Names & Taxonomy

Uniprot ID:
P36897
Entry Name:
TGFR1_HUMAN
Status:
reviewed
Protein Names:
TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
Gene Names:
TGFBR1 ALK5 SKR4
Gene Names Primary:
TGFBR1
Organism:
Homo sapiens (Human)

Structure

Length:
503
Sequence:
MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTETTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTVKSSPGLGPVELAAVIAGPVCFVCISLMLMVYICHNRTVIHHRVPNEEDPSLDRPFISEGTTLKDLIYDMTTSGSGSGLPLLVQRTIARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLSQQEGIKM
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane

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. 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.
Catalytic Activity:
ATP + = ADP + phosphate.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
ENZYME REGULATION: Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.
Active Site:
ACT_SITE 333 333 Proton acceptor.
Gene Ontology Go:
bicellular tight junction
cell
cell surface
endosome
intracellular
membrane
membrane raft
plasma membrane
receptor complex
transforming growth factor beta receptor homodimeric complex
ATP binding
I-SMAD binding
metal ion binding
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein activity
receptor signaling protein serine/threonine kinase activity
SMAD binding
transforming growth factor beta binding
transforming growth factor beta receptor activity, type I
transforming growth factor beta-activated receptor activity
type II transforming growth factor beta receptor binding
activation of MAPKK activity
activin receptor signaling pathway
angiogenesis
anterior/posterior pattern specification
apoptotic process
artery morphogenesis
blastocyst development
cardiac epithelial to mesenchymal transition
cell cycle arrest
cell motility
cellular response to transforming growth factor beta stimulus
collagen fibril organization
embryonic cranial skeleton morphogenesis
endothelial cell activation
endothelial cell migration
epithelial to mesenchymal transition
extracellular structure organization
germ cell migration
heart development
in utero embryonic development
intracellular signal transduction
kidney development
lens development in camera-type eye
male gonad development
mesenchymal cell differentiation
negative regulation of chondrocyte differentiation
negative regulation of endothelial cell proliferation
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of transforming growth factor beta receptor signaling pathway
neuron fate commitment
palate development
parathyroid gland development
pathway-restricted SMAD protein phosphorylation
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
pharyngeal system development
positive regulation of apoptotic signaling pathway
positive regulation of cell growth
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cellular component movement
positive regulation of endothelial cell proliferation
positive regulation of filopodium assembly
positive regulation of gene expression
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of protein kinase B signaling
positive regulation of SMAD protein import into nucleus
positive regulation of transcription, DNA-templated
post-embryonic development
protein phosphorylation
regulation of epithelial to mesenchymal transition
regulation of gene expression
regulation of protein binding
regulation of protein ubiquitination
regulation of transcription, DNA-templated
response to cholesterol
signal transduction
skeletal system development
skeletal system morphogenesis
thymus development
transforming growth factor beta receptor signaling pathway
wound healing
Gene Ontology Biological Process:
activation of MAPKK activity
activin receptor signaling pathway
angiogenesis
anterior/posterior pattern specification
apoptotic process
artery morphogenesis
blastocyst development
cardiac epithelial to mesenchymal transition
cell cycle arrest
cell motility
cellular response to transforming growth factor beta stimulus
collagen fibril organization
embryonic cranial skeleton morphogenesis
endothelial cell activation
endothelial cell migration
epithelial to mesenchymal transition
extracellular structure organization
germ cell migration
heart development
intracellular signal transduction
in utero embryonic development
kidney development
lens development in camera-type eye
male gonad development
mesenchymal cell differentiation
negative regulation of chondrocyte differentiation
negative regulation of endothelial cell proliferation
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of transforming growth factor beta receptor signaling pathway
neuron fate commitment
palate development
parathyroid gland development
pathway-restricted SMAD protein phosphorylation
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
pharyngeal system development
positive regulation of apoptotic signaling pathway
positive regulation of cell growth
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of cellular component movement
positive regulation of endothelial cell proliferation
positive regulation of filopodium assembly
positive regulation of gene expression
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of protein kinase B signaling
positive regulation of SMAD protein import into nucleus
positive regulation of transcription, DNA-templated
post-embryonic development
protein phosphorylation
regulation of epithelial to mesenchymal transition
regulation of gene expression
regulation of protein binding
regulation of protein ubiquitination
regulation of transcription, DNA-templated
response to cholesterol
signal transduction
skeletal system development
skeletal system morphogenesis
thymus development
transforming growth factor beta receptor signaling pathway
wound healing
Gene Ontology Molecular Function:
ATP binding
I-SMAD binding
metal ion binding
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein activity
receptor signaling protein serine/threonine kinase activity
SMAD binding
transforming growth factor beta-activated receptor activity
transforming growth factor beta binding
transforming growth factor beta receptor activity, type I
type II transforming growth factor beta receptor binding
Gene Ontology Cellular Component:
bicellular tight junction
cell
cell surface
endosome
intracellular
membrane
membrane raft
plasma membrane
receptor complex
transforming growth factor beta receptor homodimeric complex
Keywords:
3D-structure
ATP-binding
Alternative splicing
Aortic aneurysm
Apoptosis
Cell junction
Cell membrane
Complete proteome
Craniosynostosis
Differentiation
Direct protein sequencing
Disease mutation
Disulfide bond
Glycoprotein
Growth regulation
Isopeptide bond
Kinase
Magnesium
Manganese
Membrane
Metal-binding
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Serine/threonine-protein kinase
Signal
Tight junction
Transferase
Transmembrane
Transmembrane helix
Ubl conjugation
Interacts With:
Q99IB8; P62942; P01137; P63104

Publication

PubMed ID:
8242743 9417915 15164053 15489334 9661882 17845732 7774578 8752209 8980228 9233797 9311995 9346908 9865696 9472030 11163210 11278251 12941698 15496141 15761148 16754747 17099224 18758450 9759503 19369195 22344298 25893292 8521960 10025408 11583628 15177479 15317461 18243111 20207738 12947057 15385056 15731757 15505640 16596670 16791849 16928994 17344846 18987736 19883511 22113417 21358634