SIRT4 recombinant protein

SIRT4 recombinant protein

Cat. Num. AAA515139

• Gene Names: SIRT4; SIR2L4
• Applications: Western Blot
• Synonyms: SIRT4; SIRT4 recombinant protein; IR2L4; MGC57437; MGC130046; MGC130047; sirtuin 4

• Host: E Coli
• Form/Format: 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol.
• Sequence Length: 1213

• Applicable Applications for SIRT4 recombinant protein: Western Blot (WB)
• Type: Recombinant Fusion Protein
• Species: Human
• Tag Information: GST tag
• Expression System: E.coli
• Source Note: Full-length recombinant human SIRT4 was expressed in E. coli cells
• Preparation and Storage: Store product at -70 degree C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.

SDS-PAGE

Related Product Information for SIRT4 recombinant protein

Full-length recombinant human SIRT4 was expressed in E. coli cells using an N-terminal GST tag.

Scientific Background: SIRT4 is a member of the sirtuin family of proteins which are homologs to the yeast Sir2 protein. Sirtuin family contain a sirtuin core domain and are grouped into four classes with SIRT4 being a member of class IV. SIRT4 lacks deacetylase activity but has ADP-ribosyltransferase activity (1). Immunoprecipitation analysis shows that SIRT4 interacts with the mitochondrial enzyme glutamate dehydrogenase (GDH), and functional analysis show that SIRT4 ADP-ribosylates and inhibits GDH (2). Downregulation of SIRT4 by RNA interference activates GDH, thereby upregulating insulin secretion in response to glucose and amino acids.

Product Categories/Family for SIRT4 recombinant protein

Deacetylases/Demethylase Proteins; Signaling Proteins - Deacetylase/Demethylase Proteins

References

1. Frye, R. A. 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. Biochem. Biophys. Res. Commun. 260: 273-279, 1999.
2. Haigis, M. C. et al: SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126: 941-954, 2006.

NCBI and Uniprot Product Information

• NCBI GI #: 300795832
• NCBI GeneID: 23409
• NCBI Accession #: NP_036372.1
• NCBI GenBank Nucleotide #: NM_012240
• UniProt Accession #: Q9Y6E7; O43346; Q32M33
• Molecular Weight: ~62 kDa
• NCBI Official Full Name: Homo sapiens sirtuin 4 (SIRT4), mRNA
• NCBI Official Synonym Full Names: sirtuin 4
• NCBI Official Symbol: SIRT4
• NCBI Official Synonym Symbols: SIR2L4
• NCBI Protein Information: NAD-dependent protein deacetylase sirtuin-4; sir2-like 4; sirtuin type 4; SIR2-like protein 4; regulatory protein SIR2 homolog 4; NAD-dependent ADP-ribosyltransferase sirtuin-4
• UniProt Protein Name: NAD-dependent protein deacetylase sirtuin-4
• Protein Family: NAD-dependent protein deacylase
• UniProt Gene Name: SIRT4
• UniProt Synonym Gene Names: SIR2L4
• UniProt Entry Name: SIR4_HUMAN

NCBI Description

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]

Uniprot Description

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. Ref.4 Ref.5 Ref.7 Ref.8

Catalytic activity: NAD+ + a protein = nicotinamide + an N-(ADP-D-ribosyl)-protein. HAMAP-Rule MF_03161NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. HAMAP-Rule MF_03161

Cofactor: Binds 1 zinc ion per subunit

By similarity. HAMAP-Rule MF_03161

Subunit structure: Interacts with GLUD1, IDE and SLC25A5. Ref.4 Ref.5

Subcellular location: Mitochondrion matrix Ref.4 Ref.5 Ref.6.

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. Ref.1

Miscellaneous: Expression is down-regulated in a number of cancers, while overexpression reduces cell proliferation, transformation, and tumor development (Ref.7, Ref.8).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

By similarity.

Sequence similarities: Belongs to the sirtuin family. Class II subfamily.Contains 1 deacetylase sirtuin-type domain.

Sequence caution: The sequence AAB95634.1 differs from that shown. Reason: Erroneous gene model prediction.