Gene: IRS2 - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | IRS2 | ||||||||||||||||
NCBI Gene ID | : | 8660 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | INSULIN RECEPTOR SUBSTRATE 2 | insulin receptor substrate 2 | IRS-2 | IRS2 Source: GPSDB |
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Gene Homologs | : | IRS2 (Canis lupus familiaris) | IRS2 (Gallus gallus) | IRS2 (Homo sapiens) | IRS2 (Macaca mulatta) | Irs2 (Mus musculus) | IRS2 (Pan troglodytes) | Irs2 (Rattus norvegicus) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_000777 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
---|---|---|---|---|---|
Insulin receptor substrate 2 | Homo sapiens | Q9Y4H2 (UniProtKB/Swiss-Prot) | IRS2_HUMAN (UniProtKB/Swiss-Prot) | May mediate the control of various cellular processes by insulin. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
1 | OB_009656 | Homo sapiens |
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IRS2 and IRS1 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS2 is involved in the IGF1/GH1 axis that appears to influence ageing in model organisms. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [0188]. IRS2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer [1919]. In another experiment, however, IRS2 knockout mice were reported to have a shorter median lifespan. Heterozygous animals had normal lifespans [1924]. IRS2 may also be involved in the extended lifespan of other mouse strains [0292]. In humans, mutations in IRS2 have been associated with diabetes [1659]. IRS2 likely plays a role in some human age-related pathologies, but its exact impact on the human ageing process is unknown. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
# | Observation Stable ID | Homology Group Genes | #EGHG | Description | Source | Homology Source | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | OB_008511 |
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2 | The HomoloGene homology group 2778 contains 2 genes with experimental evidence for ageing relevance (IRS2 - Homo sapiens | Irs2 - Mus musculus) and 5 other genes. | AgeFactDB Homology Analysis | HomoloGene homology group 2778 |
Sequences
IRS2_HUMAN | Q9Y4H2 | Insulin receptor substrate 2 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 1338 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750 760 770 780 790 800 810 820 830 840 850 860 870 880 890 900 910 920 930 940 950 960 970 980 990 1000 1010 1020 1030 1040 1050 1060 1070 1080 1090 1100 1110 1120 1130 1140 1150 1160 1170 1180 1190 1200 1210 1220 1230 1240 1250 1260 1270 1280 1290 1300 1310 1320 1330 IRS2_HUMAN 1 MASPPRHGPPGPASGDGPNLNNNNNNNNHSVRKCGYLRKQKHGHKRFFVLRGPGAGGDEATAGGGSAPQPPRLEYYESEKKWRSKAGAPKRVIALDCCLNINKRADAKHKYLIALYTKDEYFAVAAENEQEQEGWYRALTDLVSEGRAAAGDAPPAAAPAASCSASLPGALGGSAGAAGAEDSYGLVAPATAAYREVWQVNLKPKGLGQSKNLTGVYRLCLSARTIGFVKLNCEQPSVTLQLMNIRRCGHSDSFFFIEVGRSAVTGPGELWMQADDSVVAQNIHETILEAMKALKELFEFRPRSKSQSSGSSATHPISVPGARRHHHLVNLPPSQTGLVRRSRTDSLAATPPAAKCSSCRVRTASEGDGGAAAGAAAAGARPVSVAGSPLSPGPVRAPLSRSHTLSGGCGGRGSKVALLPAGGALQHSRSMSMPVAHSPPAATSPGSLSSSSGHGSGSYPPPPGPHPPLPHPLHHGPGQRPSSGSASASGSPSDPGFMSLDEYGSSPGDLRAFCSHRSNTPESIAETPPARDGGGGGEFYGYMTMDRPLSHCGRSYRRVSGDAAQDLDRGLRKRTYSLTTPARQRPVPQPSSASLDEYTLMRATFSGSAGRLCPSCPASSPKVAYHPYPEDYGDIEIGSHRSSSSNLGADDGYMPMTPGAALAGSGSGSCRSDDYMPMSPASVSAPKQILQPRAAAAAAAAVPSAGPAGPAPTSAAGRTFPASGGGYKASSPAESSPEDSGYMRMWCGSKLSMEHADGKLLPNGDYLNVSPSDAVTTGTPPDFFSAALHPGGEPLRGVPGCCYSSLPRSYKAPYTCGGDSDQYVLMSSPVGRILEEERLEPQATPGPSQAASAFGAGPTQPPHPVVPSPVRPSGGRPEGFLGQRGRAVRPTRLSLEGLPSLPSMHEYPLPPEPKSPGEYINIDFGEPGARLSPPAPPLLASAASSSSLLSASSPASSLGSGTPGTSSDSRQRSPLSDYMNLDFSSPKSPKPGAPSGHPVGSLDGLLSPEASSPYPPLPPRPSASPSSSLQPPPPPPAPGELYRLPPASAVATAQGPGAASSLSSDTGDNGDYTEMAFGVAATPPQPIAAPPKPEAARVASPTSGVKRLSLMEQVSGVEAFLQASQPPDPHRGAKVIRADPQGGRRRHSSETFSSTTTVTPVSPSFAHNPKRHNSASVENVSLRKSSEGGVGVGPGGGDEPPTSPRQLQPAPPLAPQGRPWTPGQPGGLVGCPGSGGSPMRRETSAGFQNGLNYIAIDVREEPGLPPQPQPPPPPLPQPGDKSSWGRTRSLGGLISAVGVGSTGGGCGGPGPGALPPANTYASIDFLSHHLKEATIVKE 1338
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L:
Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein.
Science. 2001; 292: 104-6.
PubMed (ID: 11292874), doi:10.1126/science.1057991
MeSH Terms: Aging/physiology; Drosophila Proteins; Drosophila melanogaster/physiology; Insect Proteins/genetics; Insect Proteins/metabolism; Intracellular Signaling Peptides and Proteins; Longevity/physiology; Receptor Protein-Tyrosine Kinases; Receptor, Insulin/metabolism - Papaconstantinou J, Deford JH, Gerstner A, Hsieh CC, Boylston WH, Guigneaux MM, Flurkey K, Harrison DE:
Hepatic gene and protein expression of primary components of the IGF-I axis in long lived Snell dwarf mice.
Mech Ageing Dev. 2005; 126: 692-704.
PubMed (ID: 15888324), doi:10.1016/j.mad.2005.01.002
MeSH Terms: Gene Expression Regulation/physiology; Insulin-Like Growth Factor I/biosynthesis; Liver/physiology; Longevity/physiology; Signal Transduction/physiology - Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M:
Suppression of aging in mice by the hormone Klotho.
Science. 2005; 309: 1829-33.
PubMed (ID: 16123266), PubMed Central (ID: PMC2536606), doi:10.1126/science.1112766
MeSH Terms: Aging/physiology; Longevity/physiology; Membrane Proteins/genetics; Membrane Proteins/physiology - Yamamoto A, Cremona ML, Rothman JE:
Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway.
J Cell Biol. 2006; 172: 719-31.
PubMed (ID: 16505167), PubMed Central (ID: PMC2063704), doi:10.1083/jcb.200510065
MeSH Terms: Autophagy/physiology; Insulin/physiology; Nerve Tissue Proteins/metabolism; Nuclear Proteins/metabolism; Signal Transduction/physiology - Masternak MM, Al-Regaiey KA, Del Rosario Lim MM, Jimenez-Ortega V, Panici JA, Bonkowski MS, Kopchick JJ, Wang Z, Bartke A:
Caloric restriction and growth hormone receptor knockout: effects on expression of genes involved in insulin action in the heart.
Exp Gerontol. 2006; 41: 417-29.
PubMed (ID: 16524678), PubMed Central (ID: PMC3082456), doi:10.1016/j.exger.2006.01.009
MeSH Terms: Aging/metabolism; Caloric Restriction; Insulin/metabolism; Myocardium/metabolism; Receptors, Somatotropin/metabolism; Signal Transduction/physiology - Taguchi A, Wartschow LM, White MF:
Brain IRS2 signaling coordinates life span and nutrient homeostasis.
Science. 2007; 317: 369-72.
