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Q9H244

- P2Y12_HUMAN

UniProt

Q9H244 - P2Y12_HUMAN

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Protein
P2Y purinoceptor 12
Gene
P2RY12, HORK3
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei93 – 931ADP
Binding sitei97 – 971ADP; via carbonyl oxygen
Binding sitei105 – 1051ADP
Binding sitei187 – 1871ADP
Binding sitei191 – 1911ADP
Binding sitei263 – 2631ADP
Binding sitei280 – 2801ADP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi156 – 1594ADP
Nucleotide bindingi175 – 1795ADP
Nucleotide bindingi256 – 2594ADP

GO - Molecular functioni

  1. ADP receptor activity Source: UniProtKB
  2. G-protein coupled adenosine receptor activity Source: Ensembl
  3. guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

  1. G-protein coupled purinergic nucleotide receptor signaling pathway Source: GOC
  2. G-protein coupled receptor signaling pathway Source: UniProtKB
  3. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
  4. blood coagulation Source: Reactome
  5. calcium ion transmembrane transport Source: Ensembl
  6. cell projection organization Source: Ensembl
  7. hemostasis Source: UniProtKB
  8. negative regulation of cell differentiation Source: Ensembl
  9. negative regulation of norepinephrine secretion Source: Ensembl
  10. platelet activation Source: Reactome
  11. platelet aggregation Source: UniProtKB
  12. positive regulation of ion transport Source: Ensembl
  13. potassium ion transmembrane transport Source: Ensembl
  14. protein kinase B signaling Source: Ensembl
  15. regulation of GTPase activity Source: GOC
  16. regulation of calcium ion transport Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Blood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiREACT_18289. P2Y receptors.
REACT_19231. G alpha (i) signalling events.
REACT_20653. ADP signalling through P2Y purinoceptor 12.

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
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:18124. P2RY12.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2727Extracellular
Add
BLAST
Transmembranei28 – 5023Helical; Name=1
Add
BLAST
Topological domaini51 – 6111Cytoplasmic
Add
BLAST
Transmembranei62 – 8221Helical; Name=2
Add
BLAST
Topological domaini83 – 9715Extracellular
Add
BLAST
Transmembranei98 – 11821Helical; Name=3
Add
BLAST
Topological domaini119 – 14224Cytoplasmic
Add
BLAST
Transmembranei143 – 16220Helical; Name=4
Add
BLAST
Topological domaini163 – 18523Extracellular
Add
BLAST
Transmembranei186 – 20722Helical; Name=5
Add
BLAST
Topological domaini208 – 23326Cytoplasmic
Add
BLAST
Transmembranei234 – 25926Helical; Name=6
Add
BLAST
Topological domaini260 – 27819Extracellular
Add
BLAST
Transmembranei279 – 29820Helical; Name=7
Add
BLAST
Topological domaini299 – 34244Cytoplasmic
Add
BLAST

GO - Cellular componenti

  1. basal plasma membrane Source: Ensembl
  2. caveola Source: Ensembl
  3. external side of plasma membrane Source: Ensembl
  4. integral component of membrane Source: UniProtKB-KW
  5. intrinsic component of membrane Source: UniProtKB
  6. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Bleeding disorder, platelet-type 8 (BDPLT8) [MIM:609821]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti256 – 2561R → Q in BDPLT8. 1 Publication
VAR_025383
Natural varianti265 – 2651R → W in BDPLT8. 1 Publication
VAR_025384

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi80 – 801K → A: Abolishes ADP binding.
Mutagenesisi83 – 831S → A: No effect on ADP binding.
Mutagenesisi97 – 971C → A: Abolishes ADP binding.
Mutagenesisi156 – 1561S → A: Slightly decreases affinity for ADP.
Mutagenesisi159 – 1591N → A: Slightly decreases affinity for ADP.
Mutagenesisi175 – 1751C → A: Abolishes ADP binding.
Mutagenesisi256 – 2561R → A: Decreases affinity for ADP.
Mutagenesisi280 – 2801K → A: Abolishes ADP binding.
Mutagenesisi281 – 2811E → A: Abolishes ADP binding.

