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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1 246 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.  
7
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAHGNC
Contributes to growth factor bindingdefinition[GO:0019838]  
1
  • IPIHGNC
I-SMAD bindingdefinition[GO:0070411]  
1
  • IPIBHF-UCL
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
16
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
  • IPIHGNC
Protein kinase activitydefinition[GO:0004672]  
1
  • IDABHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDABHF-UCL
  • IDAHGNC
Receptor signaling protein serine/threonine kinase activitydefinition[GO:0004702] silver  
  • IEAInterPro 2 GO
SMAD bindingdefinition[GO:0046332]  
4
  • IDABHF-UCL
  • IDAHGNC
Contributes to transforming growth factor beta bindingdefinition[GO:0050431]  
4
  • IDAHGNC
  • IDABHF-UCL
Transforming growth factor beta receptor activity, type Idefinition[GO:0005025]  
1
  • IDABHF-UCL
Contributes to transforming growth factor beta-activated receptor activitydefinition[GO:0005024]  
5
  • IMPBHF-UCL
  • IDAHGNC
Type II transforming growth factor beta receptor bindingdefinition[GO:0005114]  
2
  • IDABHF-UCL
GO biological process 
Activation of MAPKK activitydefinition[GO:0000186]  
1
  • IDABHF-UCL
Angiogenesisdefinition[GO:0001525] silver  
  • IEAOrtholog Compara
Anterior/posterior pattern specificationdefinition[GO:0009952]  
  • ISSOrtholog Curator
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Artery morphogenesisdefinition[GO:0048844]  
  • ISSOrtholog Curator
Blastocyst developmentdefinition[GO:0001824] silver  
  • IEAOrtholog Compara
Cell cycle arrestdefinition[GO:0007050]  
1
  • TASUniProtKB
Cell motilitydefinition[GO:0048870]  
1
  • IMPBHF-UCL
Cellular response to transforming growth factor beta stimulusdefinition[GO:0071560]  
1
  • IDABHF-UCL
Collagen fibril organizationdefinition[GO:0030199]  
  • ISSOrtholog Curator
Embryonic cranial skeleton morphogenesisdefinition[GO:0048701]  
  • ISSOrtholog Curator
Endothelial cell migrationdefinition[GO:0043542] silver  
  • IEAOrtholog Compara
Epithelial to mesenchymal transitiondefinition[GO:0001837]  
1
  • IDAUniProtKB
Extracellular structure organizationdefinition[GO:0043062]  
1
  • TASUniProtKB
Germ cell migrationdefinition[GO:0008354]  
  • ISSOrtholog Curator
Heart developmentdefinition[GO:0007507]  
  • ISSOrtholog Curator
In utero embryonic developmentdefinition[GO:0001701]  
  • ISSOrtholog Curator
Kidney developmentdefinition[GO:0001822]  
  • ISSOrtholog Curator
Lens development in camera-type eyedefinition[GO:0002088] silver  
  • IEAOrtholog Compara
Mesenchymal cell differentiationdefinition[GO:0048762]  
1
  • TASUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066] silver  
  • IEAOrtholog Compara
Negative regulation of chondrocyte differentiationdefinition[GO:0032331]  
  • ISSOrtholog Curator
Negative regulation of endothelial cell proliferationdefinition[GO:0001937] silver  
  • IEAOrtholog Compara
Negative regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001237]  
1
  • IMPBHF-UCL
Neuron fate commitmentdefinition[GO:0048663]  
  • ISSOrtholog Curator
Palate developmentdefinition[GO:0060021]  
  • ISSOrtholog Curator
Parathyroid gland developmentdefinition[GO:0060017]  
  • ISSOrtholog Curator
Pathway-restricted SMAD protein phosphorylationdefinition[GO:0060389]  
4
  • IDABHF-UCL
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDAUniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • IDABHF-UCL
Pharyngeal system developmentdefinition[GO:0060037]  
  • ISSOrtholog Curator
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235]  
1
  • IDAUniProtKB
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • IDABHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • IMPHGNC
Positive regulation of cellular component movementdefinition[GO:0051272]  
1
  • IMPBHF-UCL
Positive regulation of filopodium assemblydefinition[GO:0051491] silver  
  • IEAOrtholog Compara
Positive regulation of pathway-restricted SMAD protein phosphorylationdefinition[GO:0010862]  
2
  • IDABHF-UCL
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • IDABHF-UCL
Positive regulation of SMAD protein import into nucleusdefinition[GO:0060391]  
1
  • IDABHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
2
  • IDABHF-UCL
Post-embryonic developmentdefinition[GO:0009791] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
2
  • IDABHF-UCL
  • IDAHGNC
Regulation of protein bindingdefinition[GO:0043393] silver  
  • IEAOrtholog Compara
Regulation of protein ubiquitinationdefinition[GO:0031396]  
1
  • IDAUniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
2
  • IMPHGNC
Response to cholesteroldefinition[GO:0070723]  
1
  • IDABHF-UCL
Signal transductiondefinition[GO:0007165]  
1
  • IDAHGNC
Signal transduction by phosphorylationdefinition[GO:0023014]  
  • IEAInterPro 2 GO
Skeletal system developmentdefinition[GO:0001501]  
  • ISSOrtholog Curator
Skeletal system morphogenesisdefinition[GO:0048705]  
  • ISSOrtholog Curator
Thymus developmentdefinition[GO:0048538]  
  • ISSOrtholog Curator
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179]  
4
  • IDABHF-UCL
Wound healingdefinition[GO:0042060]  
1
  • TASUniProtKB
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.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium or manganese (By similarity).  
  • CuratedUniProtKB
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.  
1
  • CuratedUniProtKB
 
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