cytokine-inducible SH2-containing protein; CIS; CIS-1; protein G18; suppressor of cytokine signaling; SOCS (CISH, G18)

Function

• role in negative regulation of cytokines that signal through the JAK-STAT5 pathway including:
  • erythropoietin
  • prolactin
  • IL3 receptor
• inhibits STAT5 trans-activation by suppressing its Tyr phosphorylation
• may be a substrate-recognition component of a SCF-like ECS complex (elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination & subsequent proteasomal degradation of target proteins (putative)
• protein modification; protein ubiquitination
• association with EPOR may target the protein for proteolysis by the ubiquitin-dependent proteasome pathway
• mainly monubiquitinated (37 kD form) but may also exist in a polyubiquitinated form (45 kD)
• stably associated with the Tyr-phosphorylated IL3 receptor beta chain (KH97) & Tyr-phosphorylated EPO receptor (EPOR)

Structure

• contains 1 SH2 domain
• contains 1 SOCS box domain

Alternative splicing

named isoforms=3

Expression

• expressed in various epithelial tissues
• abundantly expressed in liver & kidney,
• lesser expression in lung
• tissue distribution of isoforms 1 & 1B distinct
• induced by a subset of cytokines including erythropoietin

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=1154
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1154
• OMIM: https://mirror.omim.org/entry/602441
• UniProt: http://www.uniprot.org/uniprot/Q9NSE2.html