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)

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
  • interferons
  • interleukins
  • colony-stimulating factors

Pathology

• SOCS1 insufficiency is an inborn error of immunity affecting inhibition of cytokine & growth factor signalling

Pharmacology

• Janus kinase inhibitors may be useful in treatment

More general terms

• suppressor of cytokine signaling family (SOCS family protein)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8651
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8651
• OMIM: https://mirror.omim.org/entry/603597
• UniProt: http://www.uniprot.org/uniprot/O15524.html