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TP receptor

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Target id: 346

Nomenclature: TP receptor

Family: Prostanoid receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 343 19p13.3 TBXA2R thromboxane A2 receptor 22
Mouse 7 341 10 39.72 cM Tbxa2r thromboxane A2 receptor 9,58,73
Rat 7 341 7q11 Tbxa2r thromboxane A2 receptor 1
Previous and Unofficial Names Click here for help
prostanoid TP receptor | TXA2-R
Database Links Click here for help
Specialist databases
GPCRdb ta2r_human (Hs), ta2r_mouse (Mm), ta2r_rat (Rn)
Other databases
Alphafold P21731 (Hs), P30987 (Mm), P34978 (Rn)
ChEMBL Target CHEMBL2069 (Hs), CHEMBL1795181 (Mm), CHEMBL3156 (Rn)
DrugBank Target P21731 (Hs)
Ensembl Gene ENSG00000006638 (Hs), ENSMUSG00000034881 (Mm), ENSRNOG00000020585 (Rn)
Entrez Gene 6915 (Hs), 21390 (Mm), 24816 (Rn)
Human Protein Atlas ENSG00000006638 (Hs)
KEGG Gene hsa:6915 (Hs), mmu:21390 (Mm), rno:24816 (Rn)
OMIM 188070 (Hs)
Orphanet ORPHA293114 (Hs)
Pharos P21731 (Hs)
RefSeq Nucleotide NM_001060 (Hs), NM_009325 (Mm), NM_017054 (Rn)
RefSeq Protein NP_001051 (Hs), NP_033351 (Mm), NP_058750 (Rn)
UniProtKB P21731 (Hs), P30987 (Mm), P34978 (Rn)
Wikipedia TBXA2R (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human thromboxane A2 receptor bound to ramatroban
PDB Id:  6IIU
Ligand:  ramatroban
Resolution:  2.5Å
Species:  Human
References:  14
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human thromboxane A2 receptor bound to daltroban
PDB Id:  6IIV
Ligand:  daltroban
Resolution:  3.0Å
Species:  Human
References:  14
Natural/Endogenous Ligands Click here for help
PGD2
PGE2
PGF2α
PGI2
thromboxane A2
Comments: Thromboxane A2 is the principal endogenous agonist. PGE2 to a lesser extent can also activate the TP receptor.
Potency order of endogenous ligands
thromboxane A2 = PGH2 >> PGD2, PGE2, PGF2α, PGI2

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
I-BOP Small molecule or natural product Hs Agonist 8.9 – 9.3 pKd 46
⤷ pKd 8.9 – 9.3 (Kd 1.16x10-9 – 4.8x10-10 M) [46]
[125I]BOP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pKd 51
⤷ pKd 8.7 (Kd 2x10-9 M) [51]
[3H]U46619 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.8 pKd 2
⤷ pKd 7.8 [2]
10,10-difluoro TXA2 Small molecule or natural product Hs Full agonist 7.0 pKd 52
⤷ pKd 7.0 (Kd 1x10-7 M) [52]
I-BOP Small molecule or natural product Click here for species-specific activity table Mm Full agonist 9.3 pKi 36
⤷ pKi 9.3 [36]
EP 171 Small molecule or natural product Hs Full agonist 8.5 pKi 28
⤷ pKi 8.5 [28]
U46609 Small molecule or natural product Hs Full agonist 8.4 pKi 50
⤷ pKi 8.4 [50]
STA2 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.9 pKi 36
⤷ pKi 7.9 [36]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 7.5 pKi 2
⤷ pKi 7.5 [2]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 7.2 pKi 36
⤷ pKi 7.2 [36]
MB-28767 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.5 pKi 2
⤷ pKi 6.5 [2]
carbocyclic thromboxane A2 Small molecule or natural product Hs Full agonist 6.5 pKi 50
⤷ pKi 6.5 [50]
cloprostenol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 pKi 2
⤷ pKi 5.2 [2]
iloprost Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 5.2 pKi 2
⤷ pKi 5.2 [2]
PGF2α Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.1 pKi 2
⤷ pKi 5.1 [2]
butaprost (free acid form) Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.7 pKi 2
⤷ pKi 4.7 [2]
carbacyclin Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.7 pKi 2
⤷ pKi 4.7 [2]
PGE2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 4.5 pKi 2
⤷ pKi 4.5 [2]
fluprostenol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.3 pKi 2
⤷ pKi 4.3 [2]
SQ 26655 Small molecule or natural product Rn Full agonist 9.1 pEC50 68
⤷ pEC50 9.1 (EC50 9x10-10 M) [68]
AGN192093 Small molecule or natural product Rn Agonist 8.9 pEC50 39
⤷ pEC50 8.9 (EC50 1.3x10-9 M) [39]
AGN 191976 Small molecule or natural product Hs Full agonist 7.8 pEC50 39
⤷ pEC50 7.8 (EC50 1.6x10-8 M) [39]
STA2 Small molecule or natural product Hs Agonist 6.4 – 7.1 pIC50 6
⤷ pIC50 6.4 – 7.1 (IC50 4.2x10-7 – 8.7x10-8 M) [6]
View species-specific agonist tables
Agonist Comments
References [28,50-51] use human platelet preparations instead of transfected cells.

PGH2 and TXA2 are only rarely used as TP agonists owing to their instability under physiological conditions; U46619 is an appropriate substitute. Partial agonism is common among close analogues of PGH2 and TXA2.

References given alongside the TP receptor agonists I-BOP [46] and STA2 [6] use human platelets as the source of TP receptors for competition radio-ligand binding assays to determine the indicated activity values.

Care should be taken in handling highly potent TP agonists such as EP-171 and I-BOP as they are expected to be resistant to in vivo deactivation by 15-OH prostaglandin dehydrogenase owing to their 16-p-halophenoxy moieties.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
I-SAP Small molecule or natural product Hs Antagonist 9.3 pKd 57
⤷ pKd 9.3 (Kd 4.7x10-10 M) [57]
[3H]SQ-29548 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.0 pKd 1
⤷ pKd 9.0 [1]
[3H]S-145 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.9 pKd 22
⤷ pKd 8.9 [22]
[125I]SAP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 7.7 – 9.3 pKd 57
⤷ pKd 7.7 – 9.3 (Kd 2x10-8 – 5x10-10 M) [57]
[3H]S-145 Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Antagonist 8.5 pKd 58
⤷ pKd 8.5 [58]
[125I]SQ-29548 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.3 pKd 21
⤷ pKd 8.3 [21]
[3H]SQ-29548 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 7.4 – 8.2 pKd 2,85
⤷ pKd 7.4 – 8.2 (Kd 4x10-8 – 6.3x10-9 M) [2,85]
[125I]PTA-OH Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 7.7 pKd 19
⤷ pKd 7.7 [19]
domitroban Small molecule or natural product Hs Antagonist 9.6 pKi 37
⤷ pKi 9.6 [37]
domitroban Small molecule or natural product Mm Antagonist 9.2 pKi 36
⤷ pKi 9.2 [36]
KW-3635 Small molecule or natural product Hs Antagonist 8.9 pKi 50
⤷ pKi 8.9 [50]
vapiprost Small molecule or natural product Hs Antagonist 8.3 – 9.4 pKi 6,42
⤷ pKi 8.3 – 9.4 [6,42]
SQ-29548 Small molecule or natural product Hs Antagonist 8.1 – 9.1 pKi 2,70,85
⤷ pKi 8.1 – 9.1 [2,70,85]
ifetroban Small molecule or natural product Hs Antagonist 8.1 – 8.4 pKi 61
⤷ pKi 8.1 – 8.4 (Ki 9x10-9 – 4x10-9 M) [61]
ONO-3708 Small molecule or natural product Hs Antagonist 7.4 – 8.9 pKi 32
⤷ pKi 7.4 – 8.9 (Ki 3.98x10-8 – 1.26x10-9 M) [32]
ramatroban Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 pKi 74
⤷ pKi 8.0 [74]
vapiprost Small molecule or natural product Mm Antagonist 7.9 pKi 36
⤷ pKi 7.9 [36]
SQ-29548 Small molecule or natural product Mm Antagonist 7.9 pKi 36
⤷ pKi 7.9 [36]
daltroban Small molecule or natural product Ligand has a PDB structure Hs Antagonist 7.7 pKi 50
⤷ pKi 7.7 [50]
S-5751 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 pKi 5
⤷ pKi 7.6 [5]
ONO-8711 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 83
⤷ pKi 7.1 [83]
AH23848 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 2
⤷ pKi 6.2 [2]
laropiprant Small molecule or natural product Hs Antagonist 6.1 pKi 40
⤷ pKi 6.1 [40]
NTP42 Small molecule or natural product Hs Antagonist 7.3 – 8.1 pIC50 35
⤷ pIC50 8.1 (IC50 8.25x10-9 M) [35]
Description: Antagonism of U46619-mediated [Ca2+]i mobilization in HEK293 cells expressing TPβ
pIC50 7.3 (IC50 5.62x10-8 M) [35]
Description: Antagonism of U46619-mediated [Ca2+]i mobilization in HEK293 cells expressing TP&aipha;
ICI 192605 Small molecule or natural product Hs Antagonist 7.2 pIC50 66
⤷ pIC50 7.2 (IC50 6.5x10-8 M) [66]
terutroban Small molecule or natural product Hs Antagonist 6.5 pIC50 11
⤷ pIC50 6.5 (IC50 3.2x10-7 M) [11]
PBT-3 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 5.9 – 6.7 pIC50 62
⤷ pIC50 6.7 (IC50 2x10-7 M) [62]
Description: Antagonism of TPalpha (short) isoform expressed in COS7 cells.
pIC50 5.9 (IC50 1.2x10-6 M) [62]
Description: Antagonism of TPbeta (long) isoform expressed in COS7 cells.
View species-specific antagonist tables
Antagonist Comments
References [6,21,32,37,50,57,61,74] use human platelet preparations instead of transfected cells.

A wide range of structurally diverse TP antagonists are known; GR-32191 and SQ-29548 are in common use. Agents combining TP antagonism and IP agonism [7,20,47] and TP antagonism and TX synthase inhibition [79] are known.
A novel TP antagonist, NTP42, was found to attenuate pulmonary arterial hypertention pathophysiology, especially when it was combined together with sildenafil [54].
Immuno Process Associations
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  34
Tissue Distribution Click here for help
Prostate
Species:  Human
Technique:  Immunohistochemistry.
References:  53
Platelets.
Species:  Human
Technique:  Radioligand binding.
References:  44
Uterus.
Species:  Human
Technique:  Immunohistochemistry, immunocytochemistry, Northern blotting, in situ hybridisation, radioligand binding.
References:  69
Placenta > lung.
Species:  Human
Technique:  Northern blotting.
References:  22
Brain, thymus, small intestine.
Species:  Human
Technique:  RT-PCR.
References:  48
Endothelium.
Species:  Human
Technique:  Northern blotting.
References:  63
Prostatic cancer cells.
Species:  Human
Technique:  Radioligand binding.
References:  59
Thymocytes.
Species:  Mouse
Technique:  Radioligand binding.
References:  77
Thymus, spleen, lung.
Species:  Mouse
Technique:  Northern blotting.
References:  58
Thymus, lung, kidney, T cell line (EL-4).
Species:  Mouse
Technique:  RNase protection assay.
References:  9
Fetal: thymus, kidney.
Adult: thymus (cortex), spleen (red pulp).
Species:  Mouse
Technique:  in situ hybridisation.
References:  9
Dorsal root ganglion neurons and keratinocytes.
Species:  Mouse
Technique:  Immunohistochemistry and Ca2+ response.
References:  4
CD4+ and CD8+ T cells from the spleen.
Species:  Mouse
Technique:  RT-PCR.
References:  29
Platelets.
Species:  Rat
Technique:  Radioligand binding.
References:  44
Kidney: glomeruli, arterial walls, luminal membranes of thick ascending limbs of Henle's loop, luminal and basolateral membranes of either distal convoluted tubules or connecting tubules, the basolateral membranes of collecting tubules.
Species:  Rat
Technique:  Western blotting.
References:  71
Hepatic sinusoidal endothelial cells.
Species:  Rat
Technique:  Radioligand binding.
References:  26
Nodosa ganglion neurons.
Species:  Rabbit
Technique:  RT-PCR.
References:  80
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of Ca2+ levels in COS-7 cells transfected with the rat TP receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Increase in free Ca2+ concentration.
References:  1
Measurement of ERK and JNK activity in human uterine ULTR cell line endogenously expressing the TP receptor.
Species:  Human
Tissue:  Uterine ULTR cell line.
Response measured:  Activation of ERK signalling cascade.
References:  49
Measurement of Ca2+ levels in HEK 293 cells transfected with the human TP receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in Ca2+ concentration.
References:  34,82
Measurement of Ca2+ in human platelets endogenously expressing the TP receptor.
Species:  Human
Tissue:  Platelets.
Response measured:  Increase in Ca2+ concentration.
References:  34,82
Measurement of Ca2+ levels, using a Ca2+-activated Cl- channel, in Xenopus oocytes transfected with the human TP receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Increase in Ca2+ concentration.
References:  22
Measurement of ERK and JNK activity in HEK 293 cells transfected with the human TP receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Activation of ERK signalling cascade.
References:  49
Measurement of Ca2+ levels in Xenopus oocytes transfected with the rat TP receptor using electrophysiology.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Increase in Ca2+ concentration.
References:  1
Physiological Functions Click here for help
Contraction of pulmonary venous smooth muscle.
Species:  Human
Tissue:  Pulmonary venous preparations.
References:  60,81
Contraction of pulmonary arterial smooth muscle.
Species:  Human
Tissue:  Pulmonary vascular preparations.
References:  60
Contraction of bronchial smooth muscle.
Species:  Human
Tissue:  Bronchial smooth muscle preparations.
