IRS2とは何？ わかりやすく解説 Weblio辞書 (original) (raw)

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)[1]バンドデータ無し開始点109,752,695 bp[1]終点109,786,583 bp[1]
遺伝子の位置 (マウス)染色体8番染色体 (マウス)[2]バンドデータ無し開始点10,984,681 bp[2]終点11,008,458 bp[2]
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• mammary gland development• 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
種	ヒト	マウス
Entrez	8660	384783
Ensembl	ENSG00000185950	ENSMUSG00000038894
UniProt	Q9Y4H2	P81122
RefSeq(mRNA)	NM_003749	NM_001081212
RefSeq(タンパク質)	NP_003740	NP_001074681
場所(UCSC)	Chr 13: 109.75 – 109.79 Mb	Chr 13: 10.98 – 11.01 Mb
PubMed検索	[3]	[4]
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。

• PLCG1（英語版）[9]
• SOCS1（英語版）[10]
• PIK3R1（英語版）[11][12][13][14]

出典

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185950 - Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038894 - Ensembl, May 2017
3. ^ Human PubMed Reference:
4. ^ Mouse PubMed Reference:
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。
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC518668/.
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740672/.
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.
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.
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.
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.
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.
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.

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.