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Protein Page:
SIRT1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
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
Chromosomal Location of Human Ortholog: 10q21.3
Cellular Component: chromatin silencing complex; cytoplasm; ESC/E(Z) complex; mitochondrion; nuclear chromatin; nuclear envelope; nuclear heterochromatin; nuclear inner membrane; nucleolus; nucleoplasm; nucleus; PML body
Molecular Function: bHLH transcription factor binding; deacetylase activity; enzyme binding; histone binding; histone deacetylase activity; HLH domain binding; identical protein binding; mitogen-activated protein kinase binding; NAD+ ADP-ribosyltransferase activity; NAD-dependent histone deacetylase activity; NAD-dependent histone deacetylase activity (H3-K9 specific); nuclear hormone receptor binding; p53 binding; protein binding; protein C-terminus binding; protein deacetylase activity; transcription corepressor activity; transcription factor binding
Biological Process: angiogenesis; cell aging; cell glucose homeostasis; cellular response to starvation; cholesterol homeostasis; chromatin silencing; chromatin silencing at rDNA; circadian regulation of gene expression; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; DNA repair; DNA replication; DNA synthesis during DNA repair; establishment and/or maintenance of chromatin architecture; establishment of chromatin silencing; fatty acid homeostasis; histone deacetylation; inhibition of NF-kappaB transcription factor; leptin-mediated signaling pathway; macrophage differentiation; maintenance of chromatin silencing; methylation-dependent chromatin silencing; negative regulation of apoptosis; negative regulation of cell growth; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of fat cell differentiation; negative regulation of helicase activity; negative regulation of I-kappaB kinase/NF-kappaB cascade; negative regulation of phosphorylation; negative regulation of prostaglandin biosynthetic process; negative regulation of protein kinase B signaling cascade; negative regulation of TOR signaling pathway; negative regulation of transcription factor activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; negative regulation of transforming growth factor beta receptor signaling pathway; peptidyl-lysine acetylation; positive regulation of adaptive immune response; positive regulation of angiogenesis; positive regulation of apoptosis; positive regulation of caspase activity; positive regulation of cell proliferation; positive regulation of chromatin silencing; positive regulation of DNA repair; positive regulation of endothelial cell proliferation; positive regulation of histone H3-K9 methylation; positive regulation of insulin receptor signaling pathway; positive regulation of macroautophagy; positive regulation of MHC class II biosynthetic process; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein amino acid phosphorylation; positive regulation of transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; protein amino acid ADP-ribosylation; protein amino acid deacetylation; protein destabilization; protein ubiquitination; pyrimidine dimer repair via nucleotide-excision repair; regulation of cell proliferation; regulation of endodeoxyribonuclease activity; regulation of mitotic cell cycle; regulation of protein import into nucleus, translocation; response to DNA damage stimulus; response to hydrogen peroxide; response to insulin stimulus; response to oxidative stress; single strand break repair; triacylglycerol mobilization; white fat cell differentiation
Reference #:  Q96EB6 (UniProtKB)
Alt. Names/Synonyms: hSIR2; hSIRT1; NAD-dependent deacetylase sirtuin-1; sir2-like 1; SIR2-like protein 1; SIR2alpha; SIR2L1; SIRT1; sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae); sirtuin 1; sirtuin type 1
Gene Symbols: SIRT1
Molecular weight: 81,681 Da
Basal Isoelectric point: 4.55  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Protein Acetylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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SIRT1

Protein Structure Not Found.
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Sites Implicated In
apoptosis, induced: S682‑p
cell cycle regulation: T530‑p, S540‑p
transcription, induced: S682‑p
acetylation: T530‑p, S540‑p
enzymatic activity, induced: S27‑p, S47‑p, T530‑p, S540‑p
intracellular localization: S27‑p, S47‑p, T530‑p, S682‑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



 LTP 

LTP: 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.


