CISH

The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Full Name

Cytokine Inducible SH2 Containing Protein

Function

SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).

Biological Process

Interleukin-7-mediated signaling pathway Source: Reactome
Intracellular signal transduction Source: UniProtKB
Negative regulation of signal transduction Source: UniProtKB-KW
Phosphatidylinositol phosphorylation Source: GO_Central
Post-translational protein modification Source: Reactome
Protein kinase C-activating G protein-coupled receptor signaling pathway Source: Ensembl
Protein ubiquitination Source: UniProtKB-UniPathway
Regulation of cell growth Source: UniProtKB

Cellular Location

Cytosol; Plasma membrane; Phosphatidylinositol 3-kinase complex

PTM

Association with EPOR may target the protein for proteolysis by the ubiquitin-dependent proteasome pathway. CIS is mainly monubiquitinated (37 kDa form) but may also exist in a polyubiquitinated form (45 kDa).