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Protein

Ectonucleoside triphosphate diphosphohydrolase 5

Gene

ENTPD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei172 – 1721Proton acceptorBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

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

HGNCiHGNC:3367. ENTPD5.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391C → S: No change in quaternary structure nor enzymatic activity. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA27802.

Polymorphism and mutation databases

BioMutaiENTPD5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 428404Ectonucleoside triphosphate diphosphohydrolase 5PRO_0000019908Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi232 – 2321N-linked (GlcNAc...)2 Publications
Disulfide bondi272 ↔ 303By similarity
Disulfide bondi363 ↔ 377By similarity
Glycosylationi368 – 3681N-linked (GlcNAc...)Sequence analysis

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.
PRIDEiO75356.

PTM databases

iPTMnetiO75356.
PhosphoSiteiO75356.

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

BgeeiO75356.
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 interactions.
IntActiO75356. 1 interaction.
MINTiMINT-4773412.
STRINGi9606.ENSP00000335246.

Structurei

3D structure databases

ProteinModelPortaliO75356.
SMRiO75356. Positions 49-420.
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.
OMAiHGHRQET.
PhylomeDBiO75356.
TreeFamiTF315029.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 1 hit.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti314 – 3141K → R.
Corresponds to variant rs17094434 [ dbSNP | Ensembl ].
VAR_050308

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_001249.2.
XP_005268278.1. XM_005268221.2.
XP_005268279.1. XM_005268222.3.
XP_005268281.1. XM_005268224.3.
XP_006720387.1. XM_006720324.2.
XP_011535687.1. XM_011537385.1.
XP_011535688.1. XM_011537386.1.
UniGeneiHs.655070.
Hs.720540.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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_001249.2.
XP_005268278.1. XM_005268221.2.
XP_005268279.1. XM_005268222.3.
XP_005268281.1. XM_005268224.3.
XP_006720387.1. XM_006720324.2.
XP_011535687.1. XM_011537385.1.
XP_011535688.1. XM_011537386.1.
UniGeneiHs.655070.
Hs.720540.

3D structure databases

ProteinModelPortaliO75356.
SMRiO75356. Positions 49-420.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107395. 5 interactions.
IntActiO75356. 1 interaction.
MINTiMINT-4773412.
STRINGi9606.ENSP00000335246.

PTM databases

iPTMnetiO75356.
PhosphoSiteiO75356.

Polymorphism and mutation databases

BioMutaiENTPD5.

Proteomic databases

EPDiO75356.
MaxQBiO75356.
PaxDbiO75356.
PRIDEiO75356.

Protocols and materials databases

DNASUi957.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi957.
GeneCardsiENTPD5.
HGNCiHGNC:3367. ENTPD5.
HPAiHPA002927.
MIMi603162. gene.
neXtProtiNX_O75356.
PharmGKBiPA27802.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1385. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00510000046675.
HOGENOMiHOG000220904.
HOVERGENiHBG018208.
InParanoidiO75356.
KOiK01511.
OMAiHGHRQET.
PhylomeDBiO75356.
TreeFamiTF315029.

Enzyme and pathway databases

UniPathwayiUPA00378.

Miscellaneous databases

ChiTaRSiENTPD5. human.
GeneWikiiENTPD5.
GenomeRNAii957.
NextBioi3986.
PROiO75356.
SOURCEiSearch...

Gene expression databases

BgeeiO75356.
CleanExiHS_ENTPD5.
ExpressionAtlasiO75356. baseline and differential.
GenevisibleiO75356. HS.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 1 hit.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster."
    Chadwick B.P., Frischauf A.-M.
    Genomics 50:357-367(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Leukemia.
  2. "The human PCPH proto-oncogene: cDNA identification, primary structure, chromosomal mapping, and expression in normal and tumor cells."
    Recio J.A., Zambrano N., Pena L., Reig J.A., Rhoads A., Rouzaut A., Notario V.
    Mol. Carcinog. 27:229-236(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Bacterial expression, folding, purification and characterization of soluble NTPDase5 (CD39L4) ecto-nucleotidase."
    Murphy-Piedmonte D.M., Crawford P.A., Kirley T.L.
    Biochim. Biophys. Acta 1747:251-259(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBSTRATE PREFERENCE, COFACTOR, MUTAGENESIS OF CYS-39.
    Tissue: Hippocampus.
  4. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates."
    Mulero J.J., Yeung G., Nelken S.T., Ford J.E.
    J. Biol. Chem. 274:20064-20067(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION.
  8. Cited for: GLYCOSYLATION, SUBUNIT.
  9. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-232.
    Tissue: Plasma.
  10. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-232.
    Tissue: Liver.
  11. "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 T.W., Wang X.
    Cell 143:711-724(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiENTP5_HUMAN
AccessioniPrimary (citable) accession number: O75356
Secondary accession number(s): A1L4C5, Q96RX0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: November 1, 1998
Last modified: March 16, 2016
This is version 136 of the entry and version 1 of the sequence. [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

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.