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Protein

P2Y purinoceptor 12

Gene

P2RY12

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

Functioni

Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei93ADP1
Binding sitei97ADP; via carbonyl oxygen1
Binding sitei105ADP1
Binding sitei187ADP1
Binding sitei191ADP1
Binding sitei263ADP1
Binding sitei280ADP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi156 – 159ADP4
Nucleotide bindingi175 – 179ADP5
Nucleotide bindingi256 – 259ADP4

GO - Molecular functioni

  • ADP receptor activity Source: UniProtKB
  • G protein-coupled adenosine receptor activity Source: Ensembl
  • G protein-coupled purinergic nucleotide receptor activity Source: GO_Central
  • guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBlood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiR-HSA-392170 ADP signalling through P2Y purinoceptor 12
R-HSA-417957 P2Y receptors
R-HSA-418594 G alpha (i) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
P2Y purinoceptor 12
Short name:
P2Y12
Alternative name(s):
ADP-glucose receptor
Short name:
ADPG-R
P2T(AC)
P2Y(AC)
P2Y(cyc)
P2Y12 platelet ADP receptor
Short name:
P2Y(ADP)
SP1999
Gene namesi
Name:P2RY12
Synonyms:HORK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000169313.9
HGNCiHGNC:18124 P2RY12
MIMi600515 gene
neXtProtiNX_Q9H244

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 27ExtracellularAdd BLAST27
Transmembranei28 – 50Helical; Name=1Add BLAST23
Topological domaini51 – 61CytoplasmicAdd BLAST11
Transmembranei62 – 82Helical; Name=2Add BLAST21
Topological domaini83 – 97ExtracellularAdd BLAST15
Transmembranei98 – 118Helical; Name=3Add BLAST21
Topological domaini119 – 142CytoplasmicAdd BLAST24
Transmembranei143 – 162Helical; Name=4Add BLAST20
Topological domaini163 – 185ExtracellularAdd BLAST23
Transmembranei186 – 207Helical; Name=5Add BLAST22
Topological domaini208 – 233CytoplasmicAdd BLAST26
Transmembranei234 – 259Helical; Name=6Add BLAST26
Topological domaini260 – 278ExtracellularAdd BLAST19
Transmembranei279 – 298Helical; Name=7Add BLAST20
Topological domaini299 – 342CytoplasmicAdd BLAST44

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Bleeding disorder, platelet-type 8 (BDPLT8)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by mild to moderate mucocutaneous bleeding, and excessive bleeding after surgery or trauma. The defect is due to severe impairment of platelet response to ADP resulting in defective platelet aggregation.
See also OMIM:609821
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072802187H → Q in BDPLT8. 1 Publication1
Natural variantiVAR_025383256R → Q in BDPLT8. 1 PublicationCorresponds to variant dbSNP:rs121917885EnsemblClinVar.1
Natural variantiVAR_025384265R → W in BDPLT8. 1 PublicationCorresponds to variant dbSNP:rs121917886EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi80K → A: Abolishes ADP binding. 1 Publication1
Mutagenesisi83S → A: No effect on ADP binding. 1 Publication1
Mutagenesisi97C → A: Abolishes ADP binding. 1 Publication1
Mutagenesisi156S → A: Slightly decreases affinity for ADP. 1 Publication1
Mutagenesisi159N → A: Slightly decreases affinity for ADP. 1 Publication1
Mutagenesisi175C → A: Abolishes ADP binding. 1 Publication1
Mutagenesisi256R → A: Decreases affinity for ADP. 1 Publication1
Mutagenesisi280K → A: Abolishes ADP binding. 2 Publications1
Mutagenesisi281E → A: Abolishes ADP binding. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi64805
MalaCardsiP2RY12
MIMi609821 phenotype
OpenTargetsiENSG00000169313
Orphaneti36355 P2Y12 defect
240935 Resistance to clopidogrel
PharmGKBiPA134971947

Chemistry databases

ChEMBLiCHEMBL2001
DrugBankiDB04902 AZD6140
DB06441 Cangrelor
DB00758 Clopidogrel
DB01240 Epoprostenol
DB06209 Prasugrel
DB08816 Ticagrelor
DB00208 Ticlopidine
DB00374 Treprostinil
GuidetoPHARMACOLOGYi328

