 is Leu, Ala, Cys, Asp, Phe, Gly, Ile, Met, Thr, or Val; the amino acid at position 370 is Leu, Al a, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 371 is Gln, Ala, Cys, Asp, Glu, Phe, Gly, Ile, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp; the amino acid at position 372 is Gln, Ala, Cys, Asp, Phe, Gly, His, Ile, Leu, Asn, Arg, Ser, Val, or Tyr; the amino acid at position 373 is Asn, Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Gln, Ser, Thr, Val, or Trp; the amino acid at position 556 is Trp, Phe, Thr, or Tyr; the amino acid at position 557 is Arg, Cys, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 558 is Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Leu, Asn, Pro, Gln, Arg, Ser, Val, Trp, or Tyr; the amino acid at position 559 is Lys, Ala, Cys, Ph The amino acid at position 560 is Cys, Ala, Phe, Gly, Ile, Met, Asn, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 561 is Lys, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 562 is Asn, Cys, Asp, Glu, Gly, His, Leu, Met, Arg, Ser, Thr, Val, or Tyr.The amino acid at position 563 is Val, Ala, Cys, Asp, Phe, His, Ile, Leu, Met, Asn, Gln, Thr, or Trp; the amino acid at position 564 is Ala, Cys, Gly, Met, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 646 is Leu, Ala, Cys, Gly, Ile, Met, Asn, Gln, Ser, Thr, or Val; the amino acid at position 647 is Leu, Asp, Gly, Met, Asn, Gln, or Thr; the amino acid at position 648 is Met, Ala, Cys, Asp, Glu, Phe, Gly, H The amino acid at position 649 is Pro, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Met, Asn, Gln, Arg, Ser, Thr, Thr, Trp, or Tyr; the amino acid at position 650 is Thr, Ala, Cys, Asp, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Arg, Ser, Thr, Trp, or Tyr; the amino acid at position 651 is Glu, Ala, Cys, Asp, Gly, His, Ile, Leu. Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Tyr; the amino acid at position 652 is Leu, Cys, Phe, Ile, Lys, Met, Pro, Arg, Ser, Thr, or Val; the amino acid at position 653 is Thr, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Pro, Arg, Ser, Val, or Trp; the amino acid at position 654 is Thr, Ala, Cys, Phe, Ile, Lys, Leu, Met, Pro, Arg, Ser, Val, Trp, or Tyr; the amino acid at position 655 is Trp, Phe, or Tyr; the amino acid at position 771 is Arg, Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Asn, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 772 is Arg, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 773 is Asp, Ala, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr;The amino acid at position 774 is Gln, Ala, Asp, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 775 is Val, Ala, Cys, Asp, Glu, Gly, His, Ile, Asn, Pro, Gln, Arg, Ser, Thr, or Tyr; the amino acid at position 776 is Leu, Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Asn, Pro, Gln, Arg, Ser, T hr, Val, or Tyr; the amino acid at position 777 is Pro, Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gln, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 778 is Phe, Ala, His, Ile, Leu, Met, Asn, Gln, Ser, Val, Trp, or Tyr; the amino acid at position 779 is Gln, Ala, Cys, Asp, Glu, Gly, His, Lys, Leu, Asn, Pro, Arg, Ser, Thr, or Va. The amino acid at position 780 is Ala, Cys, Asn, Pro, Gln, or Ser; the amino acid at position 781 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 782 is Ala, Cys, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; the amino acid at position 783 is Pro, Ala, Cys, Asp, The amino acid at position 784 is Glu, Gly, His, Asn, Gln, Arg, Ser, Thr, or Val; the amino acid at position 784 is Leu, Ala, Glu, Phe, His, Ile, Lys, Met, Asn, Pro, Gln, Ser, Thr, Val, or Trp; the amino acid at position 785 is Asn, Ala, Cys, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Gln, Arg, Ser, Thr, Val, Trp, or Tyr; and the amino acid at position 786 is Tyr, Phe, Ile, Leu, or Trp.

