PIWL4_HUMAN
ID PIWL4_HUMAN Reviewed; 852 AA.
AC Q7Z3Z4; B4DEG5; Q68CZ4; Q8N8G9; Q8N9V8; Q8NEH2;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Piwi-like protein 4;
GN Name=PIWIL4; Synonyms=HIWI2, PIWI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12906857; DOI=10.1016/s0888-7543(03)00129-0;
RA Sasaki T., Shiohama A., Minoshima S., Shimizu N.;
RT "Identification of eight members of the Argonaute family in the human
RT genome.";
RL Genomics 82:323-330(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP LEU-327 AND PRO-370.
RC TISSUE=Cerebellum, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Salivary gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP POSSIBLE FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17544373; DOI=10.1016/j.bbrc.2007.05.136;
RA Sugimoto K., Kage H., Aki N., Sano A., Kitagawa H., Nagase T., Yatomi Y.,
RA Ohishi N., Takai D.;
RT "The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus.";
RL Biochem. Biophys. Res. Commun. 359:497-502(2007).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22483988; DOI=10.1016/j.febslet.2012.03.053;
RA Su C., Ren Z.J., Wang F., Liu M., Li X., Tang H.;
RT "PIWIL4 regulates cervical cancer cell line growth and is involved in down-
RT regulating the expression of p14ARF and p53.";
RL FEBS Lett. 586:1356-1362(2012).
RN [7]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND RNA-BINDING.
RX PubMed=25038252; DOI=10.1093/nar/gku620;
RA Keam S.P., Young P.E., McCorkindale A.L., Dang T.H., Clancy J.L.,
RA Humphreys D.T., Preiss T., Hutvagner G., Martin D.I., Cropley J.E.,
RA Suter C.M.;
RT "The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in
RT somatic cells.";
RL Nucleic Acids Res. 42:8984-8995(2014).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=28711973; DOI=10.1007/s00125-017-4368-2;
RA Henaoui I.S., Jacovetti C., Guerra Mollet I., Guay C., Sobel J.,
RA Eliasson L., Regazzi R.;
RT "PIWI-interacting RNAs as novel regulators of pancreatic beta cell
RT function.";
RL Diabetologia 60:1977-1986(2017).
RN [9]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=28025795; DOI=10.1007/s11010-016-2906-8;
RA Sivagurunathan S., Palanisamy K., Arunachalam J.P., Chidambaram S.;
RT "Possible role of HIWI2 in modulating tight junction proteins in retinal
RT pigment epithelial cells through Akt signaling pathway.";
RL Mol. Cell. Biochem. 427:145-156(2017).
RN [10]
RP INDUCTION.
RX PubMed=30145353; DOI=10.1016/j.exer.2018.08.018;
RA Sivagurunathan S., Raman R., Chidambaram S.;
RT "PIWI-like protein, HIWI2: A novel player in proliferative diabetic
RT retinopathy.";
RL Exp. Eye Res. 177:191-196(2018).
RN [11]
RP VARIANT PRO-370.
RX PubMed=24969058; DOI=10.4103/1008-682x.131069;
RA Munoz X., Navarro M., Mata A., Bassas L., Larriba S.;
RT "Association of PIWIL4 genetic variants with germ cell maturation arrest in
RT infertile Spanish men.";
RL Asian J. Androl. 16:931-933(2014).
CC -!- FUNCTION: Plays a central role during spermatogenesis by repressing
CC transposable elements and preventing their mobilization, which is
CC essential for the germline integrity (By similarity). Acts via the
CC piRNA metabolic process, which mediates the repression of transposable
CC elements during meiosis by forming complexes composed of piRNAs and
CC Piwi proteins and governs the methylation and subsequent repression of
CC transposons (By similarity). Directly binds piRNAs, a class of 24 to 30
CC nucleotide RNAs that are generated by a Dicer-independent mechanism and
CC are primarily derived from transposons and other repeated sequence
CC elements (By similarity). Associates with secondary piRNAs antisense
CC and PIWIL2/MILI is required for such association (By similarity). The
CC piRNA process acts upstream of known mediators of DNA methylation (By
CC similarity). Does not show endonuclease activity (By similarity). Plays
CC a key role in the piRNA amplification loop, also named ping-pong
CC amplification cycle, by acting as a 'slicer-incompetent' component that
CC loads cleaved piRNAs from the 'slicer-competent' component PIWIL2 and
CC target them on genomic transposon loci in the nucleus (By similarity).
CC May be involved in the chromatin-modifying pathway by inducing 'Lys-9'
CC methylation of histone H3 at some loci (PubMed:17544373). In addition
CC to its role in germline, PIWIL4 also plays a role in the regulation of
CC somatic cells activities. Plays a role in pancreatic beta cell function
CC and insulin secretion (By similarity). Involved in maintaining cell
CC morphology and functional integrity of retinal epithelial through
CC Akt/GSK3alpha/beta signaling pathway (PubMed:28025795). When
CC overexpressed, acts as an oncogene by inhibition of apoptosis and
CC promotion of cells proliferation in tumors (PubMed:22483988).
CC {ECO:0000250|UniProtKB:Q8CGT6, ECO:0000269|PubMed:17544373,
CC ECO:0000269|PubMed:22483988, ECO:0000269|PubMed:28025795}.
CC -!- SUBUNIT: Interacts with PRMT5 and WDR77. Interacts (when methylated on
CC arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9. Interacts with
CC MOV10L1 (By similarity). Interacts with TEX15 and SPOCD1 (By
CC similarity). {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25038252,
CC ECO:0000269|PubMed:28025795}. Cytoplasm {ECO:0000269|PubMed:15489334,
CC ECO:0000269|PubMed:25038252, ECO:0000269|PubMed:28025795}.
CC Note=Probable component of the meiotic nuage, also named P granule, a
CC germ-cell-specific organelle required to repress transposon activity
CC during meiosis. PIWIL2/MILI is required for nuclear localization (By
CC similarity). {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z3Z4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z3Z4-2; Sequence=VSP_021031, VSP_021032, VSP_021033;
CC Name=3;
CC IsoId=Q7Z3Z4-3; Sequence=VSP_036665, VSP_021032, VSP_021033;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:25038252,
CC PubMed:17544373, PubMed:28025795, PubMed:28711973, PubMed:22483988).
CC Detected in retina, retinal pigment epithelia cells (RPE) (at protein
CC level) (PubMed:28025795). {ECO:0000269|PubMed:17544373,
CC ECO:0000269|PubMed:22483988, ECO:0000269|PubMed:25038252,
CC ECO:0000269|PubMed:28025795, ECO:0000269|PubMed:28711973}.
CC -!- INDUCTION: Up-regulated in vitreous aspirates of patients with
CC proliferative diabetic retinopathies (at protein level). Up-regulated
CC after exposure to oxidative stress and VEGF in adult retinal pigment
CC epithelial cell line (ARPE19 cells) (PubMed:30145353). Up-regulated in
CC cervical cancer tissues (PubMed:22483988).
CC {ECO:0000269|PubMed:22483988, ECO:0000269|PubMed:30145353}.
CC -!- PTM: Arginine methylation by PRMT5 is required for the interaction with
CC Tudor domain-containing protein (TDRD1, TDRKH/TDRD2 and TDRD9) and
CC subsequent localization to the meiotic nuage, also named P granule.
CC {ECO:0000250|UniProtKB:Q8CGT6}.
CC -!- SIMILARITY: Belongs to the argonaute family. Piwi subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC04873.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAH18436.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB079366; BAC81341.1; -; mRNA.
DR EMBL; AK093475; BAC04179.1; -; mRNA.
DR EMBL; AK096837; BAC04873.1; ALT_INIT; mRNA.
DR EMBL; AK293616; BAG57076.1; -; mRNA.
DR EMBL; CR749642; CAH18436.1; ALT_FRAME; mRNA.
DR EMBL; BC031060; AAH31060.1; -; mRNA.
DR CCDS; CCDS31656.1; -. [Q7Z3Z4-1]
DR RefSeq; NP_689644.2; NM_152431.2. [Q7Z3Z4-1]
DR AlphaFoldDB; Q7Z3Z4; -.
DR SMR; Q7Z3Z4; -.
DR BioGRID; 126818; 17.
DR IntAct; Q7Z3Z4; 21.
DR MINT; Q7Z3Z4; -.
DR STRING; 9606.ENSP00000299001; -.
DR iPTMnet; Q7Z3Z4; -.
DR PhosphoSitePlus; Q7Z3Z4; -.
DR BioMuta; PIWIL4; -.
DR DMDM; 116242716; -.
DR EPD; Q7Z3Z4; -.
DR MassIVE; Q7Z3Z4; -.
DR PaxDb; Q7Z3Z4; -.
DR PeptideAtlas; Q7Z3Z4; -.
DR PRIDE; Q7Z3Z4; -.
DR ProteomicsDB; 69101; -. [Q7Z3Z4-1]
DR ProteomicsDB; 69102; -. [Q7Z3Z4-2]
DR ProteomicsDB; 69103; -. [Q7Z3Z4-3]
DR Antibodypedia; 31638; 287 antibodies from 30 providers.
DR DNASU; 143689; -.
DR Ensembl; ENST00000299001.11; ENSP00000299001.6; ENSG00000134627.12. [Q7Z3Z4-1]
DR Ensembl; ENST00000446230.6; ENSP00000413838.2; ENSG00000134627.12. [Q7Z3Z4-2]
DR Ensembl; ENST00000543336.5; ENSP00000444575.1; ENSG00000134627.12. [Q7Z3Z4-3]
DR GeneID; 143689; -.
DR KEGG; hsa:143689; -.
DR MANE-Select; ENST00000299001.11; ENSP00000299001.6; NM_152431.3; NP_689644.2.
DR UCSC; uc001pfa.3; human. [Q7Z3Z4-1]
DR CTD; 143689; -.
DR DisGeNET; 143689; -.
DR GeneCards; PIWIL4; -.
DR HGNC; HGNC:18444; PIWIL4.
DR HPA; ENSG00000134627; Tissue enhanced (bone).
DR MIM; 610315; gene.
DR neXtProt; NX_Q7Z3Z4; -.
DR OpenTargets; ENSG00000134627; -.
DR PharmGKB; PA38333; -.
DR VEuPathDB; HostDB:ENSG00000134627; -.
DR eggNOG; KOG1042; Eukaryota.
DR GeneTree; ENSGT00950000183200; -.
DR HOGENOM; CLU_008813_1_1_1; -.
DR InParanoid; Q7Z3Z4; -.
DR OMA; WSKDMRN; -.
DR PhylomeDB; Q7Z3Z4; -.
DR TreeFam; TF354206; -.
DR PathwayCommons; Q7Z3Z4; -.
DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis.
DR SignaLink; Q7Z3Z4; -.
DR BioGRID-ORCS; 143689; 12 hits in 1082 CRISPR screens.
DR GenomeRNAi; 143689; -.
DR Pharos; Q7Z3Z4; Tbio.
DR PRO; PR:Q7Z3Z4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q7Z3Z4; protein.
DR Bgee; ENSG00000134627; Expressed in bone marrow and 144 other tissues.
DR ExpressionAtlas; Q7Z3Z4; baseline and differential.
DR Genevisible; Q7Z3Z4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043186; C:P granule; ISS:UniProtKB.
DR GO; GO:0071547; C:piP-body; ISS:UniProtKB.
DR GO; GO:0034584; F:piRNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; ISS:UniProtKB.
DR GO; GO:0010669; P:epithelial structure maintenance; IMP:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
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 Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW Meiosis; Methylation; Nucleus; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing; Spermatogenesis; Translation regulation.
FT CHAIN 1..852
FT /note="Piwi-like protein 4"
FT /id="PRO_0000234572"
FT DOMAIN 268..384
FT /note="PAZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT DOMAIN 546..838
FT /note="Piwi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036665"
FT VAR_SEQ 1..29
FT /note="MSGRARVKARGIARSPSATEVGRIQASPL -> MG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_021031"
FT VAR_SEQ 522
FT /note="I -> M (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_021032"
FT VAR_SEQ 523..852
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_021033"
FT VARIANT 78
FT /note="Q -> R (in dbSNP:rs12276921)"
FT /id="VAR_028367"
FT VARIANT 167
FT /note="K -> R (in dbSNP:rs12272255)"
FT /id="VAR_055533"
FT VARIANT 327
FT /note="Q -> L (in dbSNP:rs11020845)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_026291"
FT VARIANT 370
FT /note="A -> P (in dbSNP:rs57607909)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:24969058"
FT /id="VAR_061025"
FT CONFLICT 99
FT /note="T -> A (in Ref. 1; BAC81341)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="K -> E (in Ref. 2; BAC04179)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="A -> T (in Ref. 2; BAC04873)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="K -> E (in Ref. 2; BAC04179)"
FT /evidence="ECO:0000305"
FT CONFLICT 719
FT /note="S -> G (in Ref. 2; BAC04179)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 852 AA; 96589 MW; 37769EE078B96D13 CRC64;
MSGRARVKAR GIARSPSATE VGRIQASPLP RSVDLSNNEA SSSNGFLGTS RISTNDKYGI
SSGDAGSTFM ERGVKNKQDF MDLSICTREK LAHVRNCKTG SSGIPVKLVT NLFNLDFPQD
WQLYQYHVTY IPDLASRRLR IALLYSHSEL SNKAKAFDGA ILFLSQKLEE KVTELSSETQ
RGETIKMTIT LKRELPSSSP VCIQVFNIIF RKILKKLSMY QIGRNFYNPS EPMEIPQHKL
SLWPGFAISV SYFERKLLFS ADVSYKVLRN ETVLEFMTAL CQRTGLSCFT QTCEKQLIGL
IVLTRYNNRT YSIDDIDWSV KPTHTFQKRD GTEITYVDYY KQQYDITVSD LNQPMLVSLL
KKKRNDNSEA QLAHLIPELC FLTGLTDQAT SDFQLMKAVA EKTRLSPSGR QQRLARLVDN
IQRNTNARFE LETWGLHFGS QISLTGRIVP SEKILMQDHI CQPVSAADWS KDIRTCKILN
AQSLNTWLIL CSDRTEYVAE SFLNCLRRVA GSMGFNVDYP KIIKVQENPA AFVRAIQQYV
DPDVQLVMCI LPSNQKTYYD SIKKYLSSDC PVPSQCVLAR TLNKQGMMMS IATKIAMQMT
CKLGGELWAV EIPLKSLMVV GIDVCKDALS KDVMVVGCVA SVNPRITRWF SRCILQRTMT
DVADCLKVFM TGALNKWYKY NHDLPARIIV YRAGVGDGQL KTLIEYEVPQ LLSSVAESSS
NTSSRLSVIV VRKKCMPRFF TEMNRTVQNP PLGTVVDSEA TRNEWYDFYL ISQVACRGTV
SPTYYNVIYD DNGLKPDHMQ RLTFKLCHLY YNWPGIVSVP APCQYAHKLT FLVAQSIHKE
PSLELANHLF YL
