Primary Information |
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BoMiProt ID | Bomi9963 |
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Protein Name | Transforming growth factor beta-1 proprotein |
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Organism | Bos taurus |
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Uniprot ID | P18341 |
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Milk Fraction | Whey |
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Ref Sequence ID | NP_001159540.1 |
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Aminoacid Length | 390 |
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Molecular Weight | 44409 |
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FASTA Sequence |
Download |
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Gene Name | TGFB1 |
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Gene ID | 282089 |
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Protein Existence Status | reviewed |
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Secondary Information |
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Protein Function | involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration.TGFB1 directly binds to transforming growth factor beta receptor 2 (TGFBR2), a type 2 transmembrane receptor, which in turn recruits TGFBR1, a type 1 transmembrane receptor, to the TGFB1-TGFBR2 complex, leading to receptor activation through the phosphorylation of multiple serine/threonine residues within its GS box, a conserved glycine and serine-rich region just preceding the receptor kinase domain. |
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Biochemical Properties | Active TGFB1 occurs as a homodimer (molecular weight of 25 kDa) composed of two polypeptide chains, each containing 112 amino acid residues that are linked by a single disulphide bond stabilized by hydrophobic interactions. |
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Significance in milk | predominant growth factors present in milk. |
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PTMs | Glycosylation,Proteolytic cleavage |
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Site(s) of PTM(s)
N-glycosylation,
O-glycosylation,
Phosphorylation
| >sp|P18341|TGFB1_BOVIN Transforming growth factor beta-1 proprotein OS=Bos taurus OX=9913 GN=TGFB1 PE=1 SV=2
MPPSGLRLLPLLLPLLWLLMLTPGRPVAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGDVPPGPLPEAILALYN*82STRDRVAGESAETEPEPEADYYAKEVTRVLMVEYGNKI
YDKMKSSSHSIYMFFN*136TSELREAVPEPVLLSRADVRLLRLKLKVEQHVELYQKYSN*176NSWR
YLSNRLLAPSDSPEWLSFDVTGVVRQWLTRREEIEGFRLSAHCSCDSKDNTLQVDINGFS
SGRRGDLATIHGMNRPFLLLMATPLERAQHLHSSRHRRALDTNYCFSSTEKNCCVRQLYI
DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
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Predicted Disorder Regions | 63-70, 88-101 |
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DisProt Annotation | |
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TM Helix Prediction | No TM helices |
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Significance of PTMs | Proteolytic cleavage of latent TGFB1, a large inactive precursor molecule within the golgi appratus by FURIN to form TGF-beta-1 and LAP chain.N-glycosylated. Deglycosylation leads to activation of Transforming growth factor beta-1 (TGF-beta-1); mechanisms triggering deglycosylation-driven activation of TGF-beta-1 |
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Additional Comments | Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of retinoic acid-binding receptor gamma (RORC) and down-regulation of IL-17 expression, favoring Treg cell development. After proteolytic cleavage by FURIN,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. |
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Bibliography | Abdel Mouti M, Pauklin S. TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment. Mol Ther. 2021 Mar 3;29(3):920-936. doi: 10.1016/j.ymthe.2021.01.002. Epub 2021 Jan 9. PMID: 33429081; PMCID: PMC7934636. |