Sirt1 Sirtuin 1 [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Sirt1provided by FlyBase
Official Full Name: Sirtuin 1provided by FlyBase
Primary source: FLYBASE:FBgn0024291
Locus tag: Dmel_CG5216
See related: AllianceGenome:FB:FBgn0024291
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: BEST:LD38188; CG5216; D.mel1; Dmel\CG5216; dmSRT406; dsir2; dSir2; dSIR2; DSir2; l(2)05326; SIR-2; sir2; Sir2; SIR2; Sir2L; sirt1; SIRT1; Sirt1/dSir2
Summary: Enables NAD-dependent histone deacetylase activity and transcription coactivator binding activity. Involved in several processes, including behavioral response to ethanol; determination of adult lifespan; and regulation of gene expression. Located in cytoplasm and nucleoplasm. Is expressed in several structures, including embryonic/larval garland cell; embryonic/larval salivary gland; germ band; larval central nervous system; and ventral nerve cord. Used to study alcohol use disorder and type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in Huntington's disease and prostate cancer. Orthologous to human SIRT1 (sirtuin 1). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 34A7-34A7; 2-47 cM

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2L	NT_033779.5 (13165564..13169551)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2L	NT_033779.4 (13165564..13169551)

Chromosome 2L - NT_033779.5 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A natural genetic variation screen identifies insulin signaling, neuronal communication, and innate immunity as modifiers of hyperglycemia in the absence of Sirt1.
Title: A natural genetic variation screen identifies insulin signaling, neuronal communication, and innate immunity as modifiers of hyperglycemia in the absence of Sirt1.
The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila.
Title: The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila.
Sirt1 terminates ethanol-induction of Hr38 to promote ethanol tolerance.
Title: Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance.
Sir2 in the mushroom bodies promotes short-term ethanol-induced behavioral plasticity by allowing changes in the expression of presynaptic molecules.
Title: Sir2/Sirt1 Links Acute Inebriation to Presynaptic Changes and the Development of Alcohol Tolerance, Preference, and Reward.
The role of Sirt1 in Notch signalling is, therefore, more complex than previously recognized, and its diverse effects may be explained by a plethora of Sirt1 substrates involved in the regulation of Notch signalling.
Title: The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila.
A lowered gene dosage of Sir2, in mutant heterozygotes, can extend normal longevity and greatly augment survivorship during amino-acid starvation in Drosophila.
Title: Extended longevity and survivorship during amino-acid starvation in a Drosophila Sir2 mutant heterozygote.
Drosophila HNF4 mutants display diabetic phenotypes similar to those of sir2 mutants, and protein levels for dHNF4 are reduced in sir2 mutant animals. Sir2 exerts these effects by deacetylating and stabilizing dHNF4 through protein interactions.
Title: Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
Low oxygen partial pressure of highly resistant Drosophila significantly reduces the time of restitution and increases the expression of Sir2 and CG14740 genes.
Title: [The effect of altered oxygen partial pressure on the resisitance to hypoxia and expression of oxygen-sensitive genes in Drosophila melanogaster].
Using two transgenic dSir2 lines that were reported not to extend life span, we show significant life span extension when dSir2 expression is induced between 2 and 5-fold.
Title: Increased expression of Drosophila Sir2 extends life span in a dose-dependent manner.
This study provides additional independent evidence for the concept of Sir2 as a longevity gene and as a promising pharmacological target to cure age-related diseases.
Title: Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables NAD+ binding	IBA Inferred from Biological aspect of Ancestor more info
enables NAD+ binding	IEA Inferred from Electronic Annotation more info
enables histone deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone deacetylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone deacetylase activity, NAD-dependent	IBA Inferred from Biological aspect of Ancestor more info
enables histone deacetylase activity, NAD-dependent	IDA Inferred from Direct Assay more info	PubMed
enables histone deacetylase activity, NAD-dependent	NAS Non-traceable Author Statement more info	PubMed
enables p53 binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein lysine deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein lysine deacetylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables transcription coactivator binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in behavioral response to ethanol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to insulin stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heterochromatin formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in heterochromatin formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lateral inhibition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of feeding behavior	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of feeding behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of response to ethanol	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in nuclear inner membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in rDNA heterochromatin	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: sirtuin 1

Names: CG5216-PA; Sir2; Sirt1-PA; silent information regulator 2; sirtuin 2

NP_477351.1

EC 3.5.1.98

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033779.5 Reference assembly

Range

13165564..13169551

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_058003.4 → NP_477351.1 sirtuin 1 [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_477351.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D5SHQ6, O96505, Q9VK34

UniProtKB/TrEMBL

I1V510

Related

FBpp0080015

Conserved Domains (2) summary

cd01408
Location:222 → 476

SIRT1; SIRT1: Eukaryotic group (class1) which includes human sirtuins SIRT1-3 and yeast Hst1-4; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 ...

pfam04574
Location:202 → 228

DUF592; Protein of unknown function (DUF592)