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
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
終止	78,360,077 bp
基因位置（小鼠）
染色體	小鼠11號染色體
終止	117,860,873 bp
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; • 翻譯後修飾; • 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
	9021
	12702
	ENSG00000184557
	ENSMUSG00000053113
	O14543; Q6FI39
	O35718
	NM_003955; NM_001378932; NM_001378933
	NM_007707
	NP_003946; NP_001365861; NP_001365862; NP_003946.3
	NP_031733
	維基數據
檢視/編輯人類	檢視/編輯小鼠

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。

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:

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

參考文獻

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000184557 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000053113 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^6.0 ^6.1 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.
^ ^7.0 ^7.1 ^7.2 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
^ 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）.
^ Entrez Gene: SOCS3 suppressor of cytokine signaling 3. （原始內容存檔於2010-03-07）.
^ ^10.0 ^10.1 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.
^ 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.
^ ^12.0 ^12.1 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.
^ 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.
^ 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.
^ 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.
^ miR-203 represses 'stemness' by repressing DeltaNp63.. Cell Death Differ. 2008, 15 (7): 1187–95. PMID 18483491. doi:10.1038/cdd.2008.69.
^ 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

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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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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（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.
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. PMID PMID 11713228（頁面存檔備份，存於網際網路檔案館）.
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（頁面存檔備份，存於網際網路檔案館）.

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000184557 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 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.

[pmid9266833-5] 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.

[pmid9344848-6] 6.0 ^6.1 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.

[pmid22961088-7] 7.0 ^7.1 ^7.2 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

[pmid19435851-8] 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）.

[pmid10882725-10] 10.0 ^10.1 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.

[pmid12027890-11] 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.

[pmid12403768-12] 12.0 ^12.1 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.

[pmid11071852-13] 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.

[pmid10421843-14] 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.

[pmid11331873-15] 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.

[pmid18483491-16] R-203 represses 'stemness' by repressing DeltaNp63.. Cell Death Differ. 2008, 15 (7): 1187–95. PMID 18483491. doi:10.1038/cdd.2008.69.

[pmid20698882-17] 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.

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