Homo sapiens Protein: TGFBR2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-23363.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gene Symbol | TGFBR2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Protein Name | transforming growth factor, beta receptor II (70/80kDa) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms | AAT3; FAA3; LDS1B; LDS2; LDS2B; MFS2; RIIC; TAAD2; TGFbeta-RII; TGFR-2; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000295754 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-23359 (TGFBR2) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. {ECO:0000269PubMed:7774578}. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | Cell membrane {ECO:0000269PubMed:1310899}; Single-pass type I membrane protein {ECO:0000269PubMed:1310899}. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disease Associations | Hereditary non-polyposis colorectal cancer 6 (HNPCC6) [MIM:614331]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors 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. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by 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. {ECO:0000269PubMed:9590282}. Note=The disease is caused by mutations affecting the gene represented in this entry.Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. {ECO:0000269PubMed:10789724}. Note=The disease is caused by mutations affecting the gene represented in this entry.Loeys-Dietz syndrome 2 (LDS2) [MIM:610168]: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. 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, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. {ECO:0000269PubMed:15235604, ECO:0000269PubMed:15731757, ECO:0000269PubMed:16027248, ECO:0000269PubMed:16251899, ECO:0000269PubMed:19883511, ECO:0000269PubMed:20101701, ECO:0000269PubMed:20358619, ECO:0000269PubMed:21949523, ECO:0000269PubMed:22113417}. Note=The disease is caused by mutations affecting the gene represented in this entry. 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 LDS2 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 LDS2 by the OMIM resource. {ECO:0000269PubMed:16027248}. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tissue Specificity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 98 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000333
Ser/Thr protein kinase, TGFB receptor IPR000719 Protein kinase domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR011009 Protein kinase-like domain IPR015013 Transforming growth factor beta receptor 2 ectodomain IPR017194 Transforming growth factor-beta receptor, type II IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00069
PF07714 PF08917 |
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PRINTS |
PR00653
PR00109 |
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PIRSF |
PIRSF037393
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SMART |
SM00220
SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SwissProt | P37173 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P37173 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TrEMBL | A3QNQ0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 7048 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.682303 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RefSeq | NP_003233 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:11773 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
OMIM | 190182 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CCDS | CCDS2648 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HPRD | 01823 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
EMBL | AK300383 AK314102 AY675319 CH471055 D28131 D50683 DQ377553 DQ377554 DQ377555 DQ377556 DQ377557 DQ377558 DQ377559 GU143402 M85079 U52240 U52241 U52242 U52244 U52245 U52246 U69146 U69147 U69148 U69149 U69150 U69151 U69152 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GenPept | AAA61164 AAB17553 AAB40916 AAT70724 ABG65632 ACZ58376 BAA05673 BAA09332 BAG36796 BAG62117 EAW64410 EAW64412 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||