ID:TGFR2_HUMAN DESCRIPTION: RecName: Full=TGF-beta receptor type-2; Short=TGFR-2; EC=2.7.11.30; AltName: Full=TGF-beta type II receptor; AltName: Full=Transforming growth factor-beta receptor type II; Short=TGF-beta receptor type II; Short=TbetaR-II; Flags: Precursor; FUNCTION: 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. CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- protein] phosphate. COFACTOR: Magnesium or manganese (By similarity). SUBUNIT: 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. INTERACTION: Q9UER7:DAXX; NbExp=2; IntAct=EBI-296151, EBI-77321; Q8IX30:SCUBE3; NbExp=6; IntAct=EBI-296151, EBI-4479975; P01137:TGFB1; NbExp=4; IntAct=EBI-296151, EBI-779636; P07200:TGFB1 (xeno); NbExp=2; IntAct=EBI-296151, EBI-907660; SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. 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:614331]. 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 (ESCR) [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]. 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. Note=TGFBR2 mutations Cys-460 and His- 460 have been reported to be associated with thoracic aortic aneurysms and dissection (TAAD). This phenotype, also known as thoracic aortic aneurysms type 3 (AAT3), is distinguised from LDS2B by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit descending aortic disease and aneurysms of other arteries (PubMed:16027248), they have been considered as LDS2B by the OMIM resource. 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.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TGFBR2"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/tgfbr2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P37173
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KJ901792 - Synthetic construct Homo sapiens clone ccsbBroadEn_11186 TGFBR2 gene, encodes complete protein. KJ905329 - Synthetic construct Homo sapiens clone ccsbBroadEn_14862 TGFBR2 gene, encodes complete protein. KR710922 - Synthetic construct Homo sapiens clone CCSBHm_00018177 TGFBR2 (TGFBR2) mRNA, encodes complete protein. KR710923 - Synthetic construct Homo sapiens clone CCSBHm_00018180 TGFBR2 (TGFBR2) mRNA, encodes complete protein. BC040499 - Homo sapiens transforming growth factor, beta receptor II (70/80kDa), mRNA (cDNA clone IMAGE:5287742). LQ499612 - Sequence 3 from Patent WO2016075339. MA129583 - JP 2018501816-A/3: Antisense-Oligonucleotides as Inhibitors of TGF-R signaling. M85079 - Human TGF-beta type II receptor mRNA, complete cds. AK314102 - Homo sapiens cDNA, FLJ94789, highly similar to Homo sapiens transforming growth factor, beta receptor II(70/80kDa) (TGFBR2), mRNA. AK300383 - Homo sapiens cDNA FLJ53920 complete cds, highly similar to TGF-beta receptor type-2 precursor (EC 2.7.11.30). D50683 - Homo sapiens mRNA for TGF-betaIIR alpha, complete cds. KC792576 - Homo sapiens transforming growth factor, beta receptor II alpha (TGFBR2) mRNA, complete cds, alternatively spliced. KC792577 - Homo sapiens transforming growth factor, beta receptor II beta (TGFBR2) mRNA, complete cds, alternatively spliced. KC792578 - Homo sapiens transforming growth factor, beta receptor II gamma (TGFBR2) mRNA, complete cds, alternatively spliced. KC792579 - Homo sapiens transforming growth factor, beta receptor II delta (TGFBR2) mRNA, complete cds, alternatively spliced. KC792580 - Homo sapiens transforming growth factor, beta receptor II epsilon (TGFBR2) mRNA, complete cds, alternatively spliced. E10743 - cDNA encoding human transforming growth factor-beta(TGF-beta) receptor type II. AB384947 - Synthetic construct DNA, clone: pF1KB4430, Homo sapiens TGFBR2 gene for TGF-beta receptor type-2 precursor, complete cds, without stop codon, in Flexi system. BC152840 - Synthetic construct Homo sapiens clone IMAGE:100016037, MGC:184184 transforming growth factor, beta receptor II (70/80kDa) (TGFBR2) mRNA, encodes complete protein. E10744 - cDNA encoding secretory signal and extracellular domain of human transforming growth factor-beta(TGF-beta) receptor type II. KU178359 - Homo sapiens transforming growth factor beta receptor II isoform 1 (TGFBR2) mRNA, partial cds. KU178360 - Homo sapiens transforming growth factor beta receptor II isoform 2 (TGFBR2) mRNA, partial cds. D28131 - Homo sapiens mRNA for TGF-beta receptor type IIB, partial cds. AK304404 - Homo sapiens cDNA FLJ51462 complete cds, highly similar to TGF-beta receptor type-2 precursor (EC 2.7.11.30). MP202692 - Sequence 3 from Patent WO2019090263. JD406172 - Sequence 