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, SSI1, TIP3)
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Function
- role in negative regulation of cytokines that signal through the JAK/STAT3 pathway
- binding to JAKs inhibits their kinase activity
- suppresses Tec tyrosine kinase activity in vitro
- role in regulation of signaling by interleukin 6 (IL6) & leukemia inhibitory factor (LIF)
- regulates interferon-gamma mediated sensory neuron survival
- probable substrate recognition component of an ECS complex (elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination & subsequent proteasomal degradation of target proteins
- seems to recognize JAK2 protein ubiquitination
- interacts with multiple activated signaling proteins of the tyrosine kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2 & VAV
- binding to JAKs is mediated through the KIR & SH2 domains to a phosphorylated Tyr within the JAK JH1 domain
- binds the SH3 domain of GRB2 via diproline determinants in the N-terminus
- binds the N-terminal regulatory domain of VAV (putative)
- interacts with the elongin BC complex (TCEB1 & TCEB2)
- component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains elongin BC, CUL5, RBX1 & SOCS1 (putative)
- interacts (via SH2 domain & SOCS box) with TRIM8 (putative)
- interacts with CUL2
Structure
- the ESS & SH2 domains are required for JAK phospho-Tyr binding
- further interaction with the KIR domain is necessary for signal & kinase inhibition
- 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] & is part of the SOCS box
- contains 1 SH2 domain
- contains 1 SOCS box domain
Expression
- expressed in all tissues
- high expression in spleen, small intestine & peripheral blood leukocytes
- induced by a subset of cytokines including
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/O15524.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/SOCS1ID42350ch16p13.html
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8651