ID:TGFB1_HUMAN DESCRIPTION: RecName: Full=Transforming growth factor beta-1; Short=TGF-beta-1; Contains: RecName: Full=Latency-associated peptide; Short=LAP; Flags: Precursor; FUNCTION: Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. SUBUNIT: Homodimer; disulfide-linked, or heterodimer with TGFB2 (By similarity). Secreted and stored as a biologically inactive form in the extracellular matrix in a 290 kDa complex (large latent TGF-beta1 complex) containing the TGFB1 homodimer, the latency-associated peptide (LAP), and the latent TGFB1 binding protein-1 (LTBP1). The complex without LTBP1 is known as the'small latent TGF-beta1 complex'. Dissociation of the TGFB1 from LAP is required for growth factor activation and biological activity. Release of the large latent TGF-beta1 complex from the extracellular matrix is carried out by the matrix metalloproteinase MMP3 (By similarity). May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling. Interacts with the serine proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated signaling. The HTRA protease activity is required for this inhibition (By similarity). Interacts with CD109, DPT and ASPN. INTERACTION: P05067:APP; NbExp=2; IntAct=EBI-779636, EBI-77613; P17813:ENG; NbExp=2; IntAct=EBI-779636, EBI-2834630; P36897:TGFBR1; NbExp=2; IntAct=EBI-779636, EBI-1027557; P37173:TGFBR2; NbExp=4; IntAct=EBI-779636, EBI-296151; Q03167:TGFBR3; NbExp=2; IntAct=EBI-779636, EBI-2852679; SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. TISSUE SPECIFICITY: 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. INDUCTION: Activated in vitro at pH below 3.5 and over 12.5. DOMAIN: The 'straitjacket' and 'arm' domains encircle the growth factor monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104. Activation of TGF-beta1 requires the binding of integrin alpha-V to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. The sheer physical force unfastens the straitjacket and releases the active growth factor dimer (By similarity). PTM: Glycosylated. PTM: The precursor is cleaved into mature TGF-beta-1 and LAP, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive. POLYMORPHISM: In post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls. DISEASE: Defects in TGFB1 are the cause of Camurati-Engelmann disease (CE) [MIM:131300]; also known as progressive diaphyseal dysplasia 1 (DPD1). CE is an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision. SIMILARITY: Belongs to the TGF-beta family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TGFB1"; WEB RESOURCE: Name=Wikipedia; Note=TGF beta-1 entry; URL="http://en.wikipedia.org/wiki/TGF_beta_1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01137
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003823 antigen binding GO:0005114 type II transforming growth factor beta receptor binding GO:0005125 cytokine activity GO:0005160 transforming growth factor beta receptor binding GO:0005515 protein binding GO:0008083 growth factor activity GO:0019899 enzyme binding GO:0034713 type I transforming growth factor beta receptor binding GO:0034714 type III transforming growth factor beta receptor binding GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0043539 protein serine/threonine kinase activator activity GO:0046982 protein heterodimerization activity GO:0047485 protein N-terminus binding
Biological Process: GO:0000060 protein import into nucleus, translocation GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000165 MAPK cascade GO:0001570 vasculogenesis GO:0001657 ureteric bud development GO:0001666 response to hypoxia GO:0001763 morphogenesis of a branching structure GO:0001775 cell activation GO:0001837 epithelial to mesenchymal transition GO:0001843 neural tube closure GO:0001933 negative regulation of protein phosphorylation GO:0001934 positive regulation of protein phosphorylation GO:0002028 regulation of sodium ion transport GO:0002062 chondrocyte differentiation GO:0002244 hematopoietic progenitor cell differentiation GO:0002248 connective tissue replacement involved in inflammatory response wound healing GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002513 tolerance induction to self antigen GO:0002576 platelet degranulation GO:0003179 heart valve morphogenesis GO:0006468 protein phosphorylation GO:0006611 protein export from nucleus GO:0006754 ATP biosynthetic process GO:0006796 phosphate-containing compound metabolic process GO:0006874 cellular calcium ion homeostasis GO:0006954 inflammatory response GO:0007050 cell cycle arrest GO:0007093 mitotic cell cycle checkpoint GO:0007173 epidermal growth factor receptor signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007182 common-partner SMAD protein phosphorylation GO:0007183 SMAD protein complex assembly GO:0007219 Notch signaling pathway GO:0007406 negative regulation of neuroblast proliferation GO:0007435 salivary gland morphogenesis GO:0007492 endoderm development GO:0007507 heart development GO:0007565 female pregnancy GO:0007568 aging GO:0008283 cell proliferation GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0008354 germ cell migration GO:0009314 response to radiation GO:0009611 response to wounding GO:0009749 response to glucose GO:0009817 defense response to fungus, incompatible interaction GO:0010033 response to organic substance GO:0010468 regulation of gene expression GO:0010469 regulation of receptor activity GO:0010575 positive regulation of vascular endothelial growth factor production GO:0010628 positive regulation of gene expression GO:0010629 negative regulation of gene expression GO:0010716 negative regulation of extracellular matrix disassembly GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0010742 macrophage derived foam cell differentiation GO:0010763 positive regulation of fibroblast migration GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010936 negative regulation of macrophage cytokine production GO:0014003 oligodendrocyte development GO:0014070 response to organic cyclic compound GO:0016202 regulation of striated muscle tissue development GO:0016477 cell migration GO:0017015 regulation of transforming growth factor beta receptor signaling pathway GO:0019049 evasion or tolerance of host defenses by virus GO:0019221 cytokine-mediated signaling pathway GO:0021915 neural tube development GO:0022408 negative regulation of cell-cell adhesion GO:0030214 hyaluronan catabolic process GO:0030217 T cell differentiation GO:0030279 negative regulation of ossification GO:0030308 negative regulation of cell growth GO:0030316 osteoclast differentiation GO:0030334 regulation of cell migration GO:0030335 positive regulation of cell migration