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TGFB1
transforming growth factor beta-1 proprotein is a precursor of Transforming growth factor beta-1 (TGF-beta-1) and the Latency-associated peptide (LAP) chains, which constitute the active and regulatory subunit of TGF-beta-1, respectively. TGF-beta-1 is a multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration. Following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Following release from LAP, active TGF-beta-1 binds TGF-beta receptors, controlling diverse biological processes. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of retinoic acid-binding receptor gamma (RORC) and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules'. Highly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Co-localizes with ASPN in chondrocytes within OA lesions of articular cartilage. Belongs to the TGF-beta family. Note: This description may include information from UniProtKB.
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| Protein type: Motility/polarity/chemotaxis; Secreted; Secreted, signal peptide |
| Chromosomal Location of human Ortholog: 19q13.2 |
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Cellular Component:
cell surface; cytoplasm; extracellular matrix; extracellular region; extracellular space; Golgi lumen; microvillus; nucleus; plasma membrane; platelet alpha granule lumen
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Molecular Function:
antigen binding; cytokine activity; deubiquitinase activator activity; enzyme binding; growth factor activity; identical protein binding; protein binding; type I transforming growth factor beta receptor binding; type II transforming growth factor beta receptor binding; type III transforming growth factor beta receptor binding
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Biological Process:
aortic valve morphogenesis; ATP biosynthetic process; cell migration; cell-cell junction organization; cellular response to hypoxia; cellular response to low-density lipoprotein particle stimulus; cellular response to organic cyclic compound; cellular response to transforming growth factor beta stimulus; chondrocyte differentiation; connective tissue replacement involved in inflammatory response wound healing; embryonic liver development; epidermal growth factor receptor signaling pathway; epithelial to mesenchymal transition; extracellular matrix assembly; extrinsic apoptotic signaling pathway; heart development; heart valve morphogenesis; hematopoietic progenitor cell differentiation; hyaluronan catabolic process; inflammatory response; lipopolysaccharide-mediated signaling pathway; lymph node development; macrophage derived foam cell differentiation; MAPK cascade; membrane protein intracellular domain proteolysis; negative regulation of biomineral tissue development; negative regulation of blood vessel endothelial cell migration; negative regulation of cell cycle; negative regulation of cell differentiation; negative regulation of cell growth; negative regulation of cell population proliferation; negative regulation of cell-cell adhesion; negative regulation of DNA-templated transcription; negative regulation of epithelial cell proliferation; negative regulation of extracellular matrix disassembly; negative regulation of fat cell differentiation; negative regulation of gene expression; negative regulation of hyaluronan biosynthetic process; negative regulation of macrophage cytokine production; negative regulation of miRNA transcription; negative regulation of myoblast differentiation; negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; negative regulation of protein localization to plasma membrane; negative regulation of protein phosphorylation; negative regulation of skeletal muscle tissue development; neural tube closure; neural tube development; pathway-restricted SMAD protein phosphorylation; phosphate-containing compound metabolic process; positive regulation of blood vessel endothelial cell migration; positive regulation of canonical Wnt signaling pathway; positive regulation of cardiac muscle cell differentiation; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell population proliferation; positive regulation of chemokine (C-X-C motif) ligand 2 production; positive regulation of chemotaxis; positive regulation of collagen biosynthetic process; positive regulation of DNA-templated transcription; positive regulation of endothelial cell apoptotic process; positive regulation of epithelial to mesenchymal transition; positive regulation of ERK1 and ERK2 cascade; positive regulation of extracellular matrix assembly; positive regulation of fibroblast migration; positive regulation of gene expression; positive regulation of inflammatory response; positive regulation of interleukin-17 production; positive regulation of interleukin-6 production; positive regulation of isotype switching to IgA isotypes; positive regulation of MAP kinase activity; positive regulation of microglia differentiation; positive regulation of miRNA transcription; positive regulation of NAD+ ADP-ribosyltransferase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of pathway-restricted SMAD protein phosphorylation; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase activity; positive regulation of primary miRNA processing; positive regulation of protein dephosphorylation; positive regulation of protein import into nucleus; positive regulation of protein kinase B signaling; positive regulation of protein localization to nucleus; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of protein secretion; positive regulation of protein-containing complex assembly; positive regulation of receptor signaling pathway via STAT; positive regulation of SMAD protein signal transduction; positive regulation of smooth muscle cell proliferation; positive regulation of superoxide anion generation; positive regulation of transcription by RNA polymerase II; positive regulation of transcription regulatory region DNA binding; positive regulation of tumor necrosis factor production; positive regulation of vascular endothelial growth factor production; positive regulation of vascular permeability; protein export from nucleus; protein kinase B signaling; receptor catabolic process; regulation of blood vessel remodeling; regulation of cell migration; regulation of cell population proliferation; regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; regulation of miRNA transcription; regulation of protein import into nucleus; regulation of SMAD protein signal transduction; regulation of striated muscle tissue development; regulation of transforming growth factor beta receptor signaling pathway; regulatory T cell differentiation; response to cholesterol; response to estradiol; response to progesterone; response to wounding; salivary gland morphogenesis; selective autophagy; sprouting angiogenesis; transforming growth factor beta receptor signaling pathway; transforming growth factor beta receptor signaling pathway involved in heart development; vasculogenesis; ventricular cardiac muscle tissue morphogenesis
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Disease: Camurati-engelmann Disease; Cystic Fibrosis; Inflammatory Bowel Disease, Immunodeficiency, And Encephalopathy
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Reference #:
P01137
(UniProtKB)
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Alt. Names/Synonyms: CED; DPD1; IBDIMDE; LAP; Latency-associated peptide; prepro-transforming growth factor beta-1; TGF beta; TGF-beta 1 protein; TGF-beta-1; TGF-beta1; TGFB; TGFB1; TGFbeta; transforming growth factor beta 1; Transforming growth factor beta-1; Transforming growth factor beta-1 proprotein; transforming growth factor beta1; transforming growth factor, beta 1
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Gene Symbols: TGFB1
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Molecular weight:
44,325 Da
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Basal Isoelectric point:
8.83
Predict pI for various phosphorylation states
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CST Pathways:
Regulation of P38 MAPKs
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Wnt/ß-Catenin Signaling
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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