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transforming growth factor beta-1; TGF-beta-1; contains: latency-associated peptide; LAP (TGFB1 TGFB)
Function:
- multifunctional protein
- controls proliferation, differentiation & other functions in many cell types
- many cells synthesize TGFB1 & have specific receptors for it
- positively & negatively regulates many other growth factors
- role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation & differentiation in committed osteoblasts
- the precursor is cleaved into mature TGF-beta-1 & latency-associated peptide (LAP_, which remains non-covalently linked to mature TGF-beta-1 rendering it inactive
- the inactive form consists of a TGFB1 homodimer non-covalently linked to a latency-associated peptide (LAP)
- later disulfide-linked to a latent TGFB1-binding protein anchored to the extracellular matrix
- the active form is a homodimer of mature TGFB1, disulfide-linked
- heterodimers of TGFB1/TGFB2 have been found in bone
- interacts with CD109 & DPT
- interacts with ASPN
- activated in vitro at pH below 3.5 & over 12.5
Structure:
- homodimer, disulfide-linked
- glycosylated
- the 'straitjacket' & 'arm' domains encircle the growth factor monomers & are fastened together by strong bonding between Lys-56 & Tyr-103/Tyr-104
- activation of TGF-beta1 requires the binding of integrin alpha-V to an RGD sequence in the prodomain & 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 & releases the active growth factor dimer (putative)
- belongs to the TGF-beta family
Compartment:
- secreted, extracellular space, extracellular matrix
Expression:
- highly expressed in bone
- abundantly expressed in articular cartilage & chondrocytes
Polymorphism:
- in post-menopausal Japanese women, the frequency of Leu-10 is higher in subjects with osteoporosis than in controls
Pathology:
- expression is increased in osteoarthritis (OA)
- co-localizes with ASPN in chondrocytes within OA lesions of articular cartilage
- defects in TGFB1 are the cause of Camurati-Engelmann disease
Related
TGF-beta 1 gene
General
glycoprotein
transforming growth factor [TGF]-beta
Properties
CONFIGURATION:
dimer
SIZE: entity length = 390 aa
MW = 44 kD
COMPARTMENT:
extracellular compartment
MOTIF:
signal sequence {1-29}
Straightjacket domain {30-74}
MOTIF: cysteine residue {C33}
MODIFICATION: cysteine residue {C1359}
Arm domain {75-271}
MOTIF: N-glycosylation site {N82}
N-glycosylation site {N136}
N-glycosylation site {N176}
cysteine residue {C223}
MODIFICATION: cysteine residue {C225}
cysteine residue {C225}
MODIFICATION: cysteine residue {C223}
Cell attachment site {244-246}
cysteine residue {C285}
MODIFICATION: cysteine residue {C294}
cysteine residue {C293}
MODIFICATION: cysteine residue {C356}
cysteine residue {C294}
MODIFICATION: cysteine residue {C285}
cysteine residue {C322}
MODIFICATION: cysteine residue {C387}
cysteine residue {C326}
MODIFICATION: cysteine residue {C389}
cysteine residue {C355}
MODIFICATION: cysteine residue {C-INTERCHAIN}
cysteine residue {C356}
MODIFICATION: cysteine residue {C293}
cysteine residue {C387}
MODIFICATION: cysteine residue {C322}
cysteine residue {C389}
MODIFICATION: cysteine residue {C326}
SECRETED-BY:
platelet
macrophage
monocyte
T-cell
endothelial cell
fibroblast
Database Correlations
OMIM correlations
MORBIDMAP 190180
UniProt P01137
PFAM correlations
Entrez Gene 7040
Kegg hsa:7040
References
- Sporn MB, Roberts AB.
Interactions of retinoids and transforming growth factor-beta
in regulation of cell differentiation and proliferation.
Mol Endocrinol. 1991 Jan;5(1):3-7. Review.
PMID: 2017191
- Entrez Gene :accession 7040
- UniProt :accession P01137
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/TGFB1
- Wikipedia; Note: TGF beta-1 entry
http://en.wikipedia.org/wiki/TGF_beta_1