Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Sirt1. (This text reflects annotations as of Wednesday, January 23, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Sirt1
  • participates in the following biological processes:
    • histone deacetylation ^{[9, 11]}
    • histone H3 deacetylation ^[11]
    • intrinsic apoptotic signaling pathway in response to DNA damage ^[3]
    • negative regulation of transcription, DNA-dependent ^[26]
    • negative regulation of transforming growth factor beta receptor signaling pathway ^[12]
    • positive regulation of cAMP-dependent protein kinase activity ^[13]
    • positive regulation of macroautophagy ^{[14, 24]}
    • positive regulation of transcription from RNA polymerase II promoter ^[4]
    • protein deacetylation ^[30]
    • protein destabilization ^[15]
    • regulation of smooth muscle cell apoptotic process ^[12]
    • response to insulin stimulus ^[34]
  • performs the following molecular functions:
    • NAD-dependent histone deacetylase activity ^[9]
    • NAD-dependent histone deacetylase activity (H3-K9 specific) ^[11]
    • NAD-dependent protein deacetylase activity ^{[4, 30]}
    • protein deacetylase activity ^[36]
  • is located in the following cellular components:
    • chromatin ^[3]
    • cytoplasm ^[28]
    • nuclear heterochromatin ^[29]
    • nucleus ^{[18, 26, 29]}
• The gene product of Sirt1 has been shown to bind to the gene products of Clock, Dyrk1a, Dyrk3, Hic1, Hnf1a, Irs2, Nhlh2, Nr0b2, Pparg, Ppargc1a, Smad7, Srebf1, Suv39h1. ^{[1, 2, 3, 4, 7, 8, 10, 12, 16, 20, 21, 22, 23, 25, 27, 29, 30, 31, 32, 34]} Researchers have inferred, based on physical interactions, that the gene product of Sirt1
  • performs the following molecular functions:
    • enzyme binding ^{[11, 36]}
    • p53 binding ^[17]
    • protein domain specific binding ^[22]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Sirt1
  • participates in the following biological processes:
    • cellular glucose homeostasis ^[27]
    • cellular response to ionizing radiation ^[33]
    • cellular response to starvation ^[22]
    • cellular triglyceride homeostasis ^[15]
    • cholesterol homeostasis ^[15]
    • DNA synthesis involved in DNA repair ^[33]
    • fatty acid homeostasis ^[5]
    • negative regulation of fat cell differentiation ^[22]
    • negative regulation of phosphorylation ^[33]
    • negative regulation of prostaglandin biosynthetic process ^[35]
    • negative regulation of protein kinase B signaling cascade ^[19]
    • negative regulation of TOR signaling cascade ^[6]
    • ovulation from ovarian follicle ^[18]
    • positive regulation of cholesterol efflux ^[15]
    • positive regulation of macrophage apoptotic process ^[35]
    • positive regulation of protein phosphorylation ^[34]
    • pyrimidine dimer repair by nucleotide-excision repair ^[19]
    • regulation of apoptotic process ^[17]
    • regulation of bile acid biosynthetic process ^[2]
    • regulation of glucose metabolic process ^[5]
    • regulation of peroxisome proliferator activated receptor signaling pathway ^[22]
    • spermatogenesis ^[18]
    • triglyceride mobilization ^[22]
    • white fat cell differentiation ^[22]
  • performs the following molecular functions:
    • deacetylase activity ^[29]
    • transcription corepressor activity ^[22]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Sirt1:
  • participates in the following biological processes:
    • angiogenesis
    • cellular response to hydrogen peroxide
    • cellular response to hypoxia
    • cellular response to tumor necrosis factor
    • chromatin silencing at rDNA
    • establishment of chromatin silencing
    • histone deacetylation
    • histone H3 deacetylation
    • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
    • maintenance of chromatin silencing
    • negative regulation of androgen receptor signaling pathway
    • negative regulation of apoptotic process
    • negative regulation of cAMP-dependent protein kinase activity
    • negative regulation of cell growth
    • negative regulation of cellular response to testosterone stimulus
    • negative regulation of cellular senescence
    • negative regulation of DNA damage response, signal transduction by p53 class mediator
    • negative regulation of helicase activity
    • negative regulation of I-kappaB kinase/NF-kappaB cascade
    • negative regulation of NF-kappaB transcription factor activity
    • negative regulation of peptidyl-lysine acetylation
    • negative regulation of phosphorylation
    • negative regulation of protein kinase B signaling cascade
    • negative regulation of sequence-specific DNA binding transcription factor activity
    • negative regulation of TOR signaling cascade
    • negative regulation of transcription from RNA polymerase II promoter
    • negative regulation of transcription, DNA-dependent
    • peptidyl-lysine acetylation
    • peptidyl-lysine deacetylation
    • positive regulation of adaptive immune response
    • positive regulation of apoptotic process
    • positive regulation of cAMP-dependent protein kinase activity
    • positive regulation of cell proliferation
    • positive regulation of cellular senescence
    • positive regulation of chromatin silencing
    • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
    • positive regulation of DNA repair
    • positive regulation of insulin receptor signaling pathway
    • positive regulation of macroautophagy
    • positive regulation of MHC class II biosynthetic process
    • positive regulation of transcription from RNA polymerase II promoter
    • proteasomal ubiquitin-dependent protein catabolic process
    • protein deacetylation
    • protein ubiquitination
    • pyrimidine dimer repair by nucleotide-excision repair
    • regulation of cell proliferation
    • regulation of endodeoxyribonuclease activity
    • regulation of mitotic cell cycle
    • regulation of protein import into nucleus, translocation
    • regulation of response to stress
    • response to DNA damage stimulus
    • response to oxidative stress
    • single strand break repair
  • performs the following molecular functions:
    • bHLH transcription factor binding
    • deacetylase activity
    • histone binding
    • histone deacetylase activity
    • HLH domain binding
    • identical protein binding
    • mitogen-activated protein kinase binding
    • NAD-dependent histone deacetylase activity
    • NAD-dependent protein deacetylase activity
    • p53 binding
    • protein C-terminus binding
    • protein deacetylase activity
    • transcription corepressor activity
  • is located in the following cellular components:
    • chromatin silencing complex
    • cytoplasm
    • nuclear chromatin
    • nuclear envelope
    • nuclear euchromatin
    • nuclear heterochromatin
    • nuclear inner membrane
    • nucleolus
    • nucleoplasm
    • nucleus
    • PML body
    • rDNA heterochromatin

