Reviewed, UniProtKB/Swiss-Prot P21731 (TA2R_HUMAN)

Names and origin

Protein names

Recommended name:
Thromboxane A2 receptor
Short name=TXA2-R

Alternative name(s):
Prostanoid TP receptor

Gene names

Name:

TBXA2R

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	343 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. Isoform 1 activates adenylyl cyclase. Isoform 2 inhibits adenylyl cyclase. Ref.11
Subunit structure	Interacts with RPGRIP1L. Interacts with PSMA3. Ref.14
Subcellular location	Cell membrane; Multi-pass membrane protein.
Involvement in disease	Defects in TBXA2R are the cause of a dominantly inherited bleeding disorder [MIM:188070].
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.1 Inferred from Experiment. Source: Reactome
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	guanyl-nucleotide exchange factor activity Inferred from Experiment. Source: Reactome protein binding Ref.14 Inferred from physical interaction. Source: UniProtKB thromboxane A2 receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21731-3)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P21731-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     329-343: SLSLQPQLTQRSGLQ → RSLTLWPSLE...PTGKALSRKD

Note: Ref.2 (AAA58957) sequence differs from that shown due to frameshifts in positions 330 and 386.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 343

343

Thromboxane A2 receptor

PRO_0000070138

Regions

Topological domain

1 – 29

29

Extracellular Potential

Transmembrane

30 – 52

23

1 Potential

Topological domain

53 – 66

14

Cytoplasmic Potential

Transmembrane

67 – 87

21

2 Potential

Topological domain

88 – 106

19

Extracellular Potential

Transmembrane

107 – 128

22

3 Potential

Topological domain

129 – 149

21

Cytoplasmic Potential

Transmembrane

150 – 172

23

4 Potential

Topological domain

173 – 193

21

Extracellular Potential

Transmembrane

194 – 219

26

5 Potential

Topological domain

220 – 246

27

Cytoplasmic Potential

Transmembrane

247 – 270

24

6 Potential

Topological domain

271 – 289

19

Extracellular Potential

Transmembrane

290 – 311

22

7 Potential

Topological domain

312 – 343

32

Cytoplasmic Potential

Amino acid modifications

Glycosylation

4

1

N-linked (GlcNAc...)

Glycosylation

16

1

N-linked (GlcNAc...)

Disulfide bond

105 ↔ 183

By similarity

Natural variations

Alternative sequence

329 – 343

15

SLSLQ…RSGLQ → RSLTLWPSLEYSGTISAHCN LRLPGSSDSRASASRAAGIT GVSHCARPCMLFDPEFDLLA GVQLLPFEPPTGKALSRKD in isoform 2.

VSP_001925

Natural variant

60

1

R → L in bleeding disorder; defective interaction with G proteins; impairs phospholipase C and adenylyl cyclase activation; isoform 1. Has no affect on adenylyl cyclase inhibition; isoform 2. dbSNP rs34377097. Ref.11 Ref.15

VAR_003515

Natural variant

68

1

C → S: dbSNP rs5743.

VAR_014688

Natural variant

80

1

V → E: dbSNP rs5744.

VAR_014689

Natural variant

94

1

E → V: dbSNP rs5746.

VAR_014690

Natural variant

160

1

A → T: dbSNP rs5749.

VAR_014691

Natural variant

176

1

V → E: dbSNP rs5750.

VAR_014692

Natural variant

217

1

V → I: dbSNP rs5751.

VAR_014693

Experimental info

Mutagenesis

291

1

L → R: Suppresses antagonist binding.

Mutagenesis

295

1

R → Q: Reduces antagonist binding.

Mutagenesis

299

1

W → L: Reduces antagonist binding.

Mutagenesis

299

1

W → R: Reduces antagonist binding.

Sequence conflict

263

1

V → W AA sequence Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

343

Helix Strand Turn

Details...

