SIRT1 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/9/98/SIRTUIN1.png/250px-SIRTUIN1.png) |
Наявні структури |
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PDB | Пошук ортологів: PDBe RCSB | Список кодів PDB | 4I5I, 4IF6, 4IG9, 4KXQ, 4ZZH, 4ZZI, 4ZZJ, 5BTR | | |
Ідентифікатори |
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Символи | SIRT1, SIR2L1, SIR2, hSIR2, SIR2alpha, Sirtuin 1 |
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Зовнішні ІД | OMIM: 604479 MGI: 2135607 HomoloGene: 56556 GeneCards: SIRT1 |
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Реагує на сполуку |
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SRT1720[1] |
Онтологія гена |
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Молекулярна функція | • GO:0001106 transcription corepressor activity • protein domain specific binding • core promoter sequence-specific DNA binding • protein C-terminus binding • keratin filament binding • transcription factor binding • зв'язування з іоном металу • HLH domain binding • enzyme binding • protein deacetylase activity • GO:0031493 histone binding • GO:0001948, GO:0016582 protein binding • NAD-dependent histone deacetylase activity • NAD-dependent protein deacetylase activity • histone deacetylase activity • p53 binding • mitogen-activated protein kinase binding • deacetylase activity • bHLH transcription factor binding • NAD+ binding • identical protein binding • NAD+ ADP-ribosyltransferase activity • hydrolase activity • NAD-dependent histone deacetylase activity (H3-K9 specific) • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific |
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Клітинна компонента | • цитоплазма • nuclear envelope • rDNA heterochromatin • chromatin silencing complex • мітохондрія • клітинне ядро • ESC/E(Z) complex • ядерце • Хроматин • нуклеоплазма • PML body • nuclear inner membrane • гіалоплазма |
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Біологічний процес | • cellular triglyceride homeostasis • positive regulation of MHC class II biosynthetic process • DNA synthesis involved in DNA repair • positive regulation of protein phosphorylation • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • ритмічний процес • single strand break repair • muscle organ development • histone H3-K9 deacetylation • negative regulation of cellular response to testosterone stimulus • regulation of peroxisome proliferator activated receptor signaling pathway • cellular response to DNA damage stimulus • regulation of bile acid biosynthetic process • реплікація ДНК • negative regulation of TOR signaling • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • regulation of glucose metabolic process • rDNA heterochromatin assembly • negative regulation of DNA damage response, signal transduction by p53 class mediator • DNA methylation-dependent heterochromatin assembly • циркадний ритм • positive regulation of cellular senescence • Сперматогенез • intrinsic apoptotic signaling pathway in response to DNA damage • cellular response to ionizing radiation • negative regulation of helicase activity • cholesterol homeostasis • response to leptin • cellular response to hypoxia • triglyceride mobilization • negative regulation of prostaglandin biosynthetic process • proteasome-mediated ubiquitin-dependent protein catabolic process • GO:0097285 апоптоз • peptidyl-lysine deacetylation • negative regulation of fat cell differentiation • negative regulation of peptidyl-lysine acetylation • GO:0009373 regulation of transcription, DNA-templated • positive regulation of adaptive immune response • stress-induced premature senescence • negative regulation of androgen receptor signaling pathway • negative regulation of transforming growth factor beta receptor signaling pathway • GO:0001306 response to oxidative stress • negative regulation of DNA-binding transcription factor activity • negative regulation of gene expression • transcription, DNA-templated • negative regulation of cAMP-dependent protein kinase activity • pyrimidine dimer repair by nucleotide-excision repair • response to insulin • histone H3-K9 modification • positive regulation of macroautophagy • positive regulation of cholesterol efflux • Убіквітин-залежний протеоліз • negative regulation of cell growth • positive regulation of macrophage apoptotic process • rRNA processing • regulation of brown fat cell differentiation • negative regulation of phosphorylation • GO:0022415 viral process • GO:0100026 Репарація ДНК • negative regulation of neuron death • positive regulation of histone H3-K9 methylation • negative regulation of histone H3-K14 acetylation • negative regulation of protein kinase B signaling • диференціація клітин • ovulation from ovarian follicle • regulation of protein serine/threonine kinase activity • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • protein ADP-ribosylation • leptin-mediated signaling pathway • negative regulation of apoptotic process • GO:1901227 negative regulation of transcription by RNA polymerase II • GO:0031497, GO:0006336, GO:0034724, GO:0001301, GO:0007580, GO:0034652, GO:0010847 chromatin organization • negative regulation of I-kappaB kinase/NF-kappaB signaling • circadian regulation of gene expression • protein deacetylation • fatty acid homeostasis • protein destabilization • regulation of mitotic cell cycle • positive regulation of cAMP-dependent protein kinase activity • white fat cell differentiation • GO:1903106 positive regulation of insulin receptor signaling pathway • GO:0045996 negative regulation of transcription, DNA-templated • negative regulation of NF-kappaB transcription factor activity • peptidyl-lysine acetylation • response to hydrogen peroxide • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • negative regulation of histone H4-K16 acetylation • positive regulation of endothelial cell proliferation • regulation of smooth muscle cell apoptotic process • behavioral response to starvation • cellular glucose homeostasis • cellular response to starvation • cellular response to tumor necrosis factor • GO:1900404 positive regulation of DNA repair • multicellular organism development • regulation of cell population proliferation • positive regulation of cell population proliferation • regulation of endodeoxyribonuclease activity • regulation of cellular response to heat • positive regulation of phosphatidylinositol 3-kinase signaling • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway • UV-damage excision repair • histone deacetylation • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • Ангіогенез • macrophage cytokine production • regulation of lipid storage • positive regulation of adipose tissue development • macrophage differentiation • transcription by RNA polymerase II • positive regulation of smooth muscle cell differentiation • negative regulation of histone H3-K9 trimethylation • positive regulation of apoptotic process • cellular response to hydrogen peroxide • histone H3 deacetylation • negative regulation of protein acetylation • regulation of apoptotic process • cellular response to leukemia inhibitory factor • positive regulation of angiogenesis • transforming growth factor beta receptor signaling pathway • positive regulation of blood vessel endothelial cell migration • negative regulation of cellular senescence |
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Джерела:Amigo / QuickGO | |
Шаблон експресії |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/0/09/PBB_GE_SIRT1_218878_s_at_fs.png/250px-PBB_GE_SIRT1_218878_s_at_fs.png) |
Більше даних |
Ортологи |
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Види | Людина | Миша |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (мРНК) | | NM_001142498 NM_001314049 NM_012238 |
| | NM_001159589 NM_001159590 NM_019812 |
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RefSeq (білок) | | NP_001135970 NP_001300978 NP_036370 |
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Локус (UCSC) | Хр. 10: 67.88 – 67.92 Mb | Хр. 10: 63.15 – 63.22 Mb |
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PubMed search | [2] | [3] |
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Вікідані |
Див./Ред. для людей | Див./Ред. для мишей |
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SIRT1 (англ. Sirtuin 1) – білок, який кодується однойменним геном, розташованим у людей на короткому плечі 10-ї хромосоми.[4] Довжина поліпептидного ланцюга білка становить 747 амінокислот, а молекулярна маса — 81 681[5].