GO:0030501 positive regulation of bone mineralization GO:0030509 BMP signaling pathway GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030879 mammary gland development GO:0031065 positive regulation of histone deacetylation GO:0031100 animal organ regeneration GO:0031293 membrane protein intracellular domain proteolysis GO:0031334 positive regulation of protein complex assembly GO:0031536 positive regulation of exit from mitosis GO:0031663 lipopolysaccharide-mediated signaling pathway GO:0032270 positive regulation of cellular protein metabolic process GO:0032355 response to estradiol GO:0032570 response to progesterone GO:0032667 regulation of interleukin-23 production GO:0032700 negative regulation of interleukin-17 production GO:0032740 positive regulation of interleukin-17 production GO:0032801 receptor catabolic process GO:0032930 positive regulation of superoxide anion generation GO:0032943 mononuclear cell proliferation GO:0032967 positive regulation of collagen biosynthetic process GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033280 response to vitamin D GO:0034616 response to laminar fluid shear stress GO:0035066 positive regulation of histone acetylation GO:0035307 positive regulation of protein dephosphorylation GO:0035902 response to immobilization stress GO:0042060 wound healing GO:0042110 T cell activation GO:0042127 regulation of cell proliferation GO:0042130 negative regulation of T cell proliferation GO:0042306 regulation of protein import into nucleus GO:0042307 positive regulation of protein import into nucleus GO:0042482 positive regulation of odontogenesis GO:0042493 response to drug GO:0042552 myelination GO:0042981 regulation of apoptotic process GO:0043011 myeloid dendritic cell differentiation GO:0043029 T cell homeostasis GO:0043065 positive regulation of apoptotic process GO:0043117 positive regulation of vascular permeability GO:0043406 positive regulation of MAP kinase activity GO:0043491 protein kinase B signaling GO:0043536 positive regulation of blood vessel endothelial cell migration GO:0043537 negative regulation of blood vessel endothelial cell migration GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity GO:0043932 ossification involved in bone remodeling GO:0045066 regulatory T cell differentiation GO:0045216 cell-cell junction organization GO:0045589 regulation of regulatory T cell differentiation GO:0045591 positive regulation of regulatory T cell differentiation GO:0045596 negative regulation of cell differentiation GO:0045599 negative regulation of fat cell differentiation GO:0045662 negative regulation of myoblast differentiation GO:0045786 negative regulation of cell cycle GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045930 negative regulation of mitotic cell cycle GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048146 positive regulation of fibroblast proliferation GO:0048298 positive regulation of isotype switching to IgA isotypes GO:0048468 cell development GO:0048535 lymph node development GO:0048565 digestive tract development GO:0048642 negative regulation of skeletal muscle tissue development GO:0048839 inner ear development GO:0050679 positive regulation of epithelial cell proliferation GO:0050680 negative regulation of epithelial cell proliferation GO:0050714 positive regulation of protein secretion GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050765 negative regulation of phagocytosis GO:0050777 negative regulation of immune response GO:0050868 negative regulation of T cell activation GO:0050900 leukocyte migration GO:0050921 positive regulation of chemotaxis GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051098 regulation of binding GO:0051101 regulation of DNA binding GO:0051152 positive regulation of smooth muscle cell differentiation GO:0051280 negative regulation of release of sequestered calcium ion into cytosol GO:0051781 positive regulation of cell division GO:0051897 positive regulation of protein kinase B signaling GO:0055010 ventricular cardiac muscle tissue morphogenesis GO:0060312 regulation of blood vessel remodeling GO:0060325 face morphogenesis GO:0060364 frontal suture morphogenesis GO:0060389 pathway-restricted SMAD protein phosphorylation GO:0060390 regulation of SMAD protein import into nucleus GO:0060391 positive regulation of SMAD protein import into nucleus GO:0060395 SMAD protein signal transduction GO:0060744 mammary gland branching involved in thelarche GO:0060751 branch elongation involved in mammary gland duct branching GO:0060762 regulation of branching involved in mammary gland duct morphogenesis GO:0060965 negative regulation of gene silencing by miRNA GO:0061035 regulation of cartilage development GO:0070306 lens fiber cell differentiation GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0070723 response to cholesterol GO:0071158 positive regulation of cell cycle arrest GO:0071260 cellular response to mechanical stimulus GO:0071363 cellular response to growth factor stimulus GO:0071407 cellular response to organic cyclic compound GO:0071479 cellular response to ionizing radiation GO:0071549 cellular response to dexamethasone stimulus GO:0071560 cellular response to transforming growth factor beta stimulus GO:0071677 positive regulation of mononuclear cell migration GO:0085029 extracellular matrix assembly GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis GO:0097191 extrinsic apoptotic signaling pathway GO:0097421 liver regeneration GO:1900126 negative regulation of hyaluronan biosynthetic process GO:1900182 positive regulation of protein localization to nucleus GO:1901203 positive regulation of extracellular matrix assembly GO:1901666 positive regulation of NAD+ ADP-ribosyltransferase activity GO:1902074 response to salt GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1903077 negative regulation of protein localization to plasma membrane GO:1903799 negative regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903911 positive regulation of receptor clustering GO:1905313 transforming growth factor beta receptor signaling pathway involved in heart development GO:1990314 cellular response to insulin-like growth factor stimulus GO:1990402 embryonic liver development GO:2000249 regulation of actin cytoskeleton reorganization GO:2000679 positive regulation of transcription regulatory region DNA binding GO:2000727 positive regulation of cardiac muscle cell differentiation GO:0006915 apoptotic process GO:1902893 regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1905005 regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
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Common Gene Haplotype Alleles 
