| Tag | Content |
|---|---|
| Uniprot ID | Q64729; A2AJN0; |
| Entrez ID | 21812 |
| Genbank protein ID | BAA05878.1; BAA05023.1; AAH63260.1; |
| Genbank nucleotide ID | NM_001312868.1; NM_001312869.1; NM_009370.3; |
| Ensembl protein ID | ENSMUSP00000048501; ENSMUSP00000007757; |
| Ensembl nucleotide ID | ENSMUSG00000007613 |
| Gene name | TGF-beta receptor type-1 |
| Gene symbol | Tgfbr1 |
| Organism | Mus musculus |
| NCBI taxa ID | 10090 |
| Cleft type | CPO,CLP,CLO |
| Developmental stage | E14.0 |
| Data sources | Manually collected |
| Reference | 18586087; 16806156; |
| Functional description | 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 (By similarity). |
| Sequence | MEAAAAAPRR PQLLIVLVAA ATLLPGAKAL QCFCHLCTKD NFTCETDGLC FVSVTETTDK 60 VIHNSMCIAE IDLIPRDRPF VCAPSSKTGA VTTTYCCNQD HCNKIELPTT GPFSEKQSAG 120 LGPVELAAVI AGPVCFVCIA LMLMVYICHN RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL 180 IYDMTTSGSG SGLPLLVQRT IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER 240 SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE 300 GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA DLGLAVRHDS 360 ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD IYAMGLVFWE IARRCSIGGI 420 HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL RPNIPNRWQS CEALRVMAKI MRECWYANGA 480 ARLTALRIKK TLSQLSQQEG IKM 503 |
Abbreviation :
CLO : cleft lip only. CPO : cleft palate only.
CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0004672 | protein kinase activity | ISO |
| GO:0004674 | protein serine/threonine kinase activity | ISO |
| GO:0004674 | protein serine/threonine kinase activity | IBA |
| GO:0005024 | transforming growth factor beta-activated receptor activity | ISO |
| GO:0005024 | transforming growth factor beta-activated receptor activity | IDA |
| GO:0005024 | transforming growth factor beta-activated receptor activity | IGI |
| GO:0005025 | transforming growth factor beta receptor activity, type I | ISS |
| GO:0005025 | transforming growth factor beta receptor activity, type I | ISO |
| GO:0005025 | transforming growth factor beta receptor activity, type I | IBA |
| GO:0005102 | signaling receptor binding | IPI |
| GO:0005114 | type II transforming growth factor beta receptor binding | ISO |
| GO:0005515 | protein binding | IPI |
| GO:0005524 | ATP binding | ISO |
| GO:0016361 | activin receptor activity, type I | IBA |
| GO:0031625 | ubiquitin protein ligase binding | ISO |
| GO:0044877 | protein-containing complex binding | ISO |
| GO:0046332 | SMAD binding | ISO |
| GO:0046332 | SMAD binding | IDA |
| GO:0046332 | SMAD binding | IBA |
| GO:0046872 | metal ion binding | IEA |
| GO:0048185 | activin binding | IBA |
| GO:0050431 | transforming growth factor beta binding | ISO |
| GO:0050431 | transforming growth factor beta binding | IPI |
| GO:0070411 | I-SMAD binding | ISO |
| GO:0019838 | growth factor binding | ISO |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0000186 | activation of MAPKK activity | ISO |
| GO:0001501 | skeletal system development | IGI |
| GO:0001525 | angiogenesis | IMP |
| GO:0001701 | in utero embryonic development | IMP |
| GO:0001822 | kidney development | IGI |
| GO:0001824 | blastocyst development | IDA |
| GO:0001837 | epithelial to mesenchymal transition | ISO |
| GO:0001937 | negative regulation of endothelial cell proliferation | IGI |
| GO:0001938 | positive regulation of endothelial cell proliferation | ISS |
| GO:0002088 | lens development in camera-type eye | IMP |
| GO:0003222 | ventricular trabecula myocardium morphogenesis | IMP |
| GO:0003223 | ventricular compact myocardium morphogenesis | IMP |
| GO:0006355 | regulation of transcription, DNA-templated | ISO |
| GO:0006468 | protein phosphorylation | ISO |
| GO:0006468 | protein phosphorylation | IBA |
| GO:0006915 | apoptotic process | IEA |
| GO:0007165 | signal transduction | ISO |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | ISO |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | IMP |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | IDA |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | IGI |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | IBA |
| GO:0007399 | nervous system development | IBA |
| GO:0007507 | heart development | ISS |
| GO:0007507 | heart development | IMP |
| GO:0007507 | heart development | IBA |
| GO:0008284 | positive regulation of cell population proliferation | ISO |
| GO:0008354 | germ cell migration | IMP |
| GO:0008584 | male gonad development | IMP |
| GO:0009791 | post-embryonic development | IMP |
| GO:0009952 | anterior/posterior pattern specification | IGI |
| GO:0010468 | regulation of gene expression | ISS |
| GO:0010468 | regulation of gene expression | IMP |
| GO:0010628 | positive regulation of gene expression | ISS |
| GO:0010628 | positive regulation of gene expression | ISO |
| GO:0010717 | regulation of epithelial to mesenchymal transition | ISS |
| GO:0010718 | positive regulation of epithelial to mesenchymal transition | IGI |
| GO:0010862 | positive regulation of pathway-restricted SMAD protein phosphorylation | ISO |
| GO:0018105 | peptidyl-serine phosphorylation | ISO |
| GO:0018107 | peptidyl-threonine phosphorylation | ISO |
| GO:0030199 | collagen fibril organization | IMP |
| GO:0030307 | positive regulation of cell growth | ISO |
| GO:0030335 | positive regulation of cell migration | ISO |
| GO:0031396 | regulation of protein ubiquitination | ISO |
| GO:0032331 | negative regulation of chondrocyte differentiation | IMP |
| GO:0032924 | activin receptor signaling pathway | ISS |
| GO:0032924 | activin receptor signaling pathway | IBA |
| GO:0035556 | intracellular signal transduction | ISS |
| GO:0042118 | endothelial cell activation | ISS |
| GO:0043065 | positive regulation of apoptotic process | IDA |
| GO:0043066 | negative regulation of apoptotic process | IMP |
| GO:0043393 | regulation of protein binding | IMP |
| GO:0043542 | endothelial cell migration | IMP |
| GO:0043627 | response to estrogen | ISO |
| GO:0045602 | negative regulation of endothelial cell differentiation | ISO |
| GO:0045893 | positive regulation of transcription, DNA-templated | ISS |
| GO:0045893 | positive regulation of transcription, DNA-templated | ISO |
| GO:0046777 | protein autophosphorylation | ISO |
| GO:0048538 | thymus development | IMP |
| GO:0048663 | neuron fate commitment | IMP |
| GO:0048701 | embryonic cranial skeleton morphogenesis | IMP |
| GO:0048705 | skeletal system morphogenesis | IGI |
| GO:0048762 | mesenchymal cell differentiation | ISS |
| GO:0048844 | artery morphogenesis | IMP |
| GO:0048870 | cell motility | ISO |
| GO:0051272 | positive regulation of cellular component movement | ISO |
| GO:0051491 | positive regulation of filopodium assembly | IMP |
| GO:0051496 | positive regulation of stress fiber assembly | IGI |
| GO:0051897 | positive regulation of protein kinase B signaling | ISO |
| GO:0060017 | parathyroid gland development | IMP |
| GO:0060021 | roof of mouth development | IMP |
| GO:0060021 | roof of mouth development | IGI |
| GO:0060037 | pharyngeal system development | IMP |
| GO:0060043 | regulation of cardiac muscle cell proliferation | IMP |
