IRS2 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/7/7c/Protein_IRS2_PDB_3FQW.png/250px-Protein_IRS2_PDB_3FQW.png) |
PDBに登録されている構造 |
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PDB | オルソログ検索: RCSB PDBe PDBj |
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識別子 |
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記号 | IRS2, IRS-2, insulin receptor substrate 2 |
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外部ID | OMIM: 600797 MGI: 109334 HomoloGene: 2778 GeneCards: IRS2 |
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遺伝子の位置 (ヒト) |
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![13番染色体 (ヒト)](//upload.wikimedia.org/wikipedia/commons/thumb/8/89/Ideogram_human_chromosome_13.svg/300px-Ideogram_human_chromosome_13.svg.png) | 染色体 | 13番染色体 (ヒト)[1] |
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| バンド | データ無し | 開始点 | 109,752,695 bp[1] |
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終点 | 109,786,583 bp[1] |
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遺伝子の位置 (マウス) |
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![8番染色体 (マウス)](//upload.wikimedia.org/wikipedia/commons/thumb/1/1f/Ideogram_house_mouse_chromosome_8.svg/260px-Ideogram_house_mouse_chromosome_8.svg.png) | 染色体 | 8番染色体 (マウス)[2] |
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| バンド | データ無し | 開始点 | 11,034,681 bp[2] |
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終点 | 11,058,458 bp[2] |
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遺伝子オントロジー |
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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
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細胞の構成要素 | • 細胞質 • 細胞質基質 • 細胞膜 • 高分子複合体
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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
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出典:Amigo / QuickGO |
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オルソログ |
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種 | ヒト | マウス |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (タンパク質) | | |
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場所 (UCSC) | Chr 13: 109.75 – 109.79 Mb | Chr 13: 11.03 – 11.06 Mb |
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PubMed検索 | [3] | [4] |
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ウィキデータ |
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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。
- PLCG1(英語版)[9]
- SOCS1(英語版)[10]
- PIK3R1(英語版)[11][12][13][14]
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC518668/.
- ^ “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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740672/.
- ^ “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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20722/.
- “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.