PubMed (ID: 17641201), doi:10.1126/science.1142179
MeSH Terms: Brain/metabolism; Glucose/metabolism; Homeostasis; Intracellular Signaling Peptides and Proteins/metabolism; Longevity; Phosphoproteins/metabolism; Signal Transduction - Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ:
Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice.
FASEB J. 2008; 22: 807-18.
PubMed (ID: 17928362), doi:10.1096/fj.07-9261com
MeSH Terms: Adaptor Proteins, Signal Transducing/genetics; Longevity/genetics - Li Y, Xu W, McBurney MW, Longo VD:
SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons.
Cell Metab. 2008; 8: 38-48.
PubMed (ID: 18590691), PubMed Central (ID: PMC2822839), doi:10.1016/j.cmet.2008.05.004
MeSH Terms: Intracellular Signaling Peptides and Proteins/metabolism; Neurons/metabolism; Phosphoproteins/metabolism; Receptor, IGF Type 1/metabolism; Signal Transduction; Sirtuins/physiology - Wang H, Rissanen J, Miettinen R, Kärkkäinen P, Kekäläinen P, Kuusisto J, Mykkänen L, Karhapää P, Laakso M:
New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.
Diabetes. 2001; 50: 1949-51.
PubMed (ID: 11473060)
MeSH Terms: Diabetes Mellitus, Type 2/genetics; Genetic Variation; Phosphoproteins/genetics - Dominici FP, Hauck S, Argentino DP, Bartke A, Turyn D:
Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice.
J Endocrinol. 2002; 173: 81-94.
PubMed (ID: 11927387)
MeSH Terms: Growth Disorders/metabolism; Insulin/metabolism; Liver/metabolism; Phosphoproteins/metabolism; Receptor, Insulin/metabolism - Tu MP, Epstein D, Tatar M:
The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico.
Aging Cell. 2002; 1: 75-80.
PubMed (ID: 12882356)
MeSH Terms: Aging/genetics; Carrier Proteins/genetics; Drosophila Proteins/genetics; Drosophila melanogaster/genetics; Intracellular Signaling Peptides and Proteins; Longevity/genetics; Mutation/genetics; Receptor, Insulin/genetics - Jünger MA, Rintelen F, Stocker H, Wasserman JD, Végh M, Radimerski T, Greenberg ME, Hafen E:
The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling.
J Biol. 2003; 2: 20.
PubMed (ID: 12908874), PubMed Central (ID: PMC333403), doi:10.1186/1475-4924-2-20
MeSH Terms: Drosophila Proteins/physiology; Drosophila/cytology; Insulin/physiology; Nuclear Proteins/genetics; Signal Transduction/physiology; Transcription Factors/genetics; Transcription Factors/physiology - Lee YH, White MF:
Insulin receptor substrate proteins and diabetes.
Arch Pharm Res. 2004; 27: 361-70.
PubMed (ID: 15180298)
MeSH Terms: Diabetes Mellitus/metabolism; Phosphoproteins/physiology; Receptor, Insulin/physiology - Quarrie JK, Riabowol KT:
Murine models of life span extension.
Sci Aging Knowledge Environ. 2004; 2004: re5.
PubMed (ID: 15295107), doi:10.1126/sageke.2004.31.re5
MeSH Terms: Aging/genetics; Longevity/genetics; Models, Animal - Wessells RJ, Fitzgerald E, Cypser JR, Tatar M, Bodmer R:
Insulin regulation of heart function in aging fruit flies.
Nat Genet. 2004; 36: 1275-81.
PubMed (ID: 15565107), doi:10.1038/ng1476
MeSH Terms: Aging/physiology; Drosophila Proteins/physiology; Drosophila melanogaster/physiology; Heart/physiology; Receptor Protein-Tyrosine Kinases/physiology; Signal Transduction/physiology - Martin DE, Hall MN:
The expanding TOR signaling network.
Curr Opin Cell Biol. 2005; 17: 158-66.
PubMed (ID: 15780592), doi:10.1016/j.ceb.2005.02.008
MeSH Terms: Cell Enlargement; Intracellular Signaling Peptides and Proteins/metabolism; Saccharomyces cerevisiae Proteins/metabolism; Signal Transduction/physiology
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot