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Protein Page:
SIRT1 (mouse)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
SIRT1 an NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separate cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. Elevation of NAD(+)/NADP(+) ratio activates SIRT1. Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG. Involved in liver and muscle metabolism. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Widely expressed. Inhibited by nicotinamide. Belongs to the sirtuin family. Class I subfamily. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 3.5.1.-; Nuclear receptor co-regulator; Deacetylase; Apoptosis
Cellular Component: PML body; mitochondrion; ESC/E(Z) complex; cell; nuclear inner membrane; nuclear envelope; nuclear heterochromatin; nucleoplasm; chromatin silencing complex; nuclear chromatin; cytoplasm; nucleus; chromatin
Molecular Function: identical protein binding; histone binding; metal ion binding; UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase activity; transcription factor binding; N-acetylgalactosamine-6-phosphate deacetylase activity; N2-acetyl-L-lysine deacetylase activity; NAD-dependent histone deacetylase activity (H3-K9 specific); enzyme binding; protein N-terminal asparagine amidohydrolase activity; mitogen-activated protein kinase binding; HLH domain binding; protein C-terminus binding; (3,5-dichlorophenylurea)acetate amidohydrolase activity; deacetylase activity; protein domain specific binding; hydrolase activity; p53 binding; protein deacetylase activity; iprodione amidohydrolase activity; protein binding; indoleacetamide hydrolase activity; NAD-dependent histone deacetylase activity; bHLH transcription factor binding; histone deacetylase activity; transcription corepressor activity; O-succinylbenzoate synthase activity
Biological Process: muscle development; establishment and/or maintenance of chromatin architecture; positive regulation of apoptosis; multicellular organismal development; regulation of mitotic cell cycle; positive regulation of caspase activity; protein ubiquitination; negative regulation of prostaglandin biosynthetic process; negative regulation of DNA damage response, signal transduction by p53 class mediator; behavioral response to starvation; positive regulation of adaptive immune response; positive regulation of histone H3-K9 methylation; positive regulation of DNA repair; transcription, DNA-dependent; negative regulation of transcription factor activity; pyrimidine dimer repair via nucleotide-excision repair; negative regulation of I-kappaB kinase/NF-kappaB cascade; negative regulation of fat cell differentiation; ovulation from ovarian follicle; cellular response to starvation; cholesterol homeostasis; regulation of endodeoxyribonuclease activity; DNA damage response, signal transduction resulting in induction of apoptosis; inhibition of NF-kappaB transcription factor; maintenance of chromatin silencing; regulation of protein import into nucleus, translocation; negative regulation of phosphorylation; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; negative regulation of transcription, DNA-dependent; triacylglycerol mobilization; rRNA processing; peptidyl-lysine acetylation; negative regulation of apoptosis; chromatin silencing at rDNA; proteasomal ubiquitin-dependent protein catabolic process; establishment of chromatin silencing; apoptosis; negative regulation of transcription from RNA polymerase II promoter; response to insulin stimulus; DNA synthesis during DNA repair; protein amino acid deacetylation; regulation of transcription, DNA-dependent; positive regulation of MHC class II biosynthetic process; positive regulation of cell proliferation; angiogenesis; cell differentiation; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; single strand break repair; positive regulation of chromatin silencing; negative regulation of TOR signaling pathway; negative regulation of protein kinase B signaling cascade; protein destabilization; histone deacetylation; regulation of cell proliferation; negative regulation of helicase activity; response to hydrogen peroxide; fatty acid homeostasis; white fat cell differentiation; cell glucose homeostasis; spermatogenesis; positive regulation of insulin receptor signaling pathway; positive regulation of protein amino acid phosphorylation; negative regulation of cell growth; negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of macroautophagy; response to DNA damage stimulus
Reference #:  Q923E4 (UniProtKB)
Alt. Names/Synonyms: AA673258; MGC150273; mSIR2a; NAD-dependent deacetylase sirtuin-1; Sir2; sir2-like 1; SIR2-like protein 1; Sir2a; SIR2alpha; Sir2l1; Sirt1; sirtuin 1 ((silent mating type information regulation 2, homolog) 1; sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae)
Gene Symbols: Sirt1
Molecular weight: 80,372 Da
Basal Isoelectric point: 4.6  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Protein Acetylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

SIRT1

Protein Structure Not Found.


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Sites Implicated In
apoptosis, altered: T522‑p
apoptosis, inhibited: S154‑p, S649‑p, S651‑p, S683‑p
acetylation: T522‑p
enzymatic activity, induced: S154‑p, T522‑p, S649‑p, S651‑p, S683‑p
molecular association, regulation: T522‑p
protein degradation: S46‑p
ubiquitination: S46‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       mouse

