SIWI_BOMMO
ID SIWI_BOMMO Reviewed; 899 AA.
AC A8D8P8; A7BJS4; A7LM14;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Piwi-like protein Siwi {ECO:0000305};
DE EC=3.1.26.- {ECO:0000269|PubMed:27693359};
GN Name=Siwi {ECO:0000303|PubMed:18191035};
OS Bombyx mori (Silk moth).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Bombycoidea;
OC Bombycidae; Bombycinae; Bombyx.
OX NCBI_TaxID=7091;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tatsuke T., Tsukioka H., Sakashita K., Mitsunobu H., Lee J., Kawaguchi Y.,
RA Kusakabe T.;
RT "Molecular cloning of Piwi and Aubergine homolog genes from the silkworm,
RT Bombyx mori.";
RL Entomotech 31:43-46(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18191035; DOI=10.1016/j.bbrc.2008.01.013;
RA Kawaoka S., Minami K., Katsuma S., Mita K., Shimada T.;
RT "Developmentally synchronized expression of two Bombyx mori Piwi subfamily
RT genes, SIWI and BmAGO3 in germ-line cells.";
RL Biochem. Biophys. Res. Commun. 367:755-760(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang G.H., Xia Q.Y., Jiang L., Chen J., Zhu L.;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=p50T;
RX PubMed=19121390; DOI=10.1016/j.ibmb.2008.11.004;
RG International Silkworm Genome Consortium;
RT "The genome of a lepidopteran model insect, the silkworm Bombyx mori.";
RL Insect Biochem. Mol. Biol. 38:1036-1045(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 181-792.
RX PubMed=17698031; DOI=10.1016/j.bbrc.2007.07.179;
RA Zhou X., Liao Z., Jia Q., Cheng L., Li F.;
RT "Identification and characterization of Piwi subfamily in insects.";
RL Biochem. Biophys. Res. Commun. 362:126-131(2007).
RN [6]
RP FUNCTION.
RX PubMed=19460866; DOI=10.1261/rna.1452209;
RA Kawaoka S., Hayashi N., Suzuki Y., Abe H., Sugano S., Tomari Y.,
RA Shimada T., Katsuma S.;
RT "The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-
RT interacting RNA complexes.";
RL RNA 15:1258-1264(2009).
RN [7]
RP INTERACTION WITH PAPI, AND DOMAIN.
RX PubMed=23970546; DOI=10.1261/rna.040428.113;
RA Honda S., Kirino Y., Maragkakis M., Alexiou P., Ohtaki A., Murali R.,
RA Mourelatos Z., Kirino Y.;
RT "Mitochondrial protein BmPAPI modulates the length of mature piRNAs.";
RL RNA 19:1405-1418(2013).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF ASN-602 AND TYR-607.
RX PubMed=24757166; DOI=10.1261/rna.044701.114;
RA Cora E., Pandey R.R., Xiol J., Taylor J., Sachidanandam R., McCarthy A.A.,
RA Pillai R.S.;
RT "The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-
RT biases of piRNAs.";
RL RNA 20:773-781(2014).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25558067; DOI=10.1016/j.celrep.2014.12.013;
RA Nishida K.M., Iwasaki Y.W., Murota Y., Nagao A., Mannen T., Kato Y.,
RA Siomi H., Siomi M.C.;
RT "Respective functions of two distinct Siwi complexes assembled during PIWI-
RT interacting RNA biogenesis in Bombyx germ cells.";
RL Cell Rep. 10:193-203(2015).
RN [10]
RP INTERACTION WITH PAPI, AND DOMAIN.
RX PubMed=26919431; DOI=10.1016/j.cell.2016.01.008;
RA Izumi N., Shoji K., Sakaguchi Y., Honda S., Kirino Y., Suzuki T.,
RA Katsuma S., Tomari Y.;
RT "Identification and functional analysis of the pre-piRNA 3' trimmer in
RT silkworms.";
RL Cell 164:962-973(2016).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS)IN COMPLEX WITH PIRNA AND MAGNESIUM,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, COFACTOR, DOMAIN, AND
RP MUTAGENESIS OF LYS-611; GLN-623; GLN-645; LYS-649; ASP-670; GLU-708;
RP ASP-740 AND HIS-874.
RX PubMed=27693359; DOI=10.1016/j.cell.2016.09.002;
RA Matsumoto N., Nishimasu H., Sakakibara K., Nishida K.M., Hirano T.,
RA Ishitani R., Siomi H., Siomi M.C., Nureki O.;
RT "Crystal structure of Silkworm PIWI-clade argonaute Siwi bound to piRNA.";
RL Cell 167:484-497(2016).
CC -!- FUNCTION: Endoribonuclease that plays a central role during
CC spermatogenesis by repressing transposable elements and preventing
CC their mobilization, which is essential for the germline integrity
CC (PubMed:19460866, PubMed:27693359). Plays an essential role in meiotic
CC differentiation of spermatocytes, germ cell differentiation and in
CC self-renewal of spermatogonial stem cells (PubMed:19460866,
CC PubMed:25558067, PubMed:27693359). Its presence in oocytes suggests
CC that it may participate in similar functions during oogenesis in
CC females (PubMed:18191035). Acts via the piRNA metabolic process, which
CC mediates the repression of transposable elements during meiosis by
CC forming complexes composed of piRNAs and Piwi proteins and govern the
CC methylation and subsequent repression of transposons (PubMed:19460866,
CC PubMed:25558067, PubMed:27693359). Directly binds piRNAs, a class of 24
CC to 30 nucleotide RNAs that are generated by a Dicer-independent
CC mechanism and are primarily derived from transposons and other repeated
CC sequence elements (PubMed:19460866, PubMed:25558067, PubMed:27693359).
CC Recognizes piRNAs containing a phosphate at the 5'-end and a 2'-O-
CC methylation modification at the 3'-end (PubMed:27693359). Strongly
CC prefers a uridine in the first position of their guide (g1U preference,
CC also named 1U-bias) and a complementary adenosine in the target (t1A
CC bias) (PubMed:24757166, PubMed:27693359). Plays a key role in the piRNA
CC amplification loop, also named ping-pong amplification cycle: antisense
CC piRNA-bound Siwi and sense piRNA-bound Ago3 reciprocally cleave
CC complementary transcripts, to couple the amplification of piRNAs with
CC the repression of transposable elements. In this process Siwi acts as a
CC 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs,
CC which are then loaded onto Ago3 (PubMed:27693359). In this process,
CC Siwi requires the RNA unwinding activity of the RNA helicase Vasa for
CC the release of the cleavage products (PubMed:25558067).
CC {ECO:0000269|PubMed:18191035, ECO:0000269|PubMed:19460866,
CC ECO:0000269|PubMed:24757166, ECO:0000269|PubMed:25558067,
CC ECO:0000269|PubMed:27693359}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27693359};
CC -!- SUBUNIT: Interacts (when symmetrically methylated) with Papi/TDRKH
CC (PubMed:23970546, PubMed:26919431). Interacts with Vasa
CC (PubMed:25558067). {ECO:0000269|PubMed:23970546,
CC ECO:0000269|PubMed:25558067, ECO:0000269|PubMed:26919431}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25558067}.
CC Note=Component of the meiotic nuage, also named P granule, a germ-cell-
CC specific organelle required to repress transposon activity during
CC meiosis (PubMed:25558067). {ECO:0000269|PubMed:25558067}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the larval testis, pupal ovary
CC and adult eggs. {ECO:0000269|PubMed:18191035}.
CC -!- DOMAIN: Shows a strong structural resemblance to the argonaute/Ago
CC subfamily. The domains (N, PAZ, MID and PIWI) and linkers (L0, L1, and
CC L2) assemble into a typical bi-lobed (N-PAZ lobe and MID-PIWI lobe)
CC architecture, in which the 5' and 3' ends of the bound piRNA are
CC anchored by the MID-PIWI and PAZ domains, respectively. However, the
CC relative orientation of these two lobes differs significantly between
CC Siwi and the Ago-clade proteins: the N-PAZ lobe in Siwi rotates
CC significantly downward. Additional hinge motions between N and PAZ
CC domains exist, due to a distinct set of contacts at the interface.
CC Three out of the four residues in the DEDH catalytic tetrad are well-
CC preserved. The fourth, Glu-708, is located in a disordered loop and
CC likely joins the active site upon the guide-target RNA duplex
CC formation. This 'unplugged' active site scheme is found in Agos of some
CC bacteria. {ECO:0000269|PubMed:27693359}.
CC -!- PTM: Arginine methylation is required for the interaction with Tudor
CC domain-containing protein Papi/TDRKH (PubMed:23970546,
CC PubMed:26919431). {ECO:0000269|PubMed:23970546,
CC ECO:0000269|PubMed:26919431}.
CC -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily.
CC {ECO:0000305}.
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DR EMBL; AB332313; BAF73718.2; -; mRNA.
DR EMBL; AB372006; BAF98574.1; -; mRNA.
DR EMBL; EU143547; ABV60274.1; -; mRNA.
DR EMBL; BABH01033344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EU034629; ABS53348.1; -; mRNA.
DR RefSeq; NP_001098066.2; NM_001104596.2.
DR RefSeq; XP_012545276.1; XM_012689822.1.
DR PDB; 5GUH; X-ray; 2.40 A; A=1-899.
DR PDBsum; 5GUH; -.
DR AlphaFoldDB; A8D8P8; -.
DR SMR; A8D8P8; -.
DR STRING; 7091.BGIBMGA010644-TA; -.
DR EnsemblMetazoa; BGIBMGA010644-RA; BGIBMGA010644-TA; BGIBMGA010644.
DR GeneID; 100125336; -.
DR KEGG; bmor:100125336; -.
DR CTD; 100125336; -.
DR eggNOG; KOG1042; Eukaryota.
DR HOGENOM; CLU_008813_0_0_1; -.
DR InParanoid; A8D8P8; -.
DR OMA; WYVITPR; -.
DR OrthoDB; 220258at2759; -.
DR Proteomes; UP000005204; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990923; C:PET complex; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IMP:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0034584; F:piRNA binding; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0034587; P:piRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR036085; PAZ_dom_sf.
DR InterPro; IPR003165; Piwi.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF02171; Piwi; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00950; Piwi; 1.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS50822; PIWI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Developmental protein; Differentiation;
KW Endonuclease; Hydrolase; Magnesium; Meiosis; Metal-binding; Methylation;
KW Nuclease; Reference proteome; RNA-binding; RNA-mediated gene silencing;
KW Spermatogenesis.
FT CHAIN 1..899
FT /note="Piwi-like protein Siwi"
FT /id="PRO_0000439355"
FT DOMAIN 339..427
FT /note="PAZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT DOMAIN 594..885
FT /note="Piwi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT REGION 1..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..168
FT /note="L0 region"
FT /evidence="ECO:0000305|PubMed:27693359"
FT REGION 169..241
FT /note="N region"
FT /evidence="ECO:0000305|PubMed:27693359"
FT REGION 242..318
FT /note="L1 region"
FT /evidence="ECO:0000305|PubMed:27693359"
FT REGION 428..527
FT /note="L2 region"
FT /evidence="ECO:0000305|PubMed:27693359"
FT REGION 528..658
FT /note="MID region"
FT /evidence="ECO:0000305|PubMed:27693359"
FT COMPBIAS 38..54
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..92
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 670
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT ACT_SITE 708
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT ACT_SITE 740
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT ACT_SITE 874
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT BINDING 645
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT BINDING 899
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27693359,
FT ECO:0007744|PDB:5GUH"
FT MUTAGEN 602
FT /note="N->Q: Does not affect ability to recognize uridine
FT at the first position of piRNAs (g1U preference, also named
FT 1U-bias)."
FT /evidence="ECO:0000269|PubMed:24757166"
FT MUTAGEN 607
FT /note="Y->E: Reduced piRNA-binding."
FT /evidence="ECO:0000269|PubMed:24757166"
FT MUTAGEN 607
FT /note="Y->L: Does not affect ability to recognize uridine
FT at the first position of piRNAs (g1U preference, also named
FT 1U-bias)."
