SOCS2
Domain
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
Function
Substrate-recognition component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex, also named CRL5 complex), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as EPOR and GHR (PubMed:11781573, PubMed:21980433, PubMed:25505247, PubMed:31182716, PubMed:34857742). Specifically recognizes and binds phosphorylated proteins via its SH2 domain, promoting their ubiquitination (PubMed:21980433, PubMed:25505247, PubMed:31182716, PubMed:34857742, PubMed:37816714). The ECS(SOCS2) complex acts as a key regulator of growth hormone receptor (GHR) levels by mediating ubiquitination and degradation of GHR, following GHR phosphorylation by JAK2 (PubMed:21980433, PubMed:25505247, PubMed:34857742). The ECS(SOCS2) also catalyzes ubiquitination and degradation of JAK2-phosphorylated EPOR (PubMed:11781573).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Ubiquitinated; mediated by AREL1 and leading to its subsequent proteasomal degradation (PubMed:31578312). Ubiquitination is dependent on its phosphorylation at Ser-52, by PKC (PubMed:31578312). Ubiquitination is stimulated by LPS (By similarity).
Phosphorylation at Ser-52 by PKC facilitates its ubiquitination and proteasomal degradation.
Tissue Specificity
High expression in heart, placenta, lung, kidney and prostate. Predominantly expressed in pulmonary epithelia cells, specifically type II pneumocytes.
Cellular localization
- Cytoplasm
Alternative names
CIS2, SSI2, STATI2, SOCS2, Suppressor of cytokine signaling 2, SOCS-2, Cytokine-inducible SH2 protein 2, STAT-induced STAT inhibitor 2, CIS-2, SSI-2