Transforming growth factor, beta 3

Last updated
TGFB3
Protein TGFB3 PDB 1ktz.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TGFB3 , ARVD, ARVD1, RNHF, TGF-beta3, Transforming growth factor, beta 3, LDS5, transforming growth factor beta 3, TGF beta 3
External IDs OMIM: 190230; MGI: 98727; HomoloGene: 2433; GeneCards: TGFB3; OMA:TGFB3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7043

21809

Ensembl

ENSG00000119699

ENSMUSG00000021253

UniProt

P10600

P17125

RefSeq (mRNA)

NM_003239
NM_001329938
NM_001329939

NM_009368

RefSeq (protein)

NP_001316867
NP_001316868
NP_003230

n/a

Location (UCSC) Chr 14: 75.96 – 75.98 Mb Chr 12: 86.1 – 86.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene. [5] [6]

Contents

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. [7]

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. [8] [9] 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, [10] and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin. [5]

Interactions

Transforming growth factor, beta 3 has been shown to interact with TGF beta receptor 2. [11] [12] [13] [14]

Clinical research

After successful phase I/II trials, [15] human recombinant TGF-β3 (avotermin, planned trade name Juvista) failed in Phase III trials. [16]

Related Research Articles

<span class="mw-page-title-main">Transforming growth factor beta</span> Cytokine

Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 3</span> Protein-coding gene in humans

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 4</span> Mammalian protein found in Homo sapiens

SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 7</span> Protein-coding gene in the species Homo sapiens

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

Smads comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the Caenorhabditis elegans SMA and MAD family of genes in Drosophila.

<span class="mw-page-title-main">TGF beta 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.

<span class="mw-page-title-main">ACVR2A</span> Protein-coding gene in the species Homo sapiens

Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene. ACVR2A is an activin type 2 receptor.

<span class="mw-page-title-main">Endoglin</span> Protein-coding gene in the species Homo sapiens

Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.

<span class="mw-page-title-main">TGF alpha</span> Protein

Transforming growth factor alpha (TGF-α) is a protein that in humans is encoded by the TGFA gene. As a member of the epidermal growth factor (EGF) family, TGF-α is a mitogenic polypeptide. The protein becomes activated when binding to receptors capable of protein kinase activity for cellular signaling.

<span class="mw-page-title-main">TGF beta 2</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor-beta 2 (TGF-β2) is a secreted protein known as a cytokine that performs many cellular functions and has a vital role during embryonic development. It is an extracellular glycosylated protein. It is known to suppress the effects of interleukin dependent T-cell tumors. There are two named isoforms of this protein, created by alternative splicing of the same gene.

<span class="mw-page-title-main">TGFBR3</span> Protein-coding gene in the species Homo sapiens

Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface chondroitin sulfate / heparan sulfate proteoglycan >300 kDa in molecular weight. Betaglycan binds to various members of the TGF-beta superfamily of ligands via its core protein, and bFGF via its heparan sulfate chains. TGFBR3 is the most widely expressed type of TGF-beta receptor. Its affinity towards all individual isoforms of TGF-beta is similarly high and therefore it plays an important role as a coreceptor mediating the binding of TGF-beta to its other receptors - specifically TGFBR2. The intrinsic kinase activity of this receptor has not yet been described. In regard of TGF-beta signalling it is generally considered a non-signaling receptor or a coreceptor. By binding to various member of the TGF-beta superfamily at the cell surface it acts as a reservoir of TGF-beta.

<span class="mw-page-title-main">TGF beta receptor 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta receptor I is a membrane-bound TGF beta receptor protein of the TGF-beta receptor family for the TGF beta superfamily of signaling ligands. TGFBR1 is its human gene.

<span class="mw-page-title-main">TGF beta receptor 2</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. TGFBR2 is its human gene.

<span class="mw-page-title-main">ACVRL1</span> Protein-coding gene in humans

Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.

<span class="mw-page-title-main">GABRB3</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.

