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P21731 (TA2R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thromboxane A2 receptor

Short name=TXA2-R
Alternative name(s):
Prostanoid TP receptor
Gene names
Name:TBXA2R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length343 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Interacts with GNB2L1/RACK1; the interaction regulates TBXA2R cell surface expression. Ref.13 Ref.14 Ref.15

Subcellular location

Cell membrane; Multi-pass membrane protein.

Involvement in disease

Bleeding disorder, platelet-type 13 (BDPLT13) [MIM:614009]: A disorder characterized by reduced platelet aggregation and a tendency to mild mucocutaneous bleeding.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.11 Ref.17

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence caution

The sequence AAA58957.1 differs from that shown. Reason: Frameshift at position 329.

Isoform 2: The sequence AAA58957.1 differs from that shown. Reason: Frameshift at positions 330 and 386.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

blood coagulation

Traceable author statement. Source: Reactome

inflammatory response

Inferred from electronic annotation. Source: Ensembl

platelet activation

Traceable author statement. Source: Reactome

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

regulation of GTPase activity

Traceable author statement. Source: GOC

response to drug

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

second-messenger-mediated signaling

Inferred from electronic annotation. Source: Ensembl

thromboxane A2 signaling pathway

Traceable author statement PubMed 8119956. Source: GOC

   Cellular_componentacrosomal vesicle

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionguanyl-nucleotide exchange factor activity

Traceable author statement. Source: Reactome

protein binding

Inferred from physical interaction Ref.15. Source: UniProtKB

thromboxane A2 receptor activity

Traceable author statement PubMed 8119956. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PRDX4Q131623EBI-2625082,EBI-2211957

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 343343Thromboxane A2 receptor
PRO_0000070138

Regions

Topological domain1 – 2929Extracellular Potential
Transmembrane30 – 5223Helical; Name=1; Potential
Topological domain53 – 6614Cytoplasmic Potential
Transmembrane67 – 8721Helical; Name=2; Potential
Topological domain88 – 10619Extracellular Potential
Transmembrane107 – 12822Helical; Name=3; Potential
Topological domain129 – 14921Cytoplasmic Potential
Transmembrane150 – 17223Helical; Name=4; Potential
Topological domain173 – 19321Extracellular Potential
Transmembrane194 – 21926Helical; Name=5; Potential
Topological domain220 – 24627Cytoplasmic Potential
Transmembrane247 – 27024Helical; Name=6; Potential
Topological domain271 – 28919Extracellular Potential
Transmembrane290 – 31122Helical; Name=7; Potential
Topological domain312 – 34332Cytoplasmic Potential

Amino acid modifications

Modified residue3291Phosphoserine Ref.16
Glycosylation41N-linked (GlcNAc...)
Glycosylation161N-linked (GlcNAc...)
Disulfide bond105 ↔ 183 By similarity

Natural variations

Alternative sequence329 – 34315SLSLQ…RSGLQ → RSLTLWPSLEYSGTISAHCN LRLPGSSDSRASASRAAGIT GVSHCARPCMLFDPEFDLLA GVQLLPFEPPTGKALSRKD in isoform 2.
VSP_001925
Natural variant601R → L in BDPLT13; does not affect TXA2 binding; defective interaction with G proteins; impairs phospholipase C and adenylyl cyclase activation; isoform 1; has no effect on adenylyl cyclase inhibition; isoform 2. Ref.11 Ref.17
Corresponds to variant rs34377097 [ dbSNP | Ensembl ].
VAR_003515
Natural variant681C → S.
Corresponds to variant rs5743 [ dbSNP | Ensembl ].
VAR_014688
Natural variant801V → E.
Corresponds to variant rs5744 [ dbSNP | Ensembl ].
VAR_014689
Natural variant941E → V.
Corresponds to variant rs5746 [ dbSNP | Ensembl ].
VAR_014690
Natural variant1601A → T.
Corresponds to variant rs5749 [ dbSNP | Ensembl ].
VAR_014691
Natural variant1761V → E.
Corresponds to variant rs5750 [ dbSNP | Ensembl ].
VAR_014692
Natural variant2171V → I.
Corresponds to variant rs5751 [ dbSNP | Ensembl ].
VAR_014693

