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FSTL5_HUMAN
ID   FSTL5_HUMAN             Reviewed;         847 AA.
AC   Q8N475; E9PCP6; Q9NSW7; Q9ULF7;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2005, sequence version 2.
DT   03-AUG-2022, entry version 161.
DE   RecName: Full=Follistatin-related protein 5;
DE   AltName: Full=Follistatin-like protein 5;
DE   Flags: Precursor;
GN   Name=FSTL5; Synonyms=KIAA1263;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA   Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:337-345(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Brain;
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 GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 75-847 (ISOFORM 1).
RC   TISSUE=Kidney;
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   [6]
RP   VARIANT [LARGE SCALE ANALYSIS] ILE-92.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8N475-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N475-2; Sequence=VSP_046215;
CC       Name=3;
CC         IsoId=Q8N475-3; Sequence=VSP_046215, VSP_046216;
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA86577.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB033089; BAA86577.1; ALT_INIT; mRNA.
DR   EMBL; AK315152; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC023136; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC079227; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC084281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC096717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC104793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC105251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC108163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC036502; AAH36502.1; -; mRNA.
DR   EMBL; AL137695; CAB70877.1; -; mRNA.
DR   CCDS; CCDS3802.1; -. [Q8N475-1]
DR   CCDS; CCDS47157.1; -. [Q8N475-3]
DR   CCDS; CCDS47158.1; -. [Q8N475-2]
DR   PIR; T46283; T46283.
DR   RefSeq; NP_001121899.1; NM_001128427.2. [Q8N475-2]
DR   RefSeq; NP_001121900.1; NM_001128428.2. [Q8N475-3]
DR   RefSeq; NP_064501.2; NM_020116.4. [Q8N475-1]
DR   AlphaFoldDB; Q8N475; -.
DR   SMR; Q8N475; -.
DR   BioGRID; 121216; 2.
DR   IntAct; Q8N475; 4.
DR   STRING; 9606.ENSP00000305334; -.
DR   MEROPS; I01.977; -.
DR   GlyGen; Q8N475; 2 sites.
DR   iPTMnet; Q8N475; -.
DR   PhosphoSitePlus; Q8N475; -.
DR   BioMuta; FSTL5; -.
DR   DMDM; 62510692; -.
DR   EPD; Q8N475; -.
DR   MassIVE; Q8N475; -.
DR   MaxQB; Q8N475; -.
DR   PaxDb; Q8N475; -.
DR   PeptideAtlas; Q8N475; -.
DR   PRIDE; Q8N475; -.
DR   ProteomicsDB; 19487; -.
DR   ProteomicsDB; 71893; -. [Q8N475-1]
DR   Antibodypedia; 28231; 98 antibodies from 18 providers.
DR   DNASU; 56884; -.
DR   Ensembl; ENST00000306100.10; ENSP00000305334.4; ENSG00000168843.14. [Q8N475-1]
DR   Ensembl; ENST00000379164.8; ENSP00000368462.4; ENSG00000168843.14. [Q8N475-2]
DR   Ensembl; ENST00000427802.2; ENSP00000389270.2; ENSG00000168843.14. [Q8N475-3]
DR   GeneID; 56884; -.
DR   KEGG; hsa:56884; -.
DR   MANE-Select; ENST00000306100.10; ENSP00000305334.4; NM_020116.5; NP_064501.2.
DR   UCSC; uc003iqh.5; human. [Q8N475-1]
DR   CTD; 56884; -.
DR   DisGeNET; 56884; -.
DR   GeneCards; FSTL5; -.
DR   HGNC; HGNC:21386; FSTL5.
DR   HPA; ENSG00000168843; Group enriched (brain, retina).
DR   neXtProt; NX_Q8N475; -.
DR   OpenTargets; ENSG00000168843; -.
DR   PharmGKB; PA134978045; -.
DR   VEuPathDB; HostDB:ENSG00000168843; -.
DR   eggNOG; ENOG502QPNV; Eukaryota.
DR   GeneTree; ENSGT00940000156495; -.
DR   HOGENOM; CLU_007849_1_0_1; -.
DR   InParanoid; Q8N475; -.
DR   OMA; KYGYVTH; -.
DR   OrthoDB; 1065760at2759; -.
DR   PhylomeDB; Q8N475; -.
DR   TreeFam; TF350473; -.
DR   PathwayCommons; Q8N475; -.
DR   SignaLink; Q8N475; -.
DR   BioGRID-ORCS; 56884; 18 hits in 1076 CRISPR screens.
DR   ChiTaRS; FSTL5; human.
DR   GenomeRNAi; 56884; -.
DR   Pharos; Q8N475; Tbio.
DR   PRO; PR:Q8N475; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q8N475; protein.
DR   Bgee; ENSG00000168843; Expressed in cerebellar vermis and 100 other tissues.
DR   Genevisible; Q8N475; HS.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   Gene3D; 2.130.10.10; -; 1.
DR   Gene3D; 2.60.40.10; -; 2.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR002350; Kazal_dom.
DR   InterPro; IPR036058; Kazal_dom_sf.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   Pfam; PF07648; Kazal_2; 1.
DR   SMART; SM00409; IG; 2.
DR   SMART; SM00408; IGc2; 2.
DR   SMART; SM00280; KAZAL; 1.
DR   SUPFAM; SSF100895; SSF100895; 1.
DR   SUPFAM; SSF47473; SSF47473; 1.
DR   SUPFAM; SSF48726; SSF48726; 2.
DR   PROSITE; PS00018; EF_HAND_1; 2.
DR   PROSITE; PS50222; EF_HAND_2; 1.
DR   PROSITE; PS50835; IG_LIKE; 2.
DR   PROSITE; PS51465; KAZAL_2; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Calcium; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Metal-binding; Reference proteome; Repeat; Secreted;
KW   Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..847
FT                   /note="Follistatin-related protein 5"
FT                   /id="PRO_0000010118"
FT   DOMAIN          83..135
FT                   /note="Kazal-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DOMAIN          175..210
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          211..246
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          250..337
FT                   /note="Ig-like 1"
FT   DOMAIN          341..426
FT                   /note="Ig-like 2"
FT   BINDING         188
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         190
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         192
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         199
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         226
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT   BINDING         228
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT   BINDING         230
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT   BINDING         232
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT   BINDING         237
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT   CARBOHYD        318
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        89..119
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DISULFID        93..112
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DISULFID        101..133
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DISULFID        270..321
FT                   /evidence="ECO:0000250"
FT   DISULFID        362..413
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         43
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10574462,
FT                   ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046215"
FT   VAR_SEQ         438..447
FT                   /note="LANILWREEG -> R (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_046216"
FT   VARIANT         92
FT                   /note="L -> I (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs747628234)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036135"
FT   VARIANT         711
FT                   /note="D -> Y (in dbSNP:rs3749598)"
FT                   /id="VAR_049092"
FT   VARIANT         815
FT                   /note="K -> E (in dbSNP:rs17040982)"
FT                   /id="VAR_049093"
FT   CONFLICT        145
FT                   /note="Y -> C (in Ref. 5; CAB70877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        159
FT                   /note="K -> R (in Ref. 5; CAB70877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        193
FT                   /note="G -> D (in Ref. 5; CAB70877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        293
FT                   /note="D -> G (in Ref. 5; CAB70877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        492
FT                   /note="K -> I (in Ref. 5; CAB70877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        560
FT                   /note="S -> G (in Ref. 2; AK315152)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        567
FT                   /note="T -> S (in Ref. 4; AAH36502)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        631
FT                   /note="L -> I (in Ref. 4; AAH36502)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   847 AA;  95751 MW;  AA8ECA182FF6CDB6 CRC64;
     MFKCWSVVLV LGFIFLESEG RPTKEGGYGL KSYQPLMRLR HKQEKNQESS RVKGFMIQDG
     PFGSCENKYC GLGRHCVTSR ETGQAECACM DLCKRHYKPV CGSDGEFYEN HCEVHRAACL
     KKQKITIVHN EDCFFKGDKC KTTEYSKMKN MLLDLQNQKY IMQENENPNG DDISRKKLLV
     DQMFKYFDAD SNGLVDINEL TQVIKQEELG KDLFDCTLYV LLKYDDFNAD KHLALEEFYR
     AFQVIQLSLP EDQKLSITAA TVGQSAVLSC AIQGTLRPPI IWKRNNIILN NLDLEDINDF
     GDDGSLYITK VTTTHVGNYT CYADGYEQVY QTHIFQVNVP PVIRVYPESQ AREPGVTASL
     RCHAEGIPKP QLGWLKNGID ITPKLSKQLT LQANGSEVHI SNVRYEDTGA YTCIAKNEAG
     VDEDISSLFV EDSARKTLAN ILWREEGLGI GNMFYVFYED GIKVIQPIEC EFQRHIKPSE
     KLLGFQDEVC PKAEGDEVQR CVWASAVNVK DKFIYVAQPT LDRVLIVDVQ SQKVVQAVST
     DPVPVKLHYD KSHDQVWVLS WGTLEKTSPT LQVITLASGN VPHHTIHTQP VGKQFDRVDD
     FFIPTTTLII THMRFGFILH KDEAALQKID LETMSYIKTI NLKDYKCVPQ SLAYTHLGGY
     YFIGCKPDST GAVSPQVMVD GVTDSVIGFN SDVTGTPYVS PDGHYLVSIN DVKGLVRVQY
     ITIRGEIQEA FDIYTNLHIS DLAFQPSFTE AHQYNIYGSS STQTDVLFVE LSSGKVKMIK
     SLKEPLKAEE WPWNRKNRQI QDSGLFGQYL MTPSKDSLFI LDGRLNKLNC EITEVEKGNT
     VIWVGDA
 
 
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