Recombinant Human Suppressor of cytokine signaling 1 (SOCS1)

Function

Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:32499645, PubMed:33087723). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec protein-tyrosine activity (PubMed:9341160). Regulates IFN-gamma (IFNG)-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 (PubMed:11278610, PubMed:11313480)

Subcellular Location

Nucleus; Cytoplasmic vesicle

Disease Association

Autoinflammatory syndrome, familial, with or without immunodeficiency (AISIMD) : An autosomal dominant, autoinflammatory disorder with incomplete penetrance characterized by autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and lymphadenopathy. Additional variable features may include autoimmune thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of systemic lupus erythematosus. Immunodeficiency is present in some patients. Disease onset is usually in the first decades of life, although later onset has been reported. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes

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). Interacts with TRIM8 (PubMed:12163497). Interacts with DCUN1D1 (PubMed:23401859). Interacts with IFNGR1 (By similarity)

Pathway

Protein modification; protein ubiquitination

• Minamoto S. et al. Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. — Biochem. Biophys. Res. Commun. (1997)
• Ohya K. et al. SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. — J. Biol. Chem. (1997)
• Starr R. et al. A family of cytokine-inducible inhibitors of signaling. — Nature (1997)
• Yandava C.N. et al. Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively. — Genomics (1999)
• Schlueter G. et al. PubMed: CI-6DUJ5KTRPEAD3 (NOV-)
• Endo T.A. et al. A new protein containing an SH2 domain that inhibits JAK kinases. — Nature (1997)
• Dey B.R. et al. Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. — J. Biol. Chem. (1998)
• Kamizono S. et al. The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2. — J. Biol. Chem. (2001)