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Protein / target

TGF-beta receptor type-2

Encoded byTGFBR2P37173Homo sapiensSwiss-Prot
UniProt: P37173Ensembl: ENSG00000163513HGNC: HGNC:11773NCBI Gene: 7048
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Transmembrane receptor protein serine/threonine kinase

Strongest disease association

Esophageal Neoplasms

Via encoding gene TGFBR2 · Genetic evidence · score 0.85

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 I serine/threonine kinase receptor, TGFBR1, 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 I serine/threonine kinase receptor, TGFBR1, 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 thus regulates 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 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

Subcellular location

Cell membraneMembrane raftSecreted
Domains and Gene Ontology detail (72)

Domains & features

Protein kinase

Gene Ontology

  • Cactivin receptor complex
  • Ccaveola
  • Ccytosol
  • Cexternal side of plasma membrane
  • Cextracellular region
  • Cextracellular space
  • Cmembrane
  • Cmembrane raft
  • Cplasma membrane
  • Creceptor complex
  • Factivin binding
  • Factivin receptor activity, type I

567 aa · 65 kDa · 3 isoforms

Biological roles

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

Cell proliferation & survivalGOCell-cycle regulationUniProtLipid & lipoprotein metabolismGOImmune signallingUniProt · GOKinase signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation
  • ·regulation of cell population proliferation

Cell-cycle regulation

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

Lipid & lipoprotein metabolism

  • ·response to cholesterol

Immune signalling

  • ·Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine…
  • ·positive regulation of B cell tolerance induction
  • ·positive regulation of CD4-positive, alpha-beta T cell proliferation
  • ·positive regulation of NK T cell differentiation

Kinase signalling

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

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 TGFBR2

Gene-level evidence surfaced through the gene TGFBR2 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.

Esophageal Neoplasms
0.90Well supported

Genetic evidence dominant · Open Targets 0.66

Neoplasms
0.42Preliminary

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

Neurodegenerative Diseases
0.38Preliminary

Pathway evidence dominant · Open Targets 0.57 · no direct causal or clinical evidence

View evidence synthesis (3)
Esophageal NeoplasmsWell supported
0.90
agreement 0.79–1.00
Genetic72%Somatic mutation27%Literature1%Genetic literaturedup

Open Targets aggregate 0.66 · 3 independent evidence families · 1 not counted as duplicate

NeoplasmsPreliminary
0.42
agreement 0.24–0.60
Pathway75%Literature25%

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

Neurodegenerative DiseasesPreliminary
0.38
agreement 0.20–0.56
Pathway99%Literature1%

Open Targets aggregate 0.57 · 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
Esophageal Neoplasms0.66
Neurodegenerative Diseases0.57
Neoplasms0.55

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

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 (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

diarrheaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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

Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.39 cites

Wang L · Molecular neurodegeneration · 2024

Recent

Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.

Wang L · Molecular neurodegeneration · 2024

Europe PMC papers linked directly to this protein.