---

Summary text based on GO annotations supported by structural data

• Sirt1 encodes a protein or proteins that contain the following InterPro domains: Sirtuin family, Sirtuin family, catalytic core domain, Sirtuin family, catalytic core small domain, indicating that the gene product:
  • performs the following molecular functions:
    • NAD+ binding

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Sirt1 indicates that it:
  • participates in the following biological processes:
    • apoptotic process
    • cell differentiation
    • multicellular organismal development
    • muscle organ development
    • regulation of transcription, DNA-dependent
    • rRNA processing
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • hydrolase activity
    • metal ion binding
  • is located in the following cellular components:
    • mitochondrion

---

References

1. Asher G et al. (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell, 134:317-28. (PubMed:18662546)
2. Chanda D et al. (2010) Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation. Nucleic Acids Res, 38:4607-19. (PubMed:20375098)
3. Chen WY et al. (2005) Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell, 123:437-48. (PubMed:16269335)
4. Daitoku H et al. (2004) Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci U S A, 101:10042-7. (PubMed:15220471)
5. Gerhart-Hines Z et al. (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J, 26:1913-23. (PubMed:17347648)
6. Ghosh HS et al. (2010) SIRT1 negatively regulates the mammalian target of rapamycin. PLoS One, 5:e9199. (PubMed:20169165)
7. Grimm AA et al. (2011) A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates Crp expression. Aging Cell, 10:305-17. (PubMed:21176092)
8. Guo X et al. (2010) DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem, 285:13223-32. (PubMed:20167603)
9. Imai S et al. (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature, 403:795-800. (PubMed:10693811)
10. Kang H et al. (2009) CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNA-damage. PLoS One, 4:e6611. (PubMed:19680552)
11. Kornberg MD et al. (2010) GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol, 12:1094-100. (PubMed:20972425)
12. Kume S et al. (2007) SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem, 282:151-8. (PubMed:17098745)
13. Lan F et al. (2008) SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation. J Biol Chem, 283:27628-35. (PubMed:18687677)
14. Lee IH et al. (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A, 105:3374-9. (PubMed:18296641)
15. Li X et al. (2007) SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell, 28:91-106. (PubMed:17936707)
16. Libert S et al. (2011) SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive. Cell, 147:1459-72. (PubMed:22169038)
17. Luo J et al. (2001) Negative Control of p53 by Sir2alpha Promotes Cell Survival under Stress. Cell, 107:137-48. (PubMed:11672522)
18. McBurney MW et al. (2003) The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol, 23:38-54. (PubMed:12482959)
19. Ming M et al. (2010) Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. Proc Natl Acad Sci U S A, 107:22623-8. (PubMed:21149730)
20. Nakahata Y et al. (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell, 134:329-40. (PubMed:18662547)
21. Nemoto S et al. (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem, 280:16456-60. (PubMed:15716268)
22. Picard F et al. (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 429:771-6. (PubMed:15175761)
23. Ponugoti B et al. (2010) SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem, 285:33959-70. (PubMed:20817729)
24. Powell MJ et al. (2011) Disruption of a Sirt1-dependent autophagy checkpoint in the prostate results in prostatic intraepithelial neoplasia lesion formation. Cancer Res, 71:964-75. (PubMed:21189328)
25. Qiang L et al. (2012) Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma. Cell, 150:620-32. (PubMed:22863012)
26. Revollo JR et al. (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem, 279:50754-63. (PubMed:15381699)
27. Rodgers JT et al. (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature, 434:113-8. (PubMed:15744310)
28. Tanno M et al. (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem, 282:6823-32. (PubMed:17197703)
29. Vaquero A et al. (2007) SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature, 450:440-4. (PubMed:18004385)
30. Vaziri H et al. (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell, 107:149-59. (PubMed:11672523)
31. Wang C et al. (2006) Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol, 8:1025-31. (PubMed:16892051)
32. Wong S et al. (2007) Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1. Biochem J, 407:451-60. (PubMed:17620057)
33. Yuan Z et al. (2007) SIRT1 regulates the function of the Nijmegen breakage syndrome protein. Mol Cell, 27:149-62. (PubMed:17612497)
34. Zhang J. (2007) The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. J Biol Chem, 282:34356-64. (PubMed:17901049)
35. Zhang R et al. (2010) SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages. J Biol Chem, 285:7097-110. (PubMed:20042607)
36. Zhou Y et al. (2009) Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing. Nat Cell Biol, 11:1010-6. (PubMed:19578370)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---