MGP Database

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MGP003118

UniProt Annotations

Entry Information
Gene Nametransforming growth factor, beta 1
Protein EntryTGFB1_HUMAN
UniProt IDP01137
SpeciesHuman
Comments
Comment typeDescription
DiseaseCamurati-Engelmann disease (CE) [MIM:131300]: 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. {ECO:0000269|PubMed:10973241, ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:15103729}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe '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). {ECO:0000250}.
FunctionMultifunctional 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.
InductionActivated in vitro at pH below 3.5 and over 12.5.
InteractionP05067:APP; NbExp=3; IntAct=EBI-779636, EBI-77613; Q14689:DIP2A; NbExp=2; IntAct=EBI-779636, EBI-2564275; P17813:ENG; NbExp=2; IntAct=EBI-779636, EBI-2834630; Q12841:FSTL1; NbExp=2; IntAct=EBI-779636, EBI-2349801; P36897:TGFBR1; NbExp=2; IntAct=EBI-779636, EBI-1027557; P37173:TGFBR2; NbExp=6; IntAct=EBI-779636, EBI-296151; Q03167:TGFBR3; NbExp=2; IntAct=EBI-779636, EBI-2852679; Q90998:TGFBR3 (xeno); NbExp=2; IntAct=EBI-779636, EBI-6620843; P07996:THBS1; NbExp=2; IntAct=EBI-779636, EBI-2530274;
PolymorphismIn post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls.
PtmGlycosylated. {ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952}.
PtmThe precursor is cleaved into mature TGF-beta-1 and LAP, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive.
SimilarityBelongs to the TGF-beta family. {ECO:0000305}.
Subcellular LocationSecreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:17827158}.
SubunitHomodimer; 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). Latency-associated peptide interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction (By similarity). Interacts with CD109, DPT and ASPN. {ECO:0000250, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:9895299}.
Tissue SpecificityHighly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage. {ECO:0000269|PubMed:11746498, ECO:0000269|PubMed:17827158}.
Web ResourceName=Wikipedia; Note=TGF beta-1 entry; URL="http://en.wikipedia.org/wiki/TGF_beta_1";
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