[0146] In some embodiments, the PtIP-83 peptide is a variant of SEQ ID NO: 1, wherein the amino acid at position 1 is Met or deleted; the amino acid at position 2 is Ala or deleted; the amino acid at position 3 is Leu, Val or deleted; the amino acid at position 4 is Val, Met or Leu; the amino acid at position 7 is Gly or Ser; the amino acid at position 8 is Lys or Thr; the amino acid at position 10 is Phe or Tyr; the amino acid at position 11 is Glu or Arg; the amino acid at position 18 is Met or Ile; the amino acid at position 19 is Gly, Pro or Ala; the amino acid at position 20 is Val or deleted; the amino acid at position 21 is Leu or Val; and the amino acid at position 23 is Arg or... Gln; the amino acid at position 37 is Val or Leu; the amino acid at position 38 is Arg or Asn; the amino acid at position 40 is Ala or Ser; the amino acid at position 43 is Asn or Asp; the amino acid at position 45 is Gly or Ala; the amino acid at position 46 is Gln or Glu; the amino acid at position 48 is Glu, Pro, or Val; the amino acid at position 51 is Glu or Gly; the amino acid at position 52 is Lys, Arg, or Thr; the amino acid at position 56 is Leu or Val; the amino acid at position 59 is Phe or Leu; the amino acid at position 66 is Pro or Ala; the amino acid at position 67 is Val or P The amino acid at position 68 is Val, Arg, Phe, or Gly; the amino acid at position 69 is Glu, Ala, or Lys; the amino acid at position 70 is Trp, Thr, His, Tyr, or Arg; the amino acid at position 71 is Arg, Pro, or missing; the amino acid at position 72 is Trp, Asp, Leu, or missing; the amino acid at position 73 is Pro, Gln, Asn, His, or missing; the amino acid at position 74 is Pro, Met, or Thr; the amino acid at position 75 is Gln, His, or Arg; the amino acid at position 76 is Ile, Met, or Leu; the amino acid at position 84 is Ile or Va. l; the amino acid at position 91 is Trp or Phe; the amino acid at position 93 is Thr or Ile; the amino acid at position 94 is Asp or Gly; the amino acid at position 96 is Arg or Ser; the amino acid at position 97 is Gln, Phe, or Arg; the amino acid at position 98 is Ser or missing; the amino acid at position 99 is Asp or Ala; the amino acid at position 100 is Thr or Ala; the amino acid at position 101 is Glu, Thr, or Trp; the amino acid at position 103 is His, Arg, Glu, or Gln; the amino acid at position 105 is Thr or Pro; the amino acid at position 108 is Lys, Gln, or Glu.The amino acid at position 109 is Leu or Val; the amino acid at position 111 is Ala or Thr; the amino acid at position 112 is Ile, Arg, Thr, or is missing; the amino acid at position 113 is Gln, Ala, Gly, or is missing; the amino acid at position 114 is Arg, Glu, or Ile; the amino acid at position 115 is Glu or Gln; the amino acid at position 116 is Glu, Asn, Gln, or Arg; the amino acid at position 117 is Asn, Val, Tyr, or Phe; the amino acid at position 118 is Arg or Lys; the amino acid at position 119 is Trp or Ser; the amino acid at position 122 is Thr, Lys, or A The amino acid at position 124 is Ala or Thr; the amino acid at position 126 is Gly or Asp; the amino acid at position 127 is Met or Ala; the amino acid at position 128 is Asn or Lys; the amino acid at position 131 is Val, Ile, or Thr; the amino acid at position 133 is Ile or Val; the amino acid at position 134 is His or Tyr; the amino acid at position 135 is Ala or Gly; the amino acid at position 137 is Glu or Lys; the amino acid at position 139 is Gin or Glu; the amino acid at position 140 is Val, Arg, or Leu; the amino acid at position 141 is Gly or Ser; the amino acid at position 142... The amino acid at position 144 is Val or Pro; the amino acid at position 145 is Thr, Leu, Phe, or Tyr; the amino acid at position 146 is Met, Pro, or Asn; the amino acid at position 147 is Serp or Asn; the amino acid at position 148 is Ser, Ala, or Pro; the amino acid at position 149 is Ser or absent; the amino acid at position 150 is Val, Ile, or Tyr; the amino acid at position 152 is Arg, Ala, Val, or Gly; the amino acid at position 154 is Ser, Trp, or Glu; the amino acid at position 156 is Leu, Asp, or Gin; The amino acid at position 158 is Ser or Cys; the amino acid at position 159 is Val, Thr, or Lie; the amino acid at position 162 is Ser or Ala; the amino acid at position 163 is Gly or is missing; the amino acid at position 164 is Phe or is missing; the amino acid at position 165 is Arg or Ala; the amino acid at position 166 is Ala, Arg, Met, or Phe; the amino acid at position 167 is Val or His; the amino acid at position 168 is Ser or Asn; the amino acid at position 169 is Val, His, or Thr; the amino acid at position 170 is Phe or Val; the amino acid at position 171 is Glu, Asn, or Asp.The amino acid at position 172 is Val, Ala, Arg, or Glu; the amino acid at position 175 is Ser, Arg, or Trp; the amino acid at position 176 is Val or Ile; the amino acid at position 177 is Arg or Ile; the amino acid at position 179 is Thr, Ile, Val, or Ser; the amino acid at position 180 is Leu, Phe, or Thr; the amino acid at position 181 is Gly, Thr, Gln, or Ser; the amino acid at position 182 is Ala, Leu, Phe, or Ile; the amino acid at position 183 is Thr or Gly; the amino acid at position 184 is Leu, Thr, Ser, or Arg; the amino acid at position 185... The amino acid at position 186 is Arg, Gly, Asp, or Ala; the amino acid at position 187 is Asp, Thr, or Ser; the amino acid at position 188 is His, Gly, or Ala; the amino acid at position 189 is Ala, Arg, Pro, or is missing; the amino acid at position 190 is Leu, Asn, or is missing; the amino acid at position 191 is Tyr or is missing; the amino acid at position 192 is Ser, Ile, Val, or Asn; the amino