Q9H244 (P2Y12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	P2RY12
Synonyms:	HORK3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	342 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-modulating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara calcium ion transmembrane transport Inferred from electronic annotation. Source: Compara cell projection organization Inferred from electronic annotation. Source: Compara negative regulation of cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of norepinephrine secretion Inferred from electronic annotation. Source: Compara platelet activation Traceable author statement. Source: Reactome platelet aggregation Inferred from electronic annotation. Source: Compara positive regulation of ion transport Inferred from electronic annotation. Source: Compara potassium ion transmembrane transport Inferred from electronic annotation. Source: Compara protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara regulation of calcium ion transport Inferred from electronic annotation. Source: Compara
Cellular_component	basal plasma membrane Inferred from electronic annotation. Source: Compara caveola Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ADP receptor activity Inferred from electronic annotation. Source: Compara G-protein coupled adenosine receptor activity Inferred from electronic annotation. Source: Compara guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 342

342

P2Y purinoceptor 12

PRO_0000070036

Regions

Topological domain

1 – 25

25

Extracellular Potential

Transmembrane

26 – 46

21

Helical; Name=1; Potential

Topological domain

47 – 58

12

Cytoplasmic Potential

Transmembrane

59 – 79

21

Helical; Name=2; Potential

Topological domain

80 – 99

20

Extracellular Potential

Transmembrane

100 – 120

21

Helical; Name=3; Potential

Topological domain

121 – 142

22

Cytoplasmic Potential

Transmembrane

143 – 163

21

Helical; Name=4; Potential

Topological domain

164 – 191

28

Extracellular Potential

Transmembrane

192 – 212

21

Helical; Name=5; Potential

Topological domain

213 – 233

21

Cytoplasmic Potential

Transmembrane

234 – 254

21

Helical; Name=6; Potential

Topological domain

255 – 281

27

Extracellular Potential

Transmembrane

282 – 302

21

Helical; Name=7; Potential

Topological domain

303 – 342

40

Cytoplasmic Potential

Amino acid modifications

Glycosylation

6

1

N-linked (GlcNAc...) Potential

Glycosylation

13

1

N-linked (GlcNAc...) Potential

Disulfide bond

97 ↔ 175

By similarity

Natural variations

Natural variant

256

1

R → Q in BDPLT8. Ref.10

VAR_025383

Natural variant

265

1

R → W in BDPLT8. Ref.10

VAR_025384

Natural variant

330

1

E → G.
Corresponds to variant rs16846673 [ dbSNP | Ensembl ].

VAR_049431

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

342

Helix Strand Turn

Details...

Beta strand

7 – 10

4

Turn

11 – 15

5

Helix

18 – 38

21

Turn

39 – 43

5

Turn

46 – 48

3

Beta strand

49 – 52

4

Helix

59 – 61

3

Helix

64 – 74

11

Helix

77 – 85

9

Beta strand

100 – 104

5

Helix

106 – 116

11

Helix

120 – 123

4

Turn

124 – 126

3

Beta strand

130 – 134

5

Turn

137 – 141

5

Helix

144 – 150

7

Turn

151 – 153

3

Helix

157 – 160

4

Beta strand

169 – 171

3

Beta strand

178 – 181

4

Helix

191 – 198

8

Helix

201 – 206

6

Helix

208 – 210

3

Turn

229 – 232

4

Helix

233 – 248

16

Turn

250 – 255

6

Helix

256 – 262

7

Helix

272 – 276

5

Helix

277 – 280

4

Beta strand

288 – 292

5

Helix

295 – 301

7

Helix

303 – 313

11

Sequences

	Sequence		Length	Mass (Da)
	Q9H244 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 8553D2746C89176D	FASTA	342	39,439
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00009729.

RefSeq

NP_073625.1. NM_022788.3.
NP_795345.1. NM_176876.1.

UniGene

Hs.591281.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T78	model	-	A	1-337	[»]
1VZ1	model	-	A	1-337	[»]
1Y9C	model	-	A	1-342	[»]

ProteinModelPortal

Q9H244.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000307259.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q9H244.

Polymorphism databases

DMDM

21263835.

Proteomic databases

PaxDb

Q9H244.

PRIDE

Q9H244.

Protocols and materials databases

DNASU

64805.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302632; ENSP00000307259; ENSG00000169313.

GeneID

64805.

KEGG

hsa:64805.

UCSC

uc003eyw.1. human.

Organism-specific databases

CTD

64805.

GeneCards

GC03M151055.

HGNC

HGNC:18124. P2RY12.

HPA

HPA013796.

MIM

600515. gene.
609821. phenotype.

neXtProt

NX_Q9H244.

Orphanet

36355. P2Y12 deficiency.

PharmGKB

PA134971947.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG147554.

HOGENOM

HOG000273884.

HOVERGEN

HBG108228.

InParanoid

Q9H244.

KO

K04298.

OMA

IKVFIII.

OrthoDB

EOG4JDH7R.

PhylomeDB

Q9H244.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

Bgee

Q9H244.

CleanEx

HS_P2RY12.

Genevestigator

Q9H244.

GermOnline

ENSG00000169313. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002286. P2_purnocptor.
IPR005394. P2Y12_purnocptor.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR01569. P2Y12PRNCPTR.
PR01157. P2YPURNOCPTR.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. False negative.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9H244.

ChEMBL

CHEMBL2001.

DrugBank

DB00758. Clopidogrel.
DB01240. Epoprostenol.
DB00208. Ticlopidine.
DB00374. Treprostinil.

GenomeRNAi

64805.

NextBio

66896.

SOURCE

Search...

Entry information

Entry name

P2Y12_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.