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Suppressor of cytokine signaling 1 (SOCS-1) (JAK-binding protein) (JAB) (STAT-induced STAT inhibitor 1) (SSI-1) (Tec-interacting protein 3) (TIP-3)

 SOCS1_HUMAN             Reviewed;         211 AA.
O15524; O15097; Q9NSA7;
16-APR-2002, integrated into UniProtKB/Swiss-Prot.
01-JAN-1998, sequence version 1.
25-OCT-2017, entry version 151.
RecName: Full=Suppressor of cytokine signaling 1;
Short=SOCS-1;
AltName: Full=JAK-binding protein;
Short=JAB;
AltName: Full=STAT-induced STAT inhibitor 1;
Short=SSI-1;
AltName: Full=Tec-interacting protein 3;
Short=TIP-3;
Name=SOCS1; Synonyms=SSI1, TIP3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=T-cell lymphoma;
PubMed=9266833; DOI=10.1006/bbrc.1997.7080;
Minamoto S., Ikegame K., Ueno K., Narazaki M., Naka T., Yamamoto H.,
Matsumoto T., Saito H., Hosoe S., Kishimoto T.;
"Cloning and functional analysis of new members of STAT induced STAT
inhibitor (SSI) family: SSI-2 and SSI-3.";
Biochem. Biophys. Res. Commun. 237:79-83(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Myeloid leukemia cell;
PubMed=9341160; DOI=10.1074/jbc.272.43.27178;
Ohya K., Kajigaya S., Yamashita Y., Miyazato A., Hatake K., Miura Y.,
Ikeda U., Shimada K., Ozawa K., Mano H.;
"SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine
kinase.";
J. Biol. Chem. 272:27178-27182(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=9202125; DOI=10.1038/43206;
Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R.,
Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A.,
Hilton D.J.;
"A family of cytokine-inducible inhibitors of signaling.";
Nature 387:917-921(1997).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=10512686; DOI=10.1006/geno.1999.5937;
Yandava C.N., Pillari A., Drazen J.M.;
"Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to
chromosomes 16p13 and 12q, respectively.";
Genomics 61:108-111(1999).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Schlueter G.;
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 15-211.
TISSUE=B-cell;
PubMed=9202126; DOI=10.1038/43213;
Endo T.A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H.,
Mitsui K., Matsumoto A., Tanimura S., Ohtsubo M., Misawa H.,
Miyazaki T., Leonor N., Taniguchi T., Fujita T., Kanakura Y.,
Komiya S., Yoshimura A.;
"A new protein containing an SH2 domain that inhibits JAK kinases.";
Nature 387:921-924(1997).
[7]
INTERACTION WITH IGF1R.
PubMed=9727029; DOI=10.1074/jbc.273.37.24095;
Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.;
"Interaction of human suppressor of cytokine signaling (SOCS)-2 with
the insulin-like growth factor-I receptor.";
J. Biol. Chem. 273:24095-24101(1998).
[8]
FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL2.
PubMed=11278610; DOI=10.1074/jbc.M010074200;
Kamizono S., Hanada T., Yasukawa H., Minoguchi S., Kato R.,
Minoguchi M., Hattori K., Hatakeyama S., Yada M., Morita S.,
Kitamura T., Kato H., Nakayama K.I., Yoshimura A.;
"The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of
TEL-JAK2.";
J. Biol. Chem. 276:12530-12538(2001).
[9]
FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.
PubMed=11313480; DOI=10.1128/MCB.21.10.3547-3557.2001;
Frantsve J., Schwaller J., Sternberg D.W., Kutok J., Gilliland D.G.;
"Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic
cells through inhibition of JAK2 kinase activity and induction of
proteasome-mediated degradation.";
Mol. Cell. Biol. 21:3547-3557(2001).
[10]
REVIEW.
PubMed=11553846; DOI=10.1634/stemcells.19-5-378;
Krebs D.L., Hilton D.J.;
"SOCS proteins: negative regulators of cytokine signaling.";
Stem Cells 19:378-387(2001).
[11]
INTERACTION WITH AXL.
PubMed=12470648; DOI=10.1016/S0006-291X(02)02718-3;
Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.;
"Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1
domain-containing protein with homology to tensin.";
Biochem. Biophys. Res. Commun. 299:793-800(2002).
[12]
REVIEW.
PubMed=11835308; DOI=10.1002/jnr.10145;
Wang J., Campbell I.L.;
"Cytokine signaling in the brain: putting a SOCS in it?";
J. Neurosci. Res. 67:423-427(2002).
[13]
INTERACTION WITH FGFR3, AND SUBCELLULAR LOCATION.
