NTPDase5 hydrolyzes nucleoside diphosphates

Stable Identifier
R-HSA-8851356
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

NTPDase5 (CD39L4), encoded by the ENTPD5 gene, is an E-NTPDase family member that is secreted to the extracellular space where it hydrolyzes nucleoside diphosphates UDP, GDP, CDP and ADP (listed in the order of preference) to nucleoside monophosphates UMP, GMP, CMP and AMP, respectively. In vitro, NTPDase5 can hydrolyze nucleoside triphosphates GTP, CTP, UTP and ATP to corresponding nucleoside diphosphates but with very low efficiency. NTPDase5 requires Ca2+ or Mg2+ for catalytic activity (Mulero et al. 1999). NTPDase5 is most catalytically active as a monomer, although it can also form disulfide-linked dimers (Mulero et al. 2000).

NTPDase5 may function in the endoplasmic reticulum (ER), where its UDPase activity could contribute to protein glycosylation and folding. NTPDase5 may alleviate ER stress induced by protein overload caused by oncogenic PI3K/AKT signaling in cancer cells. NTPDase5 is over-expressed in tumors with activated AKT and is known as the PCPH oncogene. The underlying mechanism of NTPDase5 over-expression may be AKT-mediated inhibition of FOXO proteins, which are probable transcriptional repressors of the ENTPD5 gene (Fang et al. 2010, Shen et al. 2011).

Literature References
PubMed ID Title Journal Year
22169232 ENTPD5, an endoplasmic reticulum UDPase, alleviates ER stress induced by protein overloading in AKT-activated cancer cells

Shen, Z, Huang, S, Fang, M, Wang, X

Cold Spring Harb. Symp. Quant. Biol. 2011
21074248 The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway

Fang, M, Shen, Z, Huang, S, Zhao, L, Chen, S, Mak, TW, Wang, X

Cell 2010
11041857 Biochemical characterization of CD39L4

Mulero, JJ, Yeung, G, Nelken, ST, Bright, JM, McGowan, DW, Ford, JE

Biochemistry 2000
10400613 CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates

Mulero, JJ, Yeung, G, Nelken, ST, Ford, JE

J. Biol. Chem. 1999
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
nucleoside-diphosphatase activity of NPTDase5:Ca2+,Mg2+ [extracellular region]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created