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Aliases for SIRT5 Gene

Aliases for SIRT5 Gene

  • Sirtuin 5 2 3 5
  • SIR2L5 3 4
  • Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 5 (S. Cerevisiae) 2
  • Sirtuin (Silent Mating Type Information Regulation 2, S.Cerevisiae, Homolog) 5 2
  • NAD-Dependent Lysine Demalonylase And Desuccinylase Sirtuin-5, Mitochondrial 3
  • Silent Mating Type Information Regulation 2, S.Cerevisiae, Homolog 5 3
  • NAD-Dependent Deacetylase Sirtuin-5 3
  • Regulatory Protein SIR2 Homolog 5 4
  • SIR2-Like Protein 5 4
  • Sirtuin Type 5 3
  • Sir2-Like 5 3
  • EC 3.5.1.- 4

External Ids for SIRT5 Gene

Previous GeneCards Identifiers for SIRT5 Gene

  • GC06P013632
  • GC06P013682
  • GC06P013519

Summaries for SIRT5 Gene

Entrez Gene Summary for SIRT5 Gene

  • 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 III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

GeneCards Summary for SIRT5 Gene

SIRT5 (Sirtuin 5) is a Protein Coding gene. Among its related pathways are Glucose / Energy Metabolism and p53 Signaling. GO annotations related to this gene include NAD+ ADP-ribosyltransferase activity and protein-malonyllysine demalonylase activity. An important paralog of this gene is SIRT1.

UniProtKB/Swiss-Prot for SIRT5 Gene

  • NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.

Tocris Summary for SIRT5 Gene

  • Silent information regulator (Sir2)-like family deacetylases (also known as sirtuins) are a group of enzymes closely related to histone deacetylases. These enzymes can be found in the cytoplasm, mitochondria or nucleus of the cell and are ubiquitously expressed.

Gene Wiki entry for SIRT5 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIRT5 Gene

Genomics for SIRT5 Gene

Regulatory Elements for SIRT5 Gene

Enhancers for SIRT5 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around SIRT5 on UCSC Golden Path with GeneCards custom track

Promoters for SIRT5 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around SIRT5 on UCSC Golden Path with GeneCards custom track

Genomic Location for SIRT5 Gene

Chromosome:
6
Start:
13,574,274 bp from pter
End:
13,615,158 bp from pter
Size:
40,885 bases
Orientation:
Plus strand

Genomic View for SIRT5 Gene

Genes around SIRT5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIRT5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIRT5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIRT5 Gene

Proteins for SIRT5 Gene

  • Protein details for SIRT5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NXA8-SIR5_HUMAN
    Recommended name:
    NAD-dependent protein deacylase sirtuin-5, mitochondrial
    Protein Accession:
    Q9NXA8
    Secondary Accessions:
    • B4DFM4
    • B4DYJ5
    • F5H5Z9
    • Q5T294
    • Q5T295
    • Q9Y6E6

    Protein attributes for SIRT5 Gene

    Size:
    310 amino acids
    Molecular mass:
    33881 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Interacts with CPS1 (By similarity). Monomer. Homodimer. Forms homodimers upon suramin binding.
    Miscellaneous:
    • The mechanism of demalonylation and desuccinylation involves the presence of a 1,2-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues.

    Three dimensional structures from OCA and Proteopedia for SIRT5 Gene

    Alternative splice isoforms for SIRT5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SIRT5 Gene

Proteomics data for SIRT5 Gene at MOPED

Post-translational modifications for SIRT5 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • R&D Systems Antibodies for SIRT5 (Sirtuin 5/SIRT5)
  • Cell Signaling Technology (CST) Antibodies for SIRT5 (SIRT5)

No data available for DME Specific Peptides for SIRT5 Gene

Domains & Families for SIRT5 Gene

Gene Families for SIRT5 Gene

Suggested Antigen Peptide Sequences for SIRT5 Gene

Graphical View of Domain Structure for InterPro Entry

Q9NXA8

UniProtKB/Swiss-Prot:

SIR5_HUMAN :
  • In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378).
  • Belongs to the sirtuin family. Class III subfamily.
Domain:
  • In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378).
  • Contains 1 deacetylase sirtuin-type domain.
Family:
  • Belongs to the sirtuin family. Class III subfamily.
genes like me logo Genes that share domains with SIRT5: view

