MGP Database

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MGP000462

UniProt Annotations

Entry Information
Gene Nameectonucleoside triphosphate diphosphohydrolase 5
Protein EntryENTP5_HUMAN
UniProt IDO75356
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityA nucleoside diphosphate + H(2)O = a nucleoside phosphate + phosphate.
Catalytic ActivityGDP + H(2)O = GMP + phosphate.
CofactorName=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:10400613, ECO:0000269|PubMed:15698960}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10400613, ECO:0000269|PubMed:15698960};
FunctionUridine diphosphatase (UDPase) that promotes protein N- glycosylation and ATP level regulation. UDP hydrolysis promotes protein N-glycosylation and folding in the endoplasmic reticulum, as well as elevated ATP consumption in the cytosol via an ATP hydrolysis cycle. Together with CMPK1 and AK1, constitutes an ATP hydrolysis cycle that converts ATP to AMP and results in a compensatory increase in aerobic glycolysis. The nucleotide hydrolyzing preference is GDP > IDP > UDP, but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. Plays a key role in the AKT1-PTEN signaling pathway by promoting glycolysis in proliferating cells in response to phosphoinositide 3-kinase (PI3K) signaling. {ECO:0000269|PubMed:10400613}.
InductionUp-regulated in cell lines and primary tumor samples with active AKT1. {ECO:0000269|PubMed:21074248}.
MiscellaneousMay mediate some of the cancer-related phenotypes associated with AKT1 activation: its up-regulation by AKT1 leads to the elevation of aerobic glycolysis seen in tumor cells, a phenomenon known as the Warburg effect. {ECO:0000305|PubMed:21074248}.
PathwayProtein modification; protein glycosylation.
PtmN-glycosylated; high-mannose type (By similarity). Glycosylation is not essential for enzymatic activity. {ECO:0000250, ECO:0000269|PubMed:11041857, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218}.
SimilarityBelongs to the GDA1/CD39 NTPase family. {ECO:0000305}.
Subcellular LocationEndoplasmic reticulum {ECO:0000250}. Secreted {ECO:0000269|PubMed:10400613}.
SubunitExists both as a monomer and a disulfide-linked homodimer, the dimers are enzymatically inactive. {ECO:0000269|PubMed:11041857}.
Tissue SpecificityExpressed in adult liver, kidney, prostate, testis and colon. Much weaker expression in other tissues. {ECO:0000269|PubMed:9676430}.
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