FlyBase Gene Report: Dmel\Sirt6

General Information

Symbol

Dmel\Sirt6

Species

D. melanogaster

Name

Sirtuin 6

Annotation Symbol

CG6284

Feature Type

protein_coding_gene

FlyBase ID

FBgn0037802

Gene Model Status

Current

Stock Availability

8 publicly available

Enzyme Name (EC)

histone deacetylase (3.5.1.98)

Gene Summary

Sirtuin 6 (Sirt6) encodes an NAD-dependent histone deacetylase in the class IV of the Sirtuin family. It is involved in chromatin silencing and determination of adult lifespan. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)

All Summaries

Gene Snapshot
Alliance
Auto summary
Gene Group
UniProtKB
Interactive Fly

Key Links

Genomic Location

Cytogenetic map

86A2-86A3

Sequence location

3R:10,255,349..10,261,849 [-]

Recombination map

3-49

RefSeq locus

NT_033777 REGION:10255349..10261849

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse

Other Genome Views

The following external sites may use different assemblies or annotations than FlyBase.

Function

Gene Ontology (GO) Annotations (10 terms)

Molecular Function (5 terms)

Terms Based on Experimental Evidence (2 terms)

CV Term

Evidence

References

enables histone deacetylase activity

inferred from mutant phenotype

(Feller et al., 2015)

enables NAD-dependent histone H3K9 deacetylase activity

inferred from direct assay

(Taylor et al., 2022)

Terms Based on Predictions or Assertions (4 terms)

CV Term

Evidence

References

enables NAD+ binding

inferred from biological aspect of ancestor with PANTHER:PTN000119154

(GO Reference Genome Project, 2011-)

inferred from electronic annotation with InterPro:IPR003000

(InterPro Project Members, 2004-)

enables NAD-dependent histone deacetylase activity

non-traceable author statement

(Feller et al., 2015)

enables NAD-dependent histone H3K9 deacetylase activity

inferred from biological aspect of ancestor with PANTHER:PTN000872287

(GO Reference Genome Project, 2011-)

enables transcription corepressor activity

inferred from biological aspect of ancestor with PANTHER:PTN000119157

(GO Reference Genome Project, 2011-)

Biological Process (3 terms)

Terms Based on Experimental Evidence (3 terms)

CV Term

Evidence

References

involved_in determination of adult lifespan

inferred from mutant phenotype

(Kusama et al., 2006)

inferred from direct assay

(Taylor et al., 2022)

involved_in negative regulation of DNA methylation-dependent heterochromatin formation

inferred from mutant phenotype

(Herz et al., 2014)

involved_in negative regulation of transcription by RNA polymerase II

inferred from direct assay

(Taylor et al., 2022)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

involved_in negative regulation of transcription by RNA polymerase II

inferred from biological aspect of ancestor with PANTHER:PTN000119157

(GO Reference Genome Project, 2011-)

Cellular Component (2 terms)

Terms Based on Experimental Evidence (2 terms)

CV Term

Evidence

References

part_of chromatin

inferred from direct assay

(Taylor et al., 2022)

is_active_in nucleus

inferred from direct assay

(Taylor et al., 2022)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

is_active_in nucleus

inferred from biological aspect of ancestor with PANTHER:PTN008492176

(GO Reference Genome Project, 2011-)

located_in nucleus

inferred from sequence or structural similarity with HGNC:14934

(Frye, 2000)

Gene Group (FlyBase)

SIRTUIN LYSINE DEACETYLASES

Protein Family (UniProt)

Belongs to the sirtuin family. Class IV subfamily. (Q9VH08)

Protein Signatures (InterPro)

Catalytic Activity (EC/Rhea)

histone deacetylase activity

H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone] (3.5.1.98)

RHEA 58196:

Summaries

Gene Snapshot

Gene Group (FlyBase)

SIRTUIN LYSINE DEACETYLASES -: Sirtuin family members are NAD⁺-dependent lysine deacetylases that share a common catalytic core domain. (Adapted from FBrf0159755).

Protein Function (UniProtKB)

NAD-dependent histone deacylase that acts as a regulator of life span.

(UniProt, Q9VH08)

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\Sirt6 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)

Isoform displayed:

Pfam protein domains

InterPro name

classification

start

end

Protein Domains (via SMART)

Isoform displayed:

SMART protein domains

InterPro name

classification

start

end

Structure

Protein 3D structure (Predicted by AlphaFold) (AlphaFold entry Q9VH08)

If you don't see a structure in the viewer, refresh your browser.

Model Confidence:

Very high (pLDDT > 90)
Confident (90 > pLDDT > 70)
Low (70 > pLDDT > 50)
Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures

Crossreferences

Comments on Gene Model

Gene model reviewed during 5.48

Mutation in sequenced strain: insertion of transposon.

Sequence Ontology: Class of Gene

nuclear_gene

protein_coding_gene

retrogene

(dos Santos, 2014, Metta and Schlötterer, 2010)

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

Sirt6-RB

FBtr0305358

NM_141733

1114

325

Additional Transcript Data and Comments

Reported size (kB)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

UniProt

RefSeq ID

GenBank

Sirt6-PB

FBpp0293897

36.0

325

7.73

Q9VH08

NP_649990

AAF54513

Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments

Reported size (kDa)

Comments

External Data

Crossreferences

InterPro - A database of protein families, domains and functional sites

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

Q9VH08

Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Sirt6 using the Feature Mapper tool.

External Data

Crossreferences

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Sirt6_1

Linkouts

Expression Data

Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

0.09

Transcript Expression

Additional Descriptive Data

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

Additional Descriptive Data

Marker for

Subcellular Localization

CV Term

Evidence

References

part_of chromatin

inferred from direct assay

(Taylor et al., 2022)

is_active_in nucleus

inferred from direct assay

(Taylor et al., 2022)

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Sirt6 in JBrowse

RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region

View exonic expression by developmental stage for Dmel\Sirt6

View exonic expression by tissue for Dmel\Sirt6

Bulk Downloads

RNA-Seq RPKM values for all genes

Reference

See Gelbart and Emmert, 2013 for analysis details and data files for all genes.

Developmental Proteome: Life Cycle

Developmental Proteome: Embryogenesis

External Data and Images

Linkouts

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

41254/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0037802

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0037802

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0037802

Flygut - An atlas of the Drosophila adult midgut

FBgn0037802

Images

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 4 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 11 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of Sirt6

Transgenic constructs containing regulatory region of Sirt6

Aberrations (Deficiencies and Duplications) ( 1 )

Inferred from experimentation ( 1 )

Gene disrupted in

Df(3R)Exel6156

(Ryder, 2004.4.26)

Inferred from location ( 0 )

Variants

Variant Molecular Consequences

Alleles Representing Disease-Implicated Variants

Phenotypes

For more details about a specific phenotype click on the relevant allele symbol.

Lethality

Allele

lethal - all die during P-stage, with Scer\GAL4^Mef2.PR

Sirt6^GD11877

viable, with Dcr-2^UAS.cDa, Scer\GAL4^elav.PLu

Sirt6^GD11877

viable, with Scer\GAL4^pnr-MD237

Sirt6^GD11877

viable, with Scer\GAL4^tin.CΔ4

Sirt6^GD11877

Sterility

Allele

male semi-fertile

Other Phenotypes

Allele

abnormal developmental rate | larval stage

Sirt6^bck-L1

abnormal locomotor behavior | adult stage, with Scer\GAL4^Act5C.PI, Sirt6^bck-L1

Sirt6^UAS.Tag:FLAG

abnormal locomotor behavior | adult stage, with Scer\GAL4^Act5C.PI, Sirt6^UAS.Tag:FLAG

Sirt6^bck-L1

abnormal locomotor behavior | adult stage | progressive

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^Act5C.PI

Sirt6^UAS.Tag:FLAG

abnormal locomotor behavior | adult stage | progressive, with Scer\GAL4^αTub84B.PL

Sirt6^UAS.cTa

abnormal starvation stress response | adult stage | progressive

decreased body weight | adult stage, with Scer\GAL4^αTub84B.PL

Sirt6^UAS.cTa

decreased fecundity | mated female

increased body size | adult stage

increased body size | larval stage

Sirt6^bck-L1

increased body weight | adult stage

increased body weight | larval stage

Sirt6^bck-L1

increased mortality | calorie restriction conditional

increased size | adult stage

long lived, with Scer\GAL4^Act5C.PI

Sirt6^UAS.Tag:FLAG

long lived, with Scer\GAL4^αTub84B.PL

Sirt6^UAS.cTa

long lived | RU486 conditional, with Scer\GAL4^Switch1.106

Sirt6^UAS.cTa

long lived | RU486 conditional, with Scer\GAL4^{Tub.Switch.PU}

Sirt6^UAS.cTa

short lived

short lived, with Scer\GAL4^Act5C.PU

Sirt6^RNAi.UAS.cKa

short lived | RU486 conditional, with Scer\GAL4^{Tub.Switch.PU}

Sirt6^HMS01009

visible | adult stage

Phenotype manifest in

Allele

mitochondrion | adult stage

wing

Orthologs

Downloads

Download All DIOPT Orthologs

Human Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Homo sapiens (Human) (7)

