Affinage

TBXA2R

Thromboxane A2 receptor · UniProt P21731

Length
343 aa
Mass
37.4 kDa
Annotated
2026-06-10
17 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBXA2R encodes the thromboxane A2 receptor (TPα), a G-protein-coupled receptor that couples extracellular stimulus to cytoskeletal remodeling and cell motility through Rho-family GTPase signalling (PMID:41844278, PMID:27487152). Upon activation, TPα engages the Gαq/11 and Gα12/13 subfamilies, which in turn activate Rho GTPases and their Ser/Thr kinase effectors SLK and LOK to phosphorylate and activate ERM (ezrin/radixin/moesin) proteins; this axis drives migration, invasion, and ERM-dependent metastatic colonization of triple-negative breast cancer cells in vivo (PMID:41844278). Consistent with this pro-tumorigenic role, TBXA2R knockdown is lethal to TNBC cells, and Rho signalling and its phenotypic outputs are reversed by ROCK inhibitors, while TBXA2R additionally protects these cells from DNA damage by limiting reactive oxygen species (PMID:27487152). TBXA2R expression is transcriptionally constrained: BRCA1 represses the gene through c-Myc, and a promoter SNP (-4684T>C) alters ELK-1-dependent transcription factor binding to set promoter activity (PMID:27487152, PMID:21070398). In platelets, TPα signalling is required for thrombus formation, as naturally occurring rare loss-of-function variants cause bleeding phenotypes and abnormal platelet function (PMID:30089223).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1993 High

    Establishing the chromosomal location of the human gene provided the genomic anchor needed to link TBXA2R to phenotypes and regulatory elements.

    Evidence PCR in monochromosomal somatic cell hybrids and multipoint linkage analysis in CEPH families

    PMID:8288221

    Open questions at the time
    • Does not address receptor function or signalling
    • No tissue-level expression data
  2. 1996 Medium

    Mapping and cloning the rodent ortholog with tissue expression analysis extended the receptor's relevance beyond platelets to renal vasculature and epithelium.

    Evidence FISH mapping and cDNA cloning with renal tissue expression analysis in rat

    PMID:8646890

    Open questions at the time
    • Functional role in kidney not tested
    • No signalling mechanism defined
  3. 2010 Medium

    Identifying a functional promoter SNP showed that TBXA2R expression is set by differential transcription factor binding, explaining a source of expression variation.

    Evidence Luciferase promoter assays and EMSA with mast cell nuclear extracts plus ELK-1 co-transfection

    PMID:21070398

    Open questions at the time
    • Direct ELK-1 binding at the SNP not confirmed beyond mobility shift
    • Physiological consequence of allelic expression difference untested
  4. 2016 Medium

    Demonstrating that TBXA2R drives TNBC migration/invasion via Rho/ROCK and is repressed by BRCA1 reframed the receptor as a pro-tumorigenic signalling node under transcriptional control.

    Evidence siRNA knockdown with viability/migration/invasion assays, Rho reporter and ROCK inhibitor rescue, ROS measurement, and BRCA1 knockdown promoter assays

    PMID:27487152

    Open questions at the time
    • Single-lab phenotypic work without in vivo validation at this stage
    • Mechanistic link between receptor and Rho not resolved to specific effectors
  5. 2018 Medium

    Linking rare loss-of-function variants to bleeding established that TPα signalling is causally required for normal platelet-dependent thrombus formation.

    Evidence Clinical characterization of patients with TBXA2R variants, platelet function assays, and GPCR structure-function analysis

    PMID:30089223

    Open questions at the time
    • Synthesizes patient data rather than a single controlled experiment
    • Per-residue structure-function mapping incomplete
  6. 2026 High

    Dissecting the full Gαq/11–Gα12/13 → Rho → SLK/LOK → ERM axis defined the complete signalling chain by which TPα drives invasion and metastatic colonization.

    Evidence G-protein subtype-specific assays, Rho GTPase activation, SLK/LOK kinase and ERM phosphorylation assays, in vitro invasion, and in vivo metastasis model with genetic rescue

    PMID:41844278

    Open questions at the time
    • Whether the same axis operates in platelets or kidney not tested
    • Upstream agonist/ligand context in tumors not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TBXA2R signalling outputs are differentially deployed across cell types (platelet thrombus formation versus cancer cell invasion versus renal function) remains unresolved.
  • No structural model of the receptor in the corpus
  • Tissue-specific effector wiring not compared directly

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-109582 Hemostasis 1
Partners
LOKSLK

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 TBXA2R knockdown causes dramatic cell killing in triple-negative breast cancer (TNBC) cells, and TBXA2R enhances TNBC cell migration and invasion by activating Rho signalling; these phenotypes are reversed by Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protects TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. TBXA2R mRNA and promoter activities are up-regulated following BRCA1 knockdown, with c-Myc required for BRCA1-mediated transcriptional repression of TBXA2R. siRNA knockdown with cell viability, migration, and invasion assays; Rho signalling reporter assays; ROCK inhibitor rescue experiments; ROS measurement; BRCA1 knockdown with promoter/reporter assays Oncotarget Medium 27487152
2026 TBXA2R activates ERM (ezrin, radixin, moesin) proteins to drive motility, invasion, and metastatic colonization of TNBC cells. Mechanistically, TBXA2R engages Gαq/11 and Gα12/13 subfamilies, then the Rho subfamily of Rho GTPases, and their Ser/Thr kinase effectors SLK and LOK to phosphorylate/activate ERMs. TBXA2R promotes TNBC metastatic colonization in vivo in an ERM-dependent manner. GPCR signalling pathway dissection (G-protein subtype-specific assays), Rho GTPase activation assays, SLK/LOK kinase activity assays, ERM phosphorylation assays, in vitro migration/invasion assays, in vivo metastasis colonization model, genetic rescue/loss-of-function Life science alliance High 41844278
2010 The TBXA2R -4684T allele is associated with lower TBXA2R promoter activity compared to the -4684C allele; ETS-like gene transcription factor-1 (ELK-1) co-transfection further decreases promoter activity driven by the -4684T construct. EMSA showed the -4684T allele produces a specific shifted band with greater protein-binding affinity than the -4684C allele, indicating differential transcription factor binding at this SNP affects TBXA2R expression. Dual-luciferase reporter assay for promoter activity; electrophoretic mobility shift assay (EMSA) with nuclear extracts from HMC-1 mast cell line; ELK-1 co-transfection Clinical and experimental allergy Medium 21070398
1993 The human TBXA2R gene was mapped to chromosome 19p13.3 by somatic cell hybrid PCR and linkage analysis, placing it closest to marker D19S120 between D19S120 and PMS207 at the telomeric end of 19p13.3. PCR amplification in monochoromosomal human/rodent somatic cell hybrids; multipoint linkage analysis in CEPH families (LOD score 19.55 at θ=0.05) Genomics High 8288221
1996 The rat Tbxa2r gene was mapped to chromosome 7q11 by fluorescence in situ hybridization; the cloned rat kidney Tbxa2r cDNA was shown to be expressed in the renal glomerulus, vasculature, and transitional cell epithelium of renal pelvis. Fluorescence in situ hybridization (FISH); cDNA cloning; tissue expression analysis Cytogenetics and cell genetics Medium 8646890
2018 Naturally occurring rare loss-of-function variants in TBXA2R (encoding the TPα receptor, an α-isoform GPCR) are associated with bleeding phenotypes and abnormal platelet function, providing structure-function information about critical residues required for TPα-dependent thrombus formation. Clinical characterization of patients with naturally occurring TBXA2R variants; functional platelet assays; structure-function analysis of GPCR variants Platelets Medium 30089223

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer. International seminars in surgical oncology : ISSO 49 16250911
2016 Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. Acta pharmacologica Sinica 30 27641736
2007 TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 30 18031559
2010 Association of thromboxane A2 receptor (TBXA2R) gene polymorphism in patients with aspirin-intolerant acute urticaria. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 27 21070398
2011 Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma. International journal of immunogenetics 23 22017802
2016 Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs). Oncotarget 22 27487152
2014 Regulatory SNPs and transcriptional factor binding sites in ADRBK1, AKT3, ATF3, DIO2, TBXA2R and VEGFA. Transcription 21 25483406
2018 TBXA2R gene variants associated with bleeding. Platelets 17 30089223
2015 Xueshuan Xinmaining Tablet Treats Blood Stasis through Regulating the Expression of F13a1, Car1, and Tbxa2r. Evidence-based complementary and alternative medicine : eCAM 16 25821496
2018 Single nucleotide polymorphisms in asthma candidate genes TBXA2R, ADAM33 FCER1B and ORMDL3 in Pakistani asthmatics a case control study. Asthma research and practice 13 29588858
1993 Linkage mapping of the human thromboxane A2 receptor (TBXA2R) to chromosome 19p13.3 using transcribed 3' untranslated DNA sequence polymorphisms. Genomics 13 8288221
2018 TBXA2R rs4523 G allele is associated with decreased susceptibility to Kawasaki disease. Cytokine 9 30179800
1996 Assignment of the gene for rat thromboxane receptor (Tbxa2r) to chromosome 7q11 by fluorescence in situ hybridization. Cytogenetics and cell genetics 7 8646890
2020 Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis. Clinical and investigative medicine. Medecine clinique et experimentale 6 32971583
2023 In silico analysis of single nucleotide polymorphism (rs34377097) of TBXA2R gene and pollen induced bronchial asthma susceptibility in West Bengal population, India. Frontiers in immunology 4 36936944
2024 The Impact of TBXA2R Gene Variants on the Risk of Aspirin-Induced Upper Gastrointestinal Bleeding: A Case-Control Study. Hospital pharmacy 2 39465093
2026 TBXA2R activates ERMs to drive motility, invasion, and metastatic colonization of TNBC cells. Life science alliance 0 41844278

Missed literature

Know a paper Affinage missed for TBXA2R? Flag it for the maintainers and the community.

No submissions yet.