387196 from Patent EP1572962. JD395010 - Sequence 376034 from Patent EP1572962. JD487648 - Sequence 468672 from Patent EP1572962. AJ786388 - Homo sapiens partial mRNA for transforming growth factor beta receptor type IIC, (Tbeta RIIC gene), alternative splicing. JD220065 - Sequence 201089 from Patent EP1572962. FW573294 - JP 2010529847-A/15: Oligonucleotides for modulation of target RNA activity. JD119569 - Sequence 100593 from Patent EP1572962. JD553849 - Sequence 534873 from Patent EP1572962. JD279910 - Sequence 260934 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_tgfbPathway - TGF beta signaling pathway h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae h_alkPathway - ALK in cardiac myocytes h_ctcfPathway - CTCF: First Multivalent Nuclear Factor h_tob1Pathway - Role of Tob in T-cell activation
Reactome (by CSHL, EBI, and GO)
Protein P37173 (Reactome details) participates in the following event(s):
R-HSA-170861 Dimeric TGF-beta-1 binds to the receptor R-HSA-4332235 CBL binds TGFBR2 R-HSA-4332236 CBL neddylates TGFBR2 R-HSA-3645778 TGFB1 binds TGFBR2 KD Mutant Dimers R-HSA-170843 TGFBR2 phosphorylates TGFBR1 R-HSA-170846 TGFBR2 recruits TGFBR1 R-HSA-170835 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 R-HSA-173483 BAMBI interferes with the interaction of type I receptor with type II receptor R-HSA-173512 I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1) R-HSA-178218 SMAD7:SMURF complex binds to phosphorylated TGFBR1 R-HSA-2127562 STRAP binds phosphorylated TGF-beta receptor complex R-NUL-2128982 Strap binds phosphorylated TGF-beta receptor complex R-NUL-2169036 Smad7:SMURF1 binds phosphorylated TGFBR1 R-NUL-2169043 Smad7:SMURF2 binds phosphorylated TGFBR1 R-NUL-2176431 Smad7 recruits NEDD4L to activated TGF-beta receptor complex R-HSA-3702153 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 MH2 domain mutants R-HSA-3713560 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 phosphorylation motif mutants R-HSA-2134519 TGFBR2 is recruited to tight junctions after TGF-beta stimulation R-NUL-2161160 TGFBR2 is recruited to tight junctions-associated, Pard6a-bound, TGFBR1 after TGF-beta stimulation R-HSA-3656484 TGFBR2 recruits TGFBR1 KD Mutants R-HSA-170850 Phosphorylated SMAD2/3 dissociates from TGFBR R-HSA-3702186 Phosphorylated SMAD2/3 MH2 domain mutants dissociate from TGFBR R-HSA-170868 Activated type I receptor phosphorylates SMAD2/3 directly R-HSA-178178 PP1 dephosphorylates TGFBR1 R-NUL-2167872 PP1CC dephosphorylates TGFBR1 R-NUL-2167890 Smad7 recruits GADD34:PP1CC to phosphorylated TGF-beta receptor complex R-HSA-3656517 TGFBR2 phosphorylates TGFBR1 KD Mutants R-HSA-3702184 Activated type I receptor phosphorylates SMAD2/3 MH2 domain mutants directly R-HSA-2134532 TGFBR2 phosphorylates TGFBR1 and PARD6A R-NUL-2161165 TGFBR2 phosphorylates Pard6a R-HSA-178189 SMAD7 recruits GADD34:PP1 to phosphorylated TGFBR R-HSA-2128994 STRAP stabilizes interaction of activated TGF-beta receptor complex with SMAD7 R-HSA-2160932 SMURF1 binds phosphorylated PARD6A R-HSA-2169050 SMURFs/NEDD4L ubiquitinate phosphorylated TGFBR1 and SMAD7 R-NUL-2176396 SMURF1 ubiquitinates Smad7 and phosphorylated TGFBR1 R-NUL-2176393 SMURF2 ubiquitinates Smad7 and phosphorylated TGFBR1 R-NUL-2176427 NEDD4L ubiquitinates Smad7 and TGFBR1 R-NUL-2179307 Uchl5 is recruited to TGF-beta receptor complex through Smad7 R-NUL-2179313 Uchl5 deubiquitinates TGFBR1 R-HSA-3645786 TGFBR2 mutant dimers recruit TGFBR1 R-HSA-2179293 UCHL5 binds SMAD7 in complex with ubiquitinated TGFBR1 R-HSA-2179291 UCHL5, USP15 deubiquitinate TGFBR1 R-HSA-2160935 SMURF1 ubiquitinates RHOA R-HSA-2173789 TGF-beta receptor signaling activates SMADs R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-3645790 TGFBR2 Kinase Domain Mutants in Cancer R-HSA-3642279 TGFBR2 MSI Frameshift Mutants in Cancer R-HSA-2173788 Downregulation of TGF-beta receptor signaling R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) R-HSA-3656535 TGFBR1 LBD Mutants in Cancer R-HSA-3656532 TGFBR1 KD Mutants in Cancer R-HSA-9006936 Signaling by TGF-beta family members R-HSA-3642278 Loss of Function of TGFBR2 in Cancer R-HSA-3304349 Loss of Function of SMAD2/3 in Cancer R-HSA-3656534 Loss of Function of TGFBR1 in Cancer R-HSA-162582 Signal Transduction R-HSA-3304351 Signaling by TGF-beta Receptor Complex in Cancer R-HSA-5689603 UCH proteinases R-HSA-5663202 Diseases of signal transduction R-HSA-5688426 Deubiquitination R-HSA-1643685 Disease R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
