SOCS1_HUMAN
ID SOCS1_HUMAN Reviewed; 211 AA.
AC O15524; O15097; Q9NSA7;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Suppressor of cytokine signaling 1;
DE Short=SOCS-1;
DE AltName: Full=JAK-binding protein;
DE Short=JAB;
DE AltName: Full=STAT-induced STAT inhibitor 1;
DE Short=SSI-1;
DE AltName: Full=Tec-interacting protein 3 {ECO:0000303|PubMed:9341160};
DE Short=TIP-3 {ECO:0000303|PubMed:9341160};
GN Name=SOCS1; Synonyms=SSI1, TIP3 {ECO:0000303|PubMed:9341160};
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].
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], AND FUNCTION.
RC TISSUE=Myeloid leukemia cell;
RX PubMed=9341160; DOI=10.1074/jbc.272.43.27178;
RA Ohya K., Kajigaya S., Yamashita Y., Miyazato A., Hatake K., Miura Y.,
RA Ikeda U., Shimada K., Ozawa K., Mano H.;
RT "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase.";
RL J. Biol. Chem. 272:27178-27182(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9202125; DOI=10.1038/43206;
RA Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R.,
RA Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A.,
RA Hilton D.J.;
RT "A family of cytokine-inducible inhibitors of signaling.";
RL Nature 387:917-921(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10512686; DOI=10.1006/geno.1999.5937;
RA Yandava C.N., Pillari A., Drazen J.M.;
RT "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes
RT 16p13 and 12q, respectively.";
RL Genomics 61:108-111(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Schlueter G.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-211.
RC TISSUE=B-cell;
RX PubMed=9202126; DOI=10.1038/43213;
RA Endo T.A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H., Mitsui K.,
RA Matsumoto A., Tanimura S., Ohtsubo M., Misawa H., Miyazaki T., Leonor N.,
RA Taniguchi T., Fujita T., Kanakura Y., Komiya S., Yoshimura A.;
RT "A new protein containing an SH2 domain that inhibits JAK kinases.";
RL Nature 387:921-924(1997).
RN [7]
RP INTERACTION WITH IGF1R.
RX PubMed=9727029; DOI=10.1074/jbc.273.37.24095;
RA Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.;
RT "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the
RT insulin-like growth factor-I receptor.";
RL J. Biol. Chem. 273:24095-24101(1998).
RN [8]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL2.
RX PubMed=11278610; DOI=10.1074/jbc.m010074200;
RA Kamizono S., Hanada T., Yasukawa H., Minoguchi S., Kato R., Minoguchi M.,
RA Hattori K., Hatakeyama S., Yada M., Morita S., Kitamura T., Kato H.,
RA Nakayama K.I., Yoshimura A.;
RT "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-
RT JAK2.";
RL J. Biol. Chem. 276:12530-12538(2001).
RN [9]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.
RX PubMed=11313480; DOI=10.1128/mcb.21.10.3547-3557.2001;
RA Frantsve J., Schwaller J., Sternberg D.W., Kutok J., Gilliland D.G.;
RT "Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells
RT through inhibition of JAK2 kinase activity and induction of proteasome-
RT mediated degradation.";
RL Mol. Cell. Biol. 21:3547-3557(2001).
RN [10]
RP REVIEW.
RX PubMed=11553846; DOI=10.1634/stemcells.19-5-378;
RA Krebs D.L., Hilton D.J.;
RT "SOCS proteins: negative regulators of cytokine signaling.";
RL Stem Cells 19:378-387(2001).
RN [11]
RP INTERACTION WITH AXL.
RX PubMed=12470648; DOI=10.1016/s0006-291x(02)02718-3;
RA Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.;
RT "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1
RT domain-containing protein with homology to tensin.";
RL Biochem. Biophys. Res. Commun. 299:793-800(2002).
RN [12]
RP REVIEW.
RX PubMed=11835308; DOI=10.1002/jnr.10145;
RA Wang J., Campbell I.L.;
RT "Cytokine signaling in the brain: putting a SOCS in it?";
RL J. Neurosci. Res. 67:423-427(2002).
RN [13]
RP INTERACTION WITH FGFR3, AND SUBCELLULAR LOCATION.
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 [14]
RP INTERACTION WITH TRIM8.
RX PubMed=12163497; DOI=10.1074/jbc.m205900200;
RA Toniato E., Chen X.P., Losman J., Flati V., Donahue L., Rothman P.;
RT "TRIM8/GERP RING finger protein interacts with SOCS-1.";
RL J. Biol. Chem. 277:37315-37322(2002).
RN [15]
RP INTERACTION WITH DCUN1D1.