 HTP 

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


       human

 
1 19 S14‑p LALQPGGsPsAAGAD
0 3 S16‑p LQPGGsPsAAGADRE
0 7 S26‑p GADREAAssPAGEPL
4 14 S27‑p ADREAAssPAGEPLR
5 46 S47‑p DGPGLERsPGEPGGA
0 2 G52 ERsPGEPGGAAPERE
0 1 T154 LFGDEIITNGFHsCE
0 5 S159‑p IITNGFHsCEsDEED
1 4 S162‑p NGFHsCEsDEEDRAS
0 2 S172‑p EDRASHAssSDWTPR
0 1 S173‑p DRASHAssSDWTPRP
0 3 K238‑ub PPKRKKRkDINTIED
0 1 Y280‑p FRSRDGIyARLAVDF
0 1 Y301‑p QAMFDIEyFRKDPRP
0 1 K311‑ub KDPRPFFkFAkEIYP
0 1 K314‑ub RPFFkFAkEIYPGQF
0 2 S333‑p CHKFIALsDKEGKLL
1 0 T344‑p GKLLRNYtQNIDTLE
0 1 K430‑ac HRAMKYDkDEVDLLI
0 1 S441‑p DLLIVIGssLkVRPV
1 1 S442‑p LLIVIGssLkVRPVA
0 1 K444‑ac IVIGssLkVRPVALI
0 1 K499‑ub RLGGEYAkLCCNPVK
4 32 T530‑p YLSELPPtPLHVsED
0 6 S535‑p PPtPLHVsEDsssPE
0 7 S538‑p PLHVsEDsssPERts
0 4 S539‑p LHVsEDsssPERtsP
1 8 S540‑p HVsEDsssPERtsPP
0 2 T544‑p DsssPERtsPPDsSV
0 1 S545‑p sssPERtsPPDsSVI
0 1 S549‑p ERtsPPDsSVIVTLL
0 1 S562‑p LLDQAAKsNDDLDVs
0 1 S569‑p sNDDLDVsESKGCME
0 1 K578‑ac SKGCMEEkPQEVQTS
0 1 S590‑p QTSRNVEsIAEQMEN
0 2 K601‑ub QMENPDLkNVGSSTG
0 2 K610‑ub VGSSTGEkNERtsVA
0 1 T614‑p TGEkNERtsVAGtVR
0 12 S615‑p GEkNERtsVAGtVRK
0 2 T619‑p ERtsVAGtVRKCWPN
2 0 S659‑p FHGAEVYsDsEDDVL
2 0 S661‑p GAEVYsDsEDDVLSS
1 0 S682‑p SDSGTCQsPSLEEPM
1 0 S693 EEPMEDESEIEEFYN
1 29 T719‑p AGGAGFGtDGDDQEA
1 0 K734‑sm INEAISVkQEVTDMN
0 3 S747‑p MNYPSNKs_______
2327 : Phospho-SirT1 (Ser27) Antibody
2314 : Phospho-SirT1 (Ser47) Antibody
  mouse

 
S14‑p LALQAAGsPsAAAAM
S16‑p LQAAGsPsAAAAMEA
S25 AAAMEAASQPADEPL
Q26 AAMEAASQPADEPLR
S46‑p DGPGLGRsPGEPsAA
S51‑p GRsPGEPsAAVAPAA
T146‑p LLTDGLLtNGFHsCE
S151‑p LLtNGFHsCEsDDDD
S154‑p NGFHsCEsDDDDRTS
S164 DDRTSHASSSDWTPR
S165 DRTSHASSSDWTPRP
K230 PPKRKKRKDINTIED
Y272 FRSRDGIYARLAVDF
Y293 QAMFDIEYFRKDPRP
K303 KDPRPFFKFAKEIYP
K306 RPFFKFAKEIYPGQF
S325 CHKFIALSDKEGKLL
T336 GKLLRNYTQNIDTLE
K422 HRAMKYDKDEVDLLI
S433 DLLIVIGSsLKVRPV
S434‑p LLIVIGSsLKVRPVA
K436 IVIGSsLKVRPVALI
K491 RLGGEYAKLCCNPVK
T522‑p HLSELPPtPLHIsED
S527‑p PPtPLHIsEDsssPE
S530‑p PLHIsEDsssPERTV
S531‑p LHIsEDsssPERTVP
S532‑p HIsEDsssPERTVPQ
T536 DsssPERTVPQDSSV
V537 sssPERTVPQDSSVI
S541 ERTVPQDSSVIATLV
N554 LVDQATNNNVNDLEV
S562 NVNDLEVSESSCVEE
K570 ESSCVEEKPQEVQTS
N582 QTSRNVENINVENPD
K591 NVENPDFKAVGSSTA
K600 VGSSTADKNERTSVA
T604 TADKNERTSVAETVR
S605 ADKNERTSVAETVRK
T609 ERTSVAETVRKCWPN
S649‑p FHGAEVYsDsEDDVL
S651‑p GAEVYsDsEDDVLSS
S672 SDSGTCQSPSLEEPL
S683‑p EEPLEDEsEIEEFYN
A709 AGGSGFGADGGDQEV
R724 VNEAIATRQELTDVN
S737 VNYPSDKS_______
  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
K318 RPFFKFAKEIYPGQF
S337 CHKFIALSDKEGKLL
T348 GKLLRNYTQNIDTLE
K434 HRAMKYDKDEVDLLI
S445 DLLIVIGSSLKVRPV
S446 LLIVIGSSLKVRPVA
K448 IVIGSSLKVRPVALI
K503 RLGGEYAKLCCNPVK
T534 HLSELPPTPLHISED
S539 PPTPLHISEDSSsPE
S542 PLHISEDSSsPERTV
S543 LHISEDSSsPERTVP
S544‑p HISEDSSsPERTVPQ
T548 DSSsPERTVPQDSSV
V549 SSsPERTVPQDSSVI
S553 ERTVPQDSSVIATLV
N566 LVDQTIKNKVDDLEV
S574 KVDDLEVSEPKSCVE
K583 PKSCVEEKSQEVQTY
S595 QTYRNVESINVENPD
K604 NVENPDFKAVGSSTG
K613 VGSSTGDKNERTSVA
T617 TGDKNERTSVAETVR
S618 GDKNERTSVAETVRK
T622 ERTSVAETVRKCWPN
S662 FHGAEVYSDSEDDAL
S664 GAEVYSDSEDDALSS
S685 SDSGTCQSPSLEEPL
S696 EEPLEDESEIEEFYN
A720 ECAGGSGADGGDQEA
K735 VNEAIAMKQELTDVN
S748 VNCTPDKSEHY____
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