Hsap\SIRT6

14 of 14

Yes

Hsap\SIRT2

3 of 14

Hsap\SIRT3

3 of 14

Hsap\SIRT5

3 of 14

Yes

Hsap\SIRT7

3 of 14

Hsap\SIRT1

2 of 14

Hsap\SIRT4

2 of 14

Model Organism Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Rattus norvegicus (Norway rat) (7)

Rnor\Sirt6

14 of 14

Yes

Rnor\Sirt2

3 of 14

Rnor\Sirt3

3 of 14

Rnor\Sirt5

3 of 14

Yes

Rnor\Sirt7

3 of 14

Rnor\Sirt4

2 of 14

Rnor\Sirt1

1 of 14

Mus musculus (laboratory mouse) (7)

Mmus\Sirt6

13 of 14

Yes

3 of 14

3 of 14

3 of 14

2 of 14

2 of 14

2 of 14

Yes

Xenopus tropicalis (Western clawed frog) (9)

Xtro\sirt6

7 of 13

Yes

Xtro\sirt3.1

2 of 13

Xtro\sirt5

2 of 13

Yes

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Danio rerio (Zebrafish) (8)

Drer\sirt6

13 of 14

Yes

Drer\si:dkey-103i16.6

3 of 14

3 of 14

3 of 14

2 of 14

2 of 14

2 of 14

Yes

Drer\sirt7

2 of 14

Caenorhabditis elegans (Nematode, roundworm) (4)

Cele\sir-2.4

13 of 14

Yes

Cele\sir-2.3

2 of 14

Cele\sir-2.1

1 of 14

Cele\sir-2.2

1 of 14

Anopheles gambiae (African malaria mosquito) (4)

Agam\AgaP_AGAP001458

12 of 12

Yes

Agam\AgaP_AGAP001220

2 of 12

Agam\AgaP_AGAP002943

2 of 12

Agam\AgaP_AGAP013148

2 of 12

Arabidopsis thaliana (thale-cress) (2)

Atha\SRT1

12 of 13

Yes

Atha\SRT2

2 of 13

Saccharomyces cerevisiae (Brewer's yeast) (5)

Scer\HST2

3 of 13

Yes

2 of 13

2 of 13

2 of 13

2 of 13

Schizosaccharomyces pombe (Fission yeast) (3)

Spom\hst2

3 of 12

Yes

Spom\hst4

2 of 12

Spom\sir2

2 of 12

Escherichia coli (enterobacterium) (1)

Ecol\cobB

4 of 11

Yes

Other Organism Orthologs (via OrthoDB)

Data provided directly from OrthoDB:Sirt6. Refer to their site for version information.

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v9.1)

Gene Symbol

Score

Source

Alignment

Drosophila melanogaster (Fruit fly) (9)

5 of 13

4 of 13

4 of 13

3 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Human Disease Associations

FlyBase Human Disease Model Reports

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Potential Models Based on Orthology ( 0 )

Human Ortholog

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)

Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.

Homo sapiens (Human)

Gene name

Score

OMIM

OMIM Phenotype

DO term

Complementation?

Transgene?

14 of 14

3 of 14

3 of 14

3 of 14

3 of 14

Functional Complementation Data

Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.

Interactions

Summary of Physical Interactions

esyN Network Diagram

Interactions Browser

Summary of Genetic Interactions

esyN Network Diagram

Show/hide secondary interactors
(data from AllianceMine provided by esyN)

esyN Network Key:

Suppression

Enhancement

View in Interactions Browser

Please look at the allele data for full details of the genetic interactions

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Myc

enhanceable

Sirt6

(Taylor et al., 2022)

Myc

suppressible

Sirt6

(Taylor et al., 2022)

External Data

Linkouts

BioGRID - A database of protein and genetic interactions.

