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Aliases for SIRT4 Gene

Aliases for SIRT4 Gene

  • Sirtuin 4 2 3 5
  • NAD-Dependent ADP-Ribosyltransferase Sirtuin-4 3 4
  • NAD-Dependent Protein Deacetylase Sirtuin-4 3 4
  • Regulatory Protein SIR2 Homolog 4 3 4
  • SIR2-Like Protein 4 3 4
  • EC 3.5.1.- 4 4
  • SIR2L4 3 4
  • Sirtuin (Silent Mating Type Information Regulation 2, S. Cerevisiae, Homolog) 4 2
  • Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 4 (S. Cerevisiae) 2
  • Sirtuin Type 4 3
  • Sir2-Like 4 3
  • EC 2.4.2.- 4

External Ids for SIRT4 Gene

Previous GeneCards Identifiers for SIRT4 Gene

  • GC12P119613
  • GC12P120266
  • GC12P120522
  • GC12P119152
  • GC12P119203
  • GC12P120740
  • GC12P117748

Summaries for SIRT4 Gene

Entrez Gene Summary for SIRT4 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 IV of the sirtuin family. [provided by RefSeq, Jul 2008]

GeneCards Summary for SIRT4 Gene

SIRT4 (Sirtuin 4) is a Protein Coding gene. Among its related pathways are p53 Signaling and 4-1BB Pathway. GO annotations related to this gene include NAD+ ADP-ribosyltransferase activity and NAD-dependent protein deacetylase activity. An important paralog of this gene is SIRT5.

UniProtKB/Swiss-Prot for SIRT4 Gene

  • Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573, PubMed:17715127). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of Lys-471 of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (By similarity). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion.

Tocris Summary for SIRT4 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 SIRT4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIRT4 Gene

Genomics for SIRT4 Gene

Regulatory Elements for SIRT4 Gene

Enhancers for SIRT4 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 SIRT4 on UCSC Golden Path with GeneCards custom track

Promoters for SIRT4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around SIRT4 on UCSC Golden Path with GeneCards custom track

Genomic Location for SIRT4 Gene

Chromosome:
12
Start:
120,292,199 bp from pter
End:
120,313,249 bp from pter
Size:
21,051 bases
Orientation:
Plus strand

Genomic View for SIRT4 Gene

Genes around SIRT4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIRT4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIRT4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIRT4 Gene

Proteins for SIRT4 Gene

  • Protein details for SIRT4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6E7-SIR4_HUMAN
    Recommended name:
    NAD-dependent protein lipoamidase sirtuin-4, mitochondrial
    Protein Accession:
    Q9Y6E7
    Secondary Accessions:
    • O43346
    • Q32M33

    Protein attributes for SIRT4 Gene

    Size:
    314 amino acids
    Molecular mass:
    35188 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Interacts with GLUD1, IDE and SLC25A5 (PubMed:16959573, PubMed:17715127). Interacts with DLAT and PDHX (PubMed:25525879).
    Miscellaneous:
    • According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
    • Expression is down-regulated in a number of cancers, while overexpression reduces cell proliferation, transformation, and tumor development (PubMed:23562301, PubMed:23663782).
    SequenceCaution:
    • Sequence=AAB95634.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

neXtProt entry for SIRT4 Gene

Proteomics data for SIRT4 Gene at MOPED

Post-translational modifications for SIRT4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIRT4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for SIRT4 Gene

Domains & Families for SIRT4 Gene

Gene Families for SIRT4 Gene

Suggested Antigen Peptide Sequences for SIRT4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y6E7

UniProtKB/Swiss-Prot:

SIR4_HUMAN :
  • Contains 1 deacetylase sirtuin-type domain.
  • Belongs to the sirtuin family. Class II subfamily.
Domain:
  • Contains 1 deacetylase sirtuin-type domain.
Family:
  • Belongs to the sirtuin family. Class II subfamily.
genes like me logo Genes that share domains with SIRT4: view

