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. Homodimer; disulfide-linked, or heterodimer with TGFB2. 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. 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. Interacts with CD109, DPT and ASPN. Activated in vitro at pH below 3.5 and over 12.5. 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.
Protein type: Secreted, signal peptide; Motility/polarity/chemotaxis; Secreted
Molecular Function: antigen binding; cytokine activity; enzyme binding; glycoprotein binding; growth factor activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein N-terminus binding; protein serine/threonine kinase activator activity; punt binding; transforming growth factor beta receptor binding
Biological Process: activation of NF-kappaB transcription factor; adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; ATP biosynthetic process; CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment; cell activation; cell cycle arrest; cell growth; cell migration; cell proliferation; cellular calcium ion homeostasis; chondrocyte differentiation; common-partner SMAD protein phosphorylation; defense response; defense response to fungus, incompatible interaction; endoderm development; epidermal growth factor receptor signaling pathway; epithelial to mesenchymal transition; evasion of host defenses by virus; germ cell migration; growth; hemopoietic progenitor cell differentiation; hyaluronan catabolic process; inflammatory response; intercellular junction assembly and maintenance; lipopolysaccharide-mediated signaling pathway; lymph node development; mammary gland development; MAPKKK cascade; mitotic cell cycle checkpoint; mononuclear cell proliferation; morphogenesis of a branching structure; myelination; myeloid dendritic cell differentiation; negative regulation of blood vessel endothelial cell migration; negative regulation of cell cycle; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-cell adhesion; negative regulation of DNA replication; negative regulation of epithelial cell proliferation; negative regulation of fat cell differentiation; negative regulation of immune response; negative regulation of interleukin-17 production; negative regulation of mitotic cell cycle; negative regulation of myoblast differentiation; negative regulation of neuroblast proliferation; negative regulation of ossification; negative regulation of phagocytosis; negative regulation of protein amino acid phosphorylation; negative regulation of release of sequestered calcium ion into cytosol; negative regulation of skeletal muscle development; negative regulation of T cell activation; negative regulation of T cell proliferation; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; Notch signaling pathway; oligodendrocyte development; organ morphogenesis; organ regeneration; phosphate metabolic process; positive regulation of apoptosis; positive regulation of blood vessel endothelial cell migration; positive regulation of cell division; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cellular protein metabolic process; positive regulation of chemotaxis; positive regulation of collagen biosynthetic process; positive regulation of epithelial cell proliferation; positive regulation of exit from mitosis; positive regulation of fibroblast proliferation; positive regulation of histone acetylation; positive regulation of histone deacetylation; positive regulation of interleukin-17 production; positive regulation of isotype switching to IgA isotypes; positive regulation of MAP kinase activity; positive regulation of odontogenesis; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphoinositide 3-kinase activity; positive regulation of protein amino acid dephosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of protein complex assembly; positive regulation of protein import into nucleus; positive regulation of protein kinase B signaling cascade; positive regulation of protein secretion; positive regulation of regulatory T cell differentiation; positive regulation of smooth muscle cell differentiation; positive regulation of superoxide release; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; positive regulation of vascular permeability; protein amino acid phosphorylation; protein export from nucleus; protein import into nucleus, translocation; protein kinase B signaling cascade; receptor catabolic process; regulation of apoptosis; regulation of binding; regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; regulation of cell proliferation; regulation of DNA binding; regulation of gene expression; regulation of interleukin-23 production; regulation of MAPKKK cascade; regulation of protein import into nucleus; regulation of regulatory T cell differentiation; regulation of sodium ion transport; regulation of striated muscle development; regulation of transforming growth factor beta receptor signaling pathway; regulatory T cell differentiation; response to estradiol stimulus; response to organic substance; response to progesterone stimulus; skeletal development; skeletal muscle development; SMAD protein complex assembly; SMAD protein nuclear translocation; T cell activation; T cell differentiation; T cell homeostasis; tolerance induction to self antigen; transforming growth factor beta receptor signaling pathway; wound healing
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.