Tchem TGFBR1 TGF-beta receptor type-1

Protein Summary

Description

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. The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Uniprot Accession IDs

• P36897
• Q6IR47
• Q706C0
• Q706C1
• TGFR-1

Gene Name

• TGFBR1

Ensembl ID

• ENST00000374990
• ENSP00000364129
• ENSG00000106799
• ENST00000374994
• ENSP00000364133
• ENST00000552516
• ENSP00000447297

Symbol

• ALK5
• SKR4
• AAT5
• ALK5
• ESS1
• LDS1
• MSSE
• SKR4
• TBRI
• ALK-5
• LDS1A
• LDS2A
• TBR-i
• TGFR-1
• ACVRLK4
• tbetaR-I

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	1
protein domain	0.92
microRNA	0.88

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Serine/threonine Protein Kinase Receptor / Tgf-beta Receptor Type-1

Protein / Receptor / Protein Kinase Receptor / Serine/threonine Protein Kinase Receptor / Tgf-beta Receptor Type-1

Protein / Receptor / Cytokine Receptor / Tgf-beta Receptor / Tgf-beta Receptor Type-1

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Stkr Family / Stkr Type 1 Subfamily / Tgf-beta Receptor Type-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1387.93   (req: < 5)

Gene RIFs: 365   (req: <= 3)

Antibodies: 551   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1387.93   (req: >= 5)

Gene RIFs: 365   (req: > 3)

Antibodies: 551   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 86

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 463

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0