Function for SIRT4 Gene

Molecular function for SIRT4 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=719 uM for a peptide of H3 biotinylated at Lys-9 {ECO:0000269 PubMed:25525879}; KM=814 uM for a peptide of H3 lipoylated at Lys-9 {ECO:0000269 PubMed:25525879}; KM=239 uM for a peptide of DLAT lipoylated at Lys-259 {ECO:0000269 PubMed:25525879}; Note=kcat is 0.0019 sec(-1) for the delipoylation of H3 Lys-9. kcat is 0.0005 sec(-1) for the debiotinylation of H3 Lys-9. kcat is 0.0018 sec(-1) for the delipoylation of DLAT Lys-259. {ECO:0000269 PubMed:25525879};
UniProtKB/Swiss-Prot CatalyticActivity:
NAD(+) + a protein = nicotinamide + an N-(ADP-D-ribosyl)-protein.
UniProtKB/Swiss-Prot CatalyticActivity:
NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot Function:
Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573, PubMed:17715127). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of Lys-471 of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (By similarity). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion.
UniProtKB/Swiss-Prot Induction:
Induced by glutamine (at protein level).

Enzyme Numbers (IUBMB) for SIRT4 Gene

Gene Ontology (GO) - Molecular Function for SIRT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0047708 biotinidase activity IDA 25525879
genes like me logo Genes that share ontologies with SIRT4: view
genes like me logo Genes that share phenotypes with SIRT4: view

Animal Models for SIRT4 Gene

MGI Knock Outs for SIRT4:

Animal Model Products

  • Taconic Biosciences Mouse Models for SIRT4

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SIRT4 Gene

Localization for SIRT4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIRT4 Gene

Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIRT4 Gene COMPARTMENTS Subcellular localization image for SIRT4 gene
Compartment Confidence
mitochondrion 5
cytosol 2
nucleus 2
peroxisome 1

No data available for Gene Ontology (GO) - Cellular Components for SIRT4 Gene

Pathways & Interactions for SIRT4 Gene

genes like me logo Genes that share pathways with SIRT4: view

Pathways by source for SIRT4 Gene

1 Sino Biological pathway for SIRT4 Gene
1 BioSystems pathway for SIRT4 Gene
2 GeneGo (Thomson Reuters) pathways for SIRT4 Gene
2 Qiagen pathways for SIRT4 Gene

Gene Ontology (GO) - Biological Process for SIRT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000820 regulation of glutamine family amino acid metabolic process IEA --
GO:0006471 protein ADP-ribosylation IEA,TAS 17456799
GO:0006541 glutamine metabolic process IEA,ISS --
GO:0006974 cellular response to DNA damage stimulus IEA,ISS --
GO:0046889 positive regulation of lipid biosynthetic process IEA,ISS --
genes like me logo Genes that share ontologies with SIRT4: view

No data available for SIGNOR curated interactions for SIRT4 Gene

Drugs & Compounds for SIRT4 Gene

(7) Drugs for SIRT4 Gene - From: ApexBio, DGIdb, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nicotinamide Experimental Nutra 850,854
Resveratrol Experimental, Investigational Pharma Wee1 kinase inhibtor,potent and ATP-competitive, Others, Cyclooxygenase inhibitor 106
Splitomicin Pharma Sir2p inhibitor 0
Panobinostat Pharma Inhibition, inhibitor Histone deacetylase (HDAC)inhibitors 133
NAD Pharma Full agonist, Agonist 0

(2) Additional Compounds for SIRT4 Gene - From: Tocris and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
O-acetyl-ADP-ribose
EX 527
49843-98-3

(5) Tocris Compounds for SIRT4 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 SIRT4 Gene

Compound Action Cas Number
Splitomicin 5690-03-9
genes like me logo Genes that share compounds with SIRT4: view

Transcripts for SIRT4 Gene

Unigene Clusters for SIRT4 Gene

Sirtuin 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIRT4 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3a · 3b ^ 4a · 4b
SP1:
SP2: -
SP3:
SP4: -

Relevant External Links for SIRT4 Gene

GeneLoc Exon Structure for
SIRT4
ECgene alternative splicing isoforms for
SIRT4

Expression for SIRT4 Gene

mRNA expression in normal human tissues for SIRT4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

SOURCE GeneReport for Unigene cluster for SIRT4 Gene Hs.50861

mRNA Expression by UniProt/SwissProt for SIRT4 Gene

Q9Y6E7-SIR4_HUMAN
Tissue specificity: Detected in vascular smooth muscle and striated muscle. Detected in insulin-producing beta-cells in pancreas islets of Langerhans (at protein level). Widely expressed. Weakly expressed in leukocytes and fetal thymus.
genes like me logo Genes that share expression patterns with SIRT4: view

