Twenty proteins containing a C-terminal SOCS box form five structural classes

Twenty proteins containing a C-terminal SOCS box form five structural classes

The Walter and Eliza Hall Institute for Medical Research and The Cooperative Research Center for Cellular Growth Factors, Parkville, Victoria 3050, Australia

Contributed by Donald Metcalf

Abstract

The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various means, to negatively regulate cytokine signal transduction. Structurally, the SOCS proteins are composed of an N-terminal region of variable length and amino acid composition, a central SH2 domain, and a previously unrecognized C-terminal motif that we have called the SOCS box. By using the SOCS box amino acid sequence consensus, we have searched DNA databases and have identified a further 16 proteins that contain this motif. These proteins fall into five classes based on the protein motifs found N-terminal of the SOCS box. In addition to four new SOCS proteins (SOCS-4 to SOCS-7) containing an SH2 domain and a SOCS box, we describe three new families of proteins that contain either WD-40 repeats (WSB-1 and -2), SPRY domains (SSB-1 to -3) or ankyrin repeats (ASB-1 to -3) N-terminal of the SOCS box. In addition, we show that a class of small GTPases also contains a SOCS box. The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. The function of the WSB, SSB, and ASB protein families remains to be determined.

Footnotes

↵ * To whom reprint requests should be addressed at: The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, 3050, Australia. e-mail; hilton{at}wehi.edu.au.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF033186–8).
ABBREVIATIONS:

ASB,

ankyrin-repeat-containing protein with a SOCS box;

CIS,

cytokine-inducible SH2-containing protein;

EST,

expressed sequence tag;

JAK,

Janus kinase;

STAT,

signal transducer and activator of transcription;

SOCS,

suppressor of cytokine signaling;

WSB,

WD-40-repeat-containing protein with a SOCS box;

SSB,

SPRY domain-containing protein with a SOCS box