SOCS1: 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. 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. 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. 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. Interacts (via SH2 domain and SOCS box) with TRIM8. Interacts with AXL, CUL2 and FGFR3. Interacts with INSR. By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families. Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.
Protein type: Inhibitor
Chromosomal Location of Human Ortholog: 16p13.13
Cellular Component: cytoplasm; cytoplasmic membrane-bound vesicle; cytosol; nucleus
Molecular Function: insulin-like growth factor receptor binding; kinase inhibitor activity; protein binding; protein kinase binding; protein kinase inhibitor activity
Biological Process: cytokine and chemokine mediated signaling pathway; fat cell differentiation; JAK-STAT cascade; negative regulation of insulin receptor signaling pathway; negative regulation of JAK-STAT cascade; negative regulation of tyrosine phosphorylation of Stat3 protein; organ regeneration; protein ubiquitination; regulation of cytokine secretion; regulation of growth; regulation of protein amino acid phosphorylation; regulation of tyrosine phosphorylation of Stat1 protein; response to drug; response to estradiol stimulus; response to lipopolysaccharide; response to progesterone stimulus
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