IRS2

IRS2
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	3FQW, 3FQX
識別子
記号	IRS2, IRS-2, insulin receptor substrate 2
外部ID	OMIM: 600797 MGI: 109334 HomoloGene: 2778 GeneCards: IRS2
遺伝子の位置 (ヒト)
染色体	13番染色体 (ヒト)
終点	109,786,583 bp
遺伝子の位置 (マウス)
染色体	8番染色体 (マウス)
終点	11,058,458 bp
RNA発現パターン
	; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• insulin receptor binding; • 14-3-3 protein binding; • phosphatidylinositol 3-kinase binding; • 血漿タンパク結合; • プロテインキナーゼ結合; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • 1-phosphatidylinositol-3-kinase activity; • シグナルトランスデューサー活性; • protein phosphatase binding; • protein domain specific binding;
細胞の構成要素	• 細胞質; • 細胞質基質; • 細胞膜; • 高分子複合体;
生物学的プロセス	• positive regulation of fatty acid beta-oxidation; • positive regulation of glucose import; • positive regulation of glycogen biosynthetic process; • cellular response to peptide; • positive regulation of cell migration; • positive regulation of glucose metabolic process; • response to glucose; • MAPK cascade; • 乳房発達; • regulation of lipid metabolic process; • negative regulation of long-chain fatty acid import across plasma membrane; • 脳発生; • positive regulation of mesenchymal cell proliferation; • positive regulation of B cell proliferation; • positive regulation of cell population proliferation; • lipid homeostasis; • glucose metabolic process; • cellular response to insulin stimulus; • negative regulation of B cell apoptotic process; • 細胞増殖; • phosphatidylinositol-mediated signaling; • cellular response to glucose stimulus; • シグナル伝達; • positive regulation of insulin secretion; • negative regulation of kinase activity; • phosphatidylinositol-3-phosphate biosynthetic process; • phosphatidylinositol phosphate biosynthetic process; • insulin receptor signaling pathway; • 軸索誘導; • interleukin-7-mediated signaling pathway; • positive regulation of protein kinase B signaling; • positive regulation of phosphatidylinositol 3-kinase signaling; • positive regulation of Ras protein signal transduction;
	出典:Amigo / QuickGO
オルソログ
	8660
	384783
	ENSG00000185950
	ENSMUSG00000038894
	Q9Y4H2
	P81122
	NM_003749
	NM_001081212
	NP_003740
	NP_001074681
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

IRS2（insulin receptor substrate 2、インスリン受容体基質2）は、ヒトではIRS2遺伝子によってコードされるタンパク質である^[5]。

機能

IRS2遺伝子はIRS２タンパク質をコードする。IRS2は細胞質のシグナル伝達分子であり、多様な受容体型チロシンキナーゼと下流のエフェクター分子との間のアダプタータンパク質として、インスリン、IGF-1や他のサイトカインの効果を媒介する。IRS2はインスリン受容体の刺激に伴ってリン酸化されるほか、IL-4処理に応答してIL-4受容体関連キナーゼによってもリン酸化される^[6]。

IRS2を欠失したマウスは糖尿病の表現型を示すとともに^[7]、脳の重量が40％低下する^[8]。

相互作用

IRS2は次に挙げる因子と相互作用することが示されている。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000185950 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038894 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain”. J Biol Chem 272 (40): 25267–74. (Oct 1997). doi:10.1074/jbc.272.40.25267. PMID 9312143.
^ “Entrez Gene: IRS2 insulin receptor substrate 2”. 2021年9月7日閲覧。
^ “Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes”. J. Clin. Invest. 114 (7): 908–16. (October 2004). doi:10.1172/JCI22217. PMC 518668. PMID 15467829.
^ “Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation”. J. Neurosci. 23 (18): 7084–92. (August 2003). doi:10.1523/JNEUROSCI.23-18-07084.2003. PMC 6740672. PMID 12904469.
^ “IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production”. Biochem. Biophys. Res. Commun. 244 (3): 665–70. (March 1998). doi:10.1006/bbrc.1998.8314. PMID 9535722.
^ “SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2”. J. Biol. Chem. 277 (44): 42394–8. (November 2002). doi:10.1074/jbc.C200444200. PMID 12228220.
^ “Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling”. J. Biol. Chem. 271 (46): 29415–21. (November 1996). doi:10.1074/jbc.271.46.29415. PMID 8910607.
^ “Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation”. J. Biol. Chem. 272 (42): 26173–8. (October 1997). doi:10.1074/jbc.272.42.26173. PMID 9334184.
^ “Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling”. J. Biol. Chem. 273 (51): 34543–50. (December 1998). doi:10.1074/jbc.273.51.34543. PMID 9852124.
^ “An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events”. Diabetologia 45 (5): 657–67. (May 2002). doi:10.1007/s00125-002-0798-5. PMID 12107746.

