Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TGFBR2 (P37173) - Overview - Molecular Target Synopsis

Protein


TGFBR2, TGF-beta receptor type-2
Enzyme Classification 2.7.11.30
UniProt P37173

Also Known as TGFR2_HUMAN, TGFBR2

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 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 TGFRB1 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. Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with DAXX. Interacts with TCTEX1D4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta.

5QIN
TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN IN COMPLEX WITH N- {4-[3-(6- METHOXYPYRIDIN-3-YL)-1H-PYRROLO[3,2-B]PYRIDIN-2- YL]PYRIDIN-2- YL}ACETAMIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for TGFBR2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
592ENSG00000163513ENST00000359013ENSP00000351905P37173-2
567ENSG00000163513ENST00000295754ENSP00000295754P37173-1

Sub-cellular localization


UniProt: TGFBR2 is active in the following subcellular-locations: cell membrane, membrane raft.
GO terms: TGFBR2 is active in the following subcellular-locations: caveola, cytosol, external side of plasma membrane, integral component of membrane, integral component of plasma membrane, membrane raft, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TGFBR2 has gain in 1 cell-lines, loss in 6 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: LOXIMVI, HCC_2998, IGROV1

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Panc 05.04, LOX-IMVI, HEY

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, HMEC, NHLF

(see details)

RNA Interference


TGFBR2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: BXPC3, SKGT4. (see details)

3D Structures


For TGFBR2 there are:
14 structures (17 chains) solved
6 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TGFBR2 has been screened with 202 compounds (302 bioactivities), 23 compounds have bioactivities that show binding affinity of <= 500nM (24 bioactivities). (see details)