2jz3

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]} [ELOC_MOUSE] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. [ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).^{[6] [7]} The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.^{[8] [9]}

Evolutionary Conservation

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

See Also

• Elongation factor 3D structures

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. ↑ Garrett KP, Aso T, Bradsher JN, Foundling SI, Lane WS, Conaway RC, Conaway JW. Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7172-6. PMID:7638163
7. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
8. ↑ Garrett KP, Aso T, Bradsher JN, Foundling SI, Lane WS, Conaway RC, Conaway JW. Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7172-6. PMID:7638163
9. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
10. ↑ Babon JJ, Sabo JK, Soetopo A, Yao S, Bailey MF, Zhang JG, Nicola NA, Norton RS. The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase. J Mol Biol. 2008 Sep 12;381(4):928-40. Epub 2008 Jun 20. PMID:18590740 doi:10.1016/j.jmb.2008.06.038