Helix

101 – 134

34

Beta strand

138 – 140

3

Turn

145 – 147

3

Helix

148 – 164

17

Helix

166 – 168

3

Beta strand

174 – 177

4

Turn

178 – 181

4

Beta strand

182 – 185

4

Helix

192 – 194

3

Helix

196 – 206

11

Helix

209 – 222

14

Beta strand

223 – 228

6

Turn

236 – 238

3

Helix

239 – 255

17

Helix

256 – 258

3

Helix

259 – 264

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified May 5, 2009. Version 3. Checksum: 114A7C3F3F0D35F1	FASTA	343	37,431
	10 20 30 40 50 60 MWPNGSSLGP CFRPTNITLE ERRLIASPWF AASFCVVGLA SNLLALSVLA GARQGGSHTR 70 80 90 100 110 120 SSFLTFLCGL VLTDFLGLLV TGTIVVSQHA ALFEWHAVDP GCRLCRFMGV VMIFFGLSPL 130 140 150 160 170 180 LLGAAMASER YLGITRPFSR PAVASQRRAW ATVGLVWAAA LALGLLPLLG VGRYTVQYPG 190 200 210 220 230 240 SWCFLTLGAE SGDVAFGLLF SMLGGLSVGL SFLLNTVSVA TLCHVYHGQE AAQQRPRDSE 250 260 270 280 290 300 VEMMAQLLGI MVVASVCWLP LLVFIAQTVL RNPPAMSPAG QLSRTTEKEL LIYLRVATWN 310 320 330 340 QILDPWVYIL FRRAVLRRLQ PRLSTRPRSL SLQPQLTQRS GLQ
	Isoform 2 (Beta). Checksum: 461D60349704E7AB	FASTA	407	44,205
	10 20 30 40 50 60 MWPNGSSLGP CFRPTNITLE ERRLIASPWF AASFCVVGLA SNLLALSVLA GARQGGSHTR 70 80 90 100 110 120 SSFLTFLCGL VLTDFLGLLV TGTIVVSQHA ALFEWHAVDP GCRLCRFMGV VMIFFGLSPL 130 140 150 160 170 180 LLGAAMASER YLGITRPFSR PAVASQRRAW ATVGLVWAAA LALGLLPLLG VGRYTVQYPG 190 200 210 220 230 240 SWCFLTLGAE SGDVAFGLLF SMLGGLSVGL SFLLNTVSVA TLCHVYHGQE AAQQRPRDSE 250 260 270 280 290 300 VEMMAQLLGI MVVASVCWLP LLVFIAQTVL RNPPAMSPAG QLSRTTEKEL LIYLRVATWN 310 320 330 340 350 360 QILDPWVYIL FRRAVLRRLQ PRLSTRPRRS LTLWPSLEYS GTISAHCNLR LPGSSDSRAS 370 380 390 400 ASRAAGITGV SHCARPCMLF DPEFDLLAGV QLLPFEPPTG KALSRKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of cDNA for a human thromboxane A2 receptor." Hirata M., Hayashi Y., Ushikubi F., Yokota Y., Kageyama R., Nakanishi S., Narumiya S. Nature 349:617-620(1991) [PubMed: 1825698] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Placenta.
[2]	"Characterization and chromosomal mapping of the human thromboxane A2 receptor gene." Nuesing R.M., Hirata M., Kakizuka A., Eki T., Ozawa K., Narumiya S. J. Biol. Chem. 268:25253-25259(1993) [PubMed: 8227091] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"Alternative splicing produces a divergent cytoplasmic tail in the human endothelial thromboxane A2 receptor." Raychowdhury M.K., Yukawa M., Collins L.J., McGrail S.H., Kent K.C., Ware J.A. J. Biol. Chem. 269:19256-19261(1994) [PubMed: 8034687] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING. Tissue: Endothelial cell and Placenta.
[4]	Erratum Raychowdhury M.K., Yukawa M., Collins L.J., McGrail S.H., Kent K.C., Ware J.A. J. Biol. Chem. 270:7011-7011(1995) [PubMed: 7896853] [Abstract]
[5]	"Cloning and pharmacologic characterization of a thromboxane A2 receptor from K562 (human chronic myelogenous leukemia) cells." D'Angelo D.D., Davis M.G., Ali S., Dorn G.W. II J. Pharmacol. Exp. Ther. 271:1034-1041(1994) [PubMed: 7965765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[7]	NIEHS SNPs program Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	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].
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[11]	"Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation." Hirata T., Ushikubi F., Kakizuka A., Okuma M., Narumiya S. J. Clin. Invest. 97:949-956(1996) [PubMed: 8613548] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 329-343 (ISOFORMS 1 AND 2), FUNCTION, ALTERNATIVE SPLICING, CHARACTERIZATION OF VARIANT LEU-60. Tissue: Platelet.
[12]	"Point mutation in the seventh hydrophobic domain of the human thromboxane A2 receptor allows discrimination between agonist and antagonist binding sites." Funk C.D., Furci L., Moran N., Fitzgerald G.A. Mol. Pharmacol. 44:934-939(1993) [PubMed: 8246916] [Abstract] Cited for: MUTAGENESIS.
[13]	"Low expression of cell-surface thromboxane A2 receptor beta-isoform through the negative regulation of its membrane traffic by proteasomes." Sasaki M., Sukegawa J., Miyosawa K., Yanagisawa T., Ohkubo S., Nakahata N. Prostaglandins Other Lipid Mediat. 83:237-249(2007) [PubMed: 17499743] [Abstract] Cited for: INTERACTION WITH PSMA3.
[14]	"Thromboxane A2-induced signal transduction is negatively regulated by KIAA1005 that directly interacts with thromboxane A2 receptor." Tokue S., Sasaki M., Nakahata N. Prostaglandins Other Lipid Mediat. 89:8-15(2009) [PubMed: 19464661] [Abstract] Cited for: INTERACTION WITH RPGRIP1L.
[15]	"Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder." Hirata T., Kakizuka A., Ushikubi F., Fuse I., Okuma M., Narumiya S. J. Clin. Invest. 94:1662-1667(1994) [PubMed: 7929844] [Abstract] Cited for: VARIANT BLEEDING DISORDER LEU-60.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D38081 mRNA. Translation: BAA07274.1.
D15056 Genomic DNA. Translation: BAA03649.1.
U11271 mRNA. Translation: AAA58957.1. Frameshift.
U27325 mRNA. Translation: AAA68608.1.
AY429110 mRNA. Translation: AAR07905.1.
DQ268653 Genomic DNA. Translation: ABB72549.1.
AC005175 Genomic DNA. Translation: AAC24302.1.
AC005175 Genomic DNA. Translation: AAC24303.1.
CH471139 Genomic DNA. Translation: EAW69301.1.
BC074749 mRNA. Translation: AAH74749.1.
BC074750 mRNA. Translation: AAH74750.1.