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi609821. phenotype.
Orphaneti36355. P2Y12 defect.
240935. Resistance to clopidogrel in myocardial infarction, cerebrovascular accident, oblitering arteriopathy of the lower limbs.
PharmGKBiPA134971947.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 342342P2Y purinoceptor 12
PRO_0000070036Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi6 – 61N-linked (GlcNAc...) Reviewed prediction
Glycosylationi13 – 131N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi17 ↔ 270
Modified residuei55 – 551Phosphoserine By similarity
Modified residuei57 – 571Phosphoserine By similarity
Disulfide bondi97 ↔ 175

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9H244.
PRIDEiQ9H244.

PTM databases

PhosphoSiteiQ9H244.

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.

Gene expression databases

BgeeiQ9H244.
CleanExiHS_P2RY12.
GenevestigatoriQ9H244.

Organism-specific databases

HPAiHPA013796.
HPA014518.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000307259.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi24 – 5027
Helixi58 – 7417
Helixi77 – 859
Beta strandi86 – 883
Helixi91 – 988
Helixi100 – 12728
Helixi136 – 16126
Helixi175 – 1784
Helixi181 – 22646
Helixi231 – 2333
Helixi236 – 24813
Helixi250 – 26415
Helixi270 – 29324
Helixi296 – 2994
Turni302 – 3043

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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. Positions 16-223, 239-312.

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 (1 Publication, 1 Publication).

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG147554.
HOGENOMiHOG000273884.
HOVERGENiHBG108228.
InParanoidiQ9H244.
KOiK04298.
OMAiIKVFIII.
OrthoDBiEOG7C2R1H.
PhylomeDBiQ9H244.
TreeFamiTF330969.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
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

MQAVDNLTSA PGNTSLCTRD YKITQVLFPL LYTVLFFVGL ITNGLAMRIF    50
FQIRSKSNFI IFLKNTVISD LLMILTFPFK ILSDAKLGTG PLRTFVCQVT 100
SVIFYFTMYI SISFLGLITI DRYQKTTRPF KTSNPKNLLG AKILSVVIWA 150
FMFLLSLPNM ILTNRQPRDK NVKKCSFLKS EFGLVWHEIV NYICQVIFWI 200
NFLIVIVCYT LITKELYRSY VRTRGVGKVP RKKVNVKVFI IIAVFFICFV 250
PFHFARIPYT LSQTRDVFDC TAENTLFYVK ESTLWLTSLN ACLDPFIYFF 300
LCKSFRNSLI SMLKCPNSAT SLSQDNRKKE QDGGDPNEET PM 342
Length:342
Mass (Da):39,439
Last modified:March 1, 2001 - v1
Checksum:i8553D2746C89176D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti256 – 2561R → Q in BDPLT8. 1 Publication
VAR_025383
Natural varianti265 – 2651R → W in BDPLT8. 1 Publication
VAR_025384
Natural varianti330 – 3301E → G.
Corresponds to variant rs16846673 [ dbSNP | Ensembl ].
VAR_049431

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGeneiHs.591281.
Hs.665544.

Genome annotation databases

EnsembliENST00000302632; ENSP00000307259; ENSG00000169313.
GeneIDi64805.
KEGGihsa:64805.
UCSCiuc003eyw.1. human.

Polymorphism databases

DMDMi21263835.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS3159.1.
RefSeqi NP_073625.1. NM_022788.4.
NP_795345.1. NM_176876.2.
UniGenei Hs.591281.
Hs.665544.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1T78 model - A 1-337 [» ]
1VZ1 model - A 1-337 [» ]
1Y9C model - A 1-342 [» ]
4NTJ X-ray 2.62 A 2-342 [» ]
4PXZ X-ray 2.50 A 2-342 [» ]
4PY0 X-ray 3.10 A 2-342 [» ]
ProteinModelPortali Q9H244.
SMRi Q9H244. Positions 16-223, 239-312.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000307259.

