PROSITE documentation PDOC50225
SOCS box domain profile


The SOCS box domain was first identified in SH2-domain-containing proteins of the suppressor of cytokines signaling (SOCS) family [1] but was latter also found in:

  • The WSB (WD-40-repeat-containing proteins with a SOCS box) family,
  • The SSB (SPRY domain-containing proteins with a SOCS box) family,
  • The ASB (Ankyrin-repeat-containing proteins with a SOCS box) family,
  • The RAR (GTPase domain and SOCS box-containing proteins) family [2].

The SOCS box found in these proteins is a C-terminal domain of about 50 amino acids composed of two blocks of well-conserved residues separated by between 2 to 10 nonconserved residues [2]. The C-terminal conserved region is a Leu/Pro-rich sequence of unknown function, whereas the N-terminal conserved region is called a 'BC box' [3] and binds to the elongin BC complex [3,4]. It has been proposed that this association could couple bound proteins to the ubiquitination or proteasomal compartments [4].

Some proteins known to contain a SOCS box domain are listed below:

  • Mammalian cytokine-inducible SH2-containing (CIS) protein. This protein belongs to the SOCS family and inhibits erythropoietin and interleukin 3 receptor signaling by competing with signaling molecules such as STATs for binding to phosphorylated receptor cytoplasmic domains.
  • Mammalian SOCS-1 protein. This protein is a negative regulator of interleukin 6 signaling. It acts by binding to and inhibiting the catalytic activity of members of the JAK family of cytoplasmic kinases.
  • Vertebrate WSB-1.

The profile we developed covers the entire SOCS box domain.

Last update:

May 2002 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

SOCS, PS50225; SOCS box domain profile  (MATRIX)


1AuthorsStarr R. Willson T.A. Viney E.M. Murray L.J.L. Rayner J.R. Jenkins B.J. Gonda T.J. Alexander W.S. Metcalf D. Nicola N.A. Hilton D.J.
TitleA family of cytokine-inducible inhibitors of signalling.
SourceNature 387:917-921(1997).
PubMed ID9202125

2AuthorsHilton D.J. Richardson R.T. Alexander W.S. Viney E.M. Willson T.A. Sprigg N.S. Starr R. Nicholson S.E. Metcalf D. Nicola N.A.
TitleTwenty proteins containing a C-terminal SOCS box form five structural
SourceProc. Natl. Acad. Sci. U.S.A. 95:114-119(1998).
PubMed ID9419338

3AuthorsKamura T. Sato S. Haque D. Liu L. Kaelin W.G. Jr. Conaway R.C. Conaway J.W.
TitleThe Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families.
SourceGenes Dev. 12:3872-3881(1998).
PubMed ID9869640

4AuthorsZhang J.G. Farley A. Nicholson S.E. Willson T.A. Zugaro L.M. Simpson R.J. Moritz R.L. Cary D. Richardson R. Hausmann G. Kile B.J. Kent S.B.H. Alexander W.S. Metcalf D. Hilton D.J. Nicola N.A. Baca M.
TitleThe conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.
SourceProc. Natl. Acad. Sci. U.S.A. 96:2071-2076(1999).
PubMed ID10051596

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