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MGP Database

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MGP003632

UniProt Annotations

Entry Information

Gene Name	suppressor of cytokine signaling 1
Protein Entry	SOCS1_HUMAN
UniProt ID	O15524
Species	Human

Comments

Comment type	Description
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}.
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}.
Induction	By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families.
Interaction	Q8N668:COMMD1; NbExp=3; IntAct=EBI-968198, EBI-1550112; P04626:ERBB2; NbExp=2; IntAct=EBI-968198, EBI-641062; Q04206:RELA; NbExp=2; IntAct=EBI-968198, EBI-73886; Q15369:TCEB1; NbExp=2; IntAct=EBI-968198, EBI-301231;
Pathway	Protein modification; protein ubiquitination.
Similarity	Contains 1 SH2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00191}.
Similarity	Contains 1 SOCS box domain. {ECO:0000255\|PROSITE- ProRule:PRU00194}.
Subcellular Location	Nucleus {ECO:0000269\|PubMed:16410555}. Cytoplasmic vesicle {ECO:0000269\|PubMed:16410555}. Note=Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.
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 (TCEB1 and TCEB2). 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}.
Tissue Specificity	Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SOCS1ID42350ch16p13.html";