SIRT1 Gene Summary [Human]
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]
Details
| Type | Protein Coding |
| Official Symbol | SIRT1 |
| Official Name | sirtuin 1 [Source:HGNC Symbol;Acc:HGNC:14929] |
| Ensembl ID | ENSG00000096717 |
| Bio databases IDs | |
| Aliases | sirtuin 1 |
| Synonyms | SIR2, Sir2a, SIR2alpha, SIR2L1, Sir2 α, sirtuin 1 |
| Species | Human, Homo sapiens |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in human SIRT1 often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- sirtuin domain
- transcription regulator
- transcription co-activator
- transcription co-repressor
- deacetylase motif
- poly ADP ribose polymerase domain
- NAD-dependent histone deacetylase activity (H4-K16 specific)
- transcription factor binding
- chromatin binding
- enzyme
- Hdac domain
- core domain, functional
- enzyme activator activity
- identical protein binding
- NAD-dependent histone deacetylase activity (H3-K9 specific)
- protein deacetylase activity
- linear amide carbon-nitrogen bond hydrolase
- histone deacetylase
- SIR2
- Non-amino-acyl group acyltransferase
- intermediate filament binding
- histone binding
- ligand-dependent nuclear receptor interactor
- protein kinase binding
- protease binding
- catalytic domain
- nucleic acid binding
- nuclear localization sequence
- enzyme binding
- protein domain specific binding
- protein binding
- p53 binding
- deacetylase
- sequence-specific DNA binding
- ESA domain
- NAD-dependent histone deacetylase
- double-stranded DNA binding
- active site
Pathways
Biological processes and signaling networks where the SIRT1 gene in human plays a role, providing insight into its function and relevance in health or disease.
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- neoplasia
- diabetes mellitus
- Huntington disease
- epithelial neoplasia
- benign neoplasia
- liver cancer
- liver neoplasia
- digestive system cancer
- abdominal cancer
- cancer
regulated by
- cyclosporin A
- napabucasin
- advanced glycation end-products
- lipopolysaccharide
- reactive oxygen species
- palmitic acid
- oleic acid
- THP-1 cells
- etoposide
- PRKAA
role in cell
- signaling in
- binding in
- invasion by
- proliferation
- survival
- cell survival
- migration
- expression in
- cellular infiltration by
- hyperactivation
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Nucleus
- nuclear fraction
- fibrillar center
- heterochromatin
- Cytoplasm
- Mitochondria
- cytosol
- inner nuclear membrane
- nucleoplasm
- nucleoli
- nuclear bodies
- nuclear envelope
- growth cone
- PML nuclear bodies
- chromatin
- axons
- cytosolic fraction
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human SIRT1 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- negative regulation of cAMP-dependent protein kinase activity
- positive regulation of cAMP-dependent protein kinase activity
- regulation of brown fat cell differentiation
- DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis
- DNA synthesis involved in DNA repair
- chromatin organization
- positive regulation of angiogenesis
- negative regulation of androgen receptor signaling pathway
- ovulation from ovarian follicle
- peptidyl-lysine acetylation
- negative regulation of transcription, DNA-dependent
- chromatin silencing at rDNA
- negative regulation of peptidyl-lysine acetylation
- energy homeostasis
- positive regulation of macrophage apoptotic process
- positive regulation of macroautophagy
- negative regulation of DNA damage response, signal transduction by p53 class mediator
- positive regulation of insulin receptor signaling pathway
- response to leptin stimulus
- response to hydrogen peroxide
- response to DNA damage stimulus
- cellular response to glucose starvation
- cellular glucose homeostasis
- regulation of centrosome duplication
- heterochromatin assembly
- negative regulation of helicase activity
- maintenance of nucleus location
- positive regulation of protein kinase B signaling cascade
- negative regulation of protein kinase B signaling cascade
- regulation of cellular response to heat
- positive regulation of cell proliferation
- negative regulation of cell cycle
- negative regulation of I-kappaB kinase/NF-kappaB cascade
- positive regulation of transcription from RNA polymerase II promoter