<span class="mw-page-title-main">Integrin beta 6</span> Protein-coding gene in the species Homo sapiens

Integrin beta-6 is a protein that in humans is encoded by the ITGB6 gene. It is the β6 subunit of the integrin αvβ6. Integrins are αβ heterodimeric glycoproteins which span the cell’s membrane, integrating the outside and inside of the cell. Integrins bind to specific extracellular proteins in the extracellular matrix or on other cells and subsequently transduce signals intracellularly to affect cell behaviour. One α and one β subunit associate non-covalently to form 24 unique integrins found in mammals. While some β integrin subunits partner with multiple α subunits, β6 associates exclusively with the αv subunit. Thus, the function of ITGB6 is entirely associated with the integrin αvβ6.

<span class="mw-page-title-main">LTBP1 (gene)</span> Protein-coding gene in the species Homo sapiens

Latent-transforming growth factor beta-binding protein 1 is a protein that in humans is encoded by the LTBP1 gene.

<span class="mw-page-title-main">TSC22D1</span> Protein-coding gene in the species Homo sapiens

TSC22 domain family protein 1 is a protein that in humans is encoded by the TSC22D1 gene.

<span class="mw-page-title-main">LTBP3</span> Protein-coding gene in the species Homo sapiens

Latent-transforming growth factor beta-binding protein 3 is a protein that in humans is encoded by the LTBP3 gene.

Transforming growth factor beta (TGF-β) is a potent cell regulatory polypeptide homodimer of 25kD. It is a multifunctional signaling molecule with more than 40 related family members. TGF-β plays a role in a wide array of cellular processes including early embryonic development, cell growth, differentiation, motility, and apoptosis.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000119699 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021253 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Bandyopadhyay B, Fan J, Guan S, Li Y, Chen M, Woodley DT, Li W (Mar 2006). "A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing". The Journal of Cell Biology. 172 (7): 1093–105. doi:10.1083/jcb.200507111. PMC   2063766 . PMID   16549496.
  6. ↑ "Entrez Gene: TGFB3 transforming growth factor, beta 3".
  7. ↑ Herpin A, Lelong C, Favrel P (May 2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Developmental and Comparative Immunology. 28 (5): 461–85. doi:10.1016/j.dci.2003.09.007. PMID   15062644.
  8. ↑ Taya Y, O'Kane S, Ferguson MW (Sep 1999). "Pathogenesis of cleft palate in TGF-beta3 knockout mice". Development. 126 (17): 3869–79. doi:10.1242/dev.126.17.3869. PMID   10433915.
  9. ↑ Dudas M, Nagy A, Laping NJ, Moustakas A, Kaartinen V (Feb 2004). "Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway". Developmental Biology. 266 (1): 96–108. doi:10.1016/j.ydbio.2003.10.007. PMID   14729481.
  10. ↑ Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J (Dec 1995). "Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction". Nature Genetics. 11 (4): 415–21. doi:10.1038/ng1295-415. PMID   7493022. S2CID   22365206.
  11. ↑ De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD (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". Journal of Molecular Biology. 328 (5): 1173–83. doi:10.1016/S0022-2836(03)00360-7. PMID   12729750.
  12. ↑ Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (Mar 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology. 9 (3): 203–8. doi:10.1038/nsb766. PMID   11850637. S2CID   13322593.
  13. ↑ Barbara NP, Wrana JL, 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". The Journal of Biological Chemistry. 274 (2): 584–94. doi: 10.1074/jbc.274.2.584 . PMID   9872992.
  14. ↑ 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". The EMBO Journal. 20 (3): 480–90. doi:10.1093/emboj/20.3.480. PMC   133482 . PMID   11157754.
  15. ↑ 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 (Apr 2009). "Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies". Lancet. 373 (9671): 1264–74. doi:10.1016/S0140-6736(09)60322-6. PMID   19362676. S2CID   35671002.
  16. ↑ Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints, 14 February 2011

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