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Protein / target

TGF-beta receptor type-1

Encoded byTGFBR1P36897Homo sapiensSwiss-Prot
UniProt: P36897Ensembl: ENSG00000106799HGNC: HGNC:11772NCBI Gene: 7046
Clinical-stage
Therapeutic maturity
2
Clinical candidates
Small-molecule tractable
Druggability
Advanced Clinical
1
Research papers

Protein at a glance

Biological role

Transmembrane receptor protein serine/threonine kinase

Strongest disease association

Neoplasms

Via encoding gene TGFBR1 · Pathway evidence · score 0.55

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function 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.

View complete UniProt function annotation

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 (PubMed:33914044). 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

Subcellular location

Cell membraneCell junction, tight junctionCell surfaceMembrane raft
Domains and Gene Ontology detail (91)

Domains & features

GSProtein kinase

Gene Ontology

  • Cactivin receptor complex
  • Cbicellular tight junction
  • Ccell surface
  • Cendosome
  • Cmembrane
  • Cmembrane raft
  • Cnucleus
  • Cplasma membrane
  • Creceptor complex
  • Factivin binding
  • Factivin receptor activity, type I
  • FATP binding

503 aa · 56 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationGOCell proliferation & survivalGOCell-cycle regulationUniProtLipid & lipoprotein metabolismGOKinase signallingUniProt · GOCell adhesionUniProt · GO
View supporting evidence

Cell migration

  • ·cell motility
  • ·germ cell migration
  • ·negative regulation of cell migration
  • ·positive regulation of cell migration

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Cell-cycle regulation

  • ·Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine…

Lipid & lipoprotein metabolism

  • ·response to cholesterol

Kinase signalling

  • ·Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine…
  • ·protein kinase activity
  • ·protein serine/threonine kinase activity
  • ·transmembrane receptor protein serine/threonine kinase activity

Cell adhesion

  • ·Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine…
  • ·Cell junction, tight junction
  • ·bicellular tight junction
  • ·positive regulation of extracellular matrix assembly

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TGFBR1

Gene-level evidence surfaced through the gene TGFBR1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.43Preliminary

Pathway evidence dominant · Open Targets 0.55 · no direct causal or clinical evidence

Alzheimer's Disease
0.38Preliminary

Pathway evidence dominant · Open Targets 0.48 · no direct causal or clinical evidence

Parkinson's Disease
0.31Preliminary

Pathway evidence dominant · Open Targets 0.46 · no direct causal or clinical evidence

Multiple Sclerosis
0.30Preliminary

Pathway evidence dominant · Open Targets 0.45 · no direct causal or clinical evidence

Neurodegenerative Diseases
0.30Preliminary

Pathway evidence dominant · Open Targets 0.45 · no direct causal or clinical evidence

View evidence synthesis (5)
NeoplasmsPreliminary
0.43
agreement 0.25–0.61
Pathway73%Literature27%

Open Targets aggregate 0.55 · 2 independent evidence families · no direct causal or clinical evidence

Alzheimer's DiseasePreliminary
0.38
agreement 0.23–0.52
Pathway73%Literature25%RNA expression2%

Open Targets aggregate 0.48 · 3 independent evidence families · no direct causal or clinical evidence

Parkinson's DiseasePreliminary
0.31
agreement 0.13–0.48
Pathway96%Literature4%

Open Targets aggregate 0.46 · 2 independent evidence families · no direct causal or clinical evidence

Multiple SclerosisPreliminary
0.30
agreement 0.12–0.48
Pathway99%Literature1%

Open Targets aggregate 0.45 · 2 independent evidence families · no direct causal or clinical evidence

Neurodegenerative DiseasesPreliminary
0.30
agreement 0.12–0.48
Pathway99%Literature1%

Open Targets aggregate 0.45 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neoplasms0.55
Alzheimer's Disease0.48
Parkinson's Disease0.46
Multiple Sclerosis0.45
Neurodegenerative Diseases0.45

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (2)
GALUNISERTIBPhase 2 3
VACTOSERTIBPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (14)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.7 cites

Kim NH · Cancer immunology, immunotherapy : CII · 2024

Recent

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.

Kim NH · Cancer immunology, immunotherapy : CII · 2024

Europe PMC papers linked directly to this protein.