{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Transforming growth factor beta-3''' is a protein that in humans is encoded by the {{gene|TGFB3}} gene.<ref name="pmid16549496">{{cite journal | vauthors = Bandyopadhyay B, Fan J, Guan S, Li Y, Chen M, Woodley DT, Li W | title = A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing | journal = The Journal of Cell Biology | volume = 172 | issue = 7 | pages = 1093–105 | date = Mar 2006 | pmid = 16549496 | pmc = 2063766 | doi = 10.1083/jcb.200507111 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TGFB3 transforming growth factor, beta 3| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7043}}</ref>
It is a type of protein, known as a cytokine, which is involved in cell differentiation, embryogenesis and development. It belongs to a large family of cytokines called the Transforming growth factor beta superfamily, which includes the TGF-β family, Bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), inhibins and activins.<ref name = herpin>{{cite journal | vauthors = Herpin A, Lelong C, Favrel P | title = Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans | journal = Developmental and Comparative Immunology | volume = 28 | issue = 5 | pages = 461–85 | date = May 2004 | pmid = 15062644 | doi = 10.1016/j.dci.2003.09.007 }}</ref>
TGF-β3 is believed to regulate molecules involved in cellular adhesion and extracellular matrix (ECM) formation during the process of palate development. Without TGF-β3, mammals develop a deformity known as a cleft palate.<ref>{{cite journal | vauthors = Taya Y, O'Kane S, Ferguson MW | title = Pathogenesis of cleft palate in TGF-beta3 knockout mice | journal = Development | volume = 126 | issue = 17 | pages = 3869–79 | date = Sep 1999 | doi = 10.1242/dev.126.17.3869 | pmid = 10433915 }}</ref><ref>{{cite journal | vauthors = Dudas M, Nagy A, Laping NJ, Moustakas A, Kaartinen V | title = Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway | journal = Developmental Biology | volume = 266 | issue = 1 | pages = 96–108 | date = Feb 2004 | pmid = 14729481 | doi = 10.1016/j.ydbio.2003.10.007 | doi-access = }}</ref> This is caused by failure of epithelial cells in both sides of the developing palate to fuse. TGF-β3 also plays an essential role in controlling the development of lungs in mammals, by also regulating cell adhesion and ECM formation in this tissue,<ref>{{cite journal | vauthors = Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J | title = Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction | journal = Nature Genetics | volume = 11 | issue = 4 | pages = 415–21 | date = Dec 1995 | pmid = 7493022 | doi = 10.1038/ng1295-415 | s2cid = 22365206 }}</ref> and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin.<ref name="pmid16549496"/>
== Interactions ==
Transforming growth factor, beta 3 has been shown to interact with TGF beta receptor 2.<ref name=pmid12729750>{{cite journal | vauthors = De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD | title = 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 = Journal of Molecular Biology | volume = 328 | issue = 5 | pages = 1173–83 | date = May 2003 | pmid = 12729750 | doi = 10.1016/S0022-2836(03)00360-7 }}</ref><ref name=pmid11850637>{{cite journal | vauthors = Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP | title = Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex | journal = Nature Structural Biology | volume = 9 | issue = 3 | pages = 203–8 | date = Mar 2002 | pmid = 11850637 | doi = 10.1038/nsb766 | s2cid = 13322593 }}</ref><ref name=pmid9872992>{{cite journal | vauthors = Barbara NP, Wrana JL, Letarte M | title = Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily | journal = The Journal of Biological Chemistry | volume = 274 | issue = 2 | pages = 584–94 | date = Jan 1999 | pmid = 9872992 | doi = 10.1074/jbc.274.2.584 | doi-access = free }}</ref><ref name=pmid11157754>{{cite journal | vauthors = Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P | title = Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor | journal = The EMBO Journal | volume = 20 | issue = 3 | pages = 480–90 | date = Feb 2001 | pmid = 11157754 | pmc = 133482 | doi = 10.1093/emboj/20.3.480 }}</ref>
==Clinical research==
After successful phase I/II trials,<ref>{{cite journal | vauthors = Ferguson MW, Duncan J, Bond J, Bush J, Durani P, So K, Taylor L, Chantrey J, Mason T, James G, Laverty H, Occleston NL, Sattar A, Ludlow A, O'Kane S | title = Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies | journal = Lancet | volume = 373 | issue = 9671 | pages = 1264–74 | date = Apr 2009 | pmid = 19362676 | doi = 10.1016/S0140-6736(09)60322-6 | s2cid = 35671002 | url = http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60322-6/abstract| url-access = subscription }}</ref> human recombinant TGF-β3 ('''avotermin''', planned trade name '''Juvista''') failed in Phase III trials.<ref>[http://www.thepharmaletter.com/file/102058/renovo-shares-plummet-75-as-scar-revision-product-juvista-fails-to-meet-study-endpoints.html Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints], 14 February 2011</ref>
== References == {{Reflist}}
== Further reading == {{refbegin|35em}} * {{cite journal | vauthors = Kalluri R, Neilson EG | title = Epithelial-mesenchymal transition and its implications for fibrosis | journal = The Journal of Clinical Investigation | volume = 112 | issue = 12 | pages = 1776–84 | date = Dec 2003 | pmid = 14679171 | pmc = 297008 | doi = 10.1172/JCI20530 }} * {{cite journal | vauthors = Arrick BA, Lee AL, Grendell RL, Derynck R | title = Inhibition of translation of transforming growth factor-beta 3 mRNA by its 5' untranslated region | journal = Molecular and Cellular Biology | volume = 11 | issue = 9 | pages = 4306–13 | date = Sep 1991 | pmid = 1875922 | pmc = 361291 | doi = 10.1128/mcb.11.9.4306}} * {{cite journal | vauthors = ten Dijke P, Hansen P, Iwata KK, Pieler C, Foulkes JG | title = Identification of another member of the transforming growth factor type beta gene family | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 13 | pages = 4715–9 | date = Jul 1988 | pmid = 3164476 | pmc = 280506 | doi = 10.1073/pnas.85.13.4715 | bibcode = 1988PNAS...85.4715T | doi-access = free }} * {{cite journal | vauthors = Derynck R, Lindquist PB, Lee A, Wen D, Tamm J, Graycar JL, Rhee L, Mason AJ, Miller DA, Coffey RJ | title = A new type of transforming growth factor-beta, TGF-beta 3 | journal = The EMBO Journal | volume = 7 | issue = 12 | pages = 3737–43 | date = Dec 1988 | pmid = 3208746 | pmc = 454948 | doi = 10.1002/j.1460-2075.1988.tb03257.x}} * {{cite journal | vauthors = Barton DE, Foellmer BE, Du J, Tamm J, Derynck R, Francke U | title = Chromosomal mapping of genes for transforming growth factors beta 2 and beta 3 in man and mouse: dispersion of TGF-beta gene family | journal = Oncogene Research | volume = 3 | issue = 4 | pages = 323–31 | year = 1989 | pmid = 3226728 }} * {{cite journal | vauthors = Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J | title = Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction | journal = Nature Genetics | volume = 11 | issue = 4 | pages = 415–21 | date = Dec 1995 | pmid = 7493022 | doi = 10.1038/ng1295-415 | s2cid = 22365206 }} * {{cite journal | vauthors = Nishida K, Sotozono C, Adachi W, Yamamoto S, Yokoi N, Kinoshita S | title = Transforming growth factor-beta 1, -beta 2 and -beta 3 mRNA expression in human cornea | journal = Current Eye Research | volume = 14 | issue = 3 | pages = 235–41 | date = Mar 1995 | pmid = 7796607 | doi = 10.3109/02713689509033520 }} * {{cite journal | vauthors = Lin HY, Moustakas A, Knaus P, Wells RG, Henis YI, Lodish HF | title = The soluble exoplasmic domain of the type II transforming growth factor (TGF)-beta receptor. A heterogeneously glycosylated protein with high affinity and selectivity for TGF-beta ligands | journal = The Journal of Biological Chemistry | volume = 270 | issue = 6 | pages = 2747–54 | date = Feb 1995 | pmid = 7852346 | doi = 10.1074/jbc.270.6.2747 | doi-access = free }} * {{cite journal | vauthors = Rampazzo A, Nava A, Danieli GA, Buja G, Daliento L, Fasoli G, Scognamiglio R, Corrado D, Thiene G | title = The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24 | journal = Human Molecular Genetics | volume = 3 | issue = 6 | pages = 959–62 | date = Jun 1994 | pmid = 7951245 | doi = 10.1093/hmg/3.6.959 }} * {{cite journal | vauthors = Zhao Y, Chegini N, Flanders KC | title = Human fallopian tube expresses transforming growth factor (TGF beta) isoforms, TGF beta type I-III receptor messenger ribonucleic acid and protein, and contains [125I]TGF beta-binding sites | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 79 | issue = 4 | pages = 1177–84 | date = Oct 1994 | doi = 10.1210/jcem.79.4.7962292 | pmid = 7962292 }} * {{cite journal | vauthors = Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E | title = Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta | journal = The Biochemical Journal | volume = 302 | issue = 2 | pages = 527–34 | date = Sep 1994 | pmid = 8093006 | pmc = 1137259 | doi = 10.1042/bj3020527}} * {{cite journal | vauthors = López-Casillas F, Payne HM, Andres JL, Massagué J | title = Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites | journal = The Journal of Cell Biology | volume = 124 | issue = 4 | pages = 557–68 | date = Feb 1994 | pmid = 8106553 | pmc = 2119924 | doi = 10.1083/jcb.124.4.557 }} * {{cite journal | vauthors = Mittl PR, Priestle JP, Cox DA, McMaster G, Cerletti N, Grütter MG | title = The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding | journal = Protein Science | volume = 5 | issue = 7 | pages = 1261–71 | date = Jul 1996 | pmid = 8819159 | pmc = 2143453 | doi = 10.1002/pro.5560050705 }} * {{cite journal | vauthors = Ambros RA, Kallakury BV, Malfetano JH, Mihm MC | title = Cytokine, cell adhesion receptor, and tumor suppressor gene expression in vulvar squamous carcinoma: correlation with prominent fibromyxoid stromal response | journal = International Journal of Gynecological Pathology | volume = 15 | issue = 4 | pages = 320–5 | date = Oct 1996 | pmid = 8886879 | doi = 10.1097/00004347-199610000-00004 }} * {{cite journal | vauthors = Djonov V, Ball RK, Graf S, Mottaz AE, Arnold AM, Flanders K, Studer UE, Merz VW | title = Transforming growth factor-beta 3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma | journal = The Prostate | volume = 31 | issue = 2 | pages = 103–9 | date = May 1997 | pmid = 9140123 | doi = 10.1002/(SICI)1097-0045(19970501)31:2<103::AID-PROS5>3.0.CO;2-O | s2cid = 22734222 }} * {{cite journal | vauthors = Jin L, Qian X, Kulig E, Sanno N, Scheithauer BW, Kovacs K, Young WF, Lloyd RV | title = Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and neoplastic human pituitaries | journal = The American Journal of Pathology | volume = 151 | issue = 2 | pages = 509–19 | date = Aug 1997 | pmid = 9250163 | pmc = 1858020 }} * {{cite journal | vauthors = Lidral AC, Romitti PA, Basart AM, Doetschman T, Leysens NJ, Daack-Hirsch S, Semina EV, Johnson LR, Machida J, Burds A, Parnell TJ, Rubenstein JL, Murray JC | title = Association of MSX1 and TGFB3 with nonsyndromic clefting in humans | journal = American Journal of Human Genetics | volume = 63 | issue = 2 | pages = 557–68 | date = Aug 1998 | pmid = 9683588 | pmc = 1377298 | doi = 10.1086/301956 }} * {{cite journal | vauthors = Barbara NP, Wrana JL, Letarte M | title = Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily | journal = The Journal of Biological Chemistry | volume = 274 | issue = 2 | pages = 584–94 | date = Jan 1999 | pmid = 9872992 | doi = 10.1074/jbc.274.2.584 | doi-access = free }} * {{cite journal | vauthors = Lux A, Attisano L, Marchuk DA | title = Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 9984–92 | date = Apr 1999 | pmid = 10187774 | doi = 10.1074/jbc.274.15.9984 | doi-access = free }} * {{cite journal | vauthors = Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A, Takigawa M, Nakanishi T, Takehara K | title = Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model | journal = Journal of Cellular Physiology | volume = 181 | issue = 1 | pages = 153–9 | date = Oct 1999 | pmid = 10457363 | doi = 10.1002/(SICI)1097-4652(199910)181:1<153::AID-JCP16>3.0.CO;2-K | s2cid = 21284888 }} {{Refend}}
== External links == * [https://www.ncbi.nlm.nih.gov/books/NBK1131/ GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant] * [https://omim.org/search/?index=entry&start=1&limit=10&search=604772+605676+601214+107970+125645+125647+125671+173325+180902+190230+600996+602086+602087+602861+604400+604401+607450+609040+609160+610193+610476+611528+612048+107970+125645+125647+125671+173325+180902+190230+600996+602086+602087+602861+604400+604401+607450+609040+609160+610193+610476+611528+612048&sort=score+desc&field=number OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant] * {{PDBe-KB2|P10600|Transforming growth factor beta-3}}
{{PDB Gallery|geneid=7043}}
{{TGF beta signaling}} {{Growth factors}} {{TGFβ receptor superfamily modulators}}
Category:Proteins Category:TGFβ domain