TGFB1
entrez
7040
canonical
uniprot
P01137
canonical
ensembl
ENSG00000105329
resolver
ensp
ENSP00000221930
resolver
ensp
ENSP00000560173
resolver
enst
ENST00000221930
resolver
genesymbol
TGFB1
resolver
genesymbol_syn
TGFB
resolver
hgnc
HGNC:11766
resolver
uniprot
A0A499FJK2
resolver
uniprot
A8K792
resolver
uniprot
Q9UCG4
resolver
uniprot_entry
A0A499FJK2_HUMAN
resolver
uniprot_entry
TGFB1_HUMAN
resolver
uniprot_sec
A8K792
resolver
uniprot_sec
Q9UCG4
resolver
amino_acid_sequence
MPPSGLRLLPLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEIYDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWRYLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFTTGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
uniprot
proteins
disease_involvement
DISEASE: Camurati-Engelmann disease 1 (CAEND1) [MIM:131300]: A form of Camurati-Engelmann disease, an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. Sclerotic changes at the skull base may also be present. The disease typically presents in childhood with pain, muscular weakness, and waddling gait. Systemic manifestations such as anemia, leukopenia, and hepatosplenomegaly may also occur. {ECO:0000269|PubMed:10973241, ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:12493741, ECO:0000269|PubMed:12843182, ECO:0000269|PubMed:15103729}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Inflammatory bowel disease, immunodeficiency, and encephalopathy (IBDIMDE) [MIM:618213]: 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. {ECO:0000269|PubMed:29483653}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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. {ECO:0000269|PubMed:29109152, ECO:0000303|PubMed:27252363}.; FUNCTION: [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). {ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931, ECO:0000305|PubMed:29909984}.; FUNCTION: [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). {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152, ECO:0000269|PubMed:29483653, ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}.
uniprot
proteins
mass_dalton
44325
uniprot
proteins
mutagenesis
MUTAGEN 33; /note="C->S: Abolishes interchain disulfide bond with LTBP1 and/or LRRC32, and subsequent regulation of activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200"; MUTAGEN 75; /note="E->A: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 158; /note="L->A: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 160; /note="L->A,R: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 193; /note="P->A,R: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 232..236; /note="LQVDI->GQGDG: Strongly inhibits integrin-binding and activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 234..236; /note="VDI->GDG: Strongly inhibits integrin-binding and activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 237; /note="N->A: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 254; /note="N->A: Does not affect integrin-binding or activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 257..260; /note="FLLL->GLLG: Strongly inhibits integrin-binding and activation of TGF-beta-1."; /evidence="ECO:0000269|PubMed:28117447"; MUTAGEN 278; /note="R->A: Prevents cleavage and subsequent maturation of the protein. Generated in order to mimic the structure of the Transforming growth factor beta-1 proprotein."; /evidence="ECO:0000269|PubMed:29109152
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:7737999}.; PTM: [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). {ECO:0000269|PubMed:2493139, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:3162913}.
uniprot
proteins
protein_family
TGF-beta family
uniprot
proteins
pubmed
10973241
uniprot
proteins
pubmed
11062463
uniprot
proteins
pubmed
11746498
uniprot
proteins
pubmed
12202987
uniprot
proteins
pubmed
12493741
uniprot
proteins
pubmed
12843182
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15103729
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16754747
uniprot
proteins
pubmed
17827158
uniprot
proteins
pubmed
18184661
uniprot
proteins
pubmed
19651619
uniprot
proteins
pubmed
19750484
uniprot
proteins
pubmed
20207738
uniprot
proteins
pubmed
2022183
uniprot
proteins
pubmed
20599762
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22278742
uniprot
proteins
pubmed
2493139
uniprot
proteins
pubmed
25209176
uniprot
proteins
pubmed
25310401
uniprot
proteins
pubmed
25893292
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27252363
uniprot
proteins
pubmed
27339457
uniprot
proteins
pubmed
27389696
uniprot
proteins
pubmed
28117447
uniprot
proteins
pubmed
29109152
uniprot
proteins
pubmed
29483653
uniprot
proteins
pubmed
2982829
uniprot
proteins
pubmed
29909984
uniprot
proteins
pubmed
30696809
uniprot
proteins
pubmed
3162913
uniprot
proteins
pubmed
3470709
uniprot
proteins
pubmed
3861940
uniprot
proteins
pubmed
7737999
uniprot
proteins
pubmed
8424942
uniprot
proteins
pubmed
8424943
uniprot
proteins
pubmed
8471846
uniprot
proteins
pubmed
8617200
uniprot
proteins
pubmed
8679613
uniprot
proteins
pubmed
8939931
uniprot
proteins
pubmed
9150447
uniprot
proteins
pubmed
9783545
uniprot
proteins
pubmed
9895299
uniprot
proteins
sequence_length
390
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:17827158}.; SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted {ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:29483653}.
uniprot
proteins