| GO:0060317 | cardiac epithelial to mesenchymal transition | ISS |
| GO:0060389 | pathway-restricted SMAD protein phosphorylation | ISO |
| GO:0060391 | positive regulation of SMAD protein signal transduction | ISO |
| GO:0060412 | ventricular septum morphogenesis | IMP |
| GO:0060978 | angiogenesis involved in coronary vascular morphogenesis | IMP |
| GO:0060982 | coronary artery morphogenesis | IMP |
| GO:0070723 | response to cholesterol | ISO |
| GO:0070723 | response to cholesterol | IDA |
| GO:0071363 | cellular response to growth factor stimulus | IBA |
| GO:0071560 | cellular response to transforming growth factor beta stimulus | ISO |
| GO:0071560 | cellular response to transforming growth factor beta stimulus | IDA |
| GO:1902894 | negative regulation of pri-miRNA transcription by RNA polymerase II | ISO |
| GO:1902895 | positive regulation of pri-miRNA transcription by RNA polymerase II | ISO |
| GO:1905007 | positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation | IMP |
| GO:1905075 | positive regulation of tight junction disassembly | IGI |
| GO:1905223 | epicardium morphogenesis | IMP |
| GO:2001235 | positive regulation of apoptotic signaling pathway | ISO |
| GO:2001237 | negative regulation of extrinsic apoptotic signaling pathway | ISO |
| GO:0003342 | proepicardium development | IMP |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0005634 | nucleus | ISS |
| GO:0005634 | nucleus | ISO |
| GO:0005768 | endosome | ISO |
| GO:0005768 | endosome | IDA |
| GO:0005886 | plasma membrane | ISS |
| GO:0005886 | plasma membrane | ISO |
| GO:0005886 | plasma membrane | IBA |
| GO:0005901 | caveola | ISO |
| GO:0005923 | bicellular tight junction | ISO |
| GO:0009986 | cell surface | ISS |
| GO:0009986 | cell surface | ISO |
| GO:0016020 | membrane | ISS |
| GO:0016323 | basolateral plasma membrane | ISO |
| GO:0016324 | apical plasma membrane | ISO |
| GO:0032991 | protein-containing complex | ISO |
| GO:0043235 | receptor complex | ISO |
| GO:0043235 | receptor complex | IBA |
| GO:0045121 | membrane raft | ISS |
| GO:0045121 | membrane raft | ISO |
| GO:0048179 | activin receptor complex | IBA |
| Reactome ID | Reactome Term | Evidence |
|---|---|---|
| R-MMU-162582 | Signal Transduction | IEA |
| R-MMU-170834 | Signaling by TGF-beta Receptor Complex | IEA |
| R-MMU-2173788 | Downregulation of TGF-beta receptor signaling | IEA |
| R-MMU-2173789 | TGF-beta receptor signaling activates SMADs | IEA |
| R-MMU-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | IEA |
| R-MMU-392499 | Metabolism of proteins | IEA |
| R-MMU-5688426 | Deubiquitination | IEA |
| R-MMU-5689880 | Ub-specific processing proteases | IEA |
| R-MMU-597592 | Post-translational protein modification | IEA |
| R-MMU-9006936 | Signaling by TGF-beta family members | IEA |
| Keyword ID | Keyword Term |
|---|---|
| KW-0025 | Alternative splicing |
| KW-0053 | Apoptosis |
| KW-0067 | ATP-binding |
| KW-0965 | Cell junction |
| KW-1003 | Cell membrane |
| KW-0221 | Differentiation |
| KW-1015 | Disulfide bond |
| KW-0325 | Glycoprotein |
| KW-0341 | Growth regulation |
| KW-1017 | Isopeptide bond |
| KW-0418 | Kinase |
| KW-0460 | Magnesium |
| KW-0464 | Manganese |
| KW-0472 | Membrane |
| KW-0479 | Metal-binding |
| KW-0547 | Nucleotide-binding |
| KW-0597 | Phosphoprotein |
| KW-0675 | Receptor |
| KW-1185 | Reference proteome |
| KW-0723 | Serine/threonine-protein kinase |
| KW-0732 | Signal |
| KW-0796 | Tight junction |
| KW-0808 | Transferase |
| KW-0812 | Transmembrane |
| KW-1133 | Transmembrane helix |
| KW-0832 | Ubl conjugation |