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Protein

Ectonucleoside triphosphate diphosphohydrolase 5

Gene

ENTPD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Uridine 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.1 Publication

Miscellaneous

May 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.1 Publication

Catalytic activityi

GDP + H2O = GMP + phosphate.
A nucleoside diphosphate + H2O = a nucleoside phosphate + phosphate.

Cofactori

Ca2+2 Publications, Mg2+2 Publications

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei172Proton acceptorBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandCalcium, Magnesium

Enzyme and pathway databases

ReactomeiR-HSA-8850843 Phosphate bond hydrolysis by NTPDase proteins
UniPathwayiUPA00378

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 5 (EC:3.6.1.6)
Short name:
NTPDase 5
Alternative name(s):
CD39 antigen-like 4
ER-UDPase
Guanosine-diphosphatase ENTPD5 (EC:3.6.1.42)
Short name:
GDPase ENTPD5
Nucleoside diphosphatase
Uridine-diphosphatase ENTPD5
Short name:
UDPase ENTPD5
Gene namesi
Name:ENTPD5
Synonyms:CD39L4, PCPH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000187097.12
HGNCiHGNC:3367 ENTPD5
MIMi603162 gene
neXtProtiNX_O75356

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39C → S: No change in quaternary structure nor enzymatic activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi957
OpenTargetsiENSG00000187097
PharmGKBiPA27802

Polymorphism and mutation databases

BioMutaiENTPD5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001990825 – 428Ectonucleoside triphosphate diphosphohydrolase 5Add BLAST404

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi232N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi272 ↔ 303By similarity
Disulfide bondi363 ↔ 377By similarity
Glycosylationi368N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated; high-mannose type (By similarity). Glycosylation is not essential for enzymatic activity.By similarity3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO75356
MaxQBiO75356
PaxDbiO75356
PeptideAtlasiO75356
PRIDEiO75356
ProteomicsDBi49923

PTM databases

iPTMnetiO75356
PhosphoSitePlusiO75356

Expressioni

Tissue specificityi

Expressed in adult liver, kidney, prostate, testis and colon. Much weaker expression in other tissues.1 Publication

Inductioni

Up-regulated in cell lines and primary tumor samples with active AKT1.1 Publication

Gene expression databases

BgeeiENSG00000187097
CleanExiHS_ENTPD5
ExpressionAtlasiO75356 baseline and differential
GenevisibleiO75356 HS

Organism-specific databases

HPAiHPA002927

Interactioni

Subunit structurei

Exists both as a monomer and a disulfide-linked homodimer, the dimers are enzymatically inactive.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MXI1P505393EBI-7416931,EBI-752241

Protein-protein interaction databases

BioGridi107395, 5 interactors
IntActiO75356, 1 interactor
MINTiO75356
STRINGi9606.ENSP00000335246

Structurei

3D structure databases

ProteinModelPortaliO75356
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1385 Eukaryota
COG5371 LUCA
GeneTreeiENSGT00510000046675
HOGENOMiHOG000220904
HOVERGENiHBG018208
InParanoidiO75356
KOiK01511
OMAiTPRGYLT
OrthoDBiEOG091G06ET
PhylomeDBiO75356
TreeFamiTF315029

Family and domain databases

InterProiView protein in InterPro
IPR000407 GDA1_CD39_NTPase
PANTHERiPTHR11782 PTHR11782, 1 hit
PfamiView protein in Pfam
PF01150 GDA1_CD39, 1 hit
PROSITEiView protein in PROSITE
PS01238 GDA1_CD39_NTPASE, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O75356-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATSWGTVFF MLVVSCVCSA VSHRNQQTWF EGIFLSSMCP INVSASTLYG
60 70 80 90 100
IMFDAGSTGT RIHVYTFVQK MPGQLPILEG EVFDSVKPGL SAFVDQPKQG
110 120 130 140 150
AETVQGLLEV AKDSIPRSHW KKTPVVLKAT AGLRLLPEHK AKALLFEVKE
160 170 180 190 200
IFRKSPFLVP KGSVSIMDGS DEGILAWVTV NFLTGQLHGH RQETVGTLDL
210 220 230 240 250
GGASTQITFL PQFEKTLEQT PRGYLTSFEM FNSTYKLYTH SYLGFGLKAA
260 270 280 290 300
RLATLGALET EGTDGHTFRS ACLPRWLEAE WIFGGVKYQY GGNQEGEVGF
310 320 330 340 350
EPCYAEVLRV VRGKLHQPEE VQRGSFYAFS YYYDRAVDTD MIDYEKGGIL
360 370 380 390 400
KVEDFERKAR EVCDNLENFT SGSPFLCMDL SYITALLKDG FGFADSTVLQ
410 420
LTKKVNNIET GWALGATFHL LQSLGISH
Length:428
Mass (Da):47,517
Last modified:November 1, 1998 - v1
Checksum:i830437A155DE4DDD
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050308314K → R. Corresponds to variant dbSNP:rs17094434Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039918 mRNA Translation: AAC39885.1
AF136572 mRNA Translation: AAK82950.1
AY430094 mRNA Translation: AAR06666.1
AC005480 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81153.1
BC130485 mRNA Translation: AAI30486.1
BC130487 mRNA Translation: AAI30488.1
CCDSiCCDS9825.1
RefSeqiNP_001240.1, NM_001249.3
NP_001308914.1, NM_001321985.1
NP_001308915.1, NM_001321986.1
NP_001308916.1, NM_001321987.1
NP_001308917.1, NM_001321988.1
XP_005268281.1, XM_005268224.3
XP_016877302.1, XM_017021813.1
UniGeneiHs.655070
Hs.656955
Hs.720540

Genome annotation databases

EnsembliENST00000334696; ENSP00000335246; ENSG00000187097
GeneIDi957
KEGGihsa:957
UCSCiuc010tuo.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiENTP5_HUMAN
AccessioniPrimary (citable) accession number: O75356
Secondary accession number(s): A1L4C5, Q96RX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: November 1, 1998
Last modified: July 18, 2018
This is version 157 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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