Polymorphism and mutation databases

DMDMi21263835

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000700361 – 342P2Y purinoceptor 12Add BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi6N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi13N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi17 ↔ 270
Modified residuei55PhosphoserineBy similarity1
Modified residuei57PhosphoserineBy similarity1
Disulfide bondi97 ↔ 175

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9H244
PeptideAtlasiQ9H244
PRIDEiQ9H244
ProteomicsDBi80487

PTM databases

iPTMnetiQ9H244
PhosphoSitePlusiQ9H244

Expressioni

Tissue specificityi

Highly expressed in the platelets, lower levels in the brain. Lowest levels in the lung, appendix, pituitary and adrenal gland. Expressed in the spinal cord and in the fetal brain.3 Publications

Gene expression databases

BgeeiENSG00000169313 Expressed in 156 organ(s), highest expression level in substantia nigra
CleanExiHS_P2RY12
GenevisibleiQ9H244 HS

Organism-specific databases

HPAiHPA013796
HPA014518

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122309, 62 interactors
DIPiDIP-61226N
STRINGi9606.ENSP00000307259

Chemistry databases

BindingDBiQ9H244

Structurei

Secondary structure

1342
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H244
SMRiQ9H244
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists such as AZD1283 can bind to an overlapping site, but block the inward movement of the transmembrane helices (PubMed:24670650, PubMed:24784220).2 Publications

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFYD Eukaryota
ENOG410ZJD1 LUCA
GeneTreeiENSGT00640000091213
HOGENOMiHOG000273884
HOVERGENiHBG108228
InParanoidiQ9H244
KOiK04298
OMAiFLCKSFK
OrthoDBiEOG091G0B3H
PhylomeDBiQ9H244
TreeFamiTF330969

Family and domain databases

CDDicd15150 7tmA_P2Y12, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR005394 P2Y12_rcpt
PANTHERiPTHR24233:SF0 PTHR24233:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01569 P2Y12PRNCPTR
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q9H244-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MQAVDNLTSA PGNTSLCTRD YKITQVLFPL LYTVLFFVGL ITNGLAMRIF
60 70 80 90 100
FQIRSKSNFI IFLKNTVISD LLMILTFPFK ILSDAKLGTG PLRTFVCQVT
110 120 130 140 150
SVIFYFTMYI SISFLGLITI DRYQKTTRPF KTSNPKNLLG AKILSVVIWA
160 170 180 190 200
FMFLLSLPNM ILTNRQPRDK NVKKCSFLKS EFGLVWHEIV NYICQVIFWI
210 220 230 240 250
NFLIVIVCYT LITKELYRSY VRTRGVGKVP RKKVNVKVFI IIAVFFICFV
260 270 280 290 300
PFHFARIPYT LSQTRDVFDC TAENTLFYVK ESTLWLTSLN ACLDPFIYFF
310 320 330 340
LCKSFRNSLI SMLKCPNSAT SLSQDNRKKE QDGGDPNEET PM
Length:342
Mass (Da):39,439
Last modified:March 1, 2001 - v1
Checksum:i8553D2746C89176D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072802187H → Q in BDPLT8. 1 Publication1
Natural variantiVAR_025383256R → Q in BDPLT8. 1 PublicationCorresponds to variant dbSNP:rs121917885EnsemblClinVar.1
Natural variantiVAR_025384265R → W in BDPLT8. 1 PublicationCorresponds to variant dbSNP:rs121917886EnsemblClinVar.1
Natural variantiVAR_049431330E → G. Corresponds to variant dbSNP:rs16846673Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF313449 mRNA Translation: AAG48944.1
AF321815 mRNA Translation: AAK00948.1
AB052684 mRNA Translation: BAB60824.1
AF310685 Genomic DNA Translation: AAL32292.1
AJ320495 mRNA Translation: CAC87144.1
AB083596 Genomic DNA Translation: BAB89309.1
AY136754 mRNA Translation: AAN01280.1
CH471052 Genomic DNA Translation: EAW78803.1
CH471052 Genomic DNA Translation: EAW78804.1
BC017898 mRNA Translation: AAH17898.1
CCDSiCCDS3159.1
RefSeqiNP_073625.1, NM_022788.4
NP_795345.1, NM_176876.2
XP_016862558.1, XM_017007069.1
UniGeneiHs.591281
Hs.665544

