TGF beta receptor 2

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Transforming growth factor beta receptor 2 ectodomain
Transforming growth factor beta receptor 2 ectodomain
	crystal structure of human tgf-beta type ii receptor ligand binding domain
Identifiers
Symbol	ecTbetaR2
Pfam	PF08917
InterPro	IPR015013
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

TGFBR2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1KTZ, 1M9Z, 1PLO, 2PJY, 3KFD, 4P7U, 4XJJ, 5E92, 5E91, 5E8V, 5E8Y
Identifiers
Aliases	TGFBR2, AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2, RIIC, TAAD2, TGFR-2, TGFbeta-RII, transforming growth factor beta receptor 2, TBR-ii, TBRII
External IDs	OMIM: 190182 MGI: 98729 HomoloGene: 2435 GeneCards: TGFBR2
Gene location (Human)
Chr.	Chromosome 3 (human)[1]
End	30,694,142 bp[1]
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)[2]
End	116,004,428 bp[2]
RNA expression pattern
	Top expressed in
	pericardium; ; tibia; ; parietal pleura; ; lower lobe of lung; ; visceral pleura; ; vena cava; ; superficial temporal artery; ; synovial joint; ; subcutaneous adipose tissue; ; cardia;
	Top expressed in
	left lung lobe; ; calvaria; ; lymph node; ; sciatic nerve; ; molar; ; right lung; ; stria vascularis; ; uterus; ; cervix; ; right lung lobe;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	transforming growth factor beta-activated receptor activity; kinase activity; ATP binding; type III transforming growth factor beta receptor binding; protein kinase activity; transforming growth factor beta receptor activity, type II; metal ion binding; protein serine/threonine kinase activity; transferase activity; type I transforming growth factor beta receptor binding; mitogen-activated protein kinase kinase kinase binding; protein binding; SMAD binding; nucleotide binding; glycosaminoglycan binding; transforming growth factor beta binding; transmembrane receptor protein serine/threonine kinase activity; signaling receptor activity; growth factor binding;
Cellular component	cytoplasm; cytosol; membrane; caveola; cell surface; membrane raft; integral component of membrane; receptor complex; plasma membrane; integral component of plasma membrane; external side of plasma membrane;
Biological process	growth plate cartilage development; response to cholesterol; lens fiber cell apoptotic process; response to steroid hormone; positive regulation of T cell tolerance induction; receptor-mediated endocytosis; response to organic substance; vasculogenesis; protein phosphorylation; positive regulation of B cell tolerance induction; positive regulation of reactive oxygen species metabolic process; blood vessel development; positive regulation of mesenchymal cell proliferation; animal organ regeneration; animal organ morphogenesis; transforming growth factor beta receptor signaling pathway; embryo implantation; negative regulation of cell population proliferation; apoptotic process; pathway-restricted SMAD protein phosphorylation; common-partner SMAD protein phosphorylation; bronchus morphogenesis; lung development; response to mechanical stimulus; positive regulation of epithelial cell migration; in utero embryonic development; negative regulation of transforming growth factor beta receptor signaling pathway; heart development; cartilage development; positive regulation of tolerance induction to self antigen; branching involved in blood vessel morphogenesis; positive regulation of skeletal muscle tissue regeneration; smoothened signaling pathway; negative regulation of cardiac muscle cell proliferation; Notch signaling pathway; cell differentiation; phosphorylation; response to nutrient; mammary gland morphogenesis; wound healing; response to glucose; positive regulation of epithelial to mesenchymal transition; positive regulation of angiogenesis; response to estrogen; gastrulation; regulation of gene expression; embryonic cranial skeleton morphogenesis; peptidyl-threonine phosphorylation; trachea formation; lung lobe morphogenesis; positive regulation of smooth muscle cell proliferation; lung morphogenesis; response to organic cyclic compound; trachea morphogenesis; human ageing; myeloid dendritic cell differentiation; bronchus development; brain development; transmembrane receptor protein serine/threonine kinase signaling pathway; lens development in camera-type eye; regulation of cell population proliferation; peptidyl-serine phosphorylation; positive regulation of cell population proliferation; embryonic hemopoiesis; growth plate cartilage chondrocyte growth; regulation of growth; positive regulation of NK T cell differentiation; digestive tract development; activation of protein kinase activity; response to hypoxia; heart looping; outflow tract septum morphogenesis; membranous septum morphogenesis; outflow tract morphogenesis; atrioventricular valve morphogenesis; tricuspid valve morphogenesis; cardiac left ventricle morphogenesis; endocardial cushion fusion; ventricular septum morphogenesis; positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; cell proliferation involved in endocardial cushion morphogenesis; positive regulation of CD4-positive, alpha-beta T cell proliferation; superior endocardial cushion morphogenesis; inferior endocardial cushion morphogenesis; miRNA transport; secondary palate development; pattern specification process;
	Sources:Amigo / QuickGO
Orthologs
	7048
	21813
	ENSG00000163513
	ENSMUSG00000032440
	P37173
	Q62312
	NM_001024847; NM_003242
	NM_009371; NM_029575
	NP_001020018; NP_003233
	NP_033397; NP_083851
	Wikidata
View/Edit Human	View/Edit Mouse

Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. TGFBR2 is its human gene.