- negative regulation of neuron apoptotic process
- angiogenesis
- positive regulation of cholesterol efflux
- positive regulation of cellular senescence
- negative regulation of cellular response to testosterone stimulus
- negative regulation of cellular senescence
- fatty acid homeostasis
- cellular response to starvation
- pyrimidine dimer repair by nucleotide-excision repair
- positive regulation of blood vessel endothelial cell migration
- negative regulation of phosphorylation
- muscle organ development
- positive regulation of smooth muscle cell differentiation
- positive regulation of protein phosphorylation
- positive regulation of endothelial cell proliferation
- positive regulation of double-strand break repair
- regulation of bile acid biosynthetic process
- negative regulation of transforming growth factor beta receptor signaling pathway
- regulation of lipid storage
- regulation of smooth muscle cell apoptotic process
- transforming growth factor beta receptor signaling pathway
- regulation of transcription by glucose
- positive regulation of gluconeogenesis
- triglyceride mobilization
- white fat cell differentiation
- circadian regulation of gene expression
- cellular response to hypoxia
- cellular triglyceride homeostasis
- negative regulation of TOR signaling cascade
- regulation of peroxisome proliferator activated receptor signaling pathway
- macrophage differentiation
- positive regulation of DNA repair
- UV-damage excision repair
- leptin-mediated signaling pathway
- negative regulation of NF-kappaB transcription factor activity
- negative regulation of prostaglandin biosynthetic process
- regulation of apoptotic process
- negative regulation of sequence-specific DNA binding transcription factor activity
- regulation of mitotic cell cycle
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
- negative regulation of gene expression
- proteasomal ubiquitin-dependent protein catabolic process
- regulation of glucose metabolic process
- negative regulation of triglyceride biosynthetic process
- protein ubiquitination
- regulation of endodeoxyribonuclease activity
- behavioral response to starvation
- cholesterol homeostasis
- positive regulation of MHC class II biosynthetic process
- methylation-dependent chromatin silencing
- positive regulation of macrophage cytokine production
- negative regulation of transcription from RNA polymerase II promoter
- response to oxidative stress
- response to insulin stimulus
- cellular response to ionizing radiation
- cellular response to tumor necrosis factor
- cellular response to hydrogen peroxide
- stress-induced premature senescence
- spermatogenesis
- negative regulation of fat cell differentiation
- protein deacetylation
- regulation of cell proliferation
- single strand break repair
- protein destabilization
- positive regulation of adaptive immune response
- negative regulation of apoptotic process
- positive regulation of apoptotic process
- regulation of protein serine/threonine kinase activity
Cellular Component
Where in the cell the gene product is active
- PML body
- ESC/E(Z) complex
- nucleolus
- chromatin
- chromatin silencing complex
- fibrillar center
- nucleoplasm
- nuclear envelope
- nucleus
- heterochromatin
- euchromatin
- nuclear inner membrane
- cytoplasm
- mitochondrion
- cytosol
- rDNA heterochromatin
Molecular Function
What the gene product does at the molecular level
- ligand-dependent nuclear receptor binding
- RNA polymerase II core promoter proximal region sequence-specific DNA binding
- NAD+ ADP-ribosyltransferase activity
- bHLH transcription factor binding
- p53 binding
- protein deacetylase activity
- NAD+ binding
- identical protein binding
- NAD-dependent histone deacetylase activity (H3-K9 specific)
- NAD-dependent histone deacetylase activity (H3-K14 specific)
- HLH domain binding
- protein binding
- NAD-dependent protein deacetylase activity
- NAD-dependent histone deacetylase activity (H4-K16 specific)
- transcription coactivator activity
- histone deacetylase activity
- histone binding
- metal ion binding
- transcription corepressor activity
- histone acetyl-lysine binding
- deacetylase activity
- NAD-dependent histone deacetylase activity
- mitogen-activated protein kinase binding
- enzyme binding