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Protein

Ectonucleoside triphosphate diphosphohydrolase 8

Gene

ENTPD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides. Has activity toward ATP, ADP, UTP and UDP, but not toward AMP.2 Publications

Catalytic activityi

A nucleoside 5'-triphosphate + 2 H2O = a nucleoside 5'-phosphate + 2 phosphate.2 Publications

Cofactori

Ca2+By similarity, Mg2+By similarityNote: Ca2+ or Mg2+. Has lower efficiency with Mg2+.By similarity

Enzyme regulationi

Not inhibited by ARL 67156.1 Publication

Kineticsi

  1. KM=81 µM for ATP1 Publication
  2. KM=137 µM for ADP1 Publication
  3. KM=480 µM for UTP1 Publication
  4. KM=241 µM for UDP1 Publication
  1. Vmax=790 nmol/min/mg enzyme with ATP as substrate1 Publication
  2. Vmax=163 nmol/min/mg enzyme with ADP as substrate1 Publication
  3. Vmax=1100 nmol/min/mg enzyme with UTP as substrate1 Publication
  4. Vmax=110 nmol/min/mg enzyme with UDP as substrate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei168Proton acceptorBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandATP-binding, Calcium, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-8850843. Phosphate bond hydrolysis by NTPDase proteins.
SABIO-RKiQ5MY95.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 8 (EC:3.6.1.5)
Short name:
E-NTPDase 8
Short name:
NTPDase 8
Short name:
NTPDase8
Gene namesi
Name:ENTPD8
ORF Names:UNQ2492/PRO5779
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:24860. ENTPD8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8CytoplasmicSequence analysis8
Transmembranei9 – 29HelicalSequence analysisAdd BLAST21
Topological domaini30 – 471ExtracellularSequence analysisAdd BLAST442
Transmembranei472 – 492HelicalSequence analysisAdd BLAST21
Topological domaini493 – 495CytoplasmicSequence analysis3

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi377841.
OpenTargetsiENSG00000188833.
PharmGKBiPA142671906.

Chemistry databases

ChEMBLiCHEMBL5338.

Polymorphism and mutation databases

BioMutaiENTPD8.
DMDMi158705943.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003068821 – 495Ectonucleoside triphosphate diphosphohydrolase 8Add BLAST495

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi78 ↔ 102By similarity
Disulfide bondi246 ↔ 292By similarity
Glycosylationi304N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi329 ↔ 335By similarity
Glycosylationi363N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi381 ↔ 403By similarity

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ5MY95.
PaxDbiQ5MY95.
PeptideAtlasiQ5MY95.
PRIDEiQ5MY95.

PTM databases

iPTMnetiQ5MY95.
PhosphoSitePlusiQ5MY95.

Expressioni

Gene expression databases

BgeeiENSG00000188833.
CleanExiHS_ENTPD8.
ExpressionAtlasiQ5MY95. baseline and differential.

Organism-specific databases

HPAiHPA021509.

Interactioni

Protein-protein interaction databases

IntActiQ5MY95. 1 interactor.
STRINGi9606.ENSP00000360561.

Chemistry databases

BindingDBiQ5MY95.

Structurei

3D structure databases

ProteinModelPortaliQ5MY95.
SMRiQ5MY95.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The transmembranous domains are involved in regulation of enzyme activity.1 Publication

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1386. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000059572.
HOVERGENiHBG018982.
InParanoidiQ5MY95.
KOiK01510.
OMAiIPEAQHR.
OrthoDBiEOG091G05FZ.
PhylomeDBiQ5MY95.
TreeFamiTF332859.

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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5MY95-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGLSRKEQVF LALLGASGVS GLTALILLLV EATSVLLPTD IKFGIVFDAG
60 70 80 90 100
SSHTSLFLYQ WLANKENGTG VVSQALACQV EGPGISSYTS NAAQAGESLQ
110 120 130 140 150
GCLEEALVLI PEAQHRKTPT FLGATAGMRL LSRKNSSQAR DIFAAVTQVL
160 170 180 190 200
GRSPVDFWGA ELLAGQAEGA FGWITVNYGL GTLVKYSFTG EWIQPPEEML
210 220 230 240 250
VGALDMGGAS TQITFVPGGP ILDKSTQADF RLYGSDYSVY THSYLCFGRD
260 270 280 290 300
QMLSRLLVGL VQSRPAALLR HPCYLSGYQT TLALGPLYES PCVHATPPLS
310 320 330 340 350
LPQNLTVEGT GNPGACVSAI RELFNFSSCQ GQEDCAFDGV YQPPLRGQFY
360 370 380 390 400
AFSNFYYTFH FLNLTSRQPL STVNATIWEF CQRPWKLVEA SYPGQDRWLR
410 420 430 440 450
DYCASGLYIL TLLHEGYGFS EETWPSLEFR KQAGGVDIGW TLGYMLNLTG
460 470 480 490
MIPADAPAQW RAESYGVWVA KVVFMVLALV AVVGAALVQL FWLQD
Length:495
Mass (Da):53,904
Last modified:October 2, 2007 - v2
Checksum:i030200E15F662D82
GO
Isoform 2 (identifier: Q5MY95-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-387: Missing.

Show »
Length:458
Mass (Da):49,393
Checksum:iC2BEDCB65064B6B3
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03533962L → P4 PublicationsCorresponds to variant dbSNP:rs6606582Ensembl.1
Natural variantiVAR_061385428E → K. Corresponds to variant dbSNP:rs61491031Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028559351 – 387Missing in isoform 2. 2 PublicationsAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY903953 Transcribed RNA. Translation: AAW83515.1.
AY903954 mRNA. Translation: AAW83516.1.
AY430414 mRNA. Translation: AAR04374.1.
AY359088 mRNA. Translation: AAQ89446.1.
BX322799 Genomic DNA. No translation available.
BC141810 mRNA. Translation: AAI41811.1.
CCDSiCCDS43913.1. [Q5MY95-1]
CCDS7043.1. [Q5MY95-2]
RefSeqiNP_001028285.1. NM_001033113.1. [Q5MY95-1]
NP_940987.2. NM_198585.2. [Q5MY95-2]
UniGeneiHs.512562.

Genome annotation databases

EnsembliENST00000344119; ENSP00000344089; ENSG00000188833. [Q5MY95-2]
ENST00000371506; ENSP00000360561; ENSG00000188833. [Q5MY95-1]
ENST00000472938; ENSP00000420531; ENSG00000188833. [Q5MY95-1]
GeneIDi377841.
KEGGihsa:377841.
UCSCiuc004cmw.3. human. [Q5MY95-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiENTP8_HUMAN
AccessioniPrimary (citable) accession number: Q5MY95
Secondary accession number(s): A2BG17, Q6UVZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: August 30, 2017
This is version 112 of the entry and version 2 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 9
    Human chromosome 9: 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. SIMILARITY comments
    Index of protein domains and families