66403

DroID - A comprehensive database of gene and protein interactions.

FBgn0037802

MIST (protein-protein) - An integrated Molecular Interaction Database

41254

Pathways

Signaling Pathways (FlyBase)

Metabolic Pathways

KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.

External Data

Linkouts

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

3-49

Cytogenetic map

86A2-86A3

Sequence location

3R:10,255,349..10,261,849 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

86A2-86A3

; Limits computationally determined from genome sequence between P{EP}Fmr1^EP3517&P{PZ}tws⁰²⁴¹⁴ and P{PZ}jumu⁰⁶⁴³⁹&P{lacW}l(3)j8B6^j8B6

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

Experimentally Determined Recombination Data

Location

3-49

(FlyBase, 2016)

3-46.6

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (8)

Aberrations including deletions of this gene Aberrations including duplications of this gene

Bloomington

30115

w¹¹¹⁸; P{EP}Sirt6^G5116

31399

y¹ v¹; P{TRiP.JF01583}attP2

79978

y¹ sc^* v¹ sev²¹; P{TOE.GS02694}attP40

34530

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01009}attP2

36801

y¹ sc^* v¹ sev²¹; P{TRiP.GL01008}attP40

NIG-Fly

HMS01009

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01009}attP2

VDRC

v330133

P{VSH330133}attP40

v22483

w¹¹¹⁸; P{GD11877}v22483

Genomic Clones (6)

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (11)

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced

BDGP DGC clones

Other clones

MIP29464

Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

FBgn0037802

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0037802

Antibody Information

Laboratory Generated Antibodies

polyclonal

(Wei et al., 2023)

Commercially Available Antibodies

Cell Line Information

Publicly Available Cell Lines

Other Stable Cell Lines

Other Comments

Relationship to Other Genes

Source for database merge of

Additional comments

The Sirt6 gene may have been derived from a parental gene that has since degraded or been lost in D. melanogaster, but is still present in other Drosophilids.

(Metta and Schlötterer, 2010)

Nomenclature History

Source for database identify of

Source for identity of: Sirt6 CG6284

(Barlow et al., 2001)

Nomenclature comments

Etymology

Synonyms and Secondary IDs (8)

Reported As

Symbol Synonym

CG6284

(Meadows, 2017.1.11, Ni et al., 2011.7.19, Metta and Schlötterer, 2010, Ni et al., 2010.12.1, Ni et al., 2008, Kusama et al., 2006, Giot et al., 2003, Barlow et al., 2001)

D.mel4

(Frye, 2000)

SIRT6

(Wei et al., 2023)

Sirt6

(Bhatt and Tiwari, 2023, Hao et al., 2023, Romey-Glüsing et al., 2018, Lin et al., 2017, Transgenic RNAi Project members, 2017-, dos Santos, 2014, Herz et al., 2014, Japanese National Institute of Genetics, 2012.5.21)

dSIRT6

(Barlow et al., 2001)

dmSRT408

(Pandey et al., 2002)

sirt6

(Golubev et al., 2022)

Name Synonyms

Sirt6

Sirtuin 6

Secondary FlyBase IDs

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

Study result (0)

Result

Result Type

Title

External Crossreferences and Linkouts ( 31 )

Sequence Crossreferences

NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

41254

GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.

AAF54513

RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.

UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.

Q9VH08

UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information

Q9VH08

Other crossreferences

AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.

Q9VH08

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

41254/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0037802

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0037802

FlyMine - An integrated database for Drosophila genomics

FBgn0037802

InterPro - A database of protein families, domains and functional sites

KEGG Genes - Molecular building blocks of life in the genomic space.

dme:Dmel_CG6284

MARRVEL_MODEL - MARRVEL (model organism gene)

41254

Linkouts

BioGRID - A database of protein and genetic interactions.

66403

Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones

FBgn0037802

DroID - A comprehensive database of gene and protein interactions.

FBgn0037802

DRSC - Results frm RNAi screens

FBgn0037802

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Sirt6_1

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0037802

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0037802

Flygut - An atlas of the Drosophila adult midgut

FBgn0037802

iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)

TC013536

KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

MIST (protein-protein) - An integrated Molecular Interaction Database

41254

References (49)

The following external sites may use different assemblies or annotations than FlyBase.

0.09

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