acid at position 193 is Thr or Asp; the amino acid at position 194 is Thr or Ser; the amino acid at position 195 is Met or Thr; the amino acid at position 196... The amino acid at position 197 is Gln, His, Leu, or Ser; the amino acid at position 198 is Thr, Glu, or Ala; the amino acid at position 199 is Pro or Arg; the amino acid at position 200 is Asn, Ser, Thr, or Gly; the amino acid at position 201 is Ala, Leu, Glu, or Trp; the amino acid at position 202 is Ser, Asp, Phe, or Leu; the amino acid at position 203 is His, Pro, Gly, or Ser; the amino acid at position 204 is Ile, Trp, His, or Gly; the amino acid at position 205 is Ser, Asn, or Ile; the amino acid at position 20... The amino acid at position 6 is Ala, Gly, Asp, Tyr, or Arg; the amino acid at position 207 is Phe, Val, or Leu; the amino acid at position 208 is Asn, Ser, Pro, or Leu; the amino acid at position 210 is Arg, Asp, Glu, or Tyr; the amino acid at position 211 is Ile, Ser, or Thr; the amino acid at position 212 is Val, Ala, or Asp; the amino acid at position 214 is Pro or Arg; the amino acid at position 215 is Ser or Thr; the amino acid at position 217 is Tyr or Phe; the amino acid at position 218 is Arg or Ser; and the amino acid at position 219 is Val or Ala.The amino acid at position 220 is Cys, Leu, or Ser; the amino acid at position 221 is Pro or His; the amino acid at position 222 is Leu, Arg, or Ser; the amino acid at position 224 is Asn or Ser; the amino acid at position 225 is Asp, Arg, or Thr; the amino acid at position 226 is Thr or Asn; the amino acid at position 227 is Asp, Leu, or is deleted; the amino acid at position 228 is Thr or is deleted; the amino acid at position 229 is Tyr or is deleted; the amino acid at position 230 is Leu or is deleted; the amino acid at position 231 is Gly or is deleted; the amino acid at position 232 is Ile or is deleted; the amino acid at position 233... The amino acid is Pro or missing; the amino acid at position 234 is Ala, Pro, or missing; the amino acid at position 235 is Asp, Ile, or Val; the amino acid at position 236 is Val, Ser, or Glu; the amino acid at position 237 is Ala, Phe, or Tyr; the amino acid at position 238 is Ala or Thr; the amino acid at position 239 is Val, Ser, or Gly; the amino acid at position 240 is Leu or Ile; the amino acid at position 243 is Asp or Glu; the amino acid at position 249 is Asn or Ser; the amino acid at position 252 is Leu or Met; the amino acid at position 257 is Thr or Ser; the amino acid at position 259 is... His or Leu; amino acid at position 266 is Ala or Val; amino acid at position 267 is Cys or Gly; amino acid at position 268 is His, Arg, or Tyr; amino acid at position 272 is Asp or Glu; amino acid at position 273 is Val, Met, Ile, or Leu; amino acid at position 274 is Val or Met; amino acid at position 278 is Gly or Ala; amino acid at position 279 is Glu or Val; amino acid at position 281 is Leu or Ala; amino acid at position 282 is Asn, Leu, or Ile; amino acid at position 285 is Asn or Ser; amino acid at position 286 is Lys. The amino acid at position 287 is either Asp or Glu; the amino acid at position 290 is either Pro, Gln, or Arg; the amino acid at position 291 is either Leu or Val; the amino acid at position 292 is either Lys or Val; the amino acid at position 293 is either Glu or Gln; the amino acid at position 294 is either Ser, Asn, or Lys; the amino acid at position 295 is either Thr or Ser; the amino acid at position 296 is either Gln or His; the amino acid at position 297 is either Leu or Met; the amino acid at position 300 is either Ser or Thr; the amino acid at position 301 is either Glu or Ala; the amino acid at position 302 is either Ser, Pro, or Ala.The amino acid at position 304 is Lys or Asn; the amino acid at position 313 is Val or Ile; the amino acid at position 314 is His, Glu, or Gln; the amino acid at position 315 is Ala, Cys, or Ser; the amino acid at position 316 is Ala or Val; the amino acid at position 317 is Met or Ile; the amino acid at position 319 is Met or Ile; the amino acid at position 320 is Val or Gly; the amino acid at position 321 is Arg or Pro; the amino acid at position 322 is Ile or Phe; the amino acid at position 323 is Gly or Val; the amino acid at position 324 is Leu or Ser; the amino acid at position 336... It is Ser or Asn; the amino acid at position 339 is Asn, Lys, or Arg; the amino acid at position 350 is Arg or Gln; the amino acid at position 351 is Glu or Asp; the amino acid at position 353 is Lys or Arg; the amino acid at position 354 is Gln or Arg; the amino acid at position 355 is Phe or Leu; the amino acid at position 356 is Lys or Arg; the amino acid at position 360 is Ile, Val, or Ala; the amino acid at position 365 is Leu or Phe; the amino acid at position 371 is or Glu; the amino acid at position 372 is or Lys; the amino acid at position 374 is Arg or Lys; the amino acid at position 376... The amino acid at position 378 is Phe or Leu; the amino acid at position 381 is Leu or Val; the amino acid at position 388 is Ala or Ser; the amino acid at position 395 is Arg or Lys; the amino acid at position 396 is Glu, Gln, or Gly; the amino acid at position 399 is Asp or Asn; the amino acid at position 400 is Asn, Thr, or Asp; the amino acid at position 401 is Thr or Ala; the amino acid at position 402 is Phe, Ile, or Leu; the amino acid at position 406 is Asp or Glu; the amino acid at position 408 is Leu or Met; the amino acid at position 410 is Gl. y or Leu; the amino acid at position 414 is Ala or Glu; the amino acid at position 416 is Ser, Asn, or Asp; the amino acid at position 417 is Ser, Arg, or Gly; the amino acid at position 423 is Lys or Gln; the amino acid at position 431 is Arg or Lys; the amino acid at position 432 is Gln or Glu; the amino acid at position 436 is Arg or Glu; the amino acid at position 440 is Asn or Arg; the amino acid at position 442 is Leu or Val; the amino acid at position 447 is Ser, Lys, or Arg; the amino acid at position 448 is Ala or Ser; the amino acid at position 451 is Gln or Met;The amino acid at position 453 is either Gly or Ala; the amino acid at position 455 is either Ala or Val; the amino acid at position 457 is either Leu or Val; the amino acid at position 467 is either Val or Ala; the amino acid at position 471 is either Gly or Ala; the amino acid at position 475 is either Ser or Asn; the amino acid at position 483 is either Gly or Ala; the amino acid at position 493 is either Gln or Gly; the amino acid at position 504 is either Val or Ile; the amino acid at position 506 is either Asp or His; the amino acid at position 509 is either Asp or Asn; the amino acid at position 510 is either Ser or Ala; the amino acid at position 512 is either Glu or Asp. The amino acid at position 515 is Gly or Ser; the amino acid at position 516 is Gln or His; the amino acid at position 517 is Ile or Leu; the amino acid at position 519 is Asp, Gly, or Gln; the amino acid at position 522 is Val, Glu, Pro, or Val; the amino acid at position 525 is Glu or Asp; the amino acid at position 526 is Leu or Met; the amino acid at position 539 is Val or Ile; the amino acid at position 555 is Val or Ala; the amino acid at position 557 is Arg or Lys; the amino acid at position 563 is Val or Met; the amino acid at position 571 is Ser or Cys; the amino acid at position 575... The amino acid at position 577 is Val or Glu; the amino acid at position 577 is Met or Ile; the amino acid at position 579 is Glu or Gln; the amino acid at position 583 is Asp or Glu; the amino acid at position 589 is Met or Leu; the amino acid at position 590 is Met or Leu; the amino acid at position 593 is Met or Ile; the amino acid at position 595 is Arg or Gln; the amino acid at position 596 is Ser or Thr; the amino acid at position 597 is Gln or His; the amino acid at position 607 is Ala or Val; the amino acid at position 608 is Asp or Asn; the amino acid at position 612 is Tyr, His, or Phe; the amino acid at position 61... The amino acid at position 7 is Thr or Ile; the amino acid at position 618 is Gln or His; the amino acid at position 625 is Arg or Ser; the amino acid at position 626 is Met or Ile; the amino acid at position 628 is Leu or Ile; the amino acid at position 633 is Ile or Met; the amino acid at position 634 is Leu or Met; the amino acid at position 642 is Arg or Met; the amino acid at position 648 is Met or Thr; the amino acid at position 651 is Glu or Gln; the amino acid at position 654 is Thr, Val, or Ala; the amino acid at position 658 is Gly or Arg; the amino acid at position 663 is Gly or Ala.The amino acid at position 664 is Asp or Asn; the amino acid at position 668 is Ala or Thr; the amino acid at position 669 is Gln or His; the amino acid at position 671 is Asn or Ser; the amino acid at position 675 is Ile, Val, or Ser; the amino acid at position 678 is Met, Ile, Ala, or Thr; the amino acid at position 682 is Pro or Gln; the amino acid at position 683 is Ser or Pro; the amino acid at position 685 is Asp or Asn; the amino acid at position 694 is Asp or Gly; the amino acid at position 697 is Asn or Ser; the amino acid at position 704 is Glu or Gly; the amino acid at position 714... The amino acid at position 721 is Ala or Gly; the amino acid at position 722 is Ser or Asn; the amino acid at position 724 is Ser or Thr; the amino acid at position 734 is His or Gln; the amino acid at position 736 is Val or Ala; the amino acid at position 737 is Lys or Gln; the amino acid at position 739 is Ala or Ser; the amino acid at position 740 is Ser or Met; the amino acid at position 741 is Gly or Asn; the amino acid at position 742 is Ile or Gly; the amino acid at position 743 is Gly or omitted; the amino acid at position 745 is Gly or Asp; the amino acid at position 751... The amino acid at position 753 is Thr, Ser, or Ala; the amino acid at position 754 is Thr or Ser; the amino acid at position 756 is Thr or Ile; the amino acid at position 757 is Val or Ile; the amino acid at position 766 is Ile or Val; the amino acid at position 773 is Asp or Glu; the amino acid at position 774 is Gln or Glu; the amino acid at position 776 is Leu or Met; the amino acid at position 777 is Pro or Thr; the amino acid at position 782 is Ala, Asp, or Val; the amino acid at position 786 is Tyr or Phe; the amino acid at position 787 is His or Gln. The amino acid at position 788 is Tyr or Met; the amino acid at position 789 is Ala or Arg; the amino acid at position 790 is Tyr or Thr; the amino acid at position 791 is Arg or Ala; the amino acid at position 792 is Leu or Ser; the amino acid at position 796 is Asp or Glu; the amino acid at position 797 is Ser, Thr, or Ala; the amino acid at position 802 is Glu or Gln; the amino acid at position 806 is Gln, Asp, Glu, or His; the amino acid at position 810 is Lys or Thr; the amino acid at position 819 is Arg or His; and the amino acid at position 829 is Lys, Ser, Ala, or Pro.The amino acid at position 832 is Ala, Lys, or Glu; the amino acid at position 833 is Gly or Glu; the amino acid at position 842 is Leu or Pro; the amino acid at position 847 is Gln or Glu; the amino acid at position 848 is Ile or Val; the amino acid at position 849 is Val or Ala; the amino acid at position 855 is Thr or Met; the amino acid at position 860 is Ile or Val; and the amino acid at position 864 is His or Gln.

[0147] In some embodiments, the PtIP-83 peptide is a variant of SEQ ID NO: 1, wherein the amino acid at position 1 is Met or deleted; the amino acid at position 2 is Ala or deleted; the amino acid at position 3 is Leu, Val, Ile or deleted; the amino acid at position 4 is Val, Met, Ile or Leu; the amino acid at position 7 is Gly, Thr or Ser; the amino acid at position 8 is Lys, Arg, Ser or Thr; the amino acid at position 10 is Phe, Trp or Tyr; the amino acid at position 11 is Glu, Asp, Lys or Arg; the amino acid at position 18 is Met, Val, Leu or Ile; the amino acid at position 19 is Gly, Pro or Ala; and the amino acid at position 20 is... The amino acid is Val, Ile, Leu, or is missing; the amino acid at position 21 is Leu, Ile, or Val; the amino acid at position 23 is Arg, Lys, Asn, or Gln; the amino acid at position 37 is Val, Ile, or Leu; the amino acid at position 38 is Arg, Lys, Gln, or Asn; the amino acid at position 40 is Ala, Gly, Thr, or Ser; the amino acid at position 43 is Asn, Gln, Glu, or Asp; the amino acid at position 45 is Gly or Ala; the amino acid at position 46 is Gln, Asp, Asn, or Glu; the amino acid at position 48 is Glu, Asp, Pro, Ile, or Leu. Or Val; the amino acid at position 51 is Glu, Asp, Ala, or Gly; the amino acid at position 52 is Lys, Arg, Ser, or Thr; the amino acid at position 56 is Leu, Ile, or Val; the amino acid at position 59 is Phe, Ile, Val, or Leu; the amino acid at position 66 is Pro, Gly, or Ala; the amino acid at position 67 is Val, Pro, Ile, Leu, Ser, or Thr; the amino acid at position 68 is Val, Arg, Phe, Ile, Leu, Lys, or Gly; the amino acid at position 69 is Glu, Ala, Asp, Gly, Arg, or Lys; the amino acid at position 70... The amino acid at position 71 is Trp, Thr, His, Tyr, Lys, or Arg; the amino acid at position 72 is Arg, Pro, Lys, or is missing; the amino acid at position 73 is Pro, Gln, Asn, His, or is missing; the amino acid at position 74 is Pro, Met, Ser, or Thr; the amino acid at position 75 is Gln, His, Asn, Lys, or Arg; the amino acid at position 76 is Ile, Met, Val, or Leu; the amino acid at position 84 is Ile, Leu, or Val; and the amino acid at position 91 is Trp or Phe.The amino acid at position 93 is Thr, Ser, Leu, Val, or Ile; the amino acid at position 94 is Asp, Glu, Ala, or Gly; the amino acid at position 96 is Arg, Lys, Thr, or Ser; the amino acid at position 97 is Gln, Phe, Asn, Lys, or Arg; the amino acid at position 98 is Ser, Thr, or is missing; the amino acid at position 99 is Asp, Glu, Gly, or Ala; the amino acid at position 100 is Thr, Ser, Gly, or Ala; the amino acid at position 101 is Glu, Thr, Asp, Ser, or Trp; and the amino acid at position 103 is His, Arg, Lys, or Gly. u or Gln; the amino acid at position 105 is Thr, Ser, or Pro; the amino acid at position 108 is Lys, Arg, Asn, Asp, Gln, or Glu; the amino acid at position 109 is Leu, Ile, or Val; the amino acid at position 111 is Ala, Ser, or Thr; the amino acid at position 112 is Ile, Arg, Thr, Leu, Val, Lys, Ser, or is missing; the amino acid at position 113 is Gln, Ala, Gly, Asn, or is missing; the amino acid at position 114 is Arg, Glu, Lys, Asp, or Ile; the amino acid at position 115 is Glu, Asp, Asn, or Gln; the 1st The amino acid at position 16 is Glu, Asn, Gln, Asp, Lys, or Arg; the amino acid at position 117 is Asn, Val, Tyr, Ile, Leu, Gln, Trp, or Phe; the amino acid at position 118 is Arg or Lys; the amino acid at position 119 is Trp, Thr, or Ser; the amino acid at position 122 is