[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-439.
TISSUE=Liver;
DOI=10.1016/0092-8674(92)90152-3; PubMed=1310899 [NCBI, ExPASy, EBI, Israel, Japan]
Lin H.Y.,
Wang X.-F.,
Ng-Eaton E.,
Weinberg R.A.,
Lodish H.F.;
"Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase.";
Cell 68:775-785(1992).
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[2]
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ERRATUM.
PubMed=1525823 [NCBI, ExPASy, EBI, Israel, Japan]
Lin H.Y.,
Wang X.-F.,
Ng-Eaton E.,
Weinberg R.A.,
Lodish H.F.;
Cell 70:1069-1069(1992).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Glial cell;
DOI=10.1016/0378-1119(94)90178-3; PubMed=7959019 [NCBI, ExPASy, EBI, Israel, Japan]
Nikawa J.;
"A cDNA encoding the human transforming growth factor beta receptor suppresses the growth defect of a yeast mutant.";
Gene 149:367-372(1994).
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[4]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ALA-439.
DOI=10.1006/geno.1996.0471; PubMed=8812462 [NCBI, ExPASy, EBI, Israel, Japan]
Takenoshita S.,
Hagiwara K.,
Nagashima M.,
Gemma A.,
Bennett W.P.,
Harris C.C.;
"The genomic structure of the gene encoding the human transforming growth factor beta type II receptor (TGF-beta RII).";
Genomics 36:341-344(1996).
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[5]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ALA-439.
PubMed=8840968 [NCBI, ExPASy, EBI, Israel, Japan]
Lu S.-L.,
Zhang W.C.,
Akiyama Y.,
Nomizu T.,
Yuasa Y.;
"Genomic structure of the transforming growth factor beta type II receptor gene and its mutations in hereditary nonpolyposis colorectal cancers.";
Cancer Res. 56:4595-4598(1996).
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[6]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-439.
TISSUE=Liver;
DOI=10.1016/S0378-1119(96)00501-X; PubMed=8973329 [NCBI, ExPASy, EBI, Israel, Japan]
Ogasa H.,
Noma T.,
Murata H.,
Kawai S.,
Nakazawa A.;
"Cloning of a cDNA encoding the human transforming growth factor-beta type II receptor: heterogeneity of the mRNA.";
Gene 181:185-190(1996).
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[7]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-36.
Livingston R.J.,
Rieder M.J.,
Chung M.-W.,
Ritchie T.K.,
Olson A.N.,
Nguyen C.P.,
Nguyen D.A.,
Poel C.L.,
Chambers S.W.,
Schackwitz W.S.,
Sherwood J.K.,
Sherwood A.M.,
Leithauser B.J.,
Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
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[8]
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PROTEIN SEQUENCE OF 23-37.
DOI=10.1110/ps.04682504; PubMed=15340161 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Z.,
Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
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[9]
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INTERACTION WITH DAXX, AND MUTAGENESIS OF LYS-277.
DOI=10.1038/35087019; PubMed=11483955 [NCBI, ExPASy, EBI, Israel, Japan]
Perlman R.,
Schiemann W.P.,
Brooks M.W.,
Lodish H.F.,
Weinberg R.A.;
"TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.";
Nat. Cell Biol. 3:708-714(2001).
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[10]
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PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V.,
Blagoev B.,
Gnad F.,
Macek B.,
Kumar C.,
Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
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[11]
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INTERACTION WITH TCTEX1D4.
DOI=10.1074/jbc.M608614200; PubMed=16982625 [NCBI, ExPASy, EBI, Israel, Japan]
Meng Q.-J.,
Lux A.,
Holloschi A.,
Li J.,
Hughes J.M.X.,
Foerg T.,
McCarthy J.E.G.,
Heagerty A.M.,
Kioschis P.,
Hafner M.,
Garland J.M.;
"Identification of Tctex2beta, a novel dynein light chain family member that interacts with different transforming growth factor-beta receptors.";
J. Biol. Chem. 281:37069-37080(2006).
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[12]
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X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 38-159 IN COMPLEX WITH TGF-BETA3.
DOI=10.1038/nsb766; PubMed=11850637 [NCBI, ExPASy, EBI, Israel, Japan]
Hart P.J.,
Deep S.,
Taylor A.B.,
Shu Z.,
Hinck C.S.,
Hinck A.P.;
"Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.";
Nat. Struct. Biol. 9:203-208(2002).
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[13]
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X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 49-159.