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for SIRT4 Gene

Orthologs for SIRT4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SIRT4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia SIRT4 35
  • 88.39 (n)
  • 90.1 (a)
SIRT4 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIRT4 35
  • 88 (n)
  • 84.57 (a)
SIRT4 36
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sirt4 35
  • 83.23 (n)
  • 87.01 (a)
Sirt4 16
Sirt4 36
  • 80 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia SIRT4 35
  • 99.58 (n)
  • 99.68 (a)
SIRT4 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sirt4 35
  • 82.58 (n)
  • 85.71 (a)
platypus
(Ornithorhynchus anatinus)
Mammalia SIRT4 36
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves SIRT4 35
  • 73.33 (n)
  • 75.36 (a)
SIRT4 36
  • 67 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIRT4 36
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sirt4 35
  • 62.37 (n)
  • 65.85 (a)
Str.4552 35
zebrafish
(Danio rerio)
Actinopterygii sirt4 35
  • 64.22 (n)
  • 65.38 (a)
sirt4 36
  • 59 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG3187 37
  • 49 (a)
Sirt4 35
  • 51.67 (n)
  • 48.67 (a)
Sirt4 36
  • 45 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP013148 35
  • 52.67 (n)
  • 51.96 (a)
worm
(Caenorhabditis elegans)
Secernentea sir-2.2 37
  • 49 (a)
sir-2.3 37
  • 42 (a)
sir-2.2 35
  • 50.78 (n)
  • 50.18 (a)
sir-2.2 36
  • 47 (a)
OneToMany
sir-2.3 36
  • 42 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HST1 36
  • 13 (a)
ManyToMany
SIR2 36
  • 11 (a)
ManyToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons SRT2 35
  • 50.61 (n)
  • 45.62 (a)
rice
(Oryza sativa)
Liliopsida Os12g0179800 35
  • 50.54 (n)
  • 46.43 (a)
Species with no ortholog for SIRT4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIRT4 Gene

ENSEMBL:
Gene Tree for SIRT4 (if available)
TreeFam:
Gene Tree for SIRT4 (if available)

Paralogs for SIRT4 Gene

Paralogs for SIRT4 Gene

genes like me logo Genes that share paralogs with SIRT4: view

Variants for SIRT4 Gene

Sequence variations from dbSNP and Humsavar for SIRT4 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs7134914 -- 120,296,257(+) ctgtc(A/G/T)cccag intron-variant
rs7135836 -- 120,296,252(+) tcgct(C/T)tgtcg intron-variant
rs7137625 -- 120,308,574(+) GATCC(C/T)AGAGG intron-variant
rs7294425 -- 120,295,278(+) ggcgc(A/G)atctc intron-variant
rs12816454 -- 120,297,233(+) AAATA(A/C)ATACA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SIRT4 Gene

Variant ID Type Subtype PubMed ID
nsv899555 CNV Loss 21882294
nsv832530 CNV Loss 17160897
nsv899556 CNV Gain 21882294
nsv518764 CNV Loss 19592680

Variation tolerance for SIRT4 Gene

Residual Variation Intolerance Score: 43.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.29; 40.99% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SIRT4 Gene

HapMap Linkage Disequilibrium report
SIRT4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIRT4 Gene

Disorders for SIRT4 Gene

Relevant External Links for SIRT4

Genetic Association Database (GAD)
SIRT4
Human Genome Epidemiology (HuGE) Navigator
SIRT4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SIRT4

No disorders were found for SIRT4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SIRT4 Gene

Publications for SIRT4 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. Regulation of insulin secretion by SIRT4, a mitochondrial ADP- ribosyltransferase. (PMID: 17715127) Ahuja N. … Verdin E. (J. Biol. Chem. 2007) 3 23
  3. SIRT4 Suppresses Inflammatory Responses in Human Umbilical Vein Endothelial Cells. (PMID: 25331589) Tao Y. … Qiu Y. (Cardiovasc. Toxicol. 2015) 3
  4. Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma. (PMID: 26054687) Huang G. … Peng Z. (Biomed. Pharmacother. 2015) 3
  5. Tumour-suppressive function of SIRT4 in human colorectal cancer. (PMID: 26086877) Miyo M. … Ishii H. (Br. J. Cancer 2015) 3

Products for SIRT4 Gene

Sources for SIRT4 Gene

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