Послідовність амінокислот
10 | | 20 | | 30 | | 40 | | 50 |
MADEAALALQ | | PGGSPSAAGA | | DREAASSPAG | | EPLRKRPRRD | | GPGLERSPGE |
PGGAAPEREV | | PAAARGCPGA | | AAAALWREAE | | AEAAAAGGEQ | | EAQATAAAGE |
GDNGPGLQGP | | SREPPLADNL | | YDEDDDDEGE | | EEEEAAAAAI | | GYRDNLLFGD |
EIITNGFHSC | | ESDEEDRASH | | ASSSDWTPRP | | RIGPYTFVQQ | | HLMIGTDPRT |
ILKDLLPETI | | PPPELDDMTL | | WQIVINILSE | | PPKRKKRKDI | | NTIEDAVKLL |
QECKKIIVLT | | GAGVSVSCGI | | PDFRSRDGIY | | ARLAVDFPDL | | PDPQAMFDIE |
YFRKDPRPFF | | KFAKEIYPGQ | | FQPSLCHKFI | | ALSDKEGKLL | | RNYTQNIDTL |
EQVAGIQRII | | QCHGSFATAS | | CLICKYKVDC | | EAVRGDIFNQ | | VVPRCPRCPA |
DEPLAIMKPE | | IVFFGENLPE | | QFHRAMKYDK | | DEVDLLIVIG | | SSLKVRPVAL |
IPSSIPHEVP | | QILINREPLP | | HLHFDVELLG | | DCDVIINELC | | HRLGGEYAKL |
CCNPVKLSEI | | TEKPPRTQKE | | LAYLSELPPT | | PLHVSEDSSS | | PERTSPPDSS |
VIVTLLDQAA | | KSNDDLDVSE | | SKGCMEEKPQ | | EVQTSRNVES | | IAEQMENPDL |
KNVGSSTGEK | | NERTSVAGTV | | RKCWPNRVAK | | EQISRRLDGN | | QYLFLPPNRY |
IFHGAEVYSD | | SEDDVLSSSS | | CGSNSDSGTC | | QSPSLEEPME | | DESEIEEFYN |
GLEDEPDVPE | | RAGGAGFGTD | | GDDQEAINEA | | ISVKQEVTDM | | NYPSNKS |
Кодований геном білок за функціями належить до гідролаз, білків розвитку, фосфопротеїнів. Задіяний у таких біологічних процесах, як апоптоз, взаємодія хазяїн-вірус, транскрипція, регуляція транскрипції, біологічні ритми, процесинг рРНК, диференціація клітин, міогенез, ацетилювання, альтернативний сплайсинг. Білок має сайт для зв'язування з НАД, іонами металів, іоном цинку. Локалізований у цитоплазмі, ядрі, мітохондрії.
Література
- Frye R.A. (1999). Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem. Biophys. Res. Commun. 260: 273—279. PMID 10381378 DOI:10.1006/bbrc.1999.0897
- Takata T., Ishikawa F. (2003). Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression. Biochem. Biophys. Res. Commun. 301: 250—257. PMID 12535671 DOI:10.1016/S0006-291X(02)03020-6
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 14: 2121—2127. 2004. PMID 15489334 DOI:10.1101/gr.2596504
- Bitterman K.J., Anderson R.M., Cohen H.Y., Latorre-Esteves M., Sinclair D.A. (2002). Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J. Biol. Chem. 277: 45099—45107. PMID 12297502 DOI:10.1074/jbc.M205670200
- Frye R.A., Mayo M.W. (2004). Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23: 2369—2380. PMID 15152190 DOI:10.1038/sj.emboj.7600244
- Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W. (2005). Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J. 24: 1021—1032. PMID 15692560 DOI:10.1038/sj.emboj.7600570
Примітки
- ↑ Сполуки, які фізично взаємодіють з SIRT1 переглянути/редагувати посилання на ВікіДаних.
- ↑ Human PubMed Reference:.
- ↑ Mouse PubMed Reference:.
- ↑ HUGO Gene Nomenclature Commitee, HGNC:14929 (англ.) . Процитовано 8 вересня 2017.
- ↑ UniProt, Q96EB6 (англ.) . Архів оригіналу за 22 вересня 2017. Процитовано 8 вересня 2017.
Див. також
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Портал «Біологія» Портал «Хімія» |