FT /evidence="ECO:0000269|PubMed:24757166"
FT MUTAGEN 611
FT /note="K->A: Reduced piRNA-binding."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 623
FT /note="Q->A: Reduced piRNA-binding."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 645
FT /note="Q->A: Reduced piRNA-binding."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 649
FT /note="K->A: Reduced piRNA-binding."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 670
FT /note="D->A: Abolished endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 708
FT /note="E->A: Abolished endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 740
FT /note="D->A: Abolished endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:27693359"
FT MUTAGEN 874
FT /note="H->A: Abolished endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:27693359"
FT STRAND 148..162
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 168..175
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 198..210
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 230..240
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 245..261
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 285..297
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 299..317
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 318..328
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 336..341
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:5GUH"
FT TURN 349..352
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 379..386
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 398..403
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 408..411
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 414..418
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 423..427
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 430..434
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 436..446
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 450..465
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 468..475
FT /evidence="ECO:0007829|PDB:5GUH"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 486..492
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 501..503
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:5GUH"
FT TURN 512..515
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 516..519
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 542..558
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 567..572
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 576..589
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 593..601
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 604..615
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 622..626
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 627..630
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 635..649
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 664..673
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 675..677
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 681..688
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 696..703
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 710..728
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 733..741
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 744..746
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 747..752
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 754..766
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 773..780
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 786..790
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 793..795
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 801..803
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 805..808
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 814..817
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 823..825
FT /evidence="ECO:0007829|PDB:5GUH"
FT STRAND 830..837
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 843..853
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 868..882
FT /evidence="ECO:0007829|PDB:5GUH"
FT HELIX 890..892
FT /evidence="ECO:0007829|PDB:5GUH"
SQ SEQUENCE 899 AA; 101338 MW; DAF3AD4845AC9386 CRC64;
MSEPRGRGRA RGRAGRGGDG GGPAPRRPGE QAGPSQQSMP PGPRPQPPSG WGPQSSVPPV
RAGVPTPTAQ AGRASHRVTP TTHEHPGDID VQQRMQKLEL GPHSSGGGDA SSVVGRGSRR
GGGRVLPETI SILRTRPEAV TSKKGTSGTP LDLLANYFTV ETTPKWGLYQ YHVDISPEED
STGVRKALMR VHSKTLGGYL FDGTVLYTVN RLHPDPMELY SDRKTDNERM RILIKLTCEV
SPGDYHYIQI FNIIIRKCFN LLKLQLMGRD YFDPEAKIDI PEFKLQIWPG YKTTINQYED
RLLLVTEIAH KVLRMDTVLQ MLSEYAATKG NNYKKIFLED VVGKIVMTDY NKRTYRVDDV
AWNVSPKSTF KMRDENITYI EYYYKKYNLR IQDPGQPLLI SRSKPREIRA GLPELIYLVP
ELCRQTGLSD EMRANFKLMR SLDVHTKIGP DKRIEKLNNF NRRFTSTPEV VEELATWSLK
LSKELVKIKG RQLPPENIIQ ANNVKYPAGD TTEGWTRDMR SKHLLAIAQL NSWVVITPER
QRRDTESFID LIIKTGGGVG FRMRSPDLVV IRHDGPIEYA NMCEEVIARK NPALILCVLA
RNYADRYEAI KKKCTVDRAV PTQVVCARNM SSKSAMSIAT KVAIQINCKL GGSPWTVDIP
LPSLMVVGYD VCHDTRSKEK SFGAFVATLD KQMTQYYSIV NAHTSGEELS SHMGFNIASA
VKKFREKNGT YPARIFIYRD GVGDGQIPYV HSHEVAEIKK KLAEIYAGVE IKLAFIIVSK
RINTRIFVQR GRSGENPRPG TVIDDVVTLP ERYDFYLVSQ NVREGTIAPT SYNVIEDTTG
LNPDRIQRLT YKLTHLYFNC SSQVRVPSVC QYAHKLAFLA ANSLHNQPHY SLNETLYFL