Thr, Lys, Ser, Arg, or Ala; the amino acid at position 124 is Ala, Gly, Ser, or Thr; the amino acid at position 126 is Gly, Ala, Glu, or Asp; the amino acid at position 127 is Met, Gly, or Ala; and the amino acid at position 128 is Asn, Gly ... The amino acid at position 131 is ln, Arg, or Lys; the amino acid at position 131 is Val, Ile, Leu, Ser, or Thr; the amino acid at position 133 is Ile, Leu, or Val; the amino acid at position 134 is His or Tyr; the amino acid at position 135 is Ala or Gly; the amino acid at position 137 is Glu, Asp, Arg, or Lys; the amino acid at position 139 is Gln, Asn, Asp, or Glu; the amino acid at position 140 is Val, Arg, Ile, Lys, or Leu; the amino acid at position 141 is Gly, Ala, Thr, or Ser; the amino acid at position 142 is Val, Ile, Leu, or Pro.The amino acid at position 144 is Thr, Leu, Phe, Ile, Val, or Tyr; the amino acid at position 145 is Met, Pro, Gln, or Asn; the amino acid at position 146 is Ser, Gly, Thr, Ala, Gln, or Asn; the amino acid at position 147 is Trp, Gln, Tyr, or Asn; the amino acid at position 148 is Ser, Ala, Thr, Gly, or Pro; the amino acid at position 149 is Ser, Thr, or is missing; the amino acid at position 150 is Val, Ile, Leu, or Tyr; the amino acid at position 152 is Arg, Ala, Val, Ile, Leu, Lys, or Gly; the amino acid at position 154... The amino acid at position 156 is Ser, Trp, Thr, Asp, or Glu; the amino acid at position 157 is Leu, Asp, Ile, Val, Asn, Glu, or Gln; the amino acid at position 158 is Ser, Thr, or Cys; the amino acid at position 159 is Val, Thr, Leu, or Ile; the amino acid at position 162 is Ser, Thr, Gly, or Ala; the amino acid at position 163 is Gly, Ala, or is missing; the amino acid at position 164 is Phe or is missing; the amino acid at position 165 is Arg, Lys, Gly, or Ala; the amino acid at position 166 is Ala, Arg, Met, Lys, or Phe; the amino acid at position 167... The amino acid at position 168 is Val, Ile, Leu, or His; the amino acid at position 169 is Val, His, Ile, Leu, Ser, or Thr; the amino acid at position 170 is Phe, Ile, Leu, or Val; the amino acid at position 171 is Glu, Asn, Gln, or Asp; the amino acid at position 172 is Val, Ala, Arg, Ile, Leu, Gly, Lys, Asp, or Glu; the amino acid at position 175 is Ser, Arg, Thr, Lys, or Trp; the amino acid at position 176 is Val, Leu, or Ile; and the amino acid at position 177 is A. The amino acid at position 179 is Thr, Ile, Val, Leu, or Ser; the amino acid at position 180 is Leu, Phe, Ile, Val, Ser, or Thr; the amino acid at position 181 is Gly, Thr, Gln, Asn, or Ser; the amino acid at position 182 is Ala, Leu, Phe, Val, or Ile; the amino acid at position 183 is Thr, Ser, Ala, or Gly; the amino acid at position 184 is Leu, Thr, Ser, Ile, Val, Lys, or Arg; the amino acid at position 185 is Arg, Gly, Asp, Lys, Glu, or Ala.The amino acid at position 186 is Pro, Val, Ile, Leu, Asn, or Gln; the amino acid at position 187 is Asp, Thr, Glu, or Ser; the amino acid at position 188 is His, Gly, or Ala; the amino acid at position 189 is Ala, Arg, Pro, Lys, Gly, or is missing; the amino acid at position 190 is Leu, Asn, Ile, Val, Gln, or is missing; the amino acid at position 191 is Tyr or is missing; the amino acid at position 192 is Ser, Ile, Val, Leu, Thr, or Asn; the amino acid at position 193 is Thr, Ser, Glu, or Asp; the amino acid at position 194 is Thr or... Ser; the amino acid at position 195 is Met or Thr; the amino acid at position 196 is Gln, His, Leu, Asn, Ile, Val, Thr, or Ser; the amino...