Function for SIRT5 Gene

Molecular function for SIRT5 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide {ECO:0000269 PubMed:22076378}; KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide {ECO:0000269 PubMed:22076378}; KM=8.7 uM for a synthetic GLUD1 peptide malonylated at Lys-503 {ECO:0000269 PubMed:22076378}; KM=14 uM for a synthetic GLUD1 peptide succinylated at Lys-503 {ECO:0000269 PubMed:22076378}; KM=150 uM for a synthetic ACSS1 peptide malonylated at Lys-628 {ECO:0000269 PubMed:22076378}; KM=450 uM for a synthetic ACSS1 peptide succinylated at Lys- 628 {ECO:0000269 PubMed:22076378};
UniProtKB/Swiss-Prot CatalyticActivity:
NAD(+) + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot CatalyticActivity:
NAD(+) + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot CatalyticActivity:
NAD(+) + a glutarylprotein = nicotinamide + O-glutaryl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity.
UniProtKB/Swiss-Prot Function:
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.

Enzyme Numbers (IUBMB) for SIRT5 Gene

Gene Ontology (GO) - Molecular Function for SIRT5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003950 NOT NAD+ ADP-ribosyltransferase activity TAS 17456799
GO:0008270 zinc ion binding IDA 22076378
GO:0036055 protein-succinyllysine desuccinylase activity IDA 21908771
GO:0070403 NAD+ binding IEA,IDA 21908771
genes like me logo Genes that share ontologies with SIRT5: view
genes like me logo Genes that share phenotypes with SIRT5: view

Animal Models for SIRT5 Gene

MGI Knock Outs for SIRT5:

Animal Model Products

  • Taconic Biosciences Mouse Models for SIRT5

miRNA for SIRT5 Gene

miRTarBase miRNAs that target SIRT5

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SIRT5 Gene

Localization for SIRT5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIRT5 Gene

Mitochondrion matrix. Mitochondrion intermembrane space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also present extramitochondrially: a fraction is present in the cytosol and very small amounts are also detected in the nucleus.
Isoform 1: Cytoplasm. Mitochondrion.
Isoform 2: Mitochondrion.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIRT5 Gene COMPARTMENTS Subcellular localization image for SIRT5 gene
Compartment Confidence
cytosol 5
mitochondrion 5
nucleus 5

No data available for Gene Ontology (GO) - Cellular Components for SIRT5 Gene

Pathways & Interactions for SIRT5 Gene

genes like me logo Genes that share pathways with SIRT5: view

Pathways by source for SIRT5 Gene

1 Sino Biological pathway for SIRT5 Gene
2 Cell Signaling Technology pathways for SIRT5 Gene
1 BioSystems pathway for SIRT5 Gene
2 GeneGo (Thomson Reuters) pathways for SIRT5 Gene
2 Qiagen pathways for SIRT5 Gene

Gene Ontology (GO) - Biological Process for SIRT5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006471 NOT protein ADP-ribosylation TAS 17456799
GO:0010667 negative regulation of cardiac muscle cell apoptotic process IEA --
GO:0036046 protein demalonylation IDA 24703693
GO:0036048 protein desuccinylation IDA 24140062
GO:0036049 peptidyl-lysine desuccinylation IDA 21908771
genes like me logo Genes that share ontologies with SIRT5: view

No data available for SIGNOR curated interactions for SIRT5 Gene

Drugs & Compounds for SIRT5 Gene

(10) Drugs for SIRT5 Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Suramin Approved Pharma Antagonist, Target, inhibitor 18
Nicotinamide Experimental Nutra Target 850,854
2'-O-Acetyl Adenosine-5-Diphosphoribose Experimental Pharma Target 0
Adenosine-5-Diphosphoribose Experimental Pharma Target 0
Resveratrol Experimental, Investigational Pharma Wee1 kinase inhibtor,potent and ATP-competitive, Others, Cyclooxygenase inhibitor 106

(1) Additional Compounds for SIRT5 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
EX 527
49843-98-3

(5) Tocris Compounds for SIRT5 Gene

Compound Action Cas Number
AGK 2 Selective SIRT2 inhibitor 304896-28-4
EX 527 Selective SIRT1 inhibitor 49843-98-3
Resveratrol Cyclooxygenase inhibitor 501-36-0
Sirtinol Selective sirtuin family deacetylase inhibitor 410536-97-9
Splitomicin Sir2p inhibitor 5690-03-9

(1) ApexBio Compounds for SIRT5 Gene

Compound Action Cas Number
Splitomicin 5690-03-9
genes like me logo Genes that share compounds with SIRT5: view

