TGFB3

TGFB3 is a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature TGFB3 may also form heterodimers with other TGF-beta family members. TGFB3 is involved in embryogenesis and cell differentiation, and may function in wound healing. Mutations in TGFB3 are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1.

TGFB3

Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.
Latency-associated peptide
Required to maintain the Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state during storage in extracellular matrix (By similarity).
Associates non-covalently with TGF-beta-3 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-3 (By similarity).
Interaction with integrins results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-3 (By similarity).
Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity).
Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix (By similarity).
At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus (By similarity).
TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity).
Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).

Biological Process agingSource:Ensembl
Biological Process BMP signaling pathwaySource:GO_Central1 Publication
Biological Process cell-cell junction organizationSource:BHF-UCL1 Publication
Biological Process detection of hypoxiaSource:BHF-UCL1 Publication
Biological Process digestive tract developmentSource:Ensembl
Biological Process embryonic neurocranium morphogenesisSource:Ensembl
Biological Process face morphogenesisSource:BHF-UCL1 Publication
Biological Process female pregnancySource:Ensembl
Biological Process frontal suture morphogenesisSource:Ensembl
Biological Process in utero embryonic developmentSource:BHF-UCL
Biological Process inner ear developmentSource:Ensembl
Biological Process lung alveolus developmentSource:BHF-UCL
Biological Process mammary gland developmentSource:BHF-UCL
Biological Process negative regulation of cell population proliferationSource:BHF-UCL1 Publication
Biological Process negative regulation of macrophage cytokine productionSource:DFLAT1 Publication
Biological Process negative regulation of neuron apoptotic processSource:BHF-UCL
Biological Process negative regulation of transforming growth factor beta receptor signaling pathwaySource:Ensembl
Biological Process negative regulation of vascular associated smooth muscle cell proliferationSource:BHF-UCL1 Publication
Biological Process odontogenesisSource:BHF-UCL1 Publication
Biological Process ossification involved in bone remodelingSource:BHF-UCL1 Publication
Biological Process positive regulation of apoptotic processSource:BHF-UCL
Biological Process positive regulation of bone mineralizationSource:BHF-UCL1 Publication
Biological Process positive regulation of cell divisionSource:UniProtKB-KW
Biological Process positive regulation of cell population proliferationSource:BHF-UCL1 Publication
Biological Process positive regulation of collagen biosynthetic processSource:BHF-UCL1 Publication
Biological Process positive regulation of DNA-templated transcriptionSource:BHF-UCL1 Publication
Biological Process positive regulation of epithelial to mesenchymal transitionSource:BHF-UCL2 Publications
Biological Process positive regulation of filopodium assemblySource:BHF-UCL
Biological Process positive regulation of MAPK cascadeSource:Ensembl
Biological Process positive regulation of pathway-restricted SMAD protein phosphorylationSource:BHF-UCL
Biological Process positive regulation of protein secretionSource:BHF-UCL1 Publication
Biological Process positive regulation of SMAD protein signal transductionSource:BHF-UCL
Biological Process positive regulation of stress fiber assemblySource:BHF-UCL1 Publication
Biological Process positive regulation of tight junction disassemblySource:BHF-UCL1 Publication
Biological Process positive regulation of transcription by RNA polymerase IISource:BHF-UCL
Biological Process regulation of cell population proliferationSource:GO_Central1 Publication
Biological Process response to estrogenSource:Ensembl
Biological Process response to hypoxiaSource:BHF-UCL1 Publication
Biological Process response to laminar fluid shear stressSource:Ensembl
Biological Process response to progesteroneSource:BHF-UCL1 Publication
Biological Process salivary gland morphogenesisSource:BHF-UCL1 Publication
Biological Process secondary palate developmentSource:BHF-UCL
Biological Process SMAD protein signal transductionSource:GO_Central1 Publication
Biological Process transforming growth factor beta receptor signaling pathwaySource:BHF-UCL2 Publications
Biological Process uterine wall breakdownSource:BHF-UCL1 Publication
Biological Process wound healingSource:Ensembl

Latency-associated peptide
Secreted, extracellular space, extracellular matrix
Transforming growth factor beta-3
Secreted

Arrhythmogenic right ventricular dysplasia, familial, 1 (ARVD1):
A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.
Loeys-Dietz syndrome 5 (LDS5):
A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection.

Transforming growth factor beta-3 proprotein: The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-3 (TGF-beta-3) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-3 inactive.
Methylated at Gln-293 by N6AMT1.