Transforming Growth Factor, Beta-1 (TGFB1) Active Protein

This gene encodes a member of the transforming growth factor beta (TGFB) family of cytokines, which are multifunctional peptides that regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. Many cells have TGFB receptors, and the protein positively and negatively regulates many other growth factors. The secreted protein is cleaved into a latency-associated peptide (LAP) and a mature TGFB1 peptide, and is found in either a latent form composed of a TGFB1 homodimer, a LAP homodimer, and a latent TGFB1-binding protein, or in an active form composed of a TGFB1 homodimer. The mature peptide may also form heterodimers with other TGFB family members. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease.

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 structure: The inactive form consists of a TGFB1 homodimer non-covalently linked to a latency-associated peptide (LAP) homodimer. The inactive complex can contain a latent TGFB1-binding protein. The active form is a homodimer of mature TGFB1; disulfide-linked. Heterodimers of TGFB1/TGFB2 have been found in bone. Interacts with CD109 and DPT. Interacts with ASPN. Ref.12 Ref.15 Ref.17

Subcellular location: Secreted › extracellular space › extracellular matrix Ref.17.

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. Ref.13 Ref.17

Induction: Activated in vitro at pH below 3.5 and over 12.5.

Post-translational modification: Glycosylated. Ref.14 Ref.16The 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.

Involvement in 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. Ref.22 Ref.23 Ref.25 Ref.26

Sequence similarities: Belongs to the TGF-beta family.