InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SIRT4

Summary

InnateDB Protein

IDBP-60457.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SIRT4

Protein Name

sirtuin 4

Synonyms

SIR2L4;

Species

Homo sapiens

Ensembl Protein

ENSP00000202967

InnateDB Gene

IDBG-60455 (SIRT4)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000255HAMAP-Rule:MF_03161, ECO:0000269PubMed:16959573, ECO:0000269PubMed:17715127, ECO:0000269PubMed:23562301, ECO:0000269PubMed:23663782}.

Subcellular Localization

Mitochondrion matrix {ECO:0000255HAMAP- Rule:MF_03161, ECO:0000269PubMed:16079181, ECO:0000269PubMed:16959573, ECO:0000269PubMed:17715127}.

Disease Associations

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. {ECO:0000269PubMed:10381378}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003950	NAD+ ADP-ribosyltransferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0034979	NAD-dependent protein deacetylase activity
GO:0070403	NAD+ binding

Biological Process

GO:0006342	chromatin silencing
GO:0006471	protein ADP-ribosylation
GO:0006541	glutamine metabolic process
GO:0006974	cellular response to DNA damage stimulus
GO:0034983	peptidyl-lysine deacetylation
GO:0046322	negative regulation of fatty acid oxidation
GO:0046676	negative regulation of insulin secretion
GO:0046889	positive regulation of lipid biosynthetic process
GO:0072350	tricarboxylic acid metabolic process