10         20         30         40         50         60
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MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL - 60
SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV - 120
LKLVHHYMPP PGTPSFSLPP TEPSSEVPEQ PPAQALPGST PKRAYYIYSG GEKIPLVLSR - 180
PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL

Cytokine signalling acts through membrane-bound, multisubunit receptor complexes that are phosphorylated by activated Janus kinases (JAKs), leading to subsequent activation and phosphorylation of members of the signal transduction and activators of transcription (STAT) family. The duration of the signalling response is moderated by a classic negative feedback control mechanism involving members of the suppressors of cytokine signalling (SOCS) family (SOCS-17) and cytokine-inducible SH2-containing protein (CIS). The SOCS family members share similar architecture, including an N-terminal region of varying size, a central SH2 domain and a C-terminal SOCS box. The SOCS SH2 domains are responsible for binding to phosphorylated tyrosine residues on intracellular domains of the cytokine receptors and/or the JAKs themselves. They act therefore by directly blocking signal transduction or by interfering with STAT access to the phosphorylated receptor subunits. SOCS-3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity, and is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK JH1 domain. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and EPO receptor. Binds specific activated tyrosine residues of the leptin, EPOR and gp130 receptors. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Probable 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. Seems to recognize IL6ST.