TGFBR1 - TGF-beta receptor type-1 - human protein (Function)
 
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TGFBR1 »  TGF-beta receptor type-1   [ EC 2.7.11.30 ]  (TGFR-1)
 
Protein also known as:  Activin A receptor type II-like protein kinase of 53kD.
Gene name:  TGFBR1
Entry whose protein(s) existence is based on evidence at protein level
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1 261 3
GENE REF ISO

Function

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Overview 
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.  
8
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • HGNC
Contributes to growth factor bindingdefinition[GO:0019838]  
1
  • HGNC
I-SMAD bindingdefinition[GO:0070411]  
1
  • BHF-UCL
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
19
  • IntAct
  • UniProtKB
  • BHF-UCL
  • HGNC
Protein kinase activitydefinition[GO:0004672]  
1
  • BHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • BHF-UCL
  • HGNC
Isoform  Iso 2   Receptor signaling protein activitydefinition[GO:0005057]  
1
  • Ortholog Curator
Receptor signaling protein serine/threonine kinase activitydefinition[GO:0004702] silver  
1
  • InterPro 2 GO
SMAD bindingdefinition[GO:0046332]  
4
  • BHF-UCL
  • HGNC
Contributes to transforming growth factor beta bindingdefinition[GO:0050431]  
5
  • HGNC
  • BHF-UCL
  • Ortholog Curator
Transforming growth factor beta receptor activity, type Idefinition[GO:0005025]  
2
  • BHF-UCL
  • Ortholog Curator
Contributes to transforming growth factor beta-activated receptor activitydefinition[GO:0005024]  
5
  • BHF-UCL
  • HGNC
Type II transforming growth factor beta receptor bindingdefinition[GO:0005114]  
2
  • BHF-UCL
GO biological process 
Activation of MAPKK activitydefinition[GO:0000186]  
1
  • BHF-UCL
Isoform  Iso 2   Activin receptor signaling pathwaydefinition[GO:0032924]  
1
  • Ortholog Curator
Angiogenesisdefinition[GO:0001525] silver  
1
  • Ortholog Compara
Anterior/posterior pattern specificationdefinition[GO:0009952]  
1
  • Ortholog Curator
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB KW
Artery morphogenesisdefinition[GO:0048844]  
1
  • Ortholog Curator
Blastocyst developmentdefinition[GO:0001824] silver  
1
  • Ortholog Compara
Isoform  Iso 2   Cardiac epithelial to mesenchymal transitiondefinition[GO:0060317]  
1
  • Ortholog Curator
Cell cycle arrestdefinition[GO:0007050]  
1
  • UniProtKB
Cell motilitydefinition[GO:0048870]  
1
  • BHF-UCL
Cellular response to transforming growth factor beta stimulusdefinition[GO:0071560]  
1
  • BHF-UCL
Collagen fibril organizationdefinition[GO:0030199]  
1
  • Ortholog Curator
Embryonic cranial skeleton morphogenesisdefinition[GO:0048701]  
1
  • Ortholog Curator
Isoform  Iso 2   Endothelial cell activationdefinition[GO:0042118]  
1
  • Ortholog Curator
Endothelial cell migrationdefinition[GO:0043542] silver  
1
  • Ortholog Compara
Epithelial to mesenchymal transitiondefinition[GO:0001837]  
1
  • UniProtKB
Extracellular structure organizationdefinition[GO:0043062]  
1
  • UniProtKB
Germ cell migrationdefinition[GO:0008354]  
1
  • Ortholog Curator
Heart developmentdefinition[GO:0007507]  
1
  • Ortholog Curator
In utero embryonic developmentdefinition[GO:0001701]  
1
  • Ortholog Curator
Isoform  Iso 2   Intracellular signal transductiondefinition[GO:0035556]  
1
  • Ortholog Curator
Kidney developmentdefinition[GO:0001822]  
1
  • Ortholog Curator
Lens development in camera-type eyedefinition[GO:0002088] silver  
1
  • Ortholog Compara
Male gonad developmentdefinition[GO:0008584] silver  
1
  • Ortholog Compara
Mesenchymal cell differentiationdefinition[GO:0048762]  
2
  • UniProtKB
  • Ortholog Curator
Negative regulation of chondrocyte differentiationdefinition[GO:0032331]  
1
  • Ortholog Curator
Negative regulation of endothelial cell proliferationdefinition[GO:0001937] silver  
1
  • Ortholog Compara
Negative regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001237]  
1
  • BHF-UCL
Neuron fate commitmentdefinition[GO:0048663]  
1
  • Ortholog Curator