PubMed=16410555; DOI=10.1242/jcs.02740;
Ben-Zvi T., Yayon A., Gertler A., Monsonego-Ornan E.;
"Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with
and modulate fibroblast growth factor receptor signaling.";
J. Cell Sci. 119:380-387(2006).
-!- FUNCTION: SOCS family proteins form part of a classical negative
feedback system that regulates cytokine signal transduction. SOCS1
is involved in negative regulation of cytokines that signal
through the JAK/STAT3 pathway. Through binding to JAKs, inhibits
their kinase activity. In vitro, also suppresses Tec protein-
tyrosine activity. Appears to be a major regulator of signaling by
interleukin 6 (IL6) and leukemia inhibitory factor (LIF).
Regulates interferon-gamma mediated sensory neuron survival (By
similarity). Probable substrate recognition component of an ECS
(Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex
which mediates the ubiquitination and subsequent proteasomal
degradation of target proteins. Seems to recognize JAK2. SOCS1
appears to be a negative regulator in IGF1R signaling pathway.
{ECO:0000250, ECO:0000269|PubMed:11278610,
ECO:0000269|PubMed:11313480}.
-!- PATHWAY: Protein modification; protein ubiquitination.
-!- SUBUNIT: Interacts with multiple activated signaling proteins of
the tyrosine kinase signaling pathway including JAK family
kinases, TEC, KIT, GRB2 and VAV. Binding to JAKs is mediated
through the KIR and SH2 domains to a phosphorylated tyrosine
residue within the JAK JH1 domain. Binds the SH3 domain of GRB2
via diproline determinants in the N-terminus, and the N-terminal
regulatory domain of VAV (By similarity). Interacts with the
Elongin BC complex (ELOB and ELOC). Component of an ECS CBC(SOCS1)
E3 ubiquitin-protein ligase complex which contains Elongin BC,
CUL5, RBX1 and SOCS1 (By similarity). Interacts (via SH2 domain
and SOCS box) with TRIM8 (By similarity). Interacts with AXL, CUL2
and FGFR3. Interacts with INSR (By similarity). {ECO:0000250}.
-!- INTERACTION:
Q8N668:COMMD1; NbExp=3; IntAct=EBI-968198, EBI-1550112;
Q15369:ELOC; NbExp=2; IntAct=EBI-968198, EBI-301231;
P04626:ERBB2; NbExp=2; IntAct=EBI-968198, EBI-641062;
Q77YG1:gag (xeno); NbExp=5; IntAct=EBI-968198, EBI-15678227;
Q04206:RELA; NbExp=2; IntAct=EBI-968198, EBI-73886;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16410555}.
Cytoplasmic vesicle {ECO:0000269|PubMed:16410555}. Note=Detected
in perinuclear cytoplasmic vesicles upon interaction with FGFR3.
-!- TISSUE SPECIFICITY: Expressed in all tissues with high expression
in spleen, small intestine and peripheral blood leukocytes.
-!- INDUCTION: By a subset of cytokines including those belonging to
the interferon, interleukin and colony-stimulating factor
families.
-!- DOMAIN: The ESS and SH2 domains are required for JAK
phosphotyrosine binding. Further interaction with the KIR domain
is necessary for signal and kinase inhibition.
-!- DOMAIN: The SOCS box domain mediates the interaction with the
Elongin BC complex, an adapter module in different E3 ubiquitin
ligase complexes. The Elongin BC complex binding domain is also
known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and
is part of the SOCS box (By similarity). {ECO:0000250}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/SOCS1ID42350ch16p13.html";
-----------------------------------------------------------------------
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EMBL; AB005043; BAA22431.1; -; mRNA.
EMBL; AB000734; BAA23521.1; -; mRNA.
EMBL; U88326; AAB62401.1; -; mRNA.
EMBL; AF132440; AAD27709.1; -; Genomic_DNA.
EMBL; Z46940; CAB92528.1; -; Genomic_DNA.
EMBL; AB000676; BAA21537.1; -; mRNA.
CCDS; CCDS10546.1; -.
RefSeq; NP_003736.1; NM_003745.1.
UniGene; Hs.50640; -.
ProteinModelPortal; O15524; -.
SMR; O15524; -.
BioGrid; 114203; 57.
DIP; DIP-29662N; -.
IntAct; O15524; 15.
MINT; MINT-196452; -.
STRING; 9606.ENSP00000329418; -.
iPTMnet; O15524; -.
PhosphoSitePlus; O15524; -.
BioMuta; SOCS1; -.
EPD; O15524; -.
PaxDb; O15524; -.
PeptideAtlas; O15524; -.
PRIDE; O15524; -.
DNASU; 8651; -.
Ensembl; ENST00000332029; ENSP00000329418; ENSG00000185338.
GeneID; 8651; -.
KEGG; hsa:8651; -.
CTD; 8651; -.
DisGeNET; 8651; -.
EuPathDB; HostDB:ENSG00000185338.4; -.
