SOCS3_HUMAN
ID SOCS3_HUMAN Reviewed; 225 AA.
AC O14543; O14509;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Suppressor of cytokine signaling 3 {ECO:0000305};
DE Short=SOCS-3;
DE AltName: Full=Cytokine-inducible SH2 protein 3;
DE Short=CIS-3;
DE AltName: Full=STAT-induced STAT inhibitor 3;
DE Short=SSI-3;
GN Name=SOCS3 {ECO:0000312|HGNC:HGNC:19391}; Synonyms=CIS3, SSI3;
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], AND VARIANT TYR-125.
RC TISSUE=T-cell lymphoma;
RX PubMed=9266833; DOI=10.1006/bbrc.1997.7080;
RA Minamoto S., Ikegame K., Ueno K., Narazaki M., Naka T., Yamamoto H.,
RA Matsumoto T., Saito H., Hosoe S., Kishimoto T.;
RT "Cloning and functional analysis of new members of STAT induced STAT
RT inhibitor (SSI) family: SSI-2 and SSI-3.";
RL Biochem. Biophys. Res. Commun. 237:79-83(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9344848; DOI=10.1006/bbrc.1997.7484;
RA Masuhara M., Sakamoto H., Matsumoto A., Suzuki R., Yasukawa H., Mitsui K.,
RA Wakioka T., Tanimura S., Sasaki A., Misawa H., Yokouchi M., Ohtsubo M.,
RA Yoshimura A.;
RT "Cloning and characterization of novel CIS family genes.";
RL Biochem. Biophys. Res. Commun. 239:439-446(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=11071852; DOI=10.1006/bbrc.2000.3762;
RA Dey B.R., Furlanetto R.W., Nissley P.;
RT "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the
RT insulin-like growth factor-I receptor.";
RL Biochem. Biophys. Res. Commun. 278:38-43(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 INTERACTION WITH JAK2, AND MUTAGENESIS OF LEU-22; PHE-25; GLU-30; TYR-31;
RP VAL-34; LEU-41; GLY-45 AND ARG-71.
RX PubMed=10421843; DOI=10.1046/j.1365-2443.1999.00263.x;
RA Sasaki A., Yasukawa H., Suzuki A., Kamizono S., Syoda T., Kinjyo I.,
RA Sasaki M., Johnston J.A., Yoshimura A.;
RT "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine
RT kinase by binding through the N-terminal kinase inhibitory region as well
RT as SH2 domain.";
RL Genes Cells 4:339-351(1999).
RN [6]
RP INTERACTION WITH EPOR, AND MUTAGENESIS OF GLY-53; LEU-58; LEU-93 AND
RP ARG-94.
RX PubMed=12027890; DOI=10.1046/j.1432-1033.2002.02916.x;
RA Hoertner M., Nielsch U., Mayr L.M., Heinrich P.C., Haan S.;
RT "A new high affinity binding site for suppressor of cytokine signaling-3 on
RT the erythropoietin receptor.";
RL Eur. J. Biochem. 269:2516-2526(2002).
RN [7]
RP INTERACTION WITH IL12RB2, AND MUTAGENESIS OF ARG-71.
RX PubMed=14559241; DOI=10.1016/j.bbrc.2003.09.140;
RA Yamamoto K., Yamaguchi M., Miyasaka N., Miura O.;
RT "SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2
RT domain to the STAT4 docking site in the IL-12 receptor beta2 subunit.";
RL Biochem. Biophys. Res. Commun. 310:1188-1193(2003).
RN [8]
RP INTERACTION WITH CSNK1E, AND PROTEIN STABILIZATION.
RX PubMed=15070676; DOI=10.1182/blood-2003-08-2768;
RA Okamura A., Iwata N., Nagata A., Tamekane A., Shimoyama M., Gomyo H.,
RA Yakushijin K., Urahama N., Hamaguchi M., Fukui C., Chihara K., Ito M.,
RA Matsui T.;
RT "Involvement of casein kinase Iepsilon in cytokine-induced granulocytic
RT differentiation.";
RL Blood 103:2997-3004(2004).
RN [9]
RP FUNCTION IN AN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, AND INTERACTION WITH
RP CUL5; RNF7; ELOB AND ELOC.
