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Molecule Details

General Information of the Molecule
Name
Transforming growth factor beta 1 (TGFB1)
Synonyms
Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1; TGFB; TGF-beta1; TGF-beta 1
Gene Name
TGFB1
Gene ID
7040
Sequence
MPPSGLRLLLLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI
YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR
YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT
TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI
DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
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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. 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. 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). 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; [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. 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. 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. Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal. 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). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types
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Uniprot ID
TGFB1_HUMAN
Pfam
PF00019 ; PF00688
KEGG ID
hsa7040
TTD ID
T97257
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Jerusalem artichoke + Interferon alpha-2a + Ribavirin
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Jerusalem artichoke   NP Info     Drug Info 
Interferon alpha-2a   NP Info 
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Asiaticoside   NP Info  + Rapamycin   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triamcinolone   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Anti-PD-1 antibody   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Hesperidin   NP Info  + Diethylcarbamazine   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Oxaliplatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Heparin   NP Info  + X-ray irradiation   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Paclitaxel   NP Info  + Decitabine   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Cryptotanshinone  NP Info  Investigative Salvia miltiorrhiza
2 Scutellarin  NP Info  Investigative Scutellaria indica
References
Reference 1 Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats. Asian Pac J Cancer Prev. 2016;17(4):1979-85.
Reference 2 Combination treatment with asiaticoside and rapamycin: A new hope for in-stent restenosis. Exp Ther Med. 2013 Aug;6(2):557-561.
Reference 3 A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro. J Plast Reconstr Aesthet Surg. 2013 Sep;66(9):e251-9.
Reference 4 Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma. Life Sci. 2021 Mar 19;279:119359.
Reference 5 Antifibrotic effect of diethylcarbamazine combined with hesperidin against ethanol induced liver fibrosis in rats. Biomed Pharmacother. 2017 May;89:1196-1206.
Reference 6 Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. Int J Cancer. 2011 Jul 15;129(2):476-86.
Reference 7 Combination of nadroparin with radiotherapy results in powerful synergistic antitumor effects in lung adenocarcinoma A549 cells. Oncol Rep. 2016 Oct;36(4):2200-6.
Reference 8 VHL-TGFBI signaling is involved in the synergy between 5-aza-2'-deoxycytidine and paclitaxel against human renal cell carcinoma. J BUON. Mar-Apr 2017;22(2):500-507.
Reference 9 Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats. Drug Des Devel Ther. 2016 Jul 11;10:2239-53.
Reference 10 Activation of dynamin-related protein 1 - dependent mitochondria fragmentation and suppression of osteosarcoma by cryptotanshinone. J Exp Clin Cancer Res. 2019 Jan 28;38(1):42.
Reference 11 Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFBeta1 expression and activation of p38-MAPK and ERK1/2. Br J Pharmacol. 2011 Feb;162(3):688-700.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China