GeneCards; SOCS1; -.
HGNC; HGNC:19383; SOCS1.
HPA; CAB010355; -.
HPA; HPA074108; -.
MIM; 603597; gene.
neXtProt; NX_O15524; -.
OpenTargets; ENSG00000185338; -.
PharmGKB; PA134863068; -.
eggNOG; KOG4566; Eukaryota.
eggNOG; ENOG4111V4J; LUCA.
GeneTree; ENSGT00760000119136; -.
HOGENOM; HOG000236320; -.
HOVERGEN; HBG002457; -.
InParanoid; O15524; -.
KO; K04694; -.
OMA; CGFYWGP; -.
OrthoDB; EOG091G0TJW; -.
PhylomeDB; O15524; -.
TreeFam; TF321368; -.
Reactome; R-HSA-1433559; Regulation of KIT signaling.
Reactome; R-HSA-166058; MyD88:Mal cascade initiated on plasma membrane.
Reactome; R-HSA-6785807; Interleukin-4 and 13 signaling.
Reactome; R-HSA-877300; Interferon gamma signaling.
Reactome; R-HSA-877312; Regulation of IFNG signaling.
Reactome; R-HSA-909733; Interferon alpha/beta signaling.
Reactome; R-HSA-912694; Regulation of IFNA signaling.
Reactome; R-HSA-982772; Growth hormone receptor signaling.
Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
SignaLink; O15524; -.
SIGNOR; O15524; -.
UniPathway; UPA00143; -.
GeneWiki; Suppressor_of_cytokine_signaling_1; -.
GenomeRNAi; 8651; -.
PRO; PR:O15524; -.
Proteomes; UP000005640; Chromosome 16.
Bgee; ENSG00000185338; -.
CleanEx; HS_SOCS1; -.
ExpressionAtlas; O15524; baseline and differential.
Genevisible; O15524; HS.
GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
GO; GO:0019210; F:kinase inhibitor activity; ISS:UniProtKB.
GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc.
GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
GO; GO:0007259; P:JAK-STAT cascade; TAS:ProtInc.
GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
GO; GO:0046426; P:negative regulation of JAK-STAT cascade; IMP:BHF-UCL.
GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IMP:BHF-UCL.
GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:BHF-UCL.
GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
GO; GO:0010533; P:regulation of activation of Janus kinase activity; IEA:Ensembl.
GO; GO:0050707; P:regulation of cytokine secretion; IEA:Ensembl.
GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome.
GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
CDD; cd10382; SH2_SOCS1; 1.
Gene3D; 3.30.505.10; -; 1.
InterPro; IPR000980; SH2.
InterPro; IPR036860; SH2_dom_sf.
InterPro; IPR028411; SOCS1.
InterPro; IPR035861; SOCS1_SH2.
InterPro; IPR001496; SOCS_box.
InterPro; IPR036036; SOCS_box_dom_like.
PANTHER; PTHR44621; PTHR44621; 1.
Pfam; PF00017; SH2; 1.
Pfam; PF07525; SOCS_box; 1.
SMART; SM00252; SH2; 1.
SMART; SM00253; SOCS; 1.
SMART; SM00969; SOCS_box; 1.
SUPFAM; SSF158235; SSF158235; 1.
SUPFAM; SSF55550; SSF55550; 1.
PROSITE; PS50001; SH2; 1.
PROSITE; PS50225; SOCS; 1.
1: Evidence at protein level;
Complete proteome; Cytoplasmic vesicle; Growth regulation; Nucleus;
Polymorphism; Reference proteome; SH2 domain;
Signal transduction inhibitor; Ubl conjugation pathway.
CHAIN 1 211 Suppressor of cytokine signaling 1.
/FTId=PRO_0000181235.
DOMAIN 79 174 SH2. {ECO:0000255|PROSITE-
ProRule:PRU00191}.
DOMAIN 161 210 SOCS box. {ECO:0000255|PROSITE-
ProRule:PRU00194}.
REGION 55 66 Kinase inhibitory region (KIR).
REGION 67 78 Extended SH2 subdomain (ESS).
REGION 173 182 Interaction with Elongin BC complex.
{ECO:0000250}.
COMPBIAS 26 32 Poly-Ser.
VARIANT 210 210 Q -> H (in dbSNP:rs11549428).
/FTId=VAR_061808.
CONFLICT 9 9 A -> G (in Ref. 5; CAB92528).
{ECO:0000305}.
CONFLICT 15 16 TA -> CP (in Ref. 6; BAA21537).
{ECO:0000305}.
CONFLICT 35 35 A -> G (in Ref. 5; CAB92528).
{ECO:0000305}.
CONFLICT 178 178 C -> F (in Ref. 5; CAB92528).
{ECO:0000305}.
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


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