It is a tumor suppressor gene.[5]

Function

This gene encodes a member of the serine/threonine protein kinase family and the TGFB receptor subfamily. The encoded protein is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with another receptor protein, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of a subset of genes related to cell proliferation. Mutations in this gene have been associated with Marfan syndrome, Loeys-Deitz aortic aneurysm syndrome, Osler–Weber–Rendu syndrome, and the development of various types of tumors. At least 73 disease-causing mutations in this gene have been discovered.[6] Alternatively spliced transcript variants encoding different isoforms have been characterized.[7]

Interactions

TGF beta receptor 2 has been shown to interact with:

Domain architecture

TGF beta receptor 2 consists of a C-terminal protein kinase domain and an N-terminal ectodomain. The ectodomain consists of a compact fold containing nine beta-strands and a single helix stabilised by a network of six intra strand disulphide bonds. The folding topology includes a central five-stranded antiparallel beta-sheet, eight-residues long at its centre, covered by a second layer consisting of two segments of two-stranded antiparallel beta-sheets (beta1-beta4, beta3-beta9).[18]

References

GRCh38: Ensembl release 89: ENSG00000163513 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000032440 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"TGFBR2 - transforming growth factor, beta receptor II (70/80kDa) - Genetics Home Reference". Archived from the original on 2011-08-10. Retrieved 2008-09-07.
Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.
"Entrez Gene: TGFBR2 transforming growth factor, beta receptor II (70/80kDa)".
Yao D, Ehrlich M, Henis YI, Leof EB (Nov 2002). "Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit". Molecular Biology of the Cell. 13 (11): 4001–12. doi:10.1091/mbc.02-07-0104. PMC 133610. PMID 12429842.
Liu JH, Wei S, Burnette PK, Gamero AM, Hutton M, Djeu JY (Jan 1999). "Functional association of TGF-beta receptor II with cyclin B". Oncogene. 18 (1): 269–75. doi:10.1038/sj.onc.1202263. PMID 9926943.
Barbara NP, Wrana JL, Letarte M (Jan 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry. 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.
Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C (Aug 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". The Journal of Biological Chemistry. 277 (32): 29197–209. doi:10.1074/jbc.M111991200. PMID 12015308.
Wrighton KH, Lin X, Feng XH (Jul 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proceedings of the National Academy of Sciences of the United States of America. 105 (27): 9244–9. Bibcode:2008PNAS..105.9244W. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668.
Datta PK, Chytil A, Gorska AE, Moses HL (Dec 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. PMID 9856985.
Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–67. doi:10.1128/mcb.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
Kawabata M, Chytil A, Moses HL (Mar 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". The Journal of Biological Chemistry. 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. PMID 7890683.
Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (Mar 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry. 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.
De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD (May 2003). "Transforming growth factor-beta (TGF-beta) binding to the extracellular domain of the type II TGF-beta receptor: receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding". Journal of Molecular Biology. 328 (5): 1173–83. doi:10.1016/s0022-2836(03)00360-7. PMID 12729750.
Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (Mar 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology. 9 (3): 203–8. doi:10.1038/nsb766. PMID 11850637. S2CID 13322593.
Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P (Feb 2001). "Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor". The EMBO Journal. 20 (3): 480–90. doi:10.1093/emboj/20.3.480. PMC 133482. PMID 11157754.

External links

GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections

This article incorporates text from the public domain Pfam and InterPro: IPR015013

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000163513 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032440 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[urlTGFBR2_-_transforming_growth_factor,_beta_receptor_II_(70/80kDa)_-_Genetics_Home_Reference-5] "TGFBR2 - transforming growth factor, beta receptor II (70/80kDa) - Genetics Home Reference". Archived from the original on 2011-08-10. Retrieved 2008-09-07.

[Šimčíková_2019_-_supplementary_table_S7-6] Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.

[7] "Entrez Gene: TGFBR2 transforming growth factor, beta receptor II (70/80kDa)".

[pmid12429842-8] Yao D, Ehrlich M, Henis YI, Leof EB (Nov 2002). "Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit". Molecular Biology of the Cell. 13 (11): 4001–12. doi:10.1091/mbc.02-07-0104. PMC 133610. PMID 12429842.

[pmid9926943-9] Liu JH, Wei S, Burnette PK, Gamero AM, Hutton M, Djeu JY (Jan 1999). "Functional association of TGF-beta receptor II with cyclin B". Oncogene. 18 (1): 269–75. doi:10.1038/sj.onc.1202263. PMID 9926943.

[pmid9872992-10] Barbara NP, Wrana JL, Letarte M (Jan 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry. 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.

[pmid12015308-11] Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C (Aug 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". The Journal of Biological Chemistry. 277 (32): 29197–209. doi:10.1074/jbc.M111991200. PMID 12015308.

[pmid18591668-12] Wrighton KH, Lin X, Feng XH (Jul 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proceedings of the National Academy of Sciences of the United States of America. 105 (27): 9244–9. Bibcode:2008PNAS..105.9244W. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668.

[pmid9856985-13] Datta PK, Chytil A, Gorska AE, Moses HL (Dec 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. PMID 9856985.

[pmid10757800-14] Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–67. doi:10.1128/mcb.20.9.3157-3167.2000. PMC 85610. PMID 10757800.

[pmid7890683-15] Kawabata M, Chytil A, Moses HL (Mar 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". The Journal of Biological Chemistry. 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. PMID 7890683.

[pmid11102446-16] Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (Mar 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry. 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.

[pmid12729750-17] De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD (May 2003). "Transforming growth factor-beta (TGF-beta) binding to the extracellular domain of the type II TGF-beta receptor: receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding". Journal of Molecular Biology. 328 (5): 1173–83. doi:10.1016/s0022-2836(03)00360-7. PMID 12729750.

[pmid11850637-18] Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (Mar 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology. 9 (3): 203–8. doi:10.1038/nsb766. PMID 11850637. S2CID 13322593.

[pmid11157754-19] Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P (Feb 2001). "Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor". The EMBO Journal. 20 (3): 480–90. doi:10.1093/emboj/20.3.480. PMC 133482. PMID 11157754.