2hmh

Structural highlights

Function

[SOCS3_MOUSE] SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Seems to recognize IL6ST.^{[1] [2] [3] [4] [5]} [IL6RB_MOUSE] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Interleukin receptor

References

1. ↑ Nicholson SE, Willson TA, Farley A, Starr R, Zhang JG, Baca M, Alexander WS, Metcalf D, Hilton DJ, Nicola NA. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 1999 Jan 15;18(2):375-85. PMID:9889194 doi:10.1093/emboj/18.2.375
2. ↑ Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E. SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem. 2000 May 26;275(21):15985-91. PMID:10821852
3. ↑ Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999 Sep 3;98(5):617-27. PMID:10490101
4. ↑ Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, Greenhalgh CJ, Forster I, Clausen BE, Nicola NA, Metcalf D, Hilton DJ, Roberts AW, Alexander WS. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003 Jun;4(6):540-5. Epub 2003 May 18. PMID:12754505 doi:10.1038/ni931
5. ↑ Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, Komine O, Hamano S, Himeno K, Inagaki-Ohara K, Cacalano N, O'Garra A, Oshida T, Saito H, Johnston JA, Yoshimura A, Kubo M. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003 Aug;9(8):1047-54. Epub 2003 Jun 29. PMID:12847520 doi:10.1038/nm896
6. ↑ Bergamin E, Wu J, Hubbard SR. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Structure. 2006 Aug;14(8):1285-92. PMID:16905102 doi:10.1016/j.str.2006.06.011