References:  12
Bronchoconstriction.
Species:  Human
Tissue:  In vivo.
References:  27
Vasoconstriction.
Species:  Rat
Tissue:  In vivo.
References:  78
Platelet aggregation.
Species:  Human
Tissue:  In vivo.
References:  18
Platelet aggregation.
Species:  Human
Tissue:  Platelets.
References:  43
Mediation of cellular immune responses and inflammatory tissue injury.
Species:  Mouse
Tissue:  In vivo.
References:  76
Suppression of lipopolysaccharide-induced liver injury by a TP antagonist, S-145.
Species:  Mouse
Tissue:  Liver.
References:  77
The TP agonist I-BOP induces expression of MCP-1/CCL2 in lung cancer cell lines through activation of SP-1.
Species:  Human
Tissue:  Lung cancer cells.
References:  41
TP mediates U46619-induced airway constriction through an M3 muscarinic acetycholine receptor-dependent mechanism.
Species:  Mouse
Tissue:  Lung.
References:  3
Suppression of lipopolysaccharide-induced liver injury by a TP antagonist, S-145.
Species:  Rat
Tissue:  Liver.
References:  26
A TP agonist U46619 induces itch in mice, which is inhibited by a TP antagonist ONO-3708 and is absent in TP knockout mice.
Species:  Mouse
Tissue:  Skin.
References:  4
TP receptor antagonism (ifetroban) is cardioprotective against right ventricular pressure overload.
Species:  Mouse
Tissue:  Heart
References:  84
Physiological Consequences of Altering Gene Expression Click here for help
TP knockout mice display delayed atherogenesis and impaired inflammatory tachycarcia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  38,72
TP receptor knockout mice exhibit an increase in bleeding time and impaired platelet aggregation in response to TP receptor agonists.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  75
Spleen cells from TP receptor knockout mice exhibit reduced cellular immune responsiveness and TP receptor knockout mice exhibit reduced immune-mediated tissue injury following cardiac transplant rejection in vivo.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  76
TP receptor knockout mice exhibit enhanced immune responses and the development of lymphadenopathy.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  29
TP receptor knockout mice exhibit inhibition of cytokine-induced increase in beating rate, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  72
TP receptor knockout mice enhibit altered renal vascular tone.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  65
TP knockout mice exhibit enhanced susceptibility to Trypanosoma cruzi infection.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockouts.
References:  8
TP knockout mice show a reduction in B16F1 lung colonization and mortality rate in a lung metastasis model of B16H1 melanoma cells.
Species:  Mouse
Tissue:  Lung/melanoma cells.
Technique:  Gene knockouts.
References:  45
TP knockout mice exhibit attenuated microcirculatory dysfunction as examined by leukocyte adhesion to sinusoid, non-perfused sinusoids and release of ALT in the liver in response to TNF-α.
Species:  Mouse
Tissue:  Hepatic microcirculation.
Technique:  Gene knockouts.
References:  31
TP knockout mice exhibit attenuated hypertension and cardiac hypertrophy, but enhanced kidney hypertrophy, glomerulosclerosis, tubule vacuolization, and interstitial chronic inflammation, in response to L-NAME.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockouts.
References:  16
TP knockout mice exhibit attenuation of cardiac hypertrophy and prevention of cardiac fibrosis but do not affect hypertension induced by IP deficiency in response to high salt.
Species:  Mouse
Tissue: 
Technique:  Gene knockouts.
References:  15
Mice deficient in TP selectively in neurons do not exhibit U-46619-induced bronchoconstriction after OVA-induced allergic inflamamtion in the lung.
Species:  Mouse
Tissue:  smooth muscel-TP deficient (Tbxa2rF/− Tgln-cre) mice and neural TP-deficeint (Tbxa2rF/−Nestin-cre) mice.
Technique:  Gene knockouts.
References:  13
TP knockout mice showed reduced apoptosis of thymocytes in response to systemic administration of lipopolysaccharide.
Species:  Mouse
Tissue:  Thymus, CD4+CD8+ double positive thymocytes.
Technique:  Gene knockouts.
References:  64
TP knockout mice exhibit attenuated vascular remodeling to catheter-induced injury and cancel out enhanced response by IP deficiency.
Species:  Mouse
Tissue:  Carotid artery.
Technique:  Gene knockouts.
References:  10
Mice deficient in TP selectively in smooth muscle exhibit enhanced hypertension and aortic remodeling in response to angiotensin II infusion.
Species:  Mouse
Tissue:  TP knockout in smooth muscle cells (KISM22α-Cre+Tpflox/flox).
Technique:  Gene knockouts.
References:  67
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
C.129P2(B6)-Tbxa2r		 MGI:98496  MP:0000249 abnormal blood vessel physiology PMID: 11964481 
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * 129S/SvEv)		 MGI:98496  MP:0001544 abnormal cardiovascular system physiology PMID: 9835625 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0002351 abnormal cervical lymph node morphology PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0002723 abnormal immune serum protein physiology PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0002722 abnormal immune system organ morphology PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0001790 abnormal immune system physiology PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0002339 abnormal lymph node morphology PMID: 12778172 
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * 129S/SvEv)		 MGI:98496  MP:0009548 abnormal platelet aggregation PMID: 9835625 
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
C.129P2(B6)-Tbxa2r		 MGI:98496  MP:0005464 abnormal platelet physiology PMID: 11964481 
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
C.129P2(B6)-Tbxa2r		 MGI:98496  MP:0009818 abnormal thromboxane level PMID: 11964481 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0002531 abnormal type I hypersensitivity reaction PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0000702 enlarged lymph nodes PMID: 12778172 
Tbxa2rtm1Sna Tbxa2rtm1Sna/Tbxa2rtm1Sna
either: (involves: 129/Ola * BALB/c) or (involves: 129/Ola * C57BL/6)		 MGI:98496  MP:0000691 enlarged spleen PMID: 12778172 
Tbxa2rtm1Cof Tbxa2rtm1Cof/Tbxa2rtm1Cof
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * 129S/SvEv)		 MGI:98496  MP:0005606 increased bleeding time PMID: 9835625 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Bleeding disorder, platelet-type, 13, susceptibility to
Synonyms: Bleeding diathesis due to thromboxane synthesis deficiency [Orphanet: ORPHA220443]
OMIM: 614009
Orphanet: ORPHA220443
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R60L Identified in patients suffering from a dominantly inherited bleeding disorder. This mutant receptor displays normal ligand binding but defective signal transduction when expressed in CHO cells. 23
Missense Human D304N 910G>A Mutation leads to loss of receptor binding in a patient with a bleeding diathesis. 55
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  TP SNPs are associated with susceptibility to cerebral infarction.
SNP accession:  rs2271875, rs768963
References:  30
Type:  Splice variants
Species:  Human
Description:  Two splice variants of the TP receptor have been found in humans, TPα and TPβ, containing an identical 328 amino acid sequence but differing in their 15 amino acid and 79 amino acid, respectively, C-terminal regions. They have identical ligand and G protein binding properties, similarly regulate PLC, but they are differentially expressed throughout the body and oppositely regulate adeylate cyclase activity.
References:  24,33-34,63,82
Type:  Missense mutation
Species:  Human
Description:  Platelet dysfunction, reduced response to TP agonist and reduced affinity to TP radioligand associated with the Trp29Cys TP receptor variant.
Amino acid change:  W29C
References:  56
General Comments
When dimerized with IP receptor, the TP shifts to IP-like function [25,86,88]. Heterodimerization of TP-α and -β isoforms has been reported [87]. Transcriptional regulation and promoter analysis of TP is presented in [17].

References

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