SOCS-1 protein structure and SOCS-1 mutations. (A) Structure of SOCS-1 protein. The N-terminal domain of SOCS-1 contains a proline-rich region (P), a kinase inhibitory region (KIR) including aa 55 to 66, and an extended SH2 subdomain (ESS) (aa 67 to 78). KIR, ESS, and SH2 domains are required for JAK inactivation. The SOCS box (aa 161 to 210) contains a 10 aa consensus sequence for interaction with elongin BC complex. (B) SOCS-1 mutations in PMBL. The coding sequence of the SOCS-1 gene was amplified by PCR using DNA from PMBLs as template and subjected to sequencing. The protein sequences related from the DNA sequences are schematically shown. The positions of mutation in SOCS-1 DNA and its consequences on protein sequence are indicated. del and indicate deletion; ins and □, insertion; dotted line, nonsense sequence; nt, position on cDNA sequence; aa, position on corresponding protein sequence; and fs, frame shift.