Claims

1. A purified PtIP-83 polypeptide obtained by introducing the following amino acid substitutions in SEQ ID NO: 1 : Ala, Cys, or Thr at position 53; Ala, Cys, Asp, Glu, Gly, His, lie, Leu, Met, Asn, Gin, Arg, Ser, or Thr at position 54; Ala, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gin, Ser, Thr, Val, Trp, or Tyr at position 55; Glu, Phe, lie, Met, Thr, or Val at position 56; Cys, lie, Leu, Met, Thr, or Val at position 57; Cys, lie, or Leu at position 58; Leu, Met, Val, or Tyr at position 59; Cys, Gly, Ser, Thr, or Val at position 60; Glu, His, or Ser at position 61 ; Ala, Cys, lie, Leu, or Thr at position 62; Ala, Cys, lie, Leu, Met, or Thr at position 63; Ala, Cys, Phe, Gly, His, lie, Leu, Met, Asn, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 64; Ala, Cys, Phe, His, lie, Met, Asn, Gin, Thr, Val, or Trp at position 65; Asp, Gly, Met, Gin, or Arg at position 66; Ala, Cys, Glu, Phe, Gly, His, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp at position 363; Ala, Cys, Glu, Phe, His, Lys, Leu, Met, Asn, Gin, Ser, Thr, Val, Trp, or Tyr at position 364; Ala, Glu, Phe, Gly, His, lie, Lys, Met, Asn, Arg, Val, Trp, or Tyr at position 365; Ala, Cys, Phe, His, lie, Lys, Leu, Met, Asn, Ser, Thr, or Val at position 366; Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Leu, Met, Asn, Pro, Gin, Arg, Thr, Val, or Trp at position 367; Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Val, or Trp at position 368; Leu, Ala, Cys, Asp, Phe, Gly, lie, Met, Thr, or Val at position 369.Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Asn, Arg, Ser, Thr, Val, or Trp at position 371; Ala, Cys, Asp, Phe, Gly, His, lie, Leu, Asn, Arg, Ser, Val, or Tyr at position 372; Ala, Cys, Asp, Phe, Gly, His, lie, Lys, Gin, Ser, Thr, Val, or Trp at position 373; Phe, Thr, or Tyr at position 556; Cys, Asp, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Gin, Ser, Thr, Val, Trp, or Tyr at position 557; Cys, Asp, Phe, Gly, His, lie, Lys, Leu, Asn, Pro, Gin, Arg, Ser, Val, Trp, or Tyr at position 558; Ala, Cys, Phe, Gly, His, lie, Leu, Asn, Gin, Arg, Ser, Thr, Val, or Tyr at position 559; Ala, Phe, Gly, lie, Met, Asn, Arg, Ser, Thr, or Val at position 560; Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Leu, Met, Asn, Arg, Ser, Thr, Val, or Tyr at position 561; Cys, Asp, Glu, Gly, His, Leu, Met, Arg, Ser, Thr, Val, or Tyr at position 562; Ala, Cys, Asp, Phe, His, lie, Leu, Met, Asn, Gin, Thr, or Trp at position 563; Cys, Gly, Met, Gin, Ser, Thr, Val, Trp, or Tyr at position 564; Ala, Cys, Gly, lie, Met, Asn, Gin, Ser, Thr, or Val at position 646; Asp, Gly, Met, Asn, Gin, or Thr at position 647; Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Asn, Pro, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 648; Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Met, Asn, Gin, Arg, Ser, Thr, Trp, or Tyr at position 649;Ala, Cys, Asp, Phe, Gly, His, lie, Lys, Leu, Met, Pro, Gin, Arg, Ser, Val, or Tyr at position 650; Ala, Cys, Asp, Gly, His, lie, Leu, Met, Asn, Pro, Gin, Arg, Ser, Thr, Val, or Tyr at position 651 ; Cys, Phe, lie, Lys, Met, Pro, Arg, Ser, Thr, or Val at position 652; Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Pro, Arg, Ser, Val, or Trp at position 653; Ala, Cys, Phe, lie, Lys, Leu, Met, Pro, Arg, Ser, Val, Trp, or Tyr at position 654; Phe or Tyr at position 655; Ala, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Asn, Ser, Thr, Val, Trp, or Tyr at position 771 ; Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Pro, Gin, Ser, Thr, Val, Trp, or Tyr at position 772; Ala, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Asn, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 773; Ala, Asp, Gly, His, lie, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 774; Ala, Cys, Asp, Glu, Gly, His, lie, Asn, Pro, Gin, Arg, Ser, Thr, or Tyr at position 775; Ala, Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Asn, Pro, Gin, Arg, Ser, Thr, Val, or Tyr at position 776; Ala, Cys, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Gin, Ser, Thr, Val, Trp, or Tyr at position 777; Ala, His, lie, Leu, Met, Asn, Gin, Ser, Val, Trp, or Tyr at position 778; Ala, Cys, Asp, Glu, Gly, His, Lys, Leu, Asn, Pro, Arg, Ser, Thr, or Val at position 779; Cys, Asn, Pro, Gin, or Ser at position 780;Cys, Asp, Glu, Phe, Gly, His, lie, Asn, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 781 ; Cys, Asp, Glu, Phe, Gly, His, lie, Lys, Met, Pro, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 782; Ala, Cys, Asp, Glu, Gly, His, Asn, Gin, Arg, Ser, Thr, or Val at position 783; Ala, Glu, Phe, His, lie, Lys, Met, Asn, Pro, Gin, Ser, Thr, Val, or Trp at position 784; Ala, Cys, Glu, Phe, Gly, His, lie, Lys, Leu, Met, Gin, Arg, Ser, Thr, Val, Trp, or Tyr at position 785; or Phe, lie, Leu, or Trp at position 786.

