SOCS7
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 DAB1 and IRS1 (PubMed:16127460). Specifically recognizes and binds phosphorylated proteins via its SH2 domain, promoting their ubiquitination (By similarity). The ECS(SOCS7) complex acts as a key regulator of reelin signaling by mediating ubiquitination and degradation of phosphorylated DAB1 in the cortical plate of the developing cerebral cortex, thereby regulating neuron positioning during cortex development (By similarity). Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation (PubMed:16127460). Also inhibits prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA (PubMed:15677474).
Pathway
Protein modification; protein ubiquitination.
Tissue Specificity
Expressed in brain and leukocytes (PubMed:9344857). Also in fetal lung fibroblasts and fetal brain (PubMed:9344857).
Cellular localization
- Cytoplasm
- Nucleus
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus (PubMed:17803907). Rapidly relocalizes to the nucleus after UV irradiation (PubMed:17803907). Cytoplasmic location depends upon SEPT7 presence (PubMed:17803907).
Alternative names
NAP4, SOCS6, SOCS7, Suppressor of cytokine signaling 7, SOCS-7, Nck-associated protein 4, NAP-4