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Q9H244 (P2Y12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:P2RY12
Synonyms:HORK3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length342 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Involved in platelet aggregation.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

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.

Involvement in disease

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. Ref.1 Ref.10

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

calcium ion transmembrane transport

Inferred from electronic annotation. Source: Ensembl

cell projection organization

Inferred from electronic annotation. Source: Ensembl

hemostasis

Non-traceable author statement Ref.1. Source: UniProtKB

negative regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of norepinephrine secretion

Inferred from electronic annotation. Source: Ensembl

platelet activation

Traceable author statement. Source: Reactome

platelet aggregation

Inferred from electronic annotation. Source: Ensembl

positive regulation of ion transport

Inferred from electronic annotation. Source: Ensembl

potassium ion transmembrane transport

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

regulation of GTPase activity

Traceable author statement. Source: GOC

regulation of calcium ion transport

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentbasal plasma membrane

Inferred from electronic annotation. Source: Ensembl

caveola

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionADP receptor activity

Inferred from electronic annotation. Source: Ensembl

G-protein coupled adenosine receptor activity

Inferred from electronic annotation. Source: Ensembl

guanyl-nucleotide exchange factor activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 342342P2Y purinoceptor 12
PRO_0000070036

Regions

Topological domain1 – 2525Extracellular Potential
Transmembrane26 – 4621Helical; Name=1; Potential
Topological domain47 – 5812Cytoplasmic Potential
Transmembrane59 – 7921Helical; Name=2; Potential
Topological domain80 – 9920Extracellular Potential
Transmembrane100 – 12021Helical; Name=3; Potential
Topological domain121 – 14222Cytoplasmic Potential
Transmembrane143 – 16321Helical; Name=4; Potential
Topological domain164 – 19128Extracellular Potential
Transmembrane192 – 21221Helical; Name=5; Potential
Topological domain213 – 23321Cytoplasmic Potential
Transmembrane234 – 25421Helical; Name=6; Potential
Topological domain255 – 28127Extracellular Potential
Transmembrane282 – 30221Helical; Name=7; Potential
Topological domain303 – 34240Cytoplasmic Potential

Amino acid modifications

Modified residue551Phosphoserine By similarity
Modified residue571Phosphoserine By similarity
Glycosylation61N-linked (GlcNAc...) Potential
Glycosylation131N-linked (GlcNAc...) Potential
Disulfide bond97 ↔ 175 By similarity

Natural variations

Natural variant2561R → Q in BDPLT8. Ref.10
VAR_025383
Natural variant2651R → W in BDPLT8. Ref.10
VAR_025384
Natural variant3301E → G.
Corresponds to variant rs16846673 [ dbSNP | Ensembl ].
VAR_049431

Sequences

Sequence LengthMass (Da)Tools
Q9H244 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 8553D2746C89176D

FASTA34239,439
        10         20         30         40         50         60 
MQAVDNLTSA PGNTSLCTRD YKITQVLFPL LYTVLFFVGL ITNGLAMRIF FQIRSKSNFI 

        70         80         90        100        110        120 
IFLKNTVISD LLMILTFPFK ILSDAKLGTG PLRTFVCQVT SVIFYFTMYI SISFLGLITI 

       130        140        150        160        170        180 
DRYQKTTRPF KTSNPKNLLG AKILSVVIWA FMFLLSLPNM ILTNRQPRDK NVKKCSFLKS 

       190        200        210        220        230        240 
EFGLVWHEIV NYICQVIFWI NFLIVIVCYT LITKELYRSY VRTRGVGKVP RKKVNVKVFI 

       250        260        270        280        290        300 
IIAVFFICFV PFHFARIPYT LSQTRDVFDC TAENTLFYVK ESTLWLTSLN ACLDPFIYFF 

       310        320        330        340 
LCKSFRNSLI SMLKCPNSAT SLSQDNRKKE QDGGDPNEET PM 

« Hide

References

« Hide 'large scale' references
[1]"Identification of the platelet ADP receptor targeted by antithrombotic drugs."
Hollopeter G., Jantzen H.-M., Vincent D., Li G., England L., Ramakrishnan V., Yang R.-B., Nurden P., Nurden A., Julius D.J., Conley P.B.
Nature 409:202-207(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN BDPLT8.
[2]"ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999."
Zhang F.L., Luo L., Gustafson E., Lachowicz J., Smith M., Qiao X., Liu Y.-H., Chen G., Pramanik B., Laz T.M., Palmer K., Bayne M., Monsma F.J. Jr.
J. Biol. Chem. 276:8608-8615(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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].
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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_073625.1. NM_022788.4.
NP_795345.1. NM_176876.2.
UniGeneHs.591281.
Hs.665544.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T78model-A1-337[»]
1VZ1model-A1-337[»]
1Y9Cmodel-A1-342[»]
ProteinModelPortalQ9H244.
SMRQ9H244. Positions 22-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000307259.

Chemistry

BindingDBQ9H244.
ChEMBLCHEMBL2001.
DrugBankDB00758. Clopidogrel.
DB01240. Epoprostenol.
DB00208. Ticlopidine.
DB00374. Treprostinil.
GuidetoPHARMACOLOGY328.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9H244.

Polymorphism databases

DMDM21263835.

Proteomic databases

PaxDbQ9H244.
PRIDEQ9H244.

Protocols and materials databases

DNASU64805.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302632; ENSP00000307259; ENSG00000169313.
GeneID64805.
KEGGhsa:64805.
UCSCuc003eyw.1. human.

Organism-specific databases

CTD64805.
GeneCardsGC03M151055.
HGNCHGNC:18124. P2RY12.
HPAHPA013796.
HPA014518.
MIM600515. gene.
609821. phenotype.
neXtProtNX_Q9H244.
Orphanet36355. P2Y12 defect.
240935. Resistance to clopidogrel in myocardial infarction, cerebrovascular accident, oblitering arteriopathy of the lower limbs.
PharmGKBPA134971947.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147554.
HOGENOMHOG000273884.
HOVERGENHBG108228.
InParanoidQ9H244.
KOK04298.
OMAIKVFIII.
OrthoDBEOG7C2R1H.
PhylomeDBQ9H244.
TreeFamTF330969.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

BgeeQ9H244.
CleanExHS_P2RY12.
GenevestigatorQ9H244.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005394. P2Y12_rcpt.
[Graphical view]
PANTHERPTHR24233:SF0. PTHR24233:SF0. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01569. P2Y12PRNCPTR.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiP2Y12.
GenomeRNAi64805.
NextBio66896.
PROQ9H244.
SOURCESearch...

Entry information

Entry nameP2Y12_HUMAN
AccessionPrimary (citable) accession number: Q9H244
Secondary accession number(s): D3DNJ5, Q546J7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries