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TGFB1 (transforming growth factor beta 1)

Gene
Entrez ID Entrez Gene ID - the GENE ID in NCBI Gene database.
7040
Gene nameGene Name - the full gene name approved by the HGNC.
Transforming growth factor beta 1
Gene symbolGene Symbol - the official gene symbol approved by the HGNC, which is a short abbreviated form of the gene name.
TGFB1
SynonymsGene synonyms aliases
CED, DPD1, IBDIMDE, LAP, TGF-beta1, TGFB, TGFbeta
ChromosomeChromosome number
19
Chromosome locationChromosomal Location - indicates the cytogenetic location of the gene or region on the chromosome.
19q13.2
SummarySummary of gene provided in NCBI Entrez Gene.
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]
SNPsSNP information provided by dbSNP.
SNP ID Visualize variation Clinical significance Consequence
rs1800470 G>A,C Risk-factor, benign Coding sequence variant, missense variant
rs72480429 G>A,C Conflicting-interpretations-of-pathogenicity Coding sequence variant, synonymous variant
rs104894719 A>G Pathogenic Coding sequence variant, missense variant
rs104894720 C>T Pathogenic Coding sequence variant, missense variant
rs104894721 G>A Pathogenic Coding sequence variant, missense variant
miRNAmiRNA information provided by mirtarbase database.
miRTarBase ID miRNA Experiments Reference
MIRT005918 hsa-miR-24-3p Luciferase reporter assay, Microarray, qRT-PCR, Western blot 20945401
MIRT006059 hsa-miR-29b-3p ELISA, GFP reporter assay, qRT-PCR 21273536
MIRT006059 hsa-miR-29b-3p ELISA, Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot 27895107
MIRT006114 hsa-miR-144-3p Luciferase reporter assay, qRT-PCR 21991303
MIRT006499 hsa-miR-633 Luciferase reporter assay 20637737
Transcription factors
Transcription factor Regulation Reference
ASH1L Unknown 22488473
FOSB Unknown 10843986
FOSL2 Unknown 10843986
JUND Unknown 10843986
NFKB1 Unknown 16365456
Gene ontology (GO)Gene ontology information of associated ontologies with gene provided by GO database.
GO ID Ontology Definition Evidence Reference
GO:0000165 Process MAPK cascade IMP 21147091
GO:0001570 Process Vasculogenesis ISS
GO:0001837 Process Epithelial to mesenchymal transition IDA 25893292, 29529050
GO:0001843 Process Neural tube closure ISS
GO:0001933 Process Negative regulation of protein phosphorylation IDA 8053900
Other IDsOther ids provides unique ids of gene in databases such as OMIM, HGNC, ENSEMBLE.
MIM
HGNC
e!Ensembl
Protein
UniProt ID P01137
Protein name Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
Protein 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:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). 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:19750484, PubMed:22278742, PubMed:19651619). 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:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). 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). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292, PubMed:30696809).
PDB 1KLA , 1KLC , 1KLD , 3KFD , 4KV5 , 5FFO , 5VQP , 6OM2 , 6P7J
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF00688 TGFb_propeptide
29 261
TGF-beta propeptide
Family
PF00019 TGF_beta
292 389
Transforming growth factor beta like domain
Domain
Sequence
Sequence length 390
Interactions View interactions

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