Palate developmentdefinition[GO:0060021]  
1
  • Ortholog Curator
Parathyroid gland developmentdefinition[GO:0060017]  
1
  • Ortholog Curator
Pathway-restricted SMAD protein phosphorylationdefinition[GO:0060389]  
4
  • BHF-UCL
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • UniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • BHF-UCL
Pharyngeal system developmentdefinition[GO:0060037]  
1
  • Ortholog Curator
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235]  
1
  • UniProtKB
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • BHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • HGNC
Positive regulation of cellular component movementdefinition[GO:0051272]  
1
  • BHF-UCL
Isoform  Iso 2   Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • Ortholog Curator
Positive regulation of filopodium assemblydefinition[GO:0051491] silver  
1
  • Ortholog Compara
Isoform  Iso 2   Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • Ortholog Curator
Positive regulation of pathway-restricted SMAD protein phosphorylationdefinition[GO:0010862]  
2
  • BHF-UCL
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • BHF-UCL
Positive regulation of SMAD protein import into nucleusdefinition[GO:0060391]  
1
  • BHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • BHF-UCL
  • Ortholog Curator
Post-embryonic developmentdefinition[GO:0009791] silver  
1
  • Ortholog Compara
Protein phosphorylationdefinition[GO:0006468]  
2
  • BHF-UCL
  • HGNC
Isoform  Iso 2   Regulation of epithelial to mesenchymal transitiondefinition[GO:0010717]  
1
  • Ortholog Curator
Isoform  Iso 2   Regulation of gene expressiondefinition[GO:0010468]  
1
  • Ortholog Curator
Regulation of protein bindingdefinition[GO:0043393] silver  
1
  • Ortholog Compara
Regulation of protein ubiquitinationdefinition[GO:0031396]  
1
  • UniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
2
  • HGNC
Response to cholesteroldefinition[GO:0070723]  
1
  • BHF-UCL
Signal transductiondefinition[GO:0007165]  
1
  • HGNC
Signal transduction by protein phosphorylationdefinition[GO:0023014]  
1
  • InterPro 2 GO
Skeletal system developmentdefinition[GO:0001501]  
1
  • Ortholog Curator
Skeletal system morphogenesisdefinition[GO:0048705]  
1
  • Ortholog Curator
Thymus developmentdefinition[GO:0048538]  
1
  • Ortholog Curator
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179]  
5
  • BHF-UCL
  • Ortholog Curator
Wound healingdefinition[GO:0042060]  
1
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.30: ATP + [receptor-protein] ADP + [receptor-protein] phosphate.  
1
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
It is regulated in the following manner
Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor.  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adherens junction  hsa04520+7046  
Chagas disease (American trypanosomiasis)  hsa05142+7046  
Chronic myeloid leukemia  hsa05220+7046  
Colorectal cancer  hsa05210+7046  
Cytokine-cytokine receptor interaction  hsa04060+7046  
Endocytosis  hsa04144+7046  
HTLV-I infection  hsa05166+7046  
MAPK signaling pathway  hsa04010+7046  
Osteoclast differentiation  hsa04380+7046  
Pancreatic cancer  hsa05212+7046  
Pathways in cancer  hsa05200+7046  
TGF-beta signaling pathway  hsa04350+7046  
According to Reactome, this protein belongs to the following pathways:
Downregulation of TGF-beta receptor signaling  REACT_120727  
SMAD2/3 MH2 Domain Mutants in Cancer  REACT_169165  
SMAD2/3 Phosphorylation Motif Mutants in Cancer  REACT_169103  
TGF-beta receptor signaling activates SMADs  REACT_120850  
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)  REACT_120726  
TGFBR1 KD Mutants in Cancer  REACT_169263  
TGFBR1 LBD Mutants in Cancer  REACT_169445  
TGFBR2 Kinase Domain Mutants in Cancer  REACT_169440  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Differentiation  definition   [KW-0221]
Growth regulation  definition   [KW-0341]
Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: TGF_beta_receptor_1
GenomeRNAi: 7046
PRO: PR:P36897
Chemistry
GuidetoPHARMACOLOGY: 1788