IPI

IPI00102239.
IPI00745939.

PIR

A49117.
A53959.
A56194.
T02670.

RefSeq

NP_001051.1.
NP_963998.2.

UniGene

Hs.442530

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LBN	model	-	A	100-265	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P21731.

Protein family/group databases

GPCRDB

Search...

Proteomic databases

PRIDE

P21731.

Genome annotation databases

Ensembl

ENST00000375190; ENSP00000364336; ENSG00000006638; Homo sapiens. [Genome view]

GeneID

6915.

KEGG

hsa:6915.

UCSC

uc002lyf.1. human.

Organism-specific databases

CTD

6915.

GeneCards

GC19M003545.

H-InvDB

HIX0040068.

HGNC

HGNC:11608. TBXA2R.

MIM

188070. gene+phenotype.

PharmGKB

PA348.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13508.

HOVERGEN

HBG108543.

OMA

ATLCRVY.

Enzyme and pathway databases

Pathway_Interaction_DB

txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_14797. Signaling by GPCR.
REACT_604. Hemostasis.

Gene expression databases

Bgee

P21731.

CleanEx

HS_TBXA2R.

Genevestigator

P21731.

GermOnline

ENSG00000006638. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_supfam.
IPR008365. Prostanoid_rcpt.
IPR001105. Thbox_rcpt.
[Graphical view]

Pfam

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

PRINTS

PR00237. GPCRRHODOPSN.
PR01788. PROSTANOIDR.
PR00429. THROMBOXANER.

PROSITE

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

ProtoNet

Search...

Other Resources

DrugBank

DB01207. Ridogrel.

SOURCE

Search...

Entry information

Entry name

TA2R_HUMAN

Accession

Primary (citable) accession number: P21731
Secondary accession number(s): O75228 , Q6DK52, Q9UCY1, Q9UCY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 5, 2009
Last modified:	March 2, 2010
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.