TGFB1
GeneName
TGFB1
Summary
TGFB1, also known as TGF beta 1, is a 44kDa secreted cytokine that plays a pivotal role in numerous biological processes, including cell growth, differentiation, and immune regulation. It is expressed in various tissues, including the extracellular matrix, cytoplasm, and cell surface, and is involved in pathways such as the transforming growth factor beta receptor signalling pathway and the regulation of cell migration. TGFB1 is known for its ability to modulate the immune response and is implicated in processes like wound healing, fibrosis, and tissue remodelling. Its diverse functions are mediated through interactions with type I, II, and III transforming growth factor beta receptors, influencing both positive and negative regulatory pathways in cellular activities.
Importance
TGFB1 is relevant to: - Fibrosis and tissue repair due to its role in extracellular matrix assembly and cellular responses to injury - Immune modulation in cancer and autoimmune diseases, as it regulates T cell differentiation and macrophage activity - Developmental processes such as embryogenesis and organogenesis, impacting heart and lung development - Pathological conditions like atherosclerosis and cancer metastasis, where it influences cell migration and invasion
Top Products
For researchers investigating TGFB1, we highly recommend the top-selling recombinant antibody, Anti-TGF beta 1 antibody [EPR21143] (ab215715). This well-cited antibody has garnered 437 citations, reflecting its strong reputation in the field. It has been validated in knockout models, ensuring reliable performance in various applications, particularly in Western blotting (WB) and immunohistochemistry (IHC). This versatility makes it an excellent choice for those seeking dependable detection of TGFB1 in their studies. The Human TGF beta 1 ELISA Kit (ab100647), with an impressive 102 citations, is an excellent option for researchers looking to accurately measure TGF beta 1 levels in their samples.
Abcam Product Citation Summary
The data indicates that TGFB1 is being extensively studied across various species, including humans, rats, and mice, in the context of different biological conditions such as cardiac fibrosis, NAFLD, and inflammatory responses. The use of Abcam antibodies in these studies highlights the importance of TGFB1 in cellular signalling and pathology.
Abcam Product Citation Table
Domain
Latency-associated peptide
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104.
Latency-associated peptide
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8) (PubMed:28117447). The motif locates to a long loop in the arm domain called the bowtie tail (PubMed:28117447). Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:28117447). Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1 (PubMed:28117447).
Function
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
Latency-associated peptide
Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:19651619, PubMed:19750484, PubMed:2022183, PubMed:22278742, PubMed:8617200, PubMed:8939931). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19651619, PubMed:19750484, PubMed:22278742). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447).
Transforming growth factor beta-1
Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:19651619, PubMed:19750484, PubMed:2022183, PubMed:22278742, PubMed:8617200, PubMed:8939931). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653, PubMed:30696809). Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292, PubMed:30696809).
Involvement in disease
Camurati-Engelmann disease
CAEND
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Inflammatory bowel disease, immunodeficiency, and encephalopathy
IBDIMDE
An autosomal recessive disorder characterized by severe infantile inflammatory bowel disease manifesting as bloody diarrhea and failure to thrive, global developmental delay, epilepsy, brain atrophy and encephalopathy. Affected individuals suffer from recurrent infections associated with impaired T-cell response to stimulation and decreased T-cell subsets, including regulatory and helper T cells.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Transforming growth factor beta-1 proprotein: The precursor proprotein is cleaved in the Golgi apparatus by FURIN to form Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-1 inactive.
Latency-associated peptide
N-glycosylated (PubMed:2493139, PubMed:28117447, PubMed:3162913). Deglycosylation leads to activation of Transforming growth factor beta-1 (TGF-beta-1); mechanisms triggering deglycosylation-driven activation of TGF-beta-1 are however unclear (PubMed:2493139).
Sequence Similarities
Belongs to the TGF-beta family.
Tissue Specificity
Highly expressed in bone (PubMed:11746498, PubMed:17827158). Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA) (PubMed:11746498, PubMed:17827158). Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage (PubMed:17827158).
Cellular localization
- Latency-associated peptide
- Secreted
- Extracellular space
- Extracellular matrix
- Transforming growth factor beta-1
- Secreted
Alternative names
TGFB, TGFB1, Transforming growth factor beta-1 proprotein