Chemistry

BindingDBi Q9H244.
ChEMBLi CHEMBL2001.
DrugBanki DB00758. Clopidogrel.
DB01240. Epoprostenol.
DB00208. Ticlopidine.
DB00374. Treprostinil.
GuidetoPHARMACOLOGYi 328.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei Q9H244.

Polymorphism databases

DMDMi 21263835.

Proteomic databases

PaxDbi Q9H244.
PRIDEi Q9H244.

Protocols and materials databases

DNASUi 64805.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000302632 ; ENSP00000307259 ; ENSG00000169313 .
GeneIDi 64805.
KEGGi hsa:64805.
UCSCi uc003eyw.1. human.

Organism-specific databases

CTDi 64805.
GeneCardsi GC03M151055.
HGNCi HGNC:18124. P2RY12.
HPAi HPA013796.
HPA014518.
MIMi 600515. gene.
609821. phenotype.
neXtProti NX_Q9H244.
Orphaneti 36355. P2Y12 defect.
240935. Resistance to clopidogrel in myocardial infarction, cerebrovascular accident, oblitering arteriopathy of the lower limbs.
PharmGKBi PA134971947.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG147554.
HOGENOMi HOG000273884.
HOVERGENi HBG108228.
InParanoidi Q9H244.
KOi K04298.
OMAi IKVFIII.
OrthoDBi EOG7C2R1H.
PhylomeDBi Q9H244.
TreeFami TF330969.

Enzyme and pathway databases

Reactomei REACT_18289. P2Y receptors.
REACT_19231. G alpha (i) signalling events.
REACT_20653. ADP signalling through P2Y purinoceptor 12.

Miscellaneous databases

GeneWikii P2Y12.
GenomeRNAii 64805.
NextBioi 66896.
PROi Q9H244.
SOURCEi Search...

Gene expression databases

Bgeei Q9H244.
CleanExi HS_P2RY12.
Genevestigatori Q9H244.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005394. P2Y12_rcpt.
[Graphical view ]
PANTHERi PTHR24233:SF0. PTHR24233:SF0. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PR01569. P2Y12PRNCPTR.
PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN BDPLT8.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Tissue: Hypothalamus.
  3. "Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y1 receptor."
    Takasaki J., Kamohara M., Saito T., Matsumoto M., Matsumoto S., Ohishi T., Soga T., Matsushime H., Furuichi K.
    Mol. Pharmacol. 60:432-439(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Tissue: Brain.
  4. "ADP-glucose activates a G-protein coupled receptor and inhibits smooth muscle contractions."
    Reinscheid R.K., Nothacker H.-P., Wang Z., Zeng J., Ehlert F.J., Civelli O.
    Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Cloning and characterization of a human platelet ADP-receptor."
    Bruess M., von Kugelgen I., Bonisch H.
    Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Blood.
  6. "Identification of G protein-coupled receptor genes from the human genome sequence."
    Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.
    FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  10. Cited for: X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) IN COMPLEX WITH THE AGONIST AZD1283, FUNCTION, DISULFIDE BOND, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-80; SER-156; ASN-159; LYS-280 AND GLU-281.
  11. Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-342 IN COMPLEX WITH THE ADP ANALOG 2-(METHYLSULFANYL)ADENOSINE 5'-(TRIHYDROGEN DIPHOSPHATE), FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, MUTAGENESIS OF SER-83; CYS-97; CYS-175; ARG-256 AND LYS-280.
  12. "Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding."
    Cattaneo M., Zighetti M.L., Lombardi R., Martinez C., Lecchi A., Conley P.B., Ware J., Ruggeri Z.M.
    Proc. Natl. Acad. Sci. U.S.A. 100:1978-1983(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS BDPLT8 GLN-256 AND TRP-265, FUNCTION, SUBCELLULAR LOCATION.

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: September 3, 2014
This is version 127 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

External Data

Dasty 3

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