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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]
SIRT4 (Sirtuin 4) is a Protein Coding gene. Diseases associated with SIRT4 include Monckeberg Arteriosclerosis and Hutchinson-Gilford Progeria Syndrome. Among its related pathways are NAD metabolism and Metabolism. Gene Ontology (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.
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.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0003950 | NAD+ ADP-ribosyltransferase activity | TAS | 17456799 |
GO:0005515 | protein binding | IPI | 16959573 |
GO:0008270 | zinc ion binding | IEA | -- |
GO:0016740 | transferase activity | IEA | -- |
GO:0034979 | NOT NAD-dependent protein deacetylase activity | IDA | 17715127 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005739 | mitochondrion | IEA,IDA | 16079181 |
GO:0005743 | mitochondrial inner membrane | IEA | -- |
GO:0005759 | mitochondrial matrix | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | NAD metabolism |
NAD metabolism
.53
|
.01
|
2 | p53 Signaling |
.46
|
p53 Signaling
.46
|
3 | Metabolism | ||
4 | 4-1BB Pathway |
SUMO Pathway
.30
|
|
5 | DNA damage_NHEJ mechanisms of DSBs repair |
DNA damage_NHEJ mechanisms of DSBs repair
-
|
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:0006476 | protein deacetylation | IEA | -- |
GO:0006541 | glutamine metabolic process | IEA,ISS | -- |
GO:0006974 | cellular response to DNA damage stimulus | ISS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Panobinostat | Approved, Investigational | Pharma | Inhibition, inhibitor | Histone deacetylase (HDAC)inhibitors | 145 | |
Nicotinamide | Approved, Investigational | Pharma | 427,427 | |||
NAD | Experimental | Pharma | Agonist, Full agonist, Activator | 0 | ||
Splitomicin | Pharma | Sir2p inhibitor | 0 | |||
AGK 2 | Pharma | Selective SIRT2 inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
O-acetyl-ADP-ribose |
|
|
||||
EX 527 |
|
49843-98-3 |
|
|
||
YK 3-237 |
|
1215281-19-8 |
|
|
Compound | Action | Cas Number |
---|---|---|
AGK 2 | Selective SIRT2 inhibitor | 304896-28-4 |
EX 527 | Selective SIRT1 inhibitor | 49843-98-3 |
Sirtinol | Selective sirtuin family deacetylase inhibitor | 410536-97-9 |
Splitomicin | Sir2p inhibitor | 5690-03-9 |
YK 3-237 | SIRT1 activator | 1215281-19-8 |
Compound | Action | Cas Number |
---|---|---|
Splitomicin | 5690-03-9 |
ExUns: | 1a | · | 1b | ^ | 2a | · | 2b | · | 2c | ^ | 3a | · | 3b | ^ | 4a | · | 4b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||||
SP2: | - | ||||||||||||||||
SP3: | |||||||||||||||||
SP4: | - |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | SIRT4 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | SIRT4 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | SIRT4 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Sirt4 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Sirt4 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | SIRT4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | SIRT4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | SIRT4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | sirt4 30 |
|
||
Str.4552 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | sirt4 30 31 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP013148 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Sirt4 30 31 |
|
OneToOne | |
CG3187 32 |
|
|
|||
Worm (Caenorhabditis elegans) |
Secernentea | sir-2.2 30 31 32 |
|
OneToMany | |
sir-2.3 31 32 |
|
OneToMany | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | HST1 31 |
|
ManyToMany | |
SIR2 31 |
|
ManyToMany | |||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | SRT2 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os12g0179800 30 |
|
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2763006 | CNV | loss | 21179565 |
esv3549882 | CNV | deletion | 23714750 |
esv3630921 | CNV | loss | 21293372 |
nsv518764 | CNV | loss | 19592680 |
nsv560435 | CNV | loss | 21841781 |
nsv832530 | CNV | loss | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
monckeberg arteriosclerosis |
|
|
hutchinson-gilford progeria syndrome |
|
|
body mass index quantitative trait locus 11 |
|
|
diabetes mellitus, noninsulin-dependent |
|
|