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). Protein modification; protein ubiquitination. Stably associated with the tyrosine-phosphorylated IL3 receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR). Expressed in kidney, lung and liver. Detected to a lower extent in stomach and heart. In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. By a subset of cytokines including interleukins 2, 3 and 6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO).