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Protein

Ectonucleoside triphosphate diphosphohydrolase 4

Gene

ENTPD4

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

Functioni

Hydrolyzes preferentially nucleoside 5'-diphosphates, nucleoside 5'-triphosphates are hydrolyzed only to a minor extent. The order of activity with different substrates is UDP >> GDP = CDP = TDP, AMP, ADP, ATP and UMP are not substrates. Preferred substrates for isoform 2 are CTP, UDP, CDP, GTP and GDP, while isoform 1 utilizes UTP and TTP.

Catalytic activityi

A nucleoside diphosphate + H2O = a nucleoside phosphate + phosphate.1 Publication

Cofactori

Ca2+1 Publication, Mg2+1 PublicationNote: Isoform 1 and isoform 2 require Ca2+ and can also use Mg2+, but with lower efficiency.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei222Proton acceptorBy similarity1

GO - Molecular functioni

  • uridine-diphosphatase activity Source: UniProtKB

GO - Biological processi

  • UDP catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

BioCyciMetaCyc:HS09501-MONOMER.
ZFISH:HS09501-MONOMER.
ReactomeiR-HSA-8850843. Phosphate bond hydrolysis by NTPDase proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 4 (EC:3.6.1.6)
Short name:
NTPDase 4
Alternative name(s):
Lysosomal apyrase-like protein of 70 kDa
Uridine-diphosphatase
Short name:
UDPase
Gene namesi
Name:ENTPD4
Synonyms:KIAA0392, LALP70, LYSAL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:14573. ENTPD4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 33CytoplasmicSequence analysisAdd BLAST33
Transmembranei34 – 54HelicalSequence analysisAdd BLAST21
Topological domaini55 – 559LumenalSequence analysisAdd BLAST505
Transmembranei560 – 580HelicalSequence analysisAdd BLAST21
Topological domaini581 – 616CytoplasmicSequence analysisAdd BLAST36

GO - Cellular componenti

  • cytoplasmic vesicle Source: UniProtKB-KW
  • integral component of autophagosome membrane Source: ParkinsonsUK-UCL
  • integral component of Golgi membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi9583.
OpenTargetsiENSG00000197217.
PharmGKBiPA30502.

Chemistry databases

ChEMBLiCHEMBL3313834.

Polymorphism and mutation databases

BioMutaiENTPD4.
DMDMi18203627.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002099111 – 616Ectonucleoside triphosphate diphosphohydrolase 4Add BLAST616

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi404N-linked (GlcNAc...)Sequence analysis1
Glycosylationi407N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi461 ↔ 490By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Y227.
PaxDbiQ9Y227.
PeptideAtlasiQ9Y227.
PRIDEiQ9Y227.

PTM databases

iPTMnetiQ9Y227.
PhosphoSitePlusiQ9Y227.
SwissPalmiQ9Y227.

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in testis and lowest in bladder.

Gene expression databases

BgeeiENSG00000197217.
CleanExiHS_ENTPD4.
ExpressionAtlasiQ9Y227. baseline and differential.
GenevisibleiQ9Y227. HS.

Organism-specific databases

HPAiHPA017655.

Interactioni

Protein-protein interaction databases

BioGridi114951. 8 interactors.
IntActiQ9Y227. 2 interactors.
STRINGi9606.ENSP00000351520.

Structurei

3D structure databases

ProteinModelPortaliQ9Y227.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1386. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000090205.
HOVERGENiHBG006789.
InParanoidiQ9Y227.
KOiK12305.
OMAiNSQFYGF.
OrthoDBiEOG091G04IV.
PhylomeDBiQ9Y227.
TreeFamiTF354343.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 3 hits.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y227-1) [UniParc]FASTAAdd to basket
Also known as: LALP70

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
MGRIGISCLF PASWHFSISP VGCPRILNTN LRQIMVISVL AAAVSLLYFS
60 70 80 90 100
VVIIRNKYGR LTRDKKFQRY LARVTDIEAT DTNNPNVNYG IVVDCGSSGS
110 120 130 140 150
RVFVYCWPRH NGNPHDLLDI RQMRDKNRKP VVMKIKPGIS EFATSPEKVS
160 170 180 190 200
DYISPLLNFA AEHVPRAKHK ETPLYILCTA GMRILPESQQ KAILEDLLTD
210 220 230 240 250
IPVHFDFLFS DSHAEVISGK QEGVYAWIGI NFVLGRFEHI EDDDEAVVEV
260 270 280 290 300
NIPGSESSEA IVRKRTAGIL DMGGVSTQIA YEVPKTVSFA SSQQEEVAKN
310 320 330 340 350
LLAEFNLGCD VHQTEHVYRV YVATFLGFGG NAARQRYEDR IFANTIQKNR
360 370 380 390 400
LLGKQTGLTP DMPYLDPCLP LDIKDEIQQN GQTIYLRGTG DFDLCRETIQ
410 420 430 440 450
PFMNKTNETQ TSLNGVYQPP IHFQNSEFYG FSEFYYCTED VLRMGGDYNA
460 470 480 490 500
AKFTKAAKDY CATKWSILRE RFDRGLYASH ADLHRLKYQC FKSAWMFEVF
510 520 530 540 550
HRGFSFPVNY KSLKTALQVY DKEVQWTLGA ILYRTRFLPL RDIQQEAFRA
560 570 580 590 600
SHTHWRGVSF VYNHYLFSGC FLVVLLAILL YLLRLRRIHR RTPRSSSAAA
610
LWMEEGLPAQ NAPGTL
Length:616
Mass (Da):70,255
Last modified:November 1, 1999 - v1
Checksum:i68A7EF7E9CB60544
GO
Isoform 2 (identifier: Q9Y227-2) [UniParc]FASTAAdd to basket
Also known as: LALP70V

The sequence of this isoform differs from the canonical sequence as follows:
     287-294: Missing.

Show »
Length:608
Mass (Da):69,421
Checksum:iF931A79B05D600A9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti43A → AA in AAC17217 (PubMed:9556635).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064711341I → V Found in a renal cell carcinoma case; somatic mutation. 1 PublicationCorresponds to variant rs549468877dbSNPEnsembl.1
Natural variantiVAR_020444354K → E.Corresponds to variant rs2272641dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003614287 – 294Missing in isoform 2. 2 Publications8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF016032 mRNA. Translation: AAC17217.1.
AJ131358 mRNA. Translation: CAB40415.1.
AJ246165
, AJ246166, AJ246167, AJ246168, AJ246169, AJ246170, AJ246171, AJ246172, AJ246173, AJ246174, AJ246175, AJ246176 Genomic DNA. Translation: CAB45655.1.
CH471080 Genomic DNA. Translation: EAW63622.1.
CH471080 Genomic DNA. Translation: EAW63623.1.
AB002390 mRNA. Translation: BAA21575.1.
CCDSiCCDS47827.1. [Q9Y227-2]
CCDS6041.1. [Q9Y227-1]
RefSeqiNP_001122402.1. NM_001128930.2. [Q9Y227-2]
NP_004892.1. NM_004901.4. [Q9Y227-1]
UniGeneiHs.444389.

Genome annotation databases

EnsembliENST00000358689; ENSP00000351520; ENSG00000197217. [Q9Y227-1]
ENST00000417069; ENSP00000408573; ENSG00000197217. [Q9Y227-2]
GeneIDi9583.
KEGGihsa:9583.
UCSCiuc003xdl.4. human. [Q9Y227-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF016032 mRNA. Translation: AAC17217.1.
AJ131358 mRNA. Translation: CAB40415.1.
AJ246165
, AJ246166, AJ246167, AJ246168, AJ246169, AJ246170, AJ246171, AJ246172, AJ246173, AJ246174, AJ246175, AJ246176 Genomic DNA. Translation: CAB45655.1.
CH471080 Genomic DNA. Translation: EAW63622.1.
CH471080 Genomic DNA. Translation: EAW63623.1.
AB002390 mRNA. Translation: BAA21575.1.
CCDSiCCDS47827.1. [Q9Y227-2]
CCDS6041.1. [Q9Y227-1]
RefSeqiNP_001122402.1. NM_001128930.2. [Q9Y227-2]
NP_004892.1. NM_004901.4. [Q9Y227-1]
UniGeneiHs.444389.

3D structure databases

ProteinModelPortaliQ9Y227.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114951. 8 interactors.
IntActiQ9Y227. 2 interactors.
STRINGi9606.ENSP00000351520.

Chemistry databases

ChEMBLiCHEMBL3313834.

PTM databases

iPTMnetiQ9Y227.
PhosphoSitePlusiQ9Y227.
SwissPalmiQ9Y227.

Polymorphism and mutation databases

BioMutaiENTPD4.
DMDMi18203627.

Proteomic databases

EPDiQ9Y227.
PaxDbiQ9Y227.
PeptideAtlasiQ9Y227.
PRIDEiQ9Y227.

Protocols and materials databases

DNASUi9583.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358689; ENSP00000351520; ENSG00000197217. [Q9Y227-1]
ENST00000417069; ENSP00000408573; ENSG00000197217. [Q9Y227-2]
GeneIDi9583.
KEGGihsa:9583.
UCSCiuc003xdl.4. human. [Q9Y227-1]

Organism-specific databases

CTDi9583.
DisGeNETi9583.
GeneCardsiENTPD4.
HGNCiHGNC:14573. ENTPD4.
HPAiHPA017655.
MIMi607577. gene.
neXtProtiNX_Q9Y227.
OpenTargetsiENSG00000197217.
PharmGKBiPA30502.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1386. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000090205.
HOVERGENiHBG006789.
InParanoidiQ9Y227.
KOiK12305.
OMAiNSQFYGF.
OrthoDBiEOG091G04IV.
PhylomeDBiQ9Y227.
TreeFamiTF354343.

Enzyme and pathway databases

BioCyciMetaCyc:HS09501-MONOMER.
ZFISH:HS09501-MONOMER.
ReactomeiR-HSA-8850843. Phosphate bond hydrolysis by NTPDase proteins.

Miscellaneous databases

ChiTaRSiENTPD4. human.
GenomeRNAii9583.
PROiQ9Y227.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197217.
CleanExiHS_ENTPD4.
ExpressionAtlasiQ9Y227. baseline and differential.
GenevisibleiQ9Y227. HS.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 3 hits.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiENTP4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y227
Secondary accession number(s): D3DSS3, O15092
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 151 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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

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.