P36897

Background

Protein Name
TGF-beta receptor type-1
Gene Name
TGFBR1
Organism
Homo sapiens

Annotations

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.

Mapping Statistics

Site
Maximum Consensus Site Population
Minimum Consensus Site Population
Median Consensus Site Population
EDI 17 2 14.0
MT3 15 2 4.5
PIF 4 4 4.0
ATP 28 1 14.5
DRS 10 2 3.0
AAS 20 1 8.0
MPP 18 2 8.0
DFG 17 2 5.5
LBP 15 2 10.0
CMP 8 8 8.0
PDIG 14 10 11.5

Mapping Results

PDB ID
Maximum Consensus Site Population
EDI site
MT3 site
PIF site
ATP site
DEF site
DRS site
AAS site
MPP site
DFG site
LBP site
CMP site
PDIG site
PMP site
Total Druggable Structures per Site 4 0 0 25 0 0 1 2 2 0 0 0 0
1B6C 17 0 0 28 0 0 12 0 11 2 0 0 0
1IAS 0 0 0 18 0 0 14 0 9 11 0 0 0
1PY5 0 3 0 21 0 0 8 0 3 0 0 0 0
1RW8 0 0 0 18 0 0 10 0 7 0 0 0 0
1VJY 2 4 0 18 0 2 7 0 3 9 0 0 0
2WOT 0 13 0 16 0 0 11 0 0 12 0 0 0
2WOU 14 9 0 16 0 0 6 0 3 9 0 0 0
2X7O 16 0 0 17 0 0 8 0 3 13 0 14 0
3FAA 13 15 4 18 0 4 15 0 2 15 8 0 0
3GXL 0 4 0 16 0 0 8 0 3 10 0 0 0
3HMM 0 2 0 17 0 2 20 0 4 8 0 0 0
3KCF 14 0 0 18 0 10 14 0 12 12 0 0 0
3TZM 12 0 0 17 0 0 11 0 4 8 0 0 0
4X0M 16 0 0 18 0 0 6 0 0 10 0 0 0
4X2F 0 0 0 18 0 0 6 0 0 13 0 0 0
4X2G 0 0 0 16 0 0 8 0 3 13 0 0 0
4X2J 0 0 0 18 0 0 8 0 0 12 0 0 0
4X2K 0 0 0 18 0 0 8 0 0 12 0 0 0
4X2N 15 0 0 20 0 5 8 0 0 10 0 0 0
5E8S 0 0 0 18 0 0 6 0 0 7 0 0 0
5E8T 16 5 0 13 0 0 6 17 0 13 0 0 0
5E8U 12 5 0 18 0 0 15 8 17 10 0 0 0
5E8W 13 0 0 24 0 0 13 7 0 10 0 0 0
5E8X 13 10 0 17 0 0 11 8 16 3 0 0 0
5E8Z 0 5 0 18 0 0 10 9 0 12 0 0 0
5FRI 14 0 0 18 0 0 6 0 6 12 0 0 0
5E90 14 0 0 13 0 0 12 15 15 10 0 0 0
AFP36897 0 0 0 0 0 0 0 18 15 0 0 0 0