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Protein

Bis(5'-adenosyl)-triphosphatase ENPP4

Gene

ENPP4

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

Functioni

Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors.2 Publications

Catalytic activityi

P(1)-P(3)-bis(5'-adenosyl) triphosphate + H2O = ADP + AMP.2 Publications

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi34Zinc 1; catalytic1
Active sitei70AMP-threonine intermediateBy similarity1
Metal bindingi70Zinc 1; catalytic1
Binding sitei91Substrate1
Binding sitei154Substrate1
Metal bindingi189Zinc 2; catalytic1
Binding sitei189Substrate1
Metal bindingi193Zinc 2; catalytic1
Metal bindingi237Zinc 1; catalytic1
Metal bindingi238Zinc 1; catalytic1
Metal bindingi336Zinc 2; catalytic1

GO - Molecular functioni

  • bis(5'-adenosyl)-triphosphatase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • blood coagulation Source: UniProtKB-KW
  • positive regulation of blood coagulation Source: UniProtKB
  • purine ribonucleoside catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000001561-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Bis(5'-adenosyl)-triphosphatase ENPP4 (EC:3.6.1.29)
Alternative name(s):
AP3A hydrolase
Short name:
AP3Aase
Ectonucleotide pyrophosphatase/phosphodiesterase family member 4
Short name:
E-NPP 4
Short name:
NPP-4
Gene namesi
Name:ENPP4
Synonyms:KIAA0879, NPP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3359. ENPP4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini16 – 407ExtracellularSequence analysisAdd BLAST392
Transmembranei408 – 428HelicalSequence analysisAdd BLAST21
Topological domaini429 – 453CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000001561.
PharmGKBiPA27794.

Polymorphism and mutation databases

BioMutaiENPP4.
DMDMi172045555.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 15Sequence analysisAdd BLAST15
ChainiPRO_000032479516 – 453Bis(5'-adenosyl)-triphosphatase ENPP4Add BLAST438

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi155N-linked (GlcNAc...)1 Publication1
Glycosylationi166N-linked (GlcNAc...)1 Publication1
Disulfide bondi254 ↔ 2871 Publication
Glycosylationi276N-linked (GlcNAc...)Sequence analysis1
Glycosylationi386N-linked (GlcNAc...)1 Publication1
Disulfide bondi394 ↔ 4011 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Y6X5.
MaxQBiQ9Y6X5.
PaxDbiQ9Y6X5.
PeptideAtlasiQ9Y6X5.
PRIDEiQ9Y6X5.

PTM databases

iPTMnetiQ9Y6X5.
PhosphoSitePlusiQ9Y6X5.

Expressioni

Tissue specificityi

Expressed on the surface of vascular endothelia.1 Publication

Gene expression databases

BgeeiENSG00000001561.
CleanExiHS_ENPP4.
GenevisibleiQ9Y6X5. HS.

Organism-specific databases

HPAiHPA016594.

Interactioni

Protein-protein interaction databases

BioGridi116542. 9 interactors.
STRINGi9606.ENSP00000318066.

Structurei

Secondary structure

1453
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 33Combined sources6
Helixi40 – 43Combined sources4
Helixi47 – 54Combined sources8
Beta strandi56 – 63Combined sources8
Helixi70 – 79Combined sources10
Helixi83 – 86Combined sources4
Beta strandi90 – 94Combined sources5
Turni96 – 98Combined sources3
Beta strandi104 – 106Combined sources3
Helixi110 – 112Combined sources3
Turni113 – 115Combined sources3
Helixi119 – 124Combined sources6
Beta strandi130 – 135Combined sources6
Turni137 – 140Combined sources4
Helixi160 – 172Combined sources13
Beta strandi178 – 185Combined sources8
Helixi189 – 195Combined sources7
Helixi200 – 223Combined sources24
Turni227 – 229Combined sources3
Beta strandi231 – 235Combined sources5
Beta strandi247 – 250Combined sources4
Helixi251 – 253Combined sources3
Helixi257 – 259Combined sources3
Beta strandi260 – 264Combined sources5
Beta strandi266 – 275Combined sources10
Helixi277 – 284Combined sources8
Beta strandi291 – 295Combined sources5
Helixi296 – 298Combined sources3
Helixi301 – 303Combined sources3
Beta strandi313 – 318Combined sources6
Beta strandi323 – 325Combined sources3
Beta strandi333 – 335Combined sources3
Helixi343 – 345Combined sources3
Beta strandi349 – 353Combined sources5
Beta strandi358 – 366Combined sources9
Helixi367 – 369Combined sources3
Helixi370 – 378Combined sources9
Helixi389 – 395Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LQYX-ray1.54A16-407[»]
4LR2X-ray1.50A16-407[»]
ProteinModelPortaliQ9Y6X5.
SMRiQ9Y6X5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000231018.
HOVERGENiHBG051485.
KOiK18424.
OMAiCLIIIMQ.
OrthoDBiEOG091G06NA.
PhylomeDBiQ9Y6X5.
TreeFamiTF330032.

Family and domain databases

Gene3Di3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR024873. E-NPP.
IPR029879. ENPP4.
IPR002591. Phosphodiest/P_Trfase.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF79. PTHR10151:SF79. 1 hit.
PfamiPF01663. Phosphodiest. 1 hit.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q9Y6X5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLLVILLFS GLITGFRSDS SSSLPPKLLL VSFDGFRADY LKNYEFPHLQ
60 70 80 90 100
NFIKEGVLVE HVKNVFITKT FPNHYSIVTG LYEESHGIVA NSMYDAVTKK
110 120 130 140 150
HFSDSNDKDP FWWNEAVPIW VTNQLQENRS SAAAMWPGTD VPIHDTISSY
160 170 180 190 200
FMNYNSSVSF EERLNNITMW LNNSNPPVTF ATLYWEEPDA SGHKYGPEDK
210 220 230 240 250
ENMSRVLKKI DDLIGDLVQR LKMLGLWENL NVIITSDHGM TQCSQDRLIN
260 270 280 290 300
LDSCIDHSYY TLIDLSPVAA ILPKINRTEV YNKLKNCSPH MNVYLKEDIP
310 320 330 340 350
NRFYYQHNDR IQPIILVADE GWTIVLNESS QKLGDHGYDN SLPSMHPFLA
360 370 380 390 400
AHGPAFHKGY KHSTINIVDI YPMMCHILGL KPHPNNGTFG HTKCLLVDQW
410 420 430 440 450
CINLPEAIAI VIGSLLVLTM LTCLIIIMQN RLSVPRPFSR LQLQEDDDDP

LIG
Length:453
Mass (Da):51,641
Last modified:March 18, 2008 - v3
Checksum:iBC82FA36D9B587C4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39D → G in BAF83965 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_039884144H → Q.1 PublicationCorresponds to variant rs7451713dbSNPEnsembl.1
Natural variantiVAR_039885255I → V.Corresponds to variant rs9381429dbSNPEnsembl.1
Natural variantiVAR_039886439S → A.Corresponds to variant rs16874289dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020686 mRNA. Translation: BAA74902.2.
AK291276 mRNA. Translation: BAF83965.1.
AL035701 Genomic DNA. Translation: CAB56567.1.
BC018054 mRNA. Translation: AAH18054.1.
CCDSiCCDS34468.1.
PIRiA59389.
RefSeqiNP_055751.1. NM_014936.4.
UniGeneiHs.643497.

Genome annotation databases

EnsembliENST00000321037; ENSP00000318066; ENSG00000001561.
GeneIDi22875.
KEGGihsa:22875.
UCSCiuc003oxy.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020686 mRNA. Translation: BAA74902.2.
AK291276 mRNA. Translation: BAF83965.1.
AL035701 Genomic DNA. Translation: CAB56567.1.
BC018054 mRNA. Translation: AAH18054.1.
CCDSiCCDS34468.1.
PIRiA59389.
RefSeqiNP_055751.1. NM_014936.4.
UniGeneiHs.643497.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LQYX-ray1.54A16-407[»]
4LR2X-ray1.50A16-407[»]
ProteinModelPortaliQ9Y6X5.
SMRiQ9Y6X5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116542. 9 interactors.
STRINGi9606.ENSP00000318066.

PTM databases

iPTMnetiQ9Y6X5.
PhosphoSitePlusiQ9Y6X5.

Polymorphism and mutation databases

BioMutaiENPP4.
DMDMi172045555.

Proteomic databases

EPDiQ9Y6X5.
MaxQBiQ9Y6X5.
PaxDbiQ9Y6X5.
PeptideAtlasiQ9Y6X5.
PRIDEiQ9Y6X5.

Protocols and materials databases

DNASUi22875.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321037; ENSP00000318066; ENSG00000001561.
GeneIDi22875.
KEGGihsa:22875.
UCSCiuc003oxy.4. human.

Organism-specific databases

CTDi22875.
GeneCardsiENPP4.
HGNCiHGNC:3359. ENPP4.
HPAiHPA016594.
MIMi617000. gene.
neXtProtiNX_Q9Y6X5.
OpenTargetsiENSG00000001561.
PharmGKBiPA27794.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000231018.
HOVERGENiHBG051485.
KOiK18424.
OMAiCLIIIMQ.
OrthoDBiEOG091G06NA.
PhylomeDBiQ9Y6X5.
TreeFamiTF330032.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000001561-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

GenomeRNAii22875.
PROiQ9Y6X5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000001561.
CleanExiHS_ENPP4.
GenevisibleiQ9Y6X5. HS.

Family and domain databases

Gene3Di3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR024873. E-NPP.
IPR029879. ENPP4.
IPR002591. Phosphodiest/P_Trfase.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF79. PTHR10151:SF79. 1 hit.
PfamiPF01663. Phosphodiest. 1 hit.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiENPP4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6X5
Secondary accession number(s): A8K5G1, Q7L2N1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: November 30, 2016
This is version 111 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.