Thromboxane receptor

Thromboxane A2 receptor
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1LBN
Identifiers
Symbols	TBXA2R ; BDPLT13; TXA2-R
External IDs	OMIM: 188070 MGI: 98496 HomoloGene: 825 IUPHAR: 346 ChEMBL: 2069 GeneCards: TBXA2R Gene
Gene ontology Molecular function • thromboxane A2 receptor activity • guanyl-nucleotide exchange factor activity • protein binding Cellular component • acrosomal vesicle • cytosol • plasma membrane • integral component of plasma membrane Biological process • inflammatory response • G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • response to nutrient • blood coagulation • second-messenger-mediated signaling • platelet activation • response to lipopolysaccharide • thromboxane A2 signaling pathway • response to drug • positive regulation of GTPase activity • positive regulation of angiogenesis • positive regulation of blood pressure • positive regulation of vasoconstriction • positive regulation of smooth muscle contraction Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6915	21390
Ensembl	ENSG00000006638	ENSMUSG00000034881
UniProt	P21731	P30987
RefSeq (mRNA)	NM_001060	NM_001277265
RefSeq (protein)	NP_001051	NP_001264194
Location (UCSC)	Chr 19: 3.59 – 3.61 Mb	Chr 10: 81.33 – 81.34 Mb
PubMed search	[2]	[3]

The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A₂.

The TP receptor is a G-protein coupled receptor coupled to the G protein G_q. The initial purification and cloning of the TP receptor established this protein as a member of the G protein-coupled super family of seven-transmembrane receptors. The gene responsible for the thromboxane receptor, TBXA2R is found on chromosome 19 and spans 15 kilobases.

Heterogeneity

Molecular biology findings have provided definite evidence of human TP receptor subtypes. The originally cloned TP from placenta (343 amino acids in length) is known as the α isoform, and the splice variant cloned from endothelium (with 407 amino acids) is termed the β isoform. The first 328 amino acids are the same for both isoforms, but the β isoform exhibits an extended C-terminal cytoplasmic domain. Both isoforms functionally couple to a G_q protein leading to the phospholipase C activation, calcium release and activation of protein kinase C. Nevertheless, they couple oppositely to adenylate cyclase. TP_α activates adenylate cyclase while TP_β inhibits this enzyme. Intrareceptor differences in C-terminal tail sequence also allow for significant differences in their ability to internalize in response to agonist exposure. For example, in HEK-293 cells, TP_β but not TP_α undergoes U46619-induced G protein-coupled receptor (GRK) phosphorylation and internalization, whereas the C-terminus of TPα is not capable of being phosphorylated by GRKs.

The expression of α and β isoforms is not equal within or across different cell types. For example, platelets express high concentrations of the α isoform (and possess residual RNA for the β isoform), while expression of the β isoform has not been documented in these cells. The β isoform is expressed in human endothelium.

Tissue distribution

Historically, TP receptor involvement in blood platelet function has received the greatest attention. However, it is now clear that TP receptors exhibit a wide distribution in different cell types and among different organ systems. For example, TP receptors have been localized in cardiovascular, reproductive, immune, pulmonary and neurological tissues, among others.

	Organ/Tissue	Cells/Cell lines
TP Receptor Distribution	Lung, Spleen, Uterus, Placenta, Aorta, Heart, Intestine, Liver, Eye, Thymus, Kidney, Spinal Cord, Brain	Platelets, Glomerular mesangial cells, Oligodendrocytes, Cardiac myocytes, Epithelial cells, Hela cells, Smooth muscle cells, Endothelial cells, Trophoblasts, Schwann cells, Astrocytes, Megakaryocytes, Kupffer cells, Human erythroleukemic megakaryocyte (HEL), K562 (Human chronic myelogenous leukemia) cells, Hepatoblastoma HepG2 cells, Immature thymocytes, EL-4 (mouse T cell line)

Biological roles

Over the years, different biological roles for TP receptor signaling have been established in both homeostatic and pathological processes. TP receptor activation is thought to be involved in thrombosis/hemostasis, modulation of the immune response, acute myocardial infarction, inflammatory lung disease, hypertension, nephrotic disease, etc.

Biological roles of TXA2/TP receptor

Asthma Inflammatory lung disease Hemostasis/thrombosis Sickle cell disease Cardiovascular disease Lupus nephritis Acute myocardial infarction Nephrotic syndrome, Hypertension Immune complex glomerulonephritis Pregnancy-induced hypertension (PIH) Regulating acquired immunity Chronic inflammation in atopic diseases Chronic inflammatory bowel diseases

Antagonists

TP receptor has been the easiest of the prostanoids receptors to block. Several laboratories have synthesized and developed TP receptor antagonists such as Seratrodast (AA-2414), Terutroban (S18886), PTA₂, 13-APA, GR-32191, Sulotroban (BM-13177), SQ-29,548, SQ-28,668, ONO-3708, Bay U3405, EP-045, BMS-180,291, S-145 etc. which belong to numerous structural classes. TP receptor antagonists have been evaluated as potential therapeutic agents for asthma, thrombosis and hypertension. Some studies have in fact revealed that TP receptor antagonists are more effective than thromboxane synthase inhibitors.

See also

• Eicosanoid receptor