Genome annotation databases

EnsembliENST00000302632; ENSP00000307259; ENSG00000169313
GeneIDi64805
KEGGihsa:64805
UCSCiuc003eyx.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF313449 mRNA Translation: AAG48944.1
AF321815 mRNA Translation: AAK00948.1
AB052684 mRNA Translation: BAB60824.1
AF310685 Genomic DNA Translation: AAL32292.1
AJ320495 mRNA Translation: CAC87144.1
AB083596 Genomic DNA Translation: BAB89309.1
AY136754 mRNA Translation: AAN01280.1
CH471052 Genomic DNA Translation: EAW78803.1
CH471052 Genomic DNA Translation: EAW78804.1
BC017898 mRNA Translation: AAH17898.1
CCDSiCCDS3159.1
RefSeqiNP_073625.1, NM_022788.4
NP_795345.1, NM_176876.2
XP_016862558.1, XM_017007069.1
UniGeneiHs.591281
Hs.665544

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T78model-A1-337[»]
1VZ1model-A1-337[»]
1Y9Cmodel-A1-342[»]
4NTJX-ray2.62A2-342[»]
4PXZX-ray2.50A2-342[»]
4PY0X-ray3.10A2-342[»]
ProteinModelPortaliQ9H244
SMRiQ9H244
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122309, 62 interactors
DIPiDIP-61226N
STRINGi9606.ENSP00000307259

Chemistry databases

BindingDBiQ9H244
ChEMBLiCHEMBL2001
DrugBankiDB04902 AZD6140
DB06441 Cangrelor
DB00758 Clopidogrel
DB01240 Epoprostenol
DB06209 Prasugrel
DB08816 Ticagrelor
DB00208 Ticlopidine
DB00374 Treprostinil
GuidetoPHARMACOLOGYi328

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9H244
PhosphoSitePlusiQ9H244

Polymorphism and mutation databases

DMDMi21263835

Proteomic databases

PaxDbiQ9H244
PeptideAtlasiQ9H244
PRIDEiQ9H244
ProteomicsDBi80487

Protocols and materials databases

DNASUi64805
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302632; ENSP00000307259; ENSG00000169313
GeneIDi64805
KEGGihsa:64805
UCSCiuc003eyx.3 human

Organism-specific databases

CTDi64805
DisGeNETi64805
EuPathDBiHostDB:ENSG00000169313.9
GeneCardsiP2RY12
HGNCiHGNC:18124 P2RY12
HPAiHPA013796
HPA014518
MalaCardsiP2RY12
MIMi600515 gene
609821 phenotype
neXtProtiNX_Q9H244
OpenTargetsiENSG00000169313
Orphaneti36355 P2Y12 defect
240935 Resistance to clopidogrel
PharmGKBiPA134971947
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFYD Eukaryota
ENOG410ZJD1 LUCA
GeneTreeiENSGT00640000091213
HOGENOMiHOG000273884
HOVERGENiHBG108228
InParanoidiQ9H244
KOiK04298
OMAiFLCKSFK
OrthoDBiEOG091G0B3H
PhylomeDBiQ9H244
TreeFamiTF330969

Enzyme and pathway databases

ReactomeiR-HSA-392170 ADP signalling through P2Y purinoceptor 12
R-HSA-417957 P2Y receptors
R-HSA-418594 G alpha (i) signalling events

Miscellaneous databases

GeneWikiiP2Y12
GenomeRNAii64805
PROiPR:Q9H244
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169313 Expressed in 156 organ(s), highest expression level in substantia nigra
CleanExiHS_P2RY12
GenevisibleiQ9H244 HS

Family and domain databases

CDDicd15150 7tmA_P2Y12, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR005394 P2Y12_rcpt
PANTHERiPTHR24233:SF0 PTHR24233:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01569 P2Y12PRNCPTR
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP2Y12_HUMAN
AccessioniPrimary (citable) accession number: Q9H244
Secondary accession number(s): D3DNJ5, Q546J7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 159 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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