TGFBR1

Tgfbr1 is a member of the transforming growth factor beta (TGF-beta) receptor family of proteins. These proteins comprise one component of the TGF-beta signaling pathway, which transduces extracellular signals into gene expression changes to regulate a wide range of cellular responses, including proliferation, migration, differentiation and apoptosis. Homozygous knockout mice for Tgfbr1 exhibit impaired angiogenesis and embryonic lethality.

Transforming Growth Factor, Beta Receptor I

Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.

Biological Process activin receptor signaling pathwaySource:AgBase
Biological Process angiogenesis involved in coronary vascular morphogenesisSource:BHF-UCL
Biological Process anterior/posterior pattern specificationSource:BHF-UCL
Biological Process apoptotic processSource:UniProtKB-KW
Biological Process artery morphogenesisSource:BHF-UCL
Biological Process blastocyst developmentSource:Ensembl
Biological Process cardiac epithelial to mesenchymal transitionSource:AgBase
Biological Process cell motilitySource:BHF-UCL1 Publication
Biological Process cellular response to growth factor stimulusSource:GO_Central1 Publication
Biological Process cellular response to transforming growth factor beta stimulusSource:BHF-UCL1 Publication
Biological Process collagen fibril organizationSource:BHF-UCL
Biological Process coronary artery morphogenesisSource:BHF-UCL
Biological Process embryonic cranial skeleton morphogenesisSource:BHF-UCL
Biological Process endothelial cell activationSource:AgBase
Biological Process endothelial cell migrationSource:Ensembl
Biological Process endothelial cell proliferationSource:Ensembl
Biological Process epicardium morphogenesisSource:BHF-UCL
Biological Process epithelial to mesenchymal transitionSource:UniProtKB1 Publication
Biological Process extracellular structure organizationSource:UniProtKB1 Publication
Biological Process filopodium assemblySource:Ensembl
Biological Process germ cell migrationSource:BHF-UCL
Biological Process heart developmentSource:AgBase
Biological Process in utero embryonic developmentSource:BHF-UCL
Biological Process intracellular signal transductionSource:AgBase
Biological Process kidney developmentSource:BHF-UCL
Biological Process lens development in camera-type eyeSource:Ensembl
Biological Process male gonad developmentSource:Ensembl
Biological Process mesenchymal cell differentiationSource:AgBase1 Publication
Biological Process negative regulation of chondrocyte differentiationSource:BHF-UCL
Biological Process negative regulation of endothelial cell proliferationSource:Ensembl
Biological Process negative regulation of extrinsic apoptotic signaling pathwaySource:BHF-UCL1 Publication
Biological Process nervous system developmentSource:GO_Central1 Publication
Biological Process neuron fate commitmentSource:BHF-UCL
Biological Process parathyroid gland developmentSource:BHF-UCL
Biological Process pathway-restricted SMAD protein phosphorylationSource:BHF-UCL4 Publications
Biological Process peptidyl-serine phosphorylationSource:UniProtKB1 Publication
Biological Process peptidyl-threonine phosphorylationSource:BHF-UCL1 Publication
Biological Process pharyngeal system developmentSource:BHF-UCL
Biological Process positive regulation of apoptotic signaling pathwaySource:UniProtKB1 Publication
Biological Process positive regulation of cell growthSource:BHF-UCL1 Publication
Biological Process positive regulation of cell migrationSource:BHF-UCL1 Publication
Biological Process positive regulation of cell population proliferationSource:HGNC-UCL1 Publication
Biological Process positive regulation of DNA-templated transcriptionSource:BHF-UCL2 Publications
Biological Process positive regulation of endothelial cell proliferationSource:AgBase
Biological Process positive regulation of epithelial to mesenchymal transitionSource:BHF-UCL
Biological Process positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formationSource:BHF-UCL
Biological Process positive regulation of filopodium assemblySource:Ensembl
Biological Process positive regulation of gene expressionSource:BHF-UCL1 Publication
Biological Process positive regulation of MAPK cascadeSource:BHF-UCL1 Publication
Biological Process positive regulation of pathway-restricted SMAD protein phosphorylationSource:BHF-UCL2 Publications
Biological Process positive regulation of protein kinase B signalingSource:BHF-UCL1 Publication
Biological Process positive regulation of SMAD protein signal transductionSource:BHF-UCL1 Publication
Biological Process positive regulation of stress fiber assemblySource:BHF-UCL
Biological Process positive regulation of tight junction disassemblySource:BHF-UCL
Biological Process post-embryonic developmentSource:Ensembl
Biological Process protein phosphorylationSource:BHF-UCL2 Publications
Biological Process regulation of cardiac muscle cell proliferationSource:BHF-UCL
Biological Process regulation of cell cycleSource:UniProtKB1 Publication
Biological Process regulation of DNA-templated transcriptionSource:HGNC-UCL1 Publication
Biological Process regulation of epithelial to mesenchymal transitionSource:AgBase
Biological Process regulation of gene expressionSource:AgBase
Biological Process regulation of protein bindingSource:Ensembl
Biological Process regulation of protein ubiquitinationSource:UniProtKB1 Publication
Biological Process response to cholesterolSource:BHF-UCL1 Publication
Biological Process roof of mouth developmentSource:BHF-UCL
Biological Process signal transductionSource:HGNC-UCL1 Publication
Biological Process skeletal system developmentSource:BHF-UCL
Biological Process skeletal system morphogenesisSource:BHF-UCL
Biological Process thymus developmentSource:BHF-UCL
Biological Process transforming growth factor beta receptor signaling pathwaySource:BHF-UCL2 Publications
Biological Process ventricular compact myocardium morphogenesisSource:BHF-UCL
Biological Process ventricular septum morphogenesisSource:BHF-UCL
Biological Process ventricular trabecula myocardium morphogenesisSource:BHF-UCL
Biological Process wound healingSource:UniProtKB1 Publication

Cell membrane
Cell junction, tight junction
Cell surface
Membrane raft

Loeys-Dietz syndrome 1 (LDS1):
An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit.
Multiple self-healing squamous epithelioma (MSSE):
A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.

Extracellular: 34-126
Helical: 127-147
Cytoplasmic: 148-503

Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding.
N-Glycosylated.
Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP (PubMed:25893292).