Experimental info

Mutagenesis2911L → R: Suppresses antagonist binding.
Mutagenesis2951R → Q: Reduces antagonist binding.
Mutagenesis2991W → L: Reduces antagonist binding.
Mutagenesis2991W → R: Reduces antagonist binding.
Sequence conflict2631V → W AA sequence Ref.1

Secondary structure

.......................... 343
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified May 5, 2009. Version 3.
Checksum: 114A7C3F3F0D35F1

FASTA34337,431
        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 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: 461D60349704E7AB
Show »

FASTA40744,205

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. 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].
[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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 329-343 (ISOFORMS 1 AND 2), FUNCTION, ALTERNATIVE SPLICING, CHARACTERIZATION OF VARIANT BDPLT13 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSMA3.
[14]"RACK1 regulates the cell surface expression of the G protein-coupled receptor for thromboxane A(2)."
Parent A., Laroche G., Hamelin E., Parent J.L.
Traffic 9:394-407(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNB2L1.
[15]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RPGRIP1L.
[16]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"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] [Europe PMC] [Abstract]
Cited for: VARIANT BDPLT13 LEU-60, CHARACTERIZATION OF VARIANT BDPLT13 LEU-60.
+Additional computationally mapped references.

Web resources

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.
CCDSCCDS42467.1. [P21731-3]
CCDS54198.1. [P21731-2]
PIRA49117.
A53959.
A56194.
T02670.
RefSeqNP_001051.1. NM_001060.5. [P21731-3]
NP_963998.2. NM_201636.2. [P21731-2]
UniGeneHs.442530.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LBNmodel-A100-265[»]
ProteinModelPortalP21731.
SMRP21731. Positions 66-177.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112777. 35 interactions.
DIPDIP-41465N.
IntActP21731. 4 interactions.
MINTMINT-1512445.
STRING9606.ENSP00000364336.

Chemistry

BindingDBP21731.
ChEMBLCHEMBL2069.
DrugBankDB01207. Ridogrel.
GuidetoPHARMACOLOGY346.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP21731.

Polymorphism databases

DMDM229463010.

Proteomic databases

PaxDbP21731.
PRIDEP21731.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375190; ENSP00000364336; ENSG00000006638. [P21731-3]
ENST00000411851; ENSP00000393333; ENSG00000006638. [P21731-2]
GeneID6915.
KEGGhsa:6915.
UCSCuc002lyg.2. human. [P21731-3]
uc021umv.1. human. [P21731-2]

Organism-specific databases

CTD6915.
GeneCardsGC19M003594.
H-InvDBHIX0202922.
HGNCHGNC:11608. TBXA2R.
MIM188070. gene.
614009. phenotype.
neXtProtNX_P21731.
Orphanet220443. Bleeding diathesis due to thromboxane synthesis deficiency.
PharmGKBPA348.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263172.
HOGENOMHOG000015238.
HOVERGENHBG108543.
KOK04264.
OMAATLCRVY.
OrthoDBEOG7TBC2R.
PhylomeDBP21731.
TreeFamTF324982.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkP21731.

Gene expression databases

ArrayExpressP21731.
BgeeP21731.
CleanExHS_TBXA2R.
GenevestigatorP21731.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008365. Prostanoid_rcpt.
IPR001105. Thbox_rcpt.
[Graphical view]
PANTHERPTHR11866. PTHR11866. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01788. PROSTANOIDR.
PR00429. THROMBOXANER.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTBXA2R. human.
GeneWikiThromboxane_receptor.
GenomeRNAi6915.
NextBio27045.
PROP21731.
SOURCESearch...

Entry information

Entry nameTA2R_HUMAN
AccessionPrimary (citable) accession number: P21731
Secondary accession number(s): O75228 expand/collapse secondary AC list , Q6DK52, Q9UCY1, Q9UCY2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 5, 2009
Last modified: July 9, 2014
This is version 154 of the entry and version 3 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 19

Human chromosome 19: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries