SIRT1

SIRT1
Наявні структури
PDB	Пошук ортологів: PDBe RCSB
Список кодів PDB
	4I5I, 4IF6, 4IG9, 4KXQ, 4ZZH, 4ZZI, 4ZZJ, 5BTR
Ідентифікатори
Символи	SIRT1, SIR2L1, SIR2, hSIR2, SIR2alpha, Sirtuin 1
Зовнішні ІД	OMIM: 604479 MGI: 2135607 HomoloGene: 56556 GeneCards: SIRT1
Реагує на сполуку
	SRT-1720
Онтологія гена
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;
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;
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;
	Джерела:Amigo / QuickGO
Шаблон експресії
	Більше даних
Ортологи
	23411
	93759
	ENSG00000096717
	ENSMUSG00000020063
	Q96EB6
	Q923E4
	NM_001142498; NM_001314049; NM_012238
	NM_001159589; NM_001159590; NM_019812
	NP_001135970; NP_001300978; NP_036370
	NP_001153061; NP_062786
	Вікідані
Див./Ред. для людей	Див./Ред. для мишей

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

A: Аланін

C: Цистеїн

D: Аспарагінова кислота

E: Глутамінова кислота

F: Фенілаланін

G: Гліцин

H: Гістидин

I: Ізолейцин

K: Лізин

L: Лейцин

M: Метіонін

N: Аспарагін

P: Пролін

Q: Глутамін

R: Аргінін

S: Серин

T: Треонін

V: Валін

W: Триптофан

Y: Тирозин

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