TGF beta receptor 2
Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. TGFBR2 is its human gene.
It is a tumor suppressor gene.[1]
This gene encodes a member of the Ser/Thr 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. Alternatively spliced transcript variants encoding different isoforms have been characterized.[2]
Interactions
TGF beta receptor 2 has been shown to interact with Cyclin B2,[3] TGF beta receptor 1,[4][5] Transforming growth factor, beta 3,[6][7][8][9] AP2B1,[10] Endoglin,[8][11] Heat shock protein 90kDa alpha (cytosolic), member A1[12] and STRAP.[13][14]
Domain architecture
| Transforming growth factor beta receptor 2 ectodomain |
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| crystal structure of human tgf-beta type ii receptor ligand binding domain |
| Identifiers |
| Symbol |
ecTbetaR2 |
| Pfam |
PF08917 |
| InterPro |
IPR015013 |
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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).[7]
See also
External links
References
- ^ "TGFBR2 - transforming growth factor, beta receptor II (70/80kDa) - Genetics Home Reference". http://ghr.nlm.nih.gov/gene=tgfbr2. Retrieved 2008-09-07.
- ^ "Entrez Gene: TGFBR2 transforming growth factor, beta receptor II (70/80kDa)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7048.
- ^ Liu, J H; Wei S, Burnette P K, Gamero A M, Hutton M, Djeu J Y (Jan. 1999). "Functional association of TGF-beta receptor II with cyclin B". Oncogene (ENGLAND) 18 (1): 269–75. doi:10.1038/sj.onc.1202263. ISSN 0950-9232. PMID 9926943.
- ^ Kawabata, M; Chytil A, Moses H L (Mar. 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". J. Biol. Chem. (UNITED STATES) 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. ISSN 0021-9258. PMID 7890683.
- ^ Razani, B; Zhang X L, Bitzer M, von Gersdorff G, Böttinger E P, Lisanti M P (Mar. 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". J. Biol. Chem. (United States) 276 (9): 6727–38. doi:10.1074/jbc.M008340200. ISSN 0021-9258. PMID 11102446.
- ^ De Crescenzo, Gregory; Pham Phuong L, Durocher Yves, O'Connor-McCourt Maureen D (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". J. Mol. Biol. (England) 328 (5): 1173–83. doi:10.1016/S0022-2836(03)00360-7. ISSN 0022-2836. PMID 12729750.
- ^ a b Hart, P John; Deep Shashank, Taylor Alexander B, Shu Zhanyong, Hinck Cynthia S, Hinck Andrew P (Mar. 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nat. Struct. Biol. (United States) 9 (3): 203–8. doi:10.1038/nsb766. ISSN 1072-8368. PMID 11850637.
- ^ a b Barbara, N P; Wrana J L, 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". J. Biol. Chem. (UNITED STATES) 274 (2): 584–94. doi:10.1074/jbc.274.2.584. ISSN 0021-9258. PMID 9872992.
- ^ 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". EMBO J. (England) 20 (3): 480–90. doi:10.1093/emboj/20.3.480. ISSN 0261-4189. PMC 133482. PMID 11157754. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133482.
- ^ Yao, Diying; Ehrlich Marcelo, Henis Yoav I, Leof Edward B (Nov. 2002). "Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit". Mol. Biol. Cell (United States) 13 (11): 4001–12. doi:10.1091/mbc.02-07-0104. ISSN 1059-1524. PMC 133610. PMID 12429842. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133610.
- ^ Guerrero-Esteo, Mercedes; Sanchez-Elsner Tilman, Letamendia Ainhoa, Bernabeu Carmelo (Aug. 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". J. Biol. Chem. (United States) 277 (32): 29197–209. doi:10.1074/jbc.M111991200. ISSN 0021-9258. PMID 12015308.
- ^ Wrighton, Katharine H; Lin Xia, Feng Xin-Hua (Jul. 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proc. Natl. Acad. Sci. U.S.A. (United States) 105 (27): 9244–9. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2453700.
- ^ Datta, P K; Chytil A, Gorska A E, Moses H L (Dec. 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". J. Biol. Chem. (UNITED STATES) 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. ISSN 0021-9258. PMID 9856985.
- ^ Datta, P K; Moses H L (May. 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3157–67. doi:10.1128/MCB.20.9.3157-3167.2000. ISSN 0270-7306. PMC 85610. PMID 10757800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85610.
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PDB gallery
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1ktz: Crystal Structure of the Human TGF-beta Type II Receptor Extracellular Domain in Complex with TGF-beta3
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1m9z: CRYSTAL STRUCTURE OF HUMAN TGF-BETA TYPE II RECEPTOR LIGAND BINDING DOMAIN
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1plo: TRANSFORMING GROWTH FACTOR-BETA TYPE II RECEPTOR EXTRACELLULAR DOMAIN
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Chemokine receptor
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| TNF receptor |
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| JAK-STAT |
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| Ig superfamily |
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| IL-17 family |
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| S/T |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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| Type I cytokine receptor |
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| Receptor protein serine/threonine kinase |
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| Receptor tyrosine kinase |
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| Tumor necrosis factor receptor |
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| Ig superfamily |
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| Other/ungrouped |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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This article incorporates text from the public domain Pfam and InterPro IPR015013