2. The purified PtIP-83 polypeptide according to claim 1, wherein the PtIP-83 polypeptide is effective against the corn ear borer (Eriocheir sinensis). Helicoverpa zea It has insecticidal activity.

3. The purified PtIP-83 polypeptide of claim 1 or 2, wherein the PtIP-83 polypeptide specifically binds to brush border membrane vesicles isolated from Lepidoptera.

4. The purified PtIP-83 polypeptide of any one of claims 1-3, wherein the PtIP-83 polypeptide disrupts ion balance across brush border membrane vesicles isolated from Lepidoptera.

5. The purified PtIP-83 polypeptide of claim 1, wherein the PtIP-83 polypeptide is derived from a fern or a primitive plant species.

6. The purified PtIP-83 polypeptide of claim 5, wherein the fern is from the genus Adiantum ( Adiantaceae ).​ 7. A recombinant polynucleotide encoding the PtIP-83 polypeptide of any one of claims 1 to 6.

8. The recombinant polynucleotide of claim 7, wherein the polynucleotide is a non- genomic polynucleotide.

9. The recombinant polynucleotide of claim 8, wherein the polynucleotide is a cDNA.

10. The recombinant polynucleotide of claim 8, wherein the polynucleotide is a synthetic polynucleotide.

11. The recombinant polynucleotide of claim 8, wherein the polynucleotide has codons optimized for expression in an agriculturally important crop.

12. A method of producing a transgenic plant comprising introducing the polynucleotide of any one of claims 7 to 11 into a plant.

13. A DNA construct comprising the polynucleotide of any one of claims 7 to 11 operably linked to a heterologous regulatory element.

14. A method of producing a transgenic plant or plant cell comprising introducing the DNA construct of claim 13 into a plant or plant cell.

15. An agricultural composition comprising an insecticidally effective amount of the PtIP-83 polypeptide of any one of claims 1-6.

16. The agricultural composition of claim 15, further comprising at least one agriculturally acceptable carrier.

17. A fusion protein comprising the PtIP-83 polypeptide of any one of claims 1-6.

18. A method for controlling a population of Lepidoptera insect pests, the method comprising contacting the population of Lepidoptera insect pests with the PtIP-83 polypeptide of any one of claims 1-6.

19. A method of inhibiting the growth of or killing a Lepidoptera insect pest, the method comprising contacting the Lepidoptera insect pest with a composition comprising the PtIP-83 polypeptide of any one of claims 1-6.

20. A method of controlling infestation of Lepidoptera insects in a transgenic plant and providing Lepidoptera insect resistance management, the method comprising expressing the PtIP-83 polypeptide of any one of claims 1-6 in the plant.

21. A method for controlling a population of Lepidoptera insect pests, the method comprising contacting the population of Lepidoptera insect pests with the transgenic plant or plant cell of claim 14.

22. A method of inhibiting the growth of or killing a lepidopteran insect pest, comprising contacting the lepidopteran insect pest with the transgenic plant or plant cell of claim 14.

23. The method of any one of claims 18-22, wherein the lepidopteran insect or insect population is resistant to at least one Bt toxin.

24. Use of a PtIP-83 polypeptide according to any one of claims 1-6 for inhibiting the growth of or killing a lepidopteran insect or insect population.

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