D
IPR037345

SOCS6, SOCS box domain

InterPro entry
Short nameSOCS6_SOCS
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the SOCS box domain of SOCS6.

Suppressor of cytokine signaling (SOCS) family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. However, SOCS6 does not interact with cytokine signaling intermediate molecules or inhibit cytokine receptor signaling. SOCS6 can interact with c-KIT, a receptor tyrosine kinase that mediates the cellular response to stem cell factor (SCF). SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells, suppressing c-KIT-dependent pathways
[2]
. SOCS6 negatively regulates receptor tyrosine kinase Flt3 activation, the downstream Erk signaling pathway, and cell proliferation
[3]
.

The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions
[4, 1]
.

References

1.Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Bullock AN, Debreczeni JE, Edwards AM, Sundstrom M, Knapp S. Proc. Natl. Acad. Sci. U.S.A. 103, 7637-42, (2006). View articlePMID: 16675548

2.Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. Zadjali F, Pike AC, Vesterlund M, Sun J, Wu C, Li SS, Ronnstrand L, Knapp S, Bullock AN, Flores-Morales A. J. Biol. Chem. 286, 480-90, (2011). View articlePMID: 21030588

3.Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. Kazi JU, Sun J, Phung B, Zadjali F, Flores-Morales A, Ronnstrand L. J. Biol. Chem. 287, 36509-17, (2012). View articlePMID: 22952242

4.The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Kamura T, Sato S, Haque D, Liu L, Kaelin WG Jr, Conaway RC, Conaway JW. Genes Dev. 12, 3872-81, (1998). View articlePMID: 9869640

GO terms

molecular function

  • None

cellular component

  • None
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