SOCS3

Suppressor of cytokine signaling 3
PDB rendering based on 2bbu.
Available structures PDB 2bbu
Identifiers
Symbols	SOCS3; ATOD4; CIS3; Cish3; MGC71791; SOCS-3; SSI-3; SSI3
External IDs	OMIM: 604176 MGI: 1201791 HomoloGene: 2941 GeneCards: SOCS3 Gene
Gene Ontology Molecular function • protein kinase inhibitor activity Cellular component • cytoplasm • cytosol • cytosol Biological process • response to hypoxia • regulation of protein phosphorylation • anti-apoptosis • JAK-STAT cascade • aging • response to heat • response to bacterium • response to gamma radiation • response to organic cyclic compound • cytokine-mediated signaling pathway • organ regeneration • response to food • response to estradiol stimulus • response to lipopolysaccharide • response to progesterone stimulus • response to insulin stimulus • response to cytokine stimulus • regulation of growth • response to drug • positive regulation of cell differentiation • negative regulation of insulin receptor signaling pathway • response to glucocorticoid stimulus • interferon-gamma-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • type I interferon-mediated signaling pathway • regulation of type I interferon-mediated signaling pathway • branching involved in embryonic placenta morphogenesis • placenta blood vessel development • trophoblast giant cell differentiation • spongiotrophoblast differentiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9021	12702
Ensembl	ENSG00000184557	ENSMUSG00000053113
UniProt	O14543	Q3U9J8
RefSeq (mRNA)	NM_003955.3	NM_007707.3
RefSeq (protein)	NP_003946.3	NP_031733.1
Location (UCSC)	Chr 17: 76.35 – 76.36 Mb	Chr 11: 117.83 – 117.83 Mb
PubMed search	[1]	[2]

Suppressor of cytokine signaling 3 is a protein that in humans is encoded by the SOCS3 gene.^[1][2]

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be cruicial for the inhibitory function of SOCS3. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development.^[3]

Interactions

SOCS3 has been shown to interact with PTPN11,^[4] Glycoprotein 130,^[4] Erythropoietin receptor,^[5][6] Janus kinase 2,^[2][5][7] RAS p21 protein activator 1^[8] and Insulin-like growth factor 1 receptor.^[9]

Regulation

There is some evidence that the expression of SOCS3 is regulated by the microRNA miR-203.^[10][11]

See also

• SOCS
• JAK-STAT signaling pathway

References

1. ^ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (Sep 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochem Biophys Res Commun 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833. 
2. ^ ^{a b} Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (Nov 1997). "Cloning and characterization of novel CIS family genes". Biochem Biophys Res Commun 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848. 
3. ^ "Entrez Gene: SOCS3 suppressor of cytokine signaling 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9021. 
4. ^ ^{a b} Lehmann, Ute; Schmitz Jochen, Weissenbach Manuela, Sobota Radoslaw M, Hortner Michael, Friederichs Kerstin, Behrmann Iris, Tsiaris William, Sasaki Atsuo, Schneider-Mergener Jens, Yoshimura Akihiko, Neel Benjamin G, Heinrich Peter C, Schaper Fred (Jan. 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. (United States) 278 (1): 661–71. doi:10.1074/jbc.M210552200. ISSN 0021-9258. PMID 12403768. 
5. ^ ^{a b} Sasaki, A; Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (Sep. 2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. (UNITED STATES) 275 (38): 29338–47. doi:10.1074/jbc.M003456200. ISSN 0021-9258. PMID 10882725. 
6. ^ Hörtner, Michael; Nielsch Ulrich, Mayr Lorenz M, Heinrich Peter C, Haan Serge (May. 2002). "A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor". Eur. J. Biochem. (Germany) 269 (10): 2516–26. doi:10.1046/j.1432-1033.2002.02916.x. ISSN 0014-2956. PMID 12027890. 
7. ^ Sasaki, A; Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston J A, Yoshimura A (Jun. 1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells (ENGLAND) 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. ISSN 1356-9597. PMID 10421843. 
8. ^ Cacalano, N A; Sanden D, Johnston J A (May. 2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. (England) 3 (5): 460–5. doi:10.1038/35074525. ISSN 1465-7392. PMID 11331873. 
9. ^ Dey, B R; Furlanetto R W, Nissley P (Nov. 2000). "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. (UNITED STATES) 278 (1): 38–43. doi:10.1006/bbrc.2000.3762. ISSN 0006-291X. PMID 11071852. 
10. ^ Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G, Candi E (2008). "miR-203 represses 'stemness' by repressing DeltaNp63.". Cell Death Differ 15 (7): 1187–95. doi:10.1038/cdd.2008.69. PMID 18483491. 
11. ^ Wei T, Orfanidis K, Xu N, Janson P, StÃ¥hle M, Pivarcsi A, Sonkoly E (2010). "The expression of microRNA-203 during human skin morphogenesis.". Exp Dermatol 19 (9): 854–6. doi:10.1111/j.1600-0625.2010.01118.x. PMID 20698882. 

Further reading

• Yasukawa H, Sasaki A, Yoshimura A (2000). "Negative regulation of cytokine signaling pathways.". Annu. Rev. Immunol. 18: 143–64. doi:10.1146/annurev.immunol.18.1.143. PMID 10837055. 
• Kile BT, Schulman BA, Alexander WS, et al. (2002). "The SOCS box: a tale of destruction and degradation.". Trends Biochem. Sci. 27 (5): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535. 
• Zhang JG, Farley A, Nicholson SE, et al. (1999). "The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.". Proc. Natl. Acad. Sci. U.S.A. 96 (5): 2071–6. doi:10.1073/pnas.96.5.2071. PMC 26738. PMID 10051596. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26738. 
• Sasaki A, Yasukawa H, Suzuki A, et al. (1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain.". Genes Cells 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843. 
• Marine JC, McKay C, Wang D, et al. (1999). "SOCS3 is essential in the regulation of fetal liver erythropoiesis.". Cell 98 (5): 617–27. doi:10.1016/S0092-8674(00)80049-5. PMID 10490101. 
• Schmitz J, Weissenbach, M, Haan, S, et al. (2000). "SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130.". J. Biol. Chem. 275 (17): 12848–56. doi:10.1074/jbc.275.17.12848. PMID 10777583. 
• Ram PA, Waxman DJ (2000). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms.". J. Biol. Chem. 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430. 
• Sasaki A, Yasukawa H, Shouda T, et al. (2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2.". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725. 
• Anhuf D, Weissenbach M, Schmitz J, et al. (2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation.". J. Immunol. 165 (5): 2535–43. PMID 10946280. 
• Bjorbak C, Lavery HJ, Bates SH, et al. (2001). "SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985.". J. Biol. Chem. 275 (51): 40649–57. doi:10.1074/jbc.M007577200. PMID 11018044. 
• Shen X, Hong F, Nguyen VA, Gao B (2000). "IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3.". FEBS Lett. 480 (2–3): 132–6. doi:10.1016/S0014-5793(00)01905-0. PMID 11034314. 
• Dey BR, Furlanetto RW, Nissley P (2001). "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. 278 (1): 38–43. doi:10.1006/bbrc.2000.3762. PMID 11071852. 
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948. 
• Cookson WO, Ubhi B, Lawrence R, et al. (2001). "Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci". Nat. Genet. 27 (4): 372–3. doi:10.1038/86867. PMID 11279517. 
• Cacalano NA, Sanden D, Johnston JA (2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. 3 (5): 460–5. doi:10.1038/35074525. PMID 11331873. 
• Roberts AW, Robb L, Rakar S, et al. (2001). "Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3". Proc. Natl. Acad. Sci. U.S.A. 98 (16): 9324–9. doi:10.1073/pnas.161271798. PMC 55419. PMID 11481489. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=55419. 
• Dif F, Saunier E, Demeneix B, et al. (2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. doi:10.1210/en.142.12.5286. PMID 11713228. 
• Bode JG, Ludwig S, Freitas CA, et al. (2002). "The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription". Biol. Chem. 382 (10): 1447–53. doi:10.1515/BC.2001.178. PMID 11727828.