Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

P2Y purinoceptor 12

Gene

P2RY12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Blood coagulation, Hemostasis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169313-MONOMER.
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

HGNCiHGNC:18124. P2RY12.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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 rs121917885dbSNPEnsembl.1
Natural variantiVAR_025384265R → W in BDPLT8. 1 PublicationCorresponds to variant rs121917886dbSNPEnsembl.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.
DrugBankiDB06441. 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...)Sequence analysis1
Glycosylationi13N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi17 ↔ 270
Modified residuei55PhosphoserineBy similarity1
Modified residuei57PhosphoserineBy similarity1
Disulfide bondi97 ↔ 175

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9H244.
PeptideAtlasiQ9H244.
PRIDEiQ9H244.

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.
CleanExiHS_P2RY12.
GenevisibleiQ9H244. HS.

Organism-specific databases

HPAiHPA013796.
HPA014518.

Interactioni

Protein-protein interaction databases

BioGridi122309. 60 interactors.
DIPiDIP-61226N.
STRINGi9606.ENSP00000307259.

Chemistry databases

BindingDBiQ9H244.

Structurei

Secondary structure

1342
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 50Combined sources27
Helixi58 – 74Combined sources17
Helixi77 – 85Combined sources9
Beta strandi86 – 88Combined sources3
Helixi91 – 98Combined sources8
Helixi100 – 127Combined sources28
Helixi136 – 161Combined sources26
Helixi175 – 178Combined sources4
Helixi181 – 226Combined sources46
Helixi231 – 233Combined sources3
Helixi236 – 248Combined sources13
Helixi250 – 264Combined sources15
Helixi270 – 293Combined sources24
Helixi296 – 299Combined sources4
Turni302 – 304Combined sources3

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...

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.
OMAiIKVFIII.
OrthoDBiEOG091G0B3H.
PhylomeDBiQ9H244.
TreeFamiTF330969.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005394. P2Y12_rcpt.
[Graphical view]
PANTHERiPTHR24233:SF0. PTHR24233:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01569. P2Y12PRNCPTR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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 rs121917885dbSNPEnsembl.1
Natural variantiVAR_025384265R → W in BDPLT8. 1 PublicationCorresponds to variant rs121917886dbSNPEnsembl.1
Natural variantiVAR_049431330E → G.Corresponds to variant rs16846673dbSNPEnsembl.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

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. 60 interactors.
DIPiDIP-61226N.
STRINGi9606.ENSP00000307259.

Chemistry databases

BindingDBiQ9H244.
ChEMBLiCHEMBL2001.
DrugBankiDB06441. 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.

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.
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.
OMAiIKVFIII.
OrthoDBiEOG091G0B3H.
PhylomeDBiQ9H244.
TreeFamiTF330969.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169313-MONOMER.
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.
PROiQ9H244.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169313.
CleanExiHS_P2RY12.
GenevisibleiQ9H244. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005394. P2Y12_rcpt.
[Graphical view]
PANTHERiPTHR24233:SF0. PTHR24233:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01569. P2Y12PRNCPTR.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP2Y12_HUMAN
AccessioniPrimary (citable) accession number: Q9H244
Secondary accession number(s): D3DNJ5, Q546J7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 148 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  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. 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.