RX PubMed=23401859; DOI=10.1128/mcb.01342-12;
RA Heir P., Sufan R.I., Greer S.N., Poon B.P., Lee J.E., Ohh M.;
RT "DCNL1 functions as a substrate sensor and activator of cullin 2-RING
RT ligase.";
RL Mol. Cell. Biol. 33:1621-1631(2013).
RN [16]
RP INVOLVEMENT IN AISIMD.
RX PubMed=32853638; DOI=10.1016/j.jaci.2020.07.033;
RA Lee P.Y., Platt C.D., Weeks S., Grace R.F., Maher G., Gauthier K.,
RA Devana S., Vitali S., Randolph A.G., McDonald D.R., Geha R.S., Chou J.;
RT "Immune dysregulation and multisystem inflammatory syndrome in children
RT (MIS-C) in individuals with haploinsufficiency of SOCS1.";
RL J. Allergy Clin. Immunol. 146:1194-1200(2020).
RN [17]
RP INVOLVEMENT IN AISIMD, VARIANT AISIMD 64-TYR--ILE-211 DEL, FUNCTION, AND
RP CHARACTERIZATION OF VARIANT AISIMD 64-TYR--ILE-211 DEL.
RX PubMed=32499645; DOI=10.1038/s41586-020-2265-1;
RG Primary Immunodeficiency Consortium for the NIHR Bioresource;
RA Thaventhiran J.E.D., Lango Allen H., Burren O.S., Rae W., Greene D.,
RA Staples E., Zhang Z., Farmery J.H.R., Simeoni I., Rivers E., Maimaris J.,
RA Penkett C.J., Stephens J., Deevi S.V.V., Sanchis-Juan A., Gleadall N.S.,
RA Thomas M.J., Sargur R.B., Gordins P., Baxendale H.E., Brown M.,
RA Tuijnenburg P., Worth A., Hanson S., Linger R.J., Buckland M.S.,
RA Rayner-Matthews P.J., Gilmour K.C., Samarghitean C., Seneviratne S.L.,
RA Sansom D.M., Lynch A.G., Megy K., Ellinghaus E., Ellinghaus D.,
RA Jorgensen S.F., Karlsen T.H., Stirrups K.E., Cutler A.J., Kumararatne D.S.,
RA Chandra A., Edgar J.D.M., Herwadkar A., Cooper N., Grigoriadou S.,
RA Huissoon A.P., Goddard S., Jolles S., Schuetz C., Boschann F., Lyons P.A.,
RA Hurles M.E., Savic S., Burns S.O., Kuijpers T.W., Turro E., Ouwehand W.H.,
RA Thrasher A.J., Smith K.G.C.;
RT "Whole-genome sequencing of a sporadic primary immunodeficiency cohort.";
RL Nature 583:90-95(2020).
RN [18]
RP INVOLVEMENT IN AISIMD, VARIANTS AISIMD TRP-22; ARG-123 AND HIS-154,
RP CHARACTERIZATION OF VARIANTS AISIMD TRP-22; ARG-123 AND HIS-154, AND
RP FUNCTION.
RX PubMed=33087723; DOI=10.1038/s41467-020-18925-4;
RA Hadjadj J., Castro C.N., Tusseau M., Stolzenberg M.C., Mazerolles F.,
RA Aladjidi N., Armstrong M., Ashrafian H., Cutcutache I.,
RA Ebetsberger-Dachs G., Elliott K.S., Durieu I., Fabien N., Fusaro M.,
RA Heeg M., Schmitt Y., Bras M., Knight J.C., Lega J.C., Lesca G.,
RA Mathieu A.L., Moreews M., Moreira B., Nosbaum A., Page M., Picard C.,
RA Ronan Leahy T., Rouvet I., Ryan E., Sanlaville D., Schwarz K., Skelton A.,
RA Viallard J.F., Viel S., Villard M., Callebaut I., Picard C., Walzer T.,
RA Ehl S., Fischer A., Neven B., Belot A., Rieux-Laucat F.;
RT "Early-onset autoimmunity associated with SOCS1 haploinsufficiency.";
RL Nat. Commun. 11:5341-5341(2020).
CC -!- FUNCTION: Essential negative regulator of type I and type II interferon
CC (IFN) signaling, as well as that of other cytokines, including IL2,
CC IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:32499645,
CC PubMed:33087723). Downregulates cytokine signaling by inhibiting the
CC JAK/STAT signaling pathway. Acts by binding to JAK proteins and to
CC IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec
CC protein-tyrosine activity (PubMed:9341160). Regulates IFN-gamma (IFNG)-
CC mediated sensory neuron survival (By similarity). Probable substrate
CC recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3
CC ubiquitin ligase complex which mediates the ubiquitination and
CC subsequent proteasomal degradation of target proteins (PubMed:11278610,
CC PubMed:11313480). {ECO:0000250|UniProtKB:O35716,
CC ECO:0000269|PubMed:11278610, ECO:0000269|PubMed:11313480,
CC ECO:0000269|PubMed:32499645, ECO:0000269|PubMed:33087723,
CC ECO:0000269|PubMed:9341160}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated signaling proteins of the
CC tyrosine kinase signaling pathway including JAK family kinases, TEC,
CC KIT, GRB2 and VAV. Binding to JAKs is mediated through the KIR and SH2
CC domains to a phosphorylated tyrosine residue within the JAK JH1 domain.
CC Binds the SH3 domain of GRB2 via diproline determinants in the N-
CC terminus, and the N-terminal regulatory domain of VAV (By similarity).
CC Interacts with the Elongin BC complex (ELOB and ELOC). Component of an
CC ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains
CC Elongin BC, CUL5, RBX1 and SOCS1 (By similarity). Interacts (via SH2
CC domain and SOCS box) with TRIM8 (By similarity). Interacts with AXL,
CC CUL2 and FGFR3. Interacts with INSR (By similarity). Interacts with
CC TRIM8 (PubMed:12163497). Interacts with DCUN1D1 (PubMed:23401859).
CC Interacts with IFNGR1 (By similarity). {ECO:0000250|UniProtKB:O35716,
CC ECO:0000269|PubMed:12163497, ECO:0000269|PubMed:23401859}.
CC -!- INTERACTION:
CC O15524; Q8N668: COMMD1; NbExp=3; IntAct=EBI-968198, EBI-1550112;
CC O15524; Q15369: ELOC; NbExp=4; IntAct=EBI-968198, EBI-301231;
CC O15524; P04626: ERBB2; NbExp=2; IntAct=EBI-968198, EBI-641062;
CC O15524; Q04206: RELA; NbExp=2; IntAct=EBI-968198, EBI-73886;
CC O15524; Q99961: SH3GL1; NbExp=3; IntAct=EBI-968198, EBI-697911;
CC O15524; Q77YG1: gag; Xeno; NbExp=5; IntAct=EBI-968198, EBI-15678227;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16410555}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:16410555}. Note=Detected in
CC perinuclear cytoplasmic vesicles upon interaction with FGFR3.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues with high expression in
CC spleen, small intestine and peripheral blood leukocytes.
CC -!- INDUCTION: By a subset of cytokines including those belonging to the
CC interferon, interleukin and colony-stimulating factor families.
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. The Elongin BC complex binding domain is also known as BC-
CC box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the
CC SOCS box (By similarity). {ECO:0000250}.
CC -!- DISEASE: Autoinflammatory syndrome, familial, with or without
CC immunodeficiency (AISIMD) [MIM:619375]: An autosomal dominant,
CC autoinflammatory disorder with incomplete penetrance characterized by
CC autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and
CC lymphadenopathy. Additional variable features may include autoimmune
CC thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of
CC systemic lupus erythematosus. Immunodeficiency is present in some
CC patients. Disease onset is usually in the first decades of life,
CC although later onset has been reported. {ECO:0000269|PubMed:32499645,
CC ECO:0000269|PubMed:32853638, ECO:0000269|PubMed:33087723}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the SOCS1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SOCS1ID42350ch16p13.html";
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DR EMBL; AB005043; BAA22431.1; -; mRNA.
DR EMBL; AB000734; BAA23521.1; -; mRNA.
DR EMBL; U88326; AAB62401.1; -; mRNA.
DR EMBL; AF132440; AAD27709.1; -; Genomic_DNA.
DR EMBL; Z46940; CAB92528.1; -; Genomic_DNA.
DR EMBL; AB000676; BAA21537.1; -; mRNA.
DR CCDS; CCDS10546.1; -.
DR RefSeq; NP_003736.1; NM_003745.1.
DR AlphaFoldDB; O15524; -.
DR SMR; O15524; -.
DR BioGRID; 114203; 188.
DR DIP; DIP-29662N; -.
DR IntAct; O15524; 60.
DR MINT; O15524; -.
DR STRING; 9606.ENSP00000329418; -.
DR iPTMnet; O15524; -.
DR PhosphoSitePlus; O15524; -.
DR BioMuta; SOCS1; -.
DR MassIVE; O15524; -.
DR PaxDb; O15524; -.
DR PeptideAtlas; O15524; -.
DR PRIDE; O15524; -.
DR ProteomicsDB; 48724; -.
DR Antibodypedia; 4157; 643 antibodies from 44 providers.
DR DNASU; 8651; -.
DR Ensembl; ENST00000332029.4; ENSP00000329418.2; ENSG00000185338.7.
DR Ensembl; ENST00000644787.1; ENSP00000496577.1; ENSG00000185338.7.
DR GeneID; 8651; -.
DR KEGG; hsa:8651; -.
DR MANE-Select; ENST00000332029.4; ENSP00000329418.2; NM_003745.2; NP_003736.1.
DR CTD; 8651; -.
DR DisGeNET; 8651; -.
DR GeneCards; SOCS1; -.
DR HGNC; HGNC:19383; SOCS1.
DR HPA; ENSG00000185338; Low tissue specificity.
DR MIM; 603597; gene.
DR MIM; 619375; phenotype.
DR neXtProt; NX_O15524; -.
DR OpenTargets; ENSG00000185338; -.
DR PharmGKB; PA134863068; -.
DR VEuPathDB; HostDB:ENSG00000185338; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000161164; -.
DR HOGENOM; CLU_079452_2_1_1; -.
DR InParanoid; O15524; -.
DR OMA; LERCGFY; -.
DR OrthoDB; 1135696at2759; -.
DR PhylomeDB; O15524; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; O15524; -.
DR Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
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-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; O15524; -.
DR SIGNOR; O15524; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8651; 11 hits in 1121 CRISPR screens.
DR ChiTaRS; SOCS1; human.
DR GeneWiki; Suppressor_of_cytokine_signaling_1; -.
DR GenomeRNAi; 8651; -.
DR Pharos; O15524; Tbio.
DR PRO; PR:O15524; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O15524; protein.
DR Bgee; ENSG00000185338; Expressed in type B pancreatic cell and 134 other tissues.
DR ExpressionAtlas; O15524; baseline and differential.
DR Genevisible; O15524; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0019210; F:kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0030225; P:macrophage differentiation; IMP:BHF-UCL.
DR GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
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:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:BHF-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR GO; GO:0010533; P:regulation of activation of Janus kinase activity; IEA:Ensembl.
DR GO; GO:0001817; P:regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR CDD; cd10382; SH2_SOCS1; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028411; SOCS1.
DR InterPro; IPR035861; SOCS1_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF4; PTHR10155:SF4; 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 Cytoplasmic vesicle; Disease variant; Growth regulation; Nucleus;
KW Reference proteome; SH2 domain; Signal transduction inhibitor;
KW Ubl conjugation pathway.
FT CHAIN 1..211
FT /note="Suppressor of cytokine signaling 1"
FT /id="PRO_0000181235"
FT DOMAIN 79..174
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 161..210
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..66
FT /note="Kinase inhibitory region (KIR)"
FT REGION 67..78
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 173..182
FT /note="Interaction with Elongin BC complex"
FT /evidence="ECO:0000250"
FT COMPBIAS 21..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 22
FT /note="R -> W (in AISIMD; loss of inhibition of cytokine-
FT induced STAT phosphorylation, including IFNG-induced STAT1
FT phosphorylation, IL2-induced STAT5 phosphorylation and IL4-
FT induced STAT6 phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33087723"
FT /id="VAR_085947"
FT VARIANT 64..211
FT /note="Missing (in AISIMD; heterozygous T-cells show
FT increased levels of STAT1 phosphorylation following
FT treatment with IFNG, compared to control cells)"
FT /evidence="ECO:0000269|PubMed:32499645"
FT /id="VAR_085948"
FT VARIANT 123
FT /note="P -> R (in AISIMD; loss of inhibition of cytokine-
FT induced STAT phosphorylation, including IFNG-induced STAT1
FT phosphorylation, IL2-induced STAT5 phosphorylation and IL4-
FT induced STAT6 phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33087723"
FT /id="VAR_085949"
FT VARIANT 154
FT /note="Y -> H (in AISIMD; unknown pathological
FT significance; when transfected into HEK293T cells, shows
FT impaired suppression of IFNG-mediated gene expression
FT compared to wild-type)"
FT /evidence="ECO:0000269|PubMed:33087723"
FT /id="VAR_085950"
FT VARIANT 210
FT /note="Q -> H (in dbSNP:rs11549428)"
FT /id="VAR_061808"
FT CONFLICT 9
FT /note="A -> G (in Ref. 5; CAB92528)"
FT /evidence="ECO:0000305"
FT CONFLICT 15..16
FT /note="TA -> CP (in Ref. 6; BAA21537)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="A -> G (in Ref. 5; CAB92528)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="C -> F (in Ref. 5; CAB92528)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 211 AA; 23551 MW; 7CC983533F78B127 CRC64;
MVAHNQVAAD NAVSTAAEPR RRPEPSSSSS SSPAAPARPR PCPAVPAPAP GDTHFRTFRS
HADYRRITRA SALLDACGFY WGPLSVHGAH ERLRAEPVGT FLVRDSRQRN CFFALSVKMA
SGPTSIRVHF QAGRFHLDGS RESFDCLFEL LEHYVAAPRR MLGAPLRQRR VRPLQELCRQ
RIVATVGREN LARIPLNPVL RDYLSSFPFQ I