関連文献

White MF (1999). “The IRS-signalling system: a network of docking proteins that mediate insulin action.”. Mol. Cell. Biochem. 182 (1–2): 3–11. doi:10.1023/A:1006806722619. PMID 9609109.
“IL-4/IL-13 signaling beyond JAK/STAT.”. J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. (2000). doi:10.1067/mai.2000.107604. PMID 10856136.
“Defects of the insulin receptor substrate (IRS) system in human metabolic disorders.”. FASEB J. 15 (12): 2099–111. (2001). doi:10.1096/fj.01-0009rev. PMID 11641236.
“Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis.”. Cell Cycle 6 (6): 631–7. (2007). doi:10.4161/cc.6.6.3987. PMID 17361103.
“Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2.”. Cell Cycle 6 (6): 705–13. (2007). doi:10.4161/cc.6.6.4035. PMID 17374994.
“Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases.”. J. Biol. Chem. 270 (48): 28527–30. (1996). doi:10.1074/jbc.270.48.28527. PMID 7499365.
“4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice.”. J. Biol. Chem. 270 (42): 24670–3. (1995). doi:10.1074/jbc.270.42.24670. PMID 7559579.
“Role of IRS-2 in insulin and cytokine signalling.”. Nature 377 (6545): 173–7. (1995). Bibcode: 1995Natur.377..173S. doi:10.1038/377173a0. PMID 7675087.
“Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase in primary adipocytes.”. J. Biol. Chem. 270 (8): 3471–4. (1995). doi:10.1074/jbc.270.8.3471. PMID 7876077.
“The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2.”. J. Biol. Chem. 271 (1): 278–82. (1996). doi:10.1074/jbc.271.1.278. PMID 8550573.
“The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.”. J. Biol. Chem. 271 (16): 9287–90. (1996). doi:10.1074/jbc.271.16.9287. PMID 8621590.
“Insulin receptor substrate-2 binds to the insulin receptor through its phosphotyrosine-binding domain and through a newly identified domain comprising amino acids 591-786.”. J. Biol. Chem. 271 (11): 5980–3. (1996). doi:10.1074/jbc.271.11.5980. PMID 8626379.
“Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors. Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2.”. J. Biol. Chem. 271 (20): 11641–5. (1996). doi:10.1074/jbc.271.20.11641. PMID 8662806.
“Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR.”. Mol. Endocrinol. 10 (5): 575–84. (1996). doi:10.1210/me.10.5.575. PMID 8732688.
“Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling.”. J. Biol. Chem. 271 (46): 29415–21. (1997). doi:10.1074/jbc.271.46.29415. PMID 8910607.
“Mapping the RP2 locus for X-linked retinitis pigmentosa on proximal Xp: a genetically defined 5-cM critical region and exclusion of candidate genes by physical mapping.”. Genome Res. 6 (11): 1093–102. (1997). doi:10.1101/gr.6.11.1093. PMID 8938433.
“Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells.”. Biochem. Biophys. Res. Commun. 229 (2): 624–9. (1997). doi:10.1006/bbrc.1996.1854. PMID 8954948.
“P110delta, a novel phosphoinositide 3-kinase in leukocytes.”. Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4330–5. (1997). Bibcode: 1997PNAS...94.4330V. doi:10.1073/pnas.94.9.4330. PMC 20722. PMID 9113989.
“Tyr624 and Tyr628 in insulin receptor substrate-2 mediate its association with the insulin receptor.”. J. Biol. Chem. 272 (26): 16414–20. (1997). doi:10.1074/jbc.272.26.16414. PMID 9195949.
“Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart.”. J. Biol. Chem. 272 (38): 23696–702. (1997). doi:10.1074/jbc.272.38.23696. PMID 9295312.

この項目は、生物学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:生命科学／Portal:生物学）。

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185950 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000038894 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid9312143-5] “14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain”. J Biol Chem 272 (40): 25267–74. (Oct 1997). doi:10.1074/jbc.272.40.25267. PMID 9312143.

[6] “Entrez Gene: IRS2 insulin receptor substrate 2”. 2021年9月7日閲覧。

[pmid15467829-7] “Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes”. J. Clin. Invest. 114 (7): 908–16. (October 2004). doi:10.1172/JCI22217. PMC 518668. PMID 15467829.

[pmid12904469-8] “Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation”. J. Neurosci. 23 (18): 7084–92. (August 2003). doi:10.1523/JNEUROSCI.23-18-07084.2003. PMC 6740672. PMID 12904469.

[pmid9535722-9] “IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production”. Biochem. Biophys. Res. Commun. 244 (3): 665–70. (March 1998). doi:10.1006/bbrc.1998.8314. PMID 9535722.

[pmid12228220-10] “SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2”. J. Biol. Chem. 277 (44): 42394–8. (November 2002). doi:10.1074/jbc.C200444200. PMID 12228220.

[pmid8910607-11] “Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling”. J. Biol. Chem. 271 (46): 29415–21. (November 1996). doi:10.1074/jbc.271.46.29415. PMID 8910607.

[pmid9334184-12] “Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation”. J. Biol. Chem. 272 (42): 26173–8. (October 1997). doi:10.1074/jbc.272.42.26173. PMID 9334184.

[pmid9852124-13] “Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling”. J. Biol. Chem. 273 (51): 34543–50. (December 1998). doi:10.1074/jbc.273.51.34543. PMID 9852124.

[pmid12107746-14] “An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events”. Diabetologia 45 (5): 657–67. (May 2002). doi:10.1007/s00125-002-0798-5. PMID 12107746.

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IRS2

機能

相互作用

出典

関連文献

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