Aliases for SIRT4 Gene
- Sirtuin 4 2 3
- SIR2L4 3 4 6
- NAD-Dependent ADP-Ribosyltransferase Sirtuin-4 3 4
- Regulatory Protein SIR2 Homolog 4 3 4
- SIR2-Like Protein 4 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
External Ids for SIRT4 Gene
Previous GeneCards Identifiers 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 Nicotinate and nicotinamide metabolism and Non-homologous end-joining. 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 both as NAD-dependent protein ADP-ribosyl transferase and NAD-dependent protein deacetylase. 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. In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor. 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. Down-regulates insulin secretion.
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 and are ubiquitously expressed. Sir2-like family deacetylases catalyze the removal of acetyl groups from lysine residues in histones and non-histone proteins, which is coupled to NAD+ hydrolysis. In general, sirtuins do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. Sirtuins have a role in regulation of transcription and apoptosis leading to substantial interest in inhibitors of these enzymes as possible antineoplastic agents. In addition, Sir2-like family deacteylases are involved in the normal ageing process through their role in resistance to cellular stress.