RX PubMed=15601820; DOI=10.1101/gad.1252404;
RA Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C.,
RA Conaway J.W., Nakayama K.I.;
RT "VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1
RT and Cul5-Rbx2 modules of ubiquitin ligases.";
RL Genes Dev. 18:3055-3065(2004).
RN [10]
RP POSSIBLE INVOLVEMENT IN ATOPIC DERMATITIS.
RX PubMed=16685656; DOI=10.1086/504272;
RA Ekelund E., Saeaef A., Tengvall-Linder M., Melen E., Link J., Barker J.,
RA Reynolds N.J., Meggitt S.J., Kere J., Wahlgren C.-F., Pershagen G.,
RA Wickman M., Nordenskjoeld M., Kockum I., Bradley M.;
RT "Elevated expression and genetic association links the SOCS3 gene to atopic
RT dermatitis.";
RL Am. J. Hum. Genet. 78:1060-1065(2006).
RN [11]
RP INTERACTION WITH FGFR3.
RX PubMed=16410555; DOI=10.1242/jcs.02740;
RA Ben-Zvi T., Yayon A., Gertler A., Monsonego-Ornan E.;
RT "Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and
RT modulate fibroblast growth factor receptor signaling.";
RL J. Cell Sci. 119:380-387(2006).
RN [12]
RP INTERACTION WITH NOD2.
RX PubMed=23019338; DOI=10.1074/jbc.m112.410027;
RA Lee K.H., Biswas A., Liu Y.J., Kobayashi K.S.;
RT "Proteasomal degradation of Nod2 protein mediates tolerance to bacterial
RT cell wall components.";
RL J. Biol. Chem. 287:39800-39811(2012).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. SOCS3 is
CC involved in negative regulation of cytokines that signal through the
CC JAK/STAT pathway. Inhibits cytokine signal transduction by binding to
CC tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin,
CC insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its
CC kinase activity and regulates IL6 signaling. Suppresses fetal liver
CC erythropoiesis. Regulates onset and maintenance of allergic responses
CC mediated by T-helper type 2 cells (By similarity). Probable substrate
CC recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins (PubMed:15601820). {ECO:0000250|UniProtKB:O35718,
CC ECO:0000269|PubMed:15601820}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including IGF1 receptor, insulin receptor and
CC JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a
CC phosphorylated tyrosine residue within the JAK2 JH1 domain
CC (PubMed:10421843). Binds specific activated tyrosine residues of the
CC leptin, EPO, IL12, GSCF and gp130 receptors (PubMed:12027890,
CC PubMed:14559241). Interaction with CSNK1E stabilizes SOCS3 protein
CC (PubMed:15070676). Component of the probable ECS(SOCS3) E3 ubiquitin-
CC protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC
CC complex and SOCS3 (PubMed:15601820). Interacts with CUL5, RNF7, ELOB
CC and ELOC (PubMed:15601820). Interacts with CUL2 (PubMed:15601820).
CC Interacts with FGFR3 (PubMed:16410555). Interacts with INSR (By
CC similarity). Interacts with BCL10; this interaction may interfere with
CC BCL10-binding with PELI2 (By similarity). Interacts with NOD2 (via CARD
CC domain); the interaction promotes NOD2 degradation (PubMed:23019338).
CC {ECO:0000250|UniProtKB:O35718, ECO:0000269|PubMed:10421843,
CC ECO:0000269|PubMed:12027890, ECO:0000269|PubMed:14559241,
CC ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15601820,
CC ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:23019338}.
CC -!- INTERACTION:
CC O14543; P51451: BLK; NbExp=3; IntAct=EBI-714146, EBI-2105445;
CC O14543; Q13480: GAB1; NbExp=4; IntAct=EBI-714146, EBI-517684;
CC O14543; Q8N8K9: KIAA1958; NbExp=6; IntAct=EBI-714146, EBI-10181113;
CC O14543; P10721: KIT; NbExp=3; IntAct=EBI-714146, EBI-1379503;
CC O14543; Q66K74: MAP1S; NbExp=6; IntAct=EBI-714146, EBI-2133734;
CC O14543; I6L996: PTK2; NbExp=3; IntAct=EBI-714146, EBI-10181089;
CC O14543; O95863: SNAI1; NbExp=3; IntAct=EBI-714146, EBI-1045459;
CC O14543; P42681: TXK; NbExp=3; IntAct=EBI-714146, EBI-7877438;
CC O14543; P07947: YES1; NbExp=6; IntAct=EBI-714146, EBI-515331;
CC -!- TISSUE SPECIFICITY: Widely expressed with high expression in heart,
CC placenta, skeletal muscle, peripheral blood leukocytes, fetal and adult
CC lung, and fetal liver and kidney. Lower levels in thymus.