DOI=10.1016/S0969-2126(02)00780-3; PubMed=12121646 [NCBI, ExPASy, EBI, Israel, Japan]
Boesen C.C.,
Radaev S.,
Motyka S.A.,
Patamawenu A.,
Sun P.D.;
"The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain.";
Structure 10:913-919(2002).
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[14]
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STRUCTURE BY NMR OF 38-159.
DOI=10.1021/bi034366a; PubMed=12939140 [NCBI, ExPASy, EBI, Israel, Japan]
Deep S.,
Walker K.P. III,
Shu Z.,
Hinck A.P.;
"Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain.";
Biochemistry 42:10126-10139(2003).
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[15]
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VARIANT HNPCC6 MET-315.
PubMed=9590282 [NCBI, ExPASy, EBI, Israel, Japan]
Lu S.-L.,
Kawabata M.,
Imamura T.,
Akiyama Y.,
Nomizu T.,
Miyazono K.,
Yuasa Y.;
"HNPCC associated with germline mutation in the TGF-beta type II receptor gene.";
Nat. Genet. 19:17-18(1998).
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[16]
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VARIANT ESOPHAGEAL CANCER GLN-526.
DOI=10.1054/bjoc.1999.1178; PubMed=10789724 [NCBI, ExPASy, EBI, Israel, Japan]
Tanaka S.,
Mori M.,
Mafune K.,
Ohno S.,
Sugimachi K.;
"A dominant negative mutation of transforming growth factor-beta receptor type II gene in microsatellite stable oesophageal carcinoma.";
Br. J. Cancer 82:1557-1560(2000).
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[17]
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VARIANTS BREAST TUMOR MET-387; SER-435; ALA-447 AND MET-452, AND CHARACTERIZATION OF VARIANTS BREAST TUMOR SER-435; ALA-447 AND MET-452.
PubMed=11212236 [NCBI, ExPASy, EBI, Israel, Japan]
Luecke C.D.,
Philpott A.,
Metcalfe J.C.,
Thompson A.M.,
Hughes-Davies L.,
Kemp P.R.,
Hesketh R.;
"Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer.";
Cancer Res. 61:482-485(2001).
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[18]
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VARIANT ILE-191.
DOI=10.1007/s100380200069; PubMed=12202987 [NCBI, ExPASy, EBI, Israel, Japan]
Watanabe Y.,
Kinoshita A.,
Yamada T.,
Ohta T.,
Kishino T.,
Matsumoto N.,
Ishikawa M.,
Niikawa N.,
Yoshiura K.;
"A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway.";
J. Hum. Genet. 47:478-483(2002).
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[19]
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VARIANTS LDS2B PRO-308; PHE-449 AND CYS-537, AND CHARACTERIZATION OF VARIANTS LDS2B PRO-308; PHE-449 AND CYS-537.
DOI=10.1038/ng1392; PubMed=15235604 [NCBI, ExPASy, EBI, Israel, Japan]
Mizuguchi T.,
Collod-Beroud G.,
Akiyama T.,
Abifadel M.,
Harada N.,
Morisaki T.,
Allard D.,
Varret M.,
Claustres M.,
Morisaki H.,
Ihara M.,
Kinoshita A.,
Yoshiura K.,
Junien C.,
Kajii T.,
Jondeau G.,
Ohta T.,
Kishino T.,
Furukawa Y., ![]()
Nakamura Y.,
Niikawa N.,
Boileau C.,
Matsumoto N.;
"Heterozygous TGFBR2 mutations in Marfan syndrome.";
Nat. Genet. 36:855-860(2004).
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[20]
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VARIANTS AAT3 CYS-460 AND HIS-460.
DOI=10.1161/CIRCULATIONAHA.105.537340; PubMed=16027248 [NCBI, ExPASy, EBI, Israel, Japan]
Pannu H.,
Fadulu V.T.,
Chang J.,
Lafont A.,
Hasham S.N.,
Sparks E.,
Giampietro P.F.,
Zaleski C.,
Estrera A.L.,
Safi H.J.,
Shete S.,
Willing M.C.,
Raman C.S.,
Milewicz D.M.;
"Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections.";
Circulation 112:513-520(2005).
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[21]
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VARIANTS LDS1B ASN-336; PRO-355; TRP-357; HIS-528 AND CYS-528.
DOI=10.1038/ng1511; PubMed=15731757 [NCBI, ExPASy, EBI, Israel, Japan]
Loeys B.L.,
Chen J.,
Neptune E.R.,
Judge D.P.,
Podowski M.,
Holm T.,
Meyers J.,
Leitch C.C.,
Katsanis N.,
Sharifi N.,
Xu F.L.,
Myers L.A.,
Spevak P.J.,
Cameron D.E.,
De Backer J.F.,
Hellemans J.,
Chen Y.,
Davis E.C.,
Webb C.L., ![]()
Kress W.,
Coucke P.J.,
Rifkin D.B.,
De Paepe A.M.,
Dietz H.C.;
"A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.";
Nat. Genet. 37:275-281(2005).
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[22]
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VARIANTS [LARGE SCALE ANALYSIS] VAL-73 AND HIS-528.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T.,
Jones S.,
Wood L.D.,
Parsons D.W.,
Lin J.,
Barber T.D.,
Mandelker D.,
Leary R.J.,
Ptak J.,
Silliman N.,
Szabo S.,
Buckhaults P.,
Farrell C.,
Meeh P.,
Markowitz S.D.,
Willis J.,
Dawson D.,
Willson J.K.V.,
Gazdar A.F., ![]()
Hartigan J.,
Wu L.,
Liu C.,
Parmigiani G.,
Park B.H.,
Bachman K.E.,
Papadopoulos N.,
Vogelstein B.,
Kinzler K.W.,
Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
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[23]
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VARIANTS [LARGE SCALE ANALYSIS] ARG-61; ILE-191; MET-315; TYR-328; ILE-373; MET-387 AND SER-490.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C.,
Stephens P.,
Smith R.,
Dalgliesh G.L.,
Hunter C.,
Bignell G.,
Davies H.,
Teague J.,
Butler A.,
Stevens C.,
Edkins S.,
O'Meara S.,
Vastrik I.,
Schmidt E.E.,
Avis T.,
Barthorpe S.,
Bhamra G.,
Buck G.,
Choudhury B., ![]()
Clements J.,
Cole J.,
Dicks E.,
Forbes S.,
Gray K.,
Halliday K.,
Harrison R.,
Hills K.,
Hinton J.,
Jenkinson A.,
Jones D.,
Menzies A.,
Mironenko T.,
Perry J.,
Raine K.,
Richardson D.,
Shepherd R.,
Small A.,
Tofts C.,
Varian J.,
Webb T.,
West S.,
Widaa S.,
Yates A.,
Cahill D.P.,
Louis D.N.,
Goldstraw P.,
Nicholson A.G.,
Brasseur F.,
Looijenga L.,
Weber B.L.,
Chiew Y.-E.,
DeFazio A.,
Greaves M.F.,
Green A.R.,
Campbell P.,
Birney E.,
Easton D.F.,
Chenevix-Trench G.,
Tan M.-H.,
Khoo S.K.,
Teh B.T.,
Yuen S.T.,
Leung S.Y.,
Wooster R.,
Futreal P.A.,
Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
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- FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta.
- CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
- COFACTOR: Magnesium or manganese (By similarity).
- SUBUNIT: Binds to DAXX. Interacts with TCTEX1D4.
- INTERACTION:
Q9UER7:DAXX; NbExp=1; IntAct=EBI-296151, EBI-77321;
O35613:Daxx (xeno); NbExp=1; IntAct=EBI-296151, EBI-77304;
P07200:TGFB1 (xeno); NbExp=1; IntAct=EBI-296151, EBI-907660;
P10600:TGFB3; NbExp=1; IntAct=EBI-296151, EBI-1033020;
- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
- ALTERNATIVE PRODUCTS:
2 named isoforms [FASTA] produced by alternative splicing.
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| Name | 2 |
| Isoform ID | P37173-2 |
| Features which should be applied to build the isoform sequence: VSP_012157. |
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- PTM: Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.
- DISEASE: Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:190182]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases.
- DISEASE: Defects in TGFBR2 are a cause of esophageal cancer [MIM:133239].
- DISEASE: Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:610168]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree.
- DISEASE: Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:610380]; formerly Marfan syndrome type 2. LDS2 is an aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients.
- DISEASE: Defects in TGFBR2 are the cause of aortic aneurysm familial thoracic type 3 (AAT3) [MIM:610380]. Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. AAT3 is an autosomal dominant disorder with reduced penetrance and variable expression.
- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
- SIMILARITY: Contains 1 protein kinase domain.
- WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=TGFBR2";.
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