SOCS3

細胞因子信號傳導抑制因子3(SOCS3或 SOCS-3)是一種在人體內由 SOCS3基因編碼的蛋白。^[5][6] 該基因編碼 STAT- 誘導的 STAT 抑制子(SSI)，也可稱為細胞因子信號轉導(SOCS)家族抑制子，的一個成員。 SSI 家族成員是可由細胞因子誘導的細胞因子信號轉導負調節因子。

SOCS3
已知的結構 PDB 直系同源搜尋: PDBe RCSB PDBID列表 2BBU、​2HMH、​2JZ3、​4GL9
識別號
別名	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（人類） 染色體 17號染色體[1] 基因座 17q25.3 起始 78,356,778 bp[1] 終止 78,360,077 bp[1]
基因位置（小鼠） 染色體 小鼠11號染色體[2] 基因座 11|11 E2 起始 117,856,905 bp[2] 終止 117,860,873 bp[2]
RNA表達模式
查閱更多表達數據
基因本體 分子功能 • protein kinase inhibitor activity • 血漿蛋白結合 • phosphotyrosine residue binding • 1-phosphatidylinositol-3-kinase regulator activity 細胞組分 • 細胞質基質 • 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 • 轉譯後修飾 • 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

功能

SOCS3基因的表達可由多種細胞因子的誘導，包括 IL-6，IL-10，干擾素-γ(IFN-γ)。

在 IL-6，Epo，GCSF 和瘦素的信號傳導中，已發現SOCS3在各自的細胞因子受體上的結合對 SOCS3的抑制功能而言是至關重要的。

SOCS3的過表達會抑制脂肪組織和肝臟胰島素信號轉導，但對肌肉則不然。^[7] 但是在小鼠骨骼肌中敲除 SOCS3可以保護小鼠免於肥胖相關的胰島素抵抗。^[7]

由於神經酰胺合成的增加，SOCS3會增加瘦素抵抗和胰島素抵抗。^[8] 因此，研究已表明去除 SOCS 基因可以預防肥胖症患者的胰島素抵抗^[7]

對該小鼠中基因的同源基因的研究表明，該基因在胎兒肝臟造血和胎盤發育的負調控中發揮作用。^[9]

SOCS3蛋白能與JAK2結合，抑制其活性。

相互作用

已經證明 SOCS3可以與下列物質相互作用:

• 促紅血球生成素受體^[10][11]
• 醣蛋白130^[12]
• 胰島素樣生長因子1受體^[13]
• JAK2^[6][10][14]
• PTPN11^[12]
• RAS p21蛋白活化因子1^[15]

調控

有部分證據表明 SOCS3的表達受小分子核糖核酸 miR-203的調控。^[16][17]

參見

• SOCS
• JAK-STAT信號通路

參考文獻

1. GRCh38: Ensembl release 89: ENSG00000184557 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000053113 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. Biochem Biophys Res Commun. September 1997, 237 (1): 79–83. PMID 9266833. doi:10.1006/bbrc.1997.7080.
6. Cloning and characterization of novel CIS family genes. Biochem Biophys Res Commun. November 1997, 239 (2): 439–46. PMID 9344848. doi:10.1006/bbrc.1997.7484.
7. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes. 2013, 62 (1): 56–64 [2018-11-22]. PMC 3526029 . PMID 22961088. doi:10.2337/db12-0443. （原始內容存檔於2018-11-23）. 引用錯誤：帶有name屬性「pmid22961088」的<ref>標籤用不同內容定義了多次
8. Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. American Journal of Physiology. 2009, 297 (1): E211–E224 [2018-11-22]. PMC 2711669 . PMID 19435851. doi:10.1152/ajpendo.91014.2008. （原始內容存檔於2016-08-10）.
9. Entrez Gene: SOCS3 suppressor of cytokine signaling 3. （原始內容存檔於2010-03-07）.
10. CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J. Biol. Chem. September 2000, 275 (38): 29338–47. PMID 10882725. doi:10.1074/jbc.M003456200.
11. A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. Eur. J. Biochem. May 2002, 269 (10): 2516–26. PMID 12027890. doi:10.1046/j.1432-1033.2002.02916.x.
12. SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130. J. Biol. Chem. January 2003, 278 (1): 661–71. PMID 12403768. doi:10.1074/jbc.M210552200.
13. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Biochem. Biophys. Res. Commun. November 2000, 278 (1): 38–43. PMID 11071852. doi:10.1006/bbrc.2000.3762.
14. 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. June 1999, 4 (6): 339–51. PMID 10421843. doi:10.1046/j.1365-2443.1999.00263.x.
15. Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat. Cell Biol. May 2001, 3 (5): 460–5. PMID 11331873. doi:10.1038/35074525.
16. miR-203 represses 'stemness' by repressing DeltaNp63.. Cell Death Differ. 2008, 15 (7): 1187–95. PMID 18483491. doi:10.1038/cdd.2008.69.
17. The expression of microRNA-203 during human skin morphogenesis.. Exp Dermatol. 2010, 19 (9): 854–6. PMID 20698882. doi:10.1111/j.1600-0625.2010.01118.x.

擴展閱讀

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