SOCS3

SOCS3
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 2BBU、​2HMH、​2JZ3、​4GL9
識別號
别名	SOCS3；, ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3, suppressor of cytokine signaling 3
外部ID	OMIM：604176 MGI：1201791 HomoloGene：2941 GeneCards：SOCS3
基因位置（人类） 染色体 17號染色體[1] 基因座 17q25.3 起始 78,356,778 bp[1] 终止 78,360,077 bp[1]
基因位置（小鼠） 染色体 小鼠11号染色体[2] 基因座 11|11 E2 起始 117,856,905 bp[2] 终止 117,860,873 bp[2]
RNA表达模式
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基因本體 分子功能 • protein kinase inhibitor activity • 血浆蛋白结合 • phosphotyrosine residue binding • 1-phosphatidylinositol-3-kinase regulator activity 細胞組分 • 细胞质基质 • 細胞質 • phosphatidylinositol 3-kinase complex • 胞內 生物學過程 • regulation of protein phosphorylation • trophoblast giant cell differentiation • intracellular signal transduction • spongiotrophoblast differentiation • placenta blood vessel development • negative regulation of apoptotic process • negative regulation of insulin receptor signaling pathway • regulation of interferon-gamma-mediated signaling pathway • branching involved in labyrinthine layer morphogenesis • protein ubiquitination • positive regulation of cell differentiation • regulation of cell differentiation • regulation of growth • negative regulation of signal transduction • negative regulation of inflammatory response • negative regulation of protein kinase activity • negative regulation of receptor signaling pathway via JAK-STAT • negative regulation of tyrosine phosphorylation of STAT protein • 翻译后修饰 • cellular response to leukemia inhibitory factor • positive regulation of tyrosine phosphorylation of STAT protein • receptor signaling pathway via JAK-STAT • cytokine-mediated signaling pathway • interleukin-6-mediated signaling pathway • regulation of phosphatidylinositol 3-kinase activity • phosphatidylinositol phosphate biosynthetic process Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	9021	12702
Ensembl	ENSG00000184557	ENSMUSG00000053113
UniProt	O14543 Q6FI39	O35718
mRNA​序列	NM_003955 ​NM_001378932 ​NM_001378933	NM_007707
蛋白序列	NP_003946 ​NP_001365861 ​NP_001365862 NP_003946.3	NP_031733
基因位置​（UCSC）	Chr 17: 78.36 – 78.36 Mb	Chr 11: 117.86 – 117.86 Mb
PubMed​查找	[3]	[4]
維基數據
檢視/編輯人類 檢視/編輯小鼠

细胞因子信号传导抑制因子3(SOCS3或 SOCS-3)是一种在人体内由 SOCS3基因编码的蛋白。^[5][6] 该基因编码 STAT- 诱导的 STAT 抑制子(SSI)，也可称为细胞因子信号转导(SOCS)家族抑制子，的一个成员。 SSI 家族成员是可由细胞因子诱导的细胞因子信号转导负调节因子。

SOCS3基因的表达可由多种细胞因子的诱导，包括 IL-6，IL-10，干扰素-γ(IFN-γ)。

在 IL-6，Epo，GCSF 和瘦素的信号传导中，已发现SOCS3在各自的细胞因子受体上的结合对 SOCS3的抑制功能而言是至关重要的。

SOCS3的过表达会抑制脂肪组织和肝脏胰岛素信号转导，但对肌肉则不然。^[7] 但是在小鼠骨骼肌中敲除 SOCS3可以保护小鼠免于肥胖相关的胰岛素抵抗。^[7]

由于神经酰胺合成的增加，SOCS3会增加瘦素抵抗和胰岛素抵抗。^[8] 因此，研究已表明去除 SOCS 基因可以预防肥胖症患者的胰岛素抵抗^[7]

对该小鼠中基因的同源基因的研究表明，该基因在胎儿肝脏造血和胎盘发育的负调控中发挥作用。^[9]

SOCS3蛋白能与JAK2结合，抑制其活性。

已经证明 SOCS3可以与下列物质相互作用:

• 促红细胞生成素受体^[10][11]
• 糖蛋白130^[12]
• 胰岛素样生长因子1受体^[13]
• JAK2^[6][10][14]
• PTPN11^[12]
• RAS p21蛋白激活因子1^[15]

有部分证据表明 SOCS3的表达受小分子核糖核酸 miR-203的调控。^[16][17]

• SOCS
• JAK-STAT信号通路

• 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（页面存档备份，存于互联网档案馆）.
• Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ (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 1276535（页面存档备份，存于互联网档案馆）.
• Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (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（页面存档备份，存于互联网档案馆）.
• Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (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（页面存档备份，存于互联网档案馆）.
• Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN (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（页面存档备份，存于互联网档案馆）.
• Schmitz J, Weissenbach M, Haan S, Heinrich PC, Schaper F (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（页面存档备份，存于互联网档案馆）.
• 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（页面存档备份，存于互联网档案馆）.
• Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (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（页面存档备份，存于互联网档案馆）.
• Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F (2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): 2535–43. doi:10.4049/jimmunol.165.5.2535. PMID 10946280（页面存档备份，存于互联网档案馆）.
• Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG (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（页面存档备份，存于互联网档案馆）.
• 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（页面存档备份，存于互联网档案馆）.
• 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（页面存档备份，存于互联网档案馆）.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination" （页面存档备份，存于互联网档案馆）. Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948 （页面存档备份，存于互联网档案馆）. PMID 11076863（页面存档备份，存于互联网档案馆）.
• Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, Coleman R, Leaves NI, Trembath RC, Moffatt MF, Harper JI (2001). "Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci". Nat. Genet. 27 (4): 372–3. doi:10.1038/86867. PMID 11279517（页面存档备份，存于互联网档案馆）.
• 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（页面存档备份，存于互联网档案馆）.
• Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, Hilton DJ, Alexander WS (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（页面存档备份，存于互联网档案馆）.
• Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology. 142 (12): 5286–93. doi:10.1210/endo.142.12.8549. PMIDPMID 11713228（页面存档备份，存于互联网档案馆）.
• Bode JG, Ludwig S, Freitas CA, Schaper F, Ruhl M, Melmed S, Heinrich PC, Häussinger D (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（页面存档备份，存于互联网档案馆）.