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 IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors (PubMed:10821852, PubMed:12754505, PubMed:9889194). Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling (PubMed:12754505, PubMed:9889194). Suppresses fetal liver erythropoiesis (PubMed:10490101). Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells (PubMed:12847520). 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 (By similarity). Protein modification; protein ubiquitination. Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK2 JH1 domain (By similarity). Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors (PubMed:10882725). Interaction with CSNK1E stabilizes SOCS3 protein (By similarity). Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, elongin BC complex and SOCS3 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By similarity). Interacts with FGFR3 (By similarity). Interacts with INSR (PubMed:10821852). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (PubMed:15213237). Interacts with NOD2 (via CARD domain); the interaction promotes NOD2 degradation (PubMed:23019338). Low expression in lung, spleen and thymus. Expressed in Th2 but not TH1 cells. In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. In the cortex, first expressed uniformly in all cells at 14 dpc. Not expressed in the retina. Highly expressed in fetal liver progenitors at 12.5 dpc. By a subset of cytokines including EPO, leptin, LIF, IL-2, IL-3, IL-4, IGF1, growth hormone and prolactin. The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.