| UniProt ID | TGFR1_HUMAN | |
|---|---|---|
| UniProt AC | P36897 | |
| Protein Name | TGF-beta receptor type-1 | |
| Gene Name | TGFBR1 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 503 | |
| Subcellular Localization |
Cell membrane Single-pass type I membrane protein . Cell junction, tight junction . Cell surface . Membrane raft . |
|
| Protein 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.. | |
| Protein Sequence | MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTETTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTVKSSPGLGPVELAAVIAGPVCFVCISLMLMVYICHNRTVIHHRVPNEEDPSLDRPFISEGTTLKDLIYDMTTSGSGSGLPLLVQRTIARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLSQQEGIKM | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 45 | N-linked_Glycosylation | CHLCTKDNFTCVTDG HHHHCCCCCEEEECC | 35.37 | UniProtKB CARBOHYD | |
| 59 | O-linked_Glycosylation | GLCFVSVTETTDKVI CEEEEEEEECCCCHH | 21.80 | OGP | |
| 62 | O-linked_Glycosylation | FVSVTETTDKVIHNS EEEEEECCCCHHHCC | 27.82 | OGP | |
| 96 | O-linked_Glycosylation | SSKTGSVTTTYCCNQ CCCCCCEEEEEEECC | 18.34 | OGP | |
| 108 | Acetylation | CNQDHCNKIELPTTV ECCCCCCCEECCCCC | 42.84 | 26051181 | |
| 113 | Phosphorylation | CNKIELPTTVKSSPG CCCEECCCCCCCCCC | 57.77 | 24114839 | |
| 165 | Phosphorylation | VPNEEDPSLDRPFIS CCCCCCCCCCCCCCC | 56.05 | 30266825 | |
| 172 | Phosphorylation | SLDRPFISEGTTLKD CCCCCCCCCCCCHHH | 30.28 | 8576253 | |
| 175 | Phosphorylation | RPFISEGTTLKDLIY CCCCCCCCCHHHHHH | 25.55 | 25850435 | |
| 176 | Phosphorylation | PFISEGTTLKDLIYD CCCCCCCCHHHHHHH | 42.54 | 8576253 | |
| 178 | Ubiquitination | ISEGTTLKDLIYDMT CCCCCCHHHHHHHHH | 48.69 | - | |
| 185 | Phosphorylation | KDLIYDMTTSGSGSG HHHHHHHHCCCCCCC | 18.21 | 22817900 | |
| 186 | Phosphorylation | DLIYDMTTSGSGSGL HHHHHHHCCCCCCCH | 25.18 | 22817900 | |
| 187 | Phosphorylation | LIYDMTTSGSGSGLP HHHHHHCCCCCCCHH | 23.07 | 22817900 | |
| 189 | Phosphorylation | YDMTTSGSGSGLPLL HHHHCCCCCCCHHHH | 29.56 | 22817900 | |
| 191 | Phosphorylation | MTTSGSGSGLPLLVQ HHCCCCCCCHHHHHH | 38.56 | 20207738 | |
| 200 | Phosphorylation | LPLLVQRTIARTIVL HHHHHHHHHHHEEEE | 11.25 | 22817900 | |
| 204 | Phosphorylation | VQRTIARTIVLQESI HHHHHHHEEEEHHCC | 13.35 | 22817900 | |
| 210 | Phosphorylation | RTIVLQESIGKGRFG HEEEEHHCCCCCCCC | 24.55 | - | |
| 295 | Phosphorylation | LFDYLNRYTVTVEGM HHHHHHCEEEEHHHH | 12.42 | 20068231 | |
| 296 | Phosphorylation | FDYLNRYTVTVEGMI HHHHHCEEEEHHHHH | 13.38 | 20068231 | |
| 298 | Phosphorylation | YLNRYTVTVEGMIKL HHHCEEEEHHHHHHH | 12.68 | 20068231 | |
| 337 | Ubiquitination | AHRDLKSKNILVKKN ECCCCCCCCEEEEEC | 46.55 | - | |
| 360 | Phosphorylation | GLAVRHDSATDTIDI CCEEECCCCCCCCCC | 27.26 | 20873877 | |
| 364 | Phosphorylation | RHDSATDTIDIAPNH ECCCCCCCCCCCCCC | 19.05 | 24260401 | |
| 378 | Phosphorylation | HRVGTKRYMAPEVLD CCCCCCCCCCHHHHC | 10.13 | 26503892 | |
| 391 | Ubiquitination | LDDSINMKHFESFKR HCCCCCHHHHHHHHH | 40.43 | 21906983 | |
| 395 (in isoform 2) | Ubiquitination | - | 34.81 | - | |
| 449 | Ubiquitination | RKVVCEQKLRPNIPN HHHHHHHHCCCCCCC | 24.95 | - | |
| 484 | Phosphorylation | ANGAARLTALRIKKT HCHHHHHHHHHHHHH | 20.35 | 24719451 | |
| 490 | Malonylation | LTALRIKKTLSQLSQ HHHHHHHHHHHHHHH | 52.94 | 26320211 | |
| 490 | Ubiquitination | LTALRIKKTLSQLSQ HHHHHHHHHHHHHHH | 52.94 | - | |
| 493 | Phosphorylation | LRIKKTLSQLSQQEG HHHHHHHHHHHHHHC | 34.02 | 22210691 | |
| 502 | Ubiquitination | LSQQEGIKM------ HHHHHCCCC------ | 49.79 | 21906983 | |
| 506 (in isoform 2) | Ubiquitination | - | - |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 185 | T | Phosphorylation | Kinase | TGFBR2 | P37173 | Uniprot |
| 186 | T | Phosphorylation | Kinase | TGFBR2 | P37173 | Uniprot |
| 187 | S | Phosphorylation | Kinase | TGFBR2 | P37173 | Uniprot |
| 189 | S | Phosphorylation | Kinase | TGFBR2 | P37173 | Uniprot |
| 191 | S | Phosphorylation | Kinase | TGFBR2 | P37173 | Uniprot |
| 200 | T | Phosphorylation | Kinase | PRKCA | P17252 | GPS |
| 200 | T | Phosphorylation | Kinase | TGFBR2 | P37173 | PSP |
| - | K | Ubiquitination | E3 ubiquitin ligase | TRAF6 | Q9Y4K3 | PMID:25622187 |
| - | K | Ubiquitination | E3 ubiquitin ligase | WWP1 | Q9H0M0 | PMID:15817471 |
| - | K | Ubiquitination | E3 ubiquitin ligase | SMURF2 | Q9HAU4 | PMID:14562029 |
| - | K | Ubiquitination | E3 ubiquitin ligase | SMURF1 | Q9HCE7 | PMID:12151385 |
| - | K | Ubiquitination | E3 ubiquitin ligase | NEDD4L | Q96PU5 | PMID:15496141 |
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of TGFR1_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of TGFR1_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| H00800 | Loeys-Dietz syndrome (LDS) | |||||
| H00801 | Familial thoracic aortic aneurysm and dissection (TAAD); Aortic aneurysm familial thoracic type (AAT | |||||
| OMIM Disease | ||||||
| 609192 | Loeys-Dietz syndrome 1 (LDS1) | |||||
| 132800 | Multiple self-healing squamous epithelioma (MSSE) | |||||
| Kegg Drug | ||||||
| D10437 | Galunisertib (USAN) | |||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND MASSSPECTROMETRY. | |
| "GS domain mutations that constitutively activate T beta R-I, thedownstream signaling component in the TGF-beta receptor complex."; Wieser R., Wrana J.L., Massague J.; EMBO J. 14:2199-2208(1995). Cited for: FUNCTION, PHOSPHORYLATION AT THR-185; THR-186; SER-187; SER-189 ANDSER-191 BY TGFBR2, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF185-THR-THR-186; SER-187; SER-189; SER-191; THR-200 AND THR-204. | |