CC -!- DOMAIN: The ESS and SH2 domains are required for JAK phosphotyrosine
CC binding. Further interaction with the KIR domain is necessary for
CC signal and kinase inhibition.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues after stimulation by the
CC cytokines, IL-2, EPO or IGF1.
CC -!- DISEASE: Note=There is some evidence that SOCS3 may be a susceptibility
CC gene for atopic dermatitis linked to 17q25. SOCS3 messenger RNA is
CC significantly more highly expressed in skin from patients with atopic
CC dermatitis than in skin from healthy controls. Furthermore, a genetic
CC association between atopic dermatitis and a haplotype in the SOCS3 gene
CC has been found in two independent groups of patients.
CC {ECO:0000269|PubMed:16685656}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SOCS3ID44124ch17q25.html";
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DR EMBL; AB004904; BAA22430.1; -; mRNA.
DR EMBL; AB006967; BAA22537.1; -; mRNA.
DR EMBL; AF159854; AAD42231.1; -; mRNA.
DR EMBL; BC060858; AAH60858.1; -; mRNA.
DR CCDS; CCDS11756.1; -.
DR PIR; JC5627; JC5627.
DR PIR; JC5761; JC5761.
DR RefSeq; NP_003946.3; NM_003955.4.
DR AlphaFoldDB; O14543; -.
DR BMRB; O14543; -.
DR SMR; O14543; -.
DR BioGRID; 114488; 96.
DR CORUM; O14543; -.
DR IntAct; O14543; 57.
DR MINT; O14543; -.
DR STRING; 9606.ENSP00000330341; -.
DR iPTMnet; O14543; -.
DR PhosphoSitePlus; O14543; -.
DR BioMuta; SOCS3; -.
DR EPD; O14543; -.
DR MassIVE; O14543; -.
DR PaxDb; O14543; -.
DR PeptideAtlas; O14543; -.
DR PRIDE; O14543; -.
DR Antibodypedia; 3206; 832 antibodies from 44 providers.
DR DNASU; 9021; -.
DR Ensembl; ENST00000330871.3; ENSP00000330341.2; ENSG00000184557.4.
DR GeneID; 9021; -.
DR KEGG; hsa:9021; -.
DR MANE-Select; ENST00000330871.3; ENSP00000330341.2; NM_003955.5; NP_003946.3.
DR CTD; 9021; -.
DR DisGeNET; 9021; -.
DR GeneCards; SOCS3; -.
DR HGNC; HGNC:19391; SOCS3.
DR HPA; ENSG00000184557; Low tissue specificity.
DR MalaCards; SOCS3; -.
DR MIM; 604176; gene.
DR neXtProt; NX_O14543; -.
DR OpenTargets; ENSG00000184557; -.
DR PharmGKB; PA134885765; -.
DR VEuPathDB; HostDB:ENSG00000184557; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000159620; -.
DR HOGENOM; CLU_079452_3_0_1; -.
DR InParanoid; O14543; -.
DR OMA; KLVHYYM; -.
DR OrthoDB; 1135696at2759; -.
DR PhylomeDB; O14543; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; O14543; -.
DR Reactome; R-HSA-1059683; Interleukin-6 signaling.
DR Reactome; R-HSA-2586552; Signaling by Leptin.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-877312; Regulation of IFNG signaling.
DR Reactome; R-HSA-8849474; PTK6 Activates STAT3.
DR Reactome; R-HSA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; O14543; -.
DR SIGNOR; O14543; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9021; 124 hits in 1127 CRISPR screens.
DR ChiTaRS; SOCS3; human.
