TGFBR1
entrez
7046
canonical
uniprot
P36897
canonical
ensembl
ENSG00000106799
resolver
ensp
ENSP00000364129
resolver
ensp
ENSP00000364133
resolver
ensp
ENSP00000447182
resolver
ensp
ENSP00000447297
resolver
ensp
ENSP00000447707
resolver
ensp
ENSP00000449934
resolver
ensp
ENSP00000450052
resolver
ensp
ENSP00000514048
resolver
ensp
ENSP00000528622
resolver
ensp
ENSP00000528623
resolver
ensp
ENSP00000607344
resolver
ensp
ENSP00000607345
resolver
ensp
ENSP00000641284
resolver
enst
ENST00000546584
resolver
enst
ENST00000547314
resolver
enst
ENST00000550253
resolver
enst
ENST00000552573
resolver
enst
ENST00000698941
resolver
genesymbol
TGFBR1
resolver
genesymbol_syn
ALK5
resolver
genesymbol_syn
SKR4
resolver
hgnc
HGNC:11772
resolver
uniprot
A0A8V8TMH4
resolver
uniprot
A0ACM8QGC4
resolver
uniprot
B4DXN7
resolver
uniprot
B4DY26
resolver
uniprot
F8VVC4
resolver
uniprot
F8W0K6
resolver
uniprot
H0YHS4
resolver
uniprot
Q5T7S2
resolver
uniprot
Q6IR47
resolver
uniprot
Q706C0
resolver
uniprot
Q706C1
resolver
uniprot_entry
A0ACM8QGC4_HUMAN
resolver
uniprot_entry
B4DXN7_HUMAN
resolver
uniprot_entry
B4DY26_HUMAN
resolver
uniprot_entry
F8W0K6_HUMAN
resolver
uniprot_entry
Q5T7S2_HUMAN
resolver
uniprot_entry
TGFR1_HUMAN
resolver
uniprot_sec
A0A8V8TMH4
resolver
uniprot_sec
F8VVC4
resolver
uniprot_sec
H0YHS4
resolver
uniprot_sec
Q6IR47
resolver
uniprot_sec
Q706C0
resolver
uniprot_sec
Q706C1
resolver
activity_regulation
ACTIVITY REGULATION: Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor. {ECO:0000269|PubMed:9233797}.
uniprot
proteins
amino_acid_sequence
MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTETTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTVKSSPGLGPVELAAVIAGPVCFVCISLMLMVYICHNRTVIHHRVPNEEDPSLDRPFISEGTTLKDLIYDMTTSGSGSGLPLLVQRTIARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLSQQEGIKM
uniprot
proteins
disease_involvement
DISEASE: Loeys-Dietz syndrome 1 (LDS1) [MIM:609192]: 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. {ECO:0000269|PubMed:15731757, ECO:0000269|PubMed:16596670, ECO:0000269|PubMed:16791849, ECO:0000269|PubMed:16928994, ECO:0000269|PubMed:19883511, ECO:0000269|PubMed:22113417}. Note=The disease is caused by variants affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 by the OMIM resource. {ECO:0000269|PubMed:16791849}.; DISEASE: Multiple self-healing squamous epithelioma (MSSE) [MIM:132800]: 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. {ECO:0000269|PubMed:21358634}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.30
uniprot
proteins
function
FUNCTION: 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 (PubMed:33914044). 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. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}.
uniprot
proteins
mass_dalton
55960
uniprot
proteins
mutagenesis
MUTAGEN 185..186; /note="TT->VV: Loss of phosphorylation on threonine residues. Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with A-187; A-189 and A-191."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 187; /note="S->A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-189 and A-191."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 189; /note="S->A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-191."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 191; /note="S->A: Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-189."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 193; /note="L->G: Loss of interaction with FKBP1A."; /evidence="ECO:0000269|PubMed:9233797"; MUTAGEN 194; /note="P->K: Loss of interaction with FKBP1A."; /evidence="ECO:0000269|PubMed:9233797"; MUTAGEN 200; /note="T->D: Loss of response to TGF-beta."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 200; /note="T->V: Loss of phosphorylation. Loss of response to TGF-beta."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 204; /note="T->D: Constitutive activation."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 204; /note="T->V: Reduced phosphorylation. Reduced response to TGF-beta."; /evidence="ECO:0000269|PubMed:7774578"; MUTAGEN 268; /note="K->R: Abolished its TCR-induced ubiquitination."; /evidence="ECO:0000269|PubMed:33914044
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:11583628, ECO:0000269|PubMed:7774578}.; PTM: N-Glycosylated. {ECO:0000269|PubMed:9661882}.; PTM: 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). Ubiquitinated by BFAR via'Lys-63'-linked ubiquitination at Lys-268, leading to TGF-beta signaling activation (PubMed:33914044). {ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:33914044}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TGFB receptor subfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
10025408
uniprot
proteins
pubmed
11163210
uniprot
proteins
pubmed
11278251
uniprot
proteins
pubmed
11583628
uniprot
proteins
pubmed
12941698
uniprot
proteins
pubmed
12947057
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15177479
uniprot
proteins
pubmed
15317461
uniprot
proteins
pubmed
15385056
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15496141
uniprot
proteins
pubmed
15505640
uniprot
proteins
pubmed
15731757
uniprot
proteins
pubmed
15761148
uniprot
proteins
pubmed
16596670
uniprot
proteins
pubmed
16754747
uniprot
proteins
pubmed
16791849
uniprot
proteins
pubmed
16928994
uniprot
proteins
pubmed
17099224
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17845732
uniprot
proteins
pubmed
18243111
uniprot
proteins
pubmed
18758450
uniprot
proteins
pubmed
18987736
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19883511
uniprot
proteins
pubmed
20207738
uniprot
proteins
pubmed
21358634
uniprot
proteins
pubmed
21791611
uniprot
proteins
pubmed
22113417
uniprot
proteins
pubmed
22344298
uniprot
proteins
pubmed
25893292
uniprot
proteins
pubmed
26583432
uniprot
proteins
pubmed
29572483
uniprot
proteins
pubmed
33914044
uniprot
proteins
pubmed
7774578
uniprot
proteins
pubmed
8242743
uniprot
proteins
pubmed
8521960
uniprot
proteins
pubmed
8752209
uniprot
proteins
pubmed
8980228
uniprot
proteins
pubmed
9233797
uniprot
proteins
pubmed
9311995
uniprot
proteins
pubmed
9346908
uniprot
proteins
pubmed
9417915
uniprot
proteins
pubmed
9472030
uniprot
proteins
pubmed
9661882
uniprot
proteins
pubmed
9759503
uniprot
proteins
pubmed
9865696
uniprot
proteins
sequence_length
503
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:9472030}; Single-pass type I membrane protein {ECO:0000269|PubMed:9472030}. Cell junction, tight junction {ECO:0000269|PubMed:15761148}. Cell surface {ECO:0000269|PubMed:25893292}. Membrane raft {ECO:0000269|PubMed:25893292}.
uniprot
proteins
transmembrane_region
TRANSMEM 127..147; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins