DegronMD - P01137(TGFB1)

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: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). {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: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). {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}. View more >>

GO - Biological processes (BP): aortic valve morphogenesis [GO:0003180]; ATP biosynthetic process [GO:0006754]; BMP signaling pathway [GO:0030509]; cell-cell junction organization [GO:0045216]; cell migration [GO:0016477]; cellular response to organic cyclic compound [GO:0071407]; cellular response to transforming growth factor beta stimulus [GO:0071560]; chondrocyte differentiation [GO:0002062]; common-partner SMAD protein phosphorylation [GO:0007182]; connective tissue replacement involved in inflammatory response wound healing [GO:0002248]; embryonic liver development [GO:1990402]; epidermal growth factor receptor signaling pathway [GO:0007173]; epithelial to mesenchymal transition [GO:0001837]; extracellular matrix assembly [GO:0085029]; extrinsic apoptotic signaling pathway [GO:0097191]; heart development [GO:0007507]; heart valve morphogenesis [GO:0003179]; hematopoietic progenitor cell differentiation [GO:0002244]; hyaluronan catabolic process [GO:0030214]; inflammatory response [GO:0006954]; lipopolysaccharide-mediated signaling pathway [GO:0031663]; lymph node development [GO:0048535]; macrophage derived foam cell differentiation [GO:0010742]; MAPK cascade [GO:0000165]; membrane protein intracellular domain proteolysis [GO:0031293]; negative regulation of biomineral tissue development [GO:0070168]; negative regulation of blood vessel endothelial cell migration [GO:0043537]; negative regulation of cell-cell adhesion [GO:0022408]; negative regulation of cell cycle [GO:0045786]; negative regulation of cell differentiation [GO:0045596]; negative regulation of cell growth [GO:0030308]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cytolysis [GO:0045918]; negative regulation of epithelial cell proliferation [GO:0050680]; negative regulation of extracellular matrix disassembly [GO:0010716]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of gene expression [GO:0010629]; negative regulation of gene silencing by miRNA [GO:0060965]; negative regulation of hyaluronan biosynthetic process [GO:1900126]; negative regulation of macrophage cytokine production [GO:0010936]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of myoblast differentiation [GO:0045662]; negative regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903799]; negative regulation of protein localization to plasma membrane [GO:1903077]; negative regulation of protein phosphorylation [GO:0001933]; negative regulation of skeletal muscle tissue development [GO:0048642]; negative regulation of transcription, DNA-templated [GO:0045892]; neural tube closure [GO:0001843]; neural tube development [GO:0021915]; ossification involved in bone remodeling [GO:0043932]; pathway-restricted SMAD protein phosphorylation [GO:0060389]; phosphate-containing compound metabolic process [GO:0006796]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of bone mineralization [GO:0030501]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of cardiac muscle cell differentiation [GO:2000727]; positive regulation of cell division [GO:0051781]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cellular protein metabolic process [GO:0032270]; positive regulation of chemotaxis [GO:0050921]; positive regulation of collagen biosynthetic process [GO:0032967]; positive regulation of epithelial to mesenchymal transition [GO:0010718]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of extracellular matrix assembly [GO:1901203]; positive regulation of fibroblast migration [GO:0010763]; positive regulation of gene expression [GO:0010628]; positive regulation of interleukin-17 production [GO:0032740]; positive regulation of isotype switching to IgA isotypes [GO:0048298]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of microglia differentiation [GO:0014008]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of NAD+ ADP-ribosyltransferase activity [GO:1901666]; positive regulation of pathway-restricted SMAD protein phosphorylation [GO:0010862]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-threonine phosphorylation [GO:0010800]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552]; positive regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903800]; positive regulation of protein-containing complex assembly [GO:0031334]; positive regulation of protein dephosphorylation [GO:0035307]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein secretion [GO:0050714]; positive regulation of receptor signaling pathway via STAT [GO:1904894]; positive regulation of SMAD protein signal transduction [GO:0060391]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of superoxide anion generation [GO:0032930]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription regulatory region DNA binding [GO:2000679]; positive regulation of vascular endothelial growth factor production [GO:0010575]; positive regulation of vascular permeability [GO:0043117]; protein export from nucleus [GO:0006611]; protein kinase B signaling [GO:0043491]; protein phosphorylation [GO:0006468]; receptor catabolic process [GO:0032801]; regulation of binding [GO:0051098]; regulation of blood vessel remodeling [GO:0060312]; regulation of cell migration [GO:0030334]; regulation of cell population proliferation [GO:0042127]; regulation of DNA binding [GO:0051101]; regulation of protein import into nucleus [GO:0042306]; regulation of SMAD protein signal transduction [GO:0060390]; regulation of striated muscle tissue development [GO:0016202]; regulation of transforming growth factor beta receptor signaling pathway [GO:0017015]; response to cholesterol [GO:0070723]; response to estradiol [GO:0032355]; response to progesterone [GO:0032570]; response to wounding [GO:0009611]; salivary gland morphogenesis [GO:0007435]; SMAD protein complex assembly [GO:0007183]; SMAD protein signal transduction [GO:0060395]; transforming growth factor beta receptor signaling pathway [GO:0007179]; transforming growth factor beta receptor signaling pathway involved in heart development [GO:1905313]; vasculogenesis [GO:0001570]; ventricular cardiac muscle tissue morphogenesis [GO:0055010] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P10L	DO230334	COCA	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation altering degron motif	0.7582
p.P10L	DO229016	COCA	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation altering degron motif	0.7582
p.P10L	DO229005	COCA	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation altering degron motif	0.7582
p.P10L	DO229346	LAML	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation altering degron motif	0.7582
p.P10L	DO228947	LICA	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation altering degron motif	0.7582
p.W17L	DO232838	NACA	ICGC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation rewiring degron network	0.25
p.V20M	SIDM01169	Ovarian Carcinoma	GDSC	LRLLLLLLP	DEG_APCC_DBOX_1	6:14	Mutation rewiring degron network	0.1667

DegronMD: protein-targeted degradation, mutation and drug response to degrons

TGFB1

UniProt ID: P01137

Entrez ID: 7040

Protein name: Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TGFB1 in