DR GeneWiki; SOCS3; -.
DR GenomeRNAi; 9021; -.
DR Pharos; O14543; Tbio.
DR PRO; PR:O14543; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O14543; protein.
DR Bgee; ENSG00000184557; Expressed in mucosa of stomach and 182 other tissues.
DR ExpressionAtlas; O14543; baseline and differential.
DR Genevisible; O14543; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0035198; F:miRNA binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0097398; P:cellular response to interleukin-17; IEA:Ensembl.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IMP:BHF-UCL.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:BHF-UCL.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0060674; P:placenta blood vessel development; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR CDD; cd10384; SH2_SOCS3; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028414; SOCS3.
DR InterPro; IPR035863; SOCS3_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF11; PTHR10155:SF11; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Growth regulation; Pharmaceutical; Phosphoprotein; Reference proteome;
KW SH2 domain; Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..225
FT /note="Suppressor of cytokine signaling 3"
FT /id="PRO_0000181243"
FT DOMAIN 46..142
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 177..224
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 22..33
FT /note="Kinase inhibitory region (KIR)"
FT REGION 34..45
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 131..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..146
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 125
FT /note="H -> Y (in dbSNP:rs1061489)"
FT /evidence="ECO:0000269|PubMed:9266833"
FT /id="VAR_030033"
FT MUTAGEN 22
FT /note="L->A,F: Little effect on EPO-induced STAT5 signaling
FT suppression."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 22
FT /note="L->D: Complete loss of EPO-induced STAT5 signaling
FT suppression. No suppression of JAK2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 25
FT /note="F->A: Complete loss of EPO-induced STAT5 signaling
FT suppression. Abolishes binding to JH1."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 30
FT /note="E->R: Partial loss of EPO-induced STAT5 signaling
FT suppression. No effect on LIF-induced signaling
FT suppression. Abolishes binding to JH1. Inhibits JAK2
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 31
FT /note="Y->A: Complete loss of EPO-induced STAT5 signaling
FT suppression. No effect on LIF-induced STAT3 signaling.
FT Abolishes binding to JH1."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 31
FT /note="Y->F: Little effect on EPO-induced signaling
FT suppression."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 34
FT /note="V->E: Complete loss of EPO/LIF-induced signaling
FT suppression."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 41
FT /note="L->R: Complete loss of EPO/LIF-induced signaling
FT inhibition. Abolishes binding to JH1."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 45
FT /note="G->A: Little effect on EPO/LIF signaling."
FT /evidence="ECO:0000269|PubMed:10421843"
FT MUTAGEN 53
FT /note="G->V: No effect on binding to Y429/Y431
FT phosphorylated EPOR."
FT /evidence="ECO:0000269|PubMed:12027890"
FT MUTAGEN 58
FT /note="L->A: Impaired binding to Y429/Y431 phosphorylated
FT EPOR."
FT /evidence="ECO:0000269|PubMed:12027890"
FT MUTAGEN 71
FT /note="R->E: Complete loss of EPO/LIF-induced signaling
FT suppression. No inhibition of JAK2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:10421843,
FT ECO:0000269|PubMed:14559241"
FT MUTAGEN 71
FT /note="R->K: No effect on EPO/LIF-induced signaling
FT suppression. Partial suppression of JAK2 phosphorylation.
FT No effect on binding to JH1. Loss of binding to IL12RB2."
FT /evidence="ECO:0000269|PubMed:10421843,
FT ECO:0000269|PubMed:14559241"
FT MUTAGEN 93
FT /note="L->A: Impaired binding to Y429/Y431 phosphorylated
FT EPOR."
FT /evidence="ECO:0000269|PubMed:12027890"
FT MUTAGEN 94
FT /note="R->E: Greatly impaired binding to Y429/Y431
FT phosphorylated EPOR."
FT /evidence="ECO:0000269|PubMed:12027890"
FT CONFLICT 81
FT /note="T -> A (in Ref. 1; BAA22430)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 225 AA; 24770 MW; 08581DC411EFFF19 CRC64;
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL
SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV
LKLVHHYMPP PGAPSFPSPP TEPSSEVPEQ PSAQPLPGSP PRRAYYIYSG GEKIPLVLSR
PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL
