The SOCS (suppressor of cytokine signaling) gene family consists of a group of proteins that negatively regulate cytokine signal transduction. The SOCS family proteins contain a central SH2 domain and a carboxy-terminal region termed the “SOCS box.” The SOCS-1 (also called SSI-1 and JAB), SOCS-2 (also called SSI-2 and CIS2) and SOC-3 (also called SSI-3 and CIS3) genes are known to be upregulated by IL-6 and other cytokines. SOCS-4, SOCS-5, SOCS-6 and SOCS-7 were identified by their sequence homology with the SOCS box. CIS (for cytokine-inducible SH2-containing protein) is also a member of the SOCS family.