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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei222 – 2221Proton acceptorBy similarity

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3333CytoplasmicSequence analysisAdd
BLAST
Transmembranei34 – 5421HelicalSequence analysisAdd
BLAST
Topological domaini55 – 559505LumenalSequence analysisAdd
BLAST
Transmembranei560 – 58021HelicalSequence analysisAdd
BLAST
Topological domaini581 – 61636CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30502.

Chemistry

ChEMBLiCHEMBL3313834.

Polymorphism and mutation databases

BioMutaiENTPD4.
DMDMi18203627.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 616616Ectonucleoside triphosphate diphosphohydrolase 4PRO_0000209911Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi404 – 4041N-linked (GlcNAc...)Sequence analysis
Glycosylationi407 – 4071N-linked (GlcNAc...)Sequence analysis
Disulfide bondi461 ↔ 490By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9Y227.
PaxDbiQ9Y227.
PRIDEiQ9Y227.

PTM databases

iPTMnetiQ9Y227.
PhosphoSiteiQ9Y227.
SwissPalmiQ9Y227.

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in testis and lowest in bladder.

Gene expression databases

BgeeiQ9Y227.
CleanExiHS_ENTPD4.
ExpressionAtlasiQ9Y227. baseline and differential.
GenevisibleiQ9Y227. HS.

Organism-specific databases

HPAiHPA017655.

Interactioni

Protein-protein interaction databases

BioGridi114951. 8 interactions.
IntActiQ9Y227. 2 interactions.
STRINGi9606.ENSP00000351520.

Structurei

3D structure databases

ProteinModelPortaliQ9Y227.
SMRiQ9Y227. Positions 87-535.
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.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti43 – 431A → AA in AAC17217 (PubMed:9556635).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti341 – 3411I → V Found in a renal cell carcinoma case; somatic mutation. 1 Publication
VAR_064711
Natural varianti354 – 3541K → E.
Corresponds to variant rs2272641 [ dbSNP | Ensembl ].
VAR_020444

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei287 – 2948Missing in isoform 2. 2 PublicationsVSP_003614

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.
SMRiQ9Y227. Positions 87-535.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114951. 8 interactions.
IntActiQ9Y227. 2 interactions.
STRINGi9606.ENSP00000351520.

Chemistry

ChEMBLiCHEMBL3313834.

PTM databases

iPTMnetiQ9Y227.
PhosphoSiteiQ9Y227.
SwissPalmiQ9Y227.

Polymorphism and mutation databases

BioMutaiENTPD4.
DMDMi18203627.

Proteomic databases

MaxQBiQ9Y227.
PaxDbiQ9Y227.
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.
GeneCardsiENTPD4.
HGNCiHGNC:14573. ENTPD4.
HPAiHPA017655.
MIMi607577. gene.
neXtProtiNX_Q9Y227.
PharmGKBiPA30502.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciMetaCyc:HS09501-MONOMER.

Miscellaneous databases

ChiTaRSiENTPD4. human.
GenomeRNAii9583.
NextBioi35949.
PROiQ9Y227.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y227.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Golgi localization and functional expression of human uridine diphosphatase."
    Wang T.-F., Guidotti G.
    J. Biol. Chem. 273:11392-11399(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION.
    Tissue: Brain.
  2. "A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles."
    Biederbick A., Rose S., Elsaesser H.-P.
    J. Cell Sci. 112:2473-2484(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Pancreatic adenocarcinoma.
  3. "First apyrase splice variants have different enzymatic properties."
    Biederbick A., Kosan C., Kunz J., Elsaesser H.-P.
    J. Biol. Chem. 275:19018-19024(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), ALTERNATIVE SPLICING.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
    Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-616 (ISOFORM 2).
    Tissue: Brain.
  6. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
    Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
    Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. Cited for: VARIANT VAL-341.

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: May 11, 2016
This is version 146 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.