Transcripts for SIRT5 Gene

Unigene Clusters for SIRT5 Gene

Sirtuin 5:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIRT5 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b · 14c ^ 15a · 15b
SP1: - - - - - -
SP2: - - - - - - - -
SP3: - - -
SP4:
SP5: - -
SP6: - - - - - - -
SP7:
SP8:

Relevant External Links for SIRT5 Gene

GeneLoc Exon Structure for
SIRT5
ECgene alternative splicing isoforms for
SIRT5

Expression for SIRT5 Gene

mRNA expression in normal human tissues for SIRT5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SIRT5 Gene

This gene is overexpressed in Heart (9.5) and Brain (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for SIRT5 Gene



SOURCE GeneReport for Unigene cluster for SIRT5 Gene Hs.567431

mRNA Expression by UniProt/SwissProt for SIRT5 Gene

Q9NXA8-SIR5_HUMAN
Tissue specificity: Widely expressed.
genes like me logo Genes that share expression patterns with SIRT5: view

Protein tissue co-expression partners for SIRT5 Gene

Primer Products

No data available for mRNA differential expression in normal tissues for SIRT5 Gene

Orthologs for SIRT5 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SIRT5 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia SIRT5 35
  • 86.45 (n)
  • 87.42 (a)
SIRT5 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIRT5 35
  • 86.77 (n)
  • 87.1 (a)
SIRT5 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sirt5 35
  • 84.09 (n)
  • 86.13 (a)
Sirt5 16
Sirt5 36
  • 86 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia SIRT5 35
  • 98.92 (n)
  • 98.39 (a)
SIRT5 36
  • 98 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sirt5 35
  • 83.98 (n)
  • 85.48 (a)
oppossum
(Monodelphis domestica)
Mammalia SIRT5 36
  • 61 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SIRT5 36
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIRT5 35
  • 73.66 (n)
  • 77.7 (a)
SIRT5 36
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIRT5 36
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sirt5 35
  • 71.78 (n)
  • 79 (a)
Str.16272 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.15494 35
zebrafish
(Danio rerio)
Actinopterygii sirt5 35
  • 68.59 (n)
  • 75.18 (a)
sirt5 36
  • 69 (a)
OneToMany
SIRT5 (2 of 2) 36
  • 52 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10779 35
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ABL004W 35
  • 45.02 (n)
  • 40.3 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HST1 36
  • 13 (a)
ManyToMany
SIR2 36
  • 11 (a)
ManyToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.8513 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 57 (a)
OneToOne
Species with no ortholog for SIRT5:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SIRT5 Gene

ENSEMBL:
Gene Tree for SIRT5 (if available)
TreeFam:
Gene Tree for SIRT5 (if available)

Paralogs for SIRT5 Gene

Paralogs for SIRT5 Gene

(1) SIMAP similar genes for SIRT5 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for SIRT5 Gene

genes like me logo Genes that share paralogs with SIRT5: view

Variants for SIRT5 Gene

Sequence variations from dbSNP and Humsavar for SIRT5 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
VAR_029042 -
VAR_051980 -
rs11751539 -- 13,598,324(+) GCTAC(A/T)TACTG intron-variant
rs11757746 -- 13,597,270(+) AGTTT(C/T)TGAAG intron-variant
rs11961680 -- 13,595,334(+) GTACT(A/G)CTACA intron-variant

Variation tolerance for SIRT5 Gene

Residual Variation Intolerance Score: 81.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.48; 64.31% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SIRT5 Gene

Human Gene Mutation Database (HGMD)
SIRT5

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for SIRT5 Gene

Disorders for SIRT5 Gene

Relevant External Links for SIRT5

Genetic Association Database (GAD)
SIRT5
Human Genome Epidemiology (HuGE) Navigator
SIRT5
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SIRT5

No disorders were found for SIRT5 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SIRT5 Gene

Publications for SIRT5 Gene

  1. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. (PMID: 10381378) Frye R.A. (Biochem. Biophys. Res. Commun. 1999) 2 3 4 67
  2. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. (PMID: 18680753) Schlicker C. … Steegborn C. (J. Mol. Biol. 2008) 3 23
  3. Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. (PMID: 17355872) Schuetz A. … Plotnikov A.N. (Structure 2007) 25 26
  4. Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization. (PMID: 16484774) Mahlknecht U. … Voelter-Mahlknecht S. (Cytogenet. Genome Res. 2006) 3 23
  5. Drugs, their targets and the nature and number of drug targets. (PMID: 17016423) Imming P. … Meyer A. (Nat Rev Drug Discov 2006) 25 26

Products for SIRT5 Gene

Sources for SIRT5 Gene

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