 
1 11 S14-p LALQAAGsPsAAAAM
0 2 S16-p LQAAGsPsAAAAMEA
0 4 S25 AAAMEAASQPADEPL
2 9 Q26 AAMEAASQPADEPLR
3 30 S46-p DGPGLGRsPGEPsAA
0 2 S51-p GRsPGEPsAAVAPAA
0 1 T146-p LLTDGLLtNGFHsCE
0 5 S151-p LLtNGFHsCEsDDDD
1 4 S154-p NGFHsCEsDDDDRTS
0 1 S164 DDRTSHASSSDWTPR
0 1 S165 DRTSHASSSDWTPRP
0 2 K230 PPKRKKRKDINTIED
0 1 Y272 FRSRDGIYARLAVDF
0 1 Y293 QAMFDIEYFRKDPRP
0 1 K303 KDPRPFFKFAKEIYP
0 2 S325 CHKFIALSDKEGKLL
1 0 T336 GKLLRNYTQNIDTLE
0 1 K422 HRAMKYDKDEVDLLI
0 1 S433 DLLIVIGSsLKVRPV
1 1 S434-p LLIVIGSsLKVRPVA
0 1 K436 IVIGSsLKVRPVALI
0 1 K491 RLGGEYAKLCCNPVK
4 32 T522-p HLSELPPtPLHIsED
0 6 S527-p PPtPLHIsEDsssPE
0 7 S530-p PLHIsEDsssPERTV
0 4 S531-p LHIsEDsssPERTVP
1 7 S532-p HIsEDsssPERTVPQ
0 1 T536 DsssPERTVPQDSSV
0 1 S541 ERTVPQDSSVIATLV
0 1 K570 ESSCVEEKPQEVQTS
0 2 K591 NVENPDFKAVGSSTA
0 2 K600 VGSSTADKNERTSVA
0 1 T604 TADKNERTSVAETVR
0 11 S605 ADKNERTSVAETVRK
0 1 T609 ERTSVAETVRKCWPN
2 0 S649-p FHGAEVYsDsEDDVL
2 0 S651-p GAEVYsDsEDDVLSS
1 0 S683-p EEPLEDEsEIEEFYN
1 23 A709 AGGSGFGADGGDQEV
1 0 R724 VNEAIATRQELTDVN
0 1 S737-p VNYPSDKs_______
  human

 
S14-p LALQPGGsPsAAGAD
S16-p LQPGGsPsAAGADRE
S26-p GADREAAssPAGEPL
S27-p ADREAAssPAGEPLR
S47-p DGPGLERsPGEPGGA
G52 ERsPGEPGGAAPERE
T154-p LFGDEIItNGFHsCE
S159-p IItNGFHsCEsDEED
S162-p NGFHsCEsDEEDRAS
S172-p EDRASHAssSDWTPR
S173-p DRASHAssSDWTPRP
K238-ub PPKRKKRkDINTIED
Y280-p FRSRDGIyARLAVDF
Y301-p QAMFDIEyFRKDPRP
K311-ub KDPRPFFkFAKEIYP
S333-p CHKFIALsDKEGKLL
T344-p GKLLRNYtQNIDTLE
K430-ac HRAMKYDkDEVDLLI
S441-p DLLIVIGssLkVRPV
S442-p LLIVIGssLkVRPVA
K444-ac IVIGssLkVRPVALI
K499-ub RLGGEYAkLCCNPVK
T530-p YLSELPPtPLHVsED
S535-p PPtPLHVsEDsssPE
S538-p PLHVsEDsssPERtS
S539-p LHVsEDsssPERtSP
S540-p HVsEDsssPERtSPP
T544-p DsssPERtSPPDsSV
S549-p ERtSPPDsSVIVTLL
K578-ac SKGCMEEkPQEVQTS
K601-ub QMENPDLkNVGSSTG
K610-ub VGSSTGEkNERtsVA
T614-p TGEkNERtsVAGtVR
S615-p GEkNERtsVAGtVRK
T619-p ERtsVAGtVRKCWPN
S659-p FHGAEVYsDsEDDVL
S661-p GAEVYsDsEDDVLSS
S693 EEPMEDESEIEEFYN
T719-p AGGAGFGtDGDDQEA
K734-sm INEAISVkQEVTDMN
S747-p MNYPSNKs_______
2327 : Phospho-SirT1 (Ser27) Antibody
2314 : Phospho-SirT1 (Ser47) Antibody
  rat

 
- gap
- gap
- gap
- gap
- gap
- gap
T158 LLADEIITNGFHSCE
S163 IITNGFHSCESDDDD
S166 NGFHSCESDDDDRAS
S176 DDRASHASSSDWTPR
S177 DRASHASSSDWTPRP
K242 PPKRKKRKDINTIED
Y284 FRSRDGIYARLAVDF
Y305 QAMFDIEYFRKDPRP
K315 KDPRPFFKFAKEIYP
S337 CHKFIALSDKEGKLL
T348 GKLLRNYTQNIDTLE
K434 HRAMKYDKDEVDLLI
S445 DLLIVIGSSLKVRPV
S446 LLIVIGSSLKVRPVA
K448 IVIGSSLKVRPVALI
K503 RLGGEYAKLCCNPVK
T534 HLSELPPTPLHISED
S539 PPTPLHISEDSSSPE
S542 PLHISEDSSSPERTV
S543 LHISEDSSSPERTVP
S544 HISEDSSSPERTVPQ
T548 DSSSPERTVPQDSSV
S553 ERTVPQDSSVIATLV
K583 PKSCVEEKSQEVQTY
K604 NVENPDFKAVGSSTG
K613 VGSSTGDKNERTSVA
T617 TGDKNERTSVAETVR
S618 GDKNERTSVAETVRK
T622 ERTSVAETVRKCWPN
S662 FHGAEVYSDSEDDAL
S664 GAEVYSDSEDDALSS
S696 EEPLEDESEIEEFYN
A720 ECAGGSGADGGDQEA
K735 VNEAIAMKQELTDVN
S748 VNCTPDKSEHY____
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