ID TGFB1_MOUSE Reviewed; 390 AA. AC P04202; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-1987, sequence version 1. DT 02-SEP-2026, entry version 246. DE RecName: Full=Transforming growth factor beta-1 proprotein; DE Contains: DE RecName: Full=Latency-associated peptide {ECO:0000250|UniProtKB:P01137}; DE Short=LAP; DE Contains: DE RecName: Full=Transforming growth factor beta-1 {ECO:0000250|UniProtKB:P01137}; DE Short=TGF-beta-1; DE Flags: Precursor; GN Name=Tgfb1 {ECO:0000312|MGI:MGI:98725}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3007454; DOI=10.1016/s0021-9258(17)38511-3; RA Derynck R., Jarrett J.A., Chen E.Y., Goeddel D.V.; RT "The murine transforming growth factor-beta precursor."; RL J. Biol. Chem. 261:4377-4379(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=BALB/cJ; RX PubMed=8522200; DOI=10.1016/0378-1119(95)00460-n; RA Guron C., Sudarshan C., Raghow R.; RT "Molecular organization of the gene encoding murine transforming growth RT factor beta 1."; RL Gene 165:325-326(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J, and NOD/LT; TISSUE=Spleen; RA Poirot L., Benoist C., Mathis D.; RT "Transforming growth factor-beta 1 sequence and expression: no difference RT between NOD/Lt and C57Bl/6 mouse strains."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, AND INTERACTION WITH ITGAV AND ITGB6. RX PubMed=10025398; DOI=10.1016/s0092-8674(00)80545-0; RA Munger J.S., Huang X., Kawakatsu H., Griffiths M.J., Dalton S.L., Wu J., RA Pittet J.F., Kaminski N., Garat C., Matthay M.A., Rifkin D.B., Sheppard D.; RT "The integrin alpha v beta 6 binds and activates latent TGF beta 1: a RT mechanism for regulating pulmonary inflammation and fibrosis."; RL Cell 96:319-328(1999). RN [6] RP INTERACTION WITH NREP. RX PubMed=14985127; DOI=10.1016/j.bbrc.2004.01.171; RA Paliwal S., Shi J., Dhru U., Zhou Y., Schuger L.; RT "P311 binds to the latency associated protein and downregulates the RT expression of TGF-beta1 and TGF-beta2."; RL Biochem. Biophys. Res. Commun. 315:1104-1109(2004). RN [7] RP INTERACTION WITH HTRA3. RX PubMed=15206957; DOI=10.1111/j.1440-169x.2004.00743.x; RA Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.; RT "Developmentally regulated expression of mouse HtrA3 and its role as an RT inhibitor of TGF-beta signaling."; RL Dev. Growth Differ. 46:257-274(2004). RN [8] RP INTERACTION WITH HTRA1. RX PubMed=14973287; DOI=10.1242/dev.00999; RA Oka C., Tsujimoto R., Kajikawa M., Koshiba-Takeuchi K., Ina J., Yano M., RA Tsuchiya A., Ueta Y., Soma A., Kanda H., Matsumoto M., Kawaichi M.; RT "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family RT proteins."; RL Development 131:1041-1053(2004). RN [9] RP FUNCTION. RX PubMed=18368049; DOI=10.1038/nature06878; RA Zhou L., Lopes J.E., Chong M.M., Ivanov I.I., Min R., Victora G.D., RA Shen Y., Du J., Rubtsov Y.P., Rudensky A.Y., Ziegler S.F., Littman D.R.; RT "TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by RT antagonizing RORgammat function."; RL Nature 453:236-240(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [11] RP TISSUE SPECIFICITY. RX PubMed=19745830; DOI=10.1038/cdd.2009.126; RA Huser C.A., Pringle M.A., Heath V.J., Bell A.K., Kendrick H., Smalley M.J., RA Crighton D., Ryan K.M., Gusterson B.A., Stein T.; RT "TSC-22D1 isoforms have opposing roles in mammary epithelial cell RT survival."; RL Cell Death Differ. 17:304-315(2010). RN [12] RP INTERACTION WITH THSD4. RX PubMed=21880733; DOI=10.1074/jbc.m111.243451; RA Saito M., Kurokawa M., Oda M., Oshima M., Tsutsui K., Kosaka K., Nakao K., RA Ogawa M., Manabe R., Suda N., Ganjargal G., Hada Y., Noguchi T., RA Teranaka T., Sekiguchi K., Yoneda T., Tsuji T.; RT "ADAMTSL6beta protein rescues fibrillin-1 microfibril disorder in a Marfan RT syndrome mouse model through the promotion of fibrillin-1 assembly."; RL J. Biol. Chem. 286:38602-38613(2011). RN [13] RP FUNCTION. RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003; RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.; RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth RT factor-beta pathway."; RL Cell. Signal. 24:1999-2006(2012). RN [14] RP INTERACTION WITH TSKU. RX PubMed=22995554; DOI=10.1016/j.ydbio.2012.08.030; RA Niimori D., Kawano R., Felemban A., Niimori-Kita K., Tanaka H., Ihn H., RA Ohta K.; RT "Tsukushi controls the hair cycle by regulating TGF-beta1 signaling."; RL Dev. Biol. 372:81-87(2012). RN [15] RP TISSUE SPECIFICITY. RX PubMed=26858265; DOI=10.1083/jcb.201507018; RA Dubash A.D., Kam C.Y., Aguado B.A., Patel D.M., Delmar M., Shea L.D., RA Green K.J.; RT "Plakophilin-2 loss promotes TGF-beta1/p38 MAPK-dependent fibrotic gene RT expression in cardiomyocytes."; RL J. Cell Biol. 212:425-438(2016). RN [16] RP FUNCTION, AND INTERACTION WITH NRROS. RX PubMed=29909984; DOI=10.1016/j.cell.2018.05.027; RA Qin Y., Garrison B.S., Ma W., Wang R., Jiang A., Li J., Mistry M., RA Bronson R.T., Santoro D., Franco C., Robinton D.A., Stevens B., Rossi D.J., RA Lu C., Springer T.A.; RT "A milieu molecule for TGF-beta required for microglia function in the RT nervous system."; RL Cell 174:156-171(2018). RN [17] RP FUNCTION. RX PubMed=33548622; DOI=10.1016/j.bbrc.2021.01.076; RA Zhang Y., Zhang H., Yuan G., Yang G.; RT "Effects of transforming growth factor-beta1 on odontoblastic RT differentiation in dental papilla cells is determined by IPO7 expression RT level."; RL Biochem. Biophys. Res. Commun. 545:105-111(2021). CC -!- FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of CC the Latency-associated peptide (LAP) and Transforming growth factor CC beta-1 (TGF-beta-1) chains, which constitute the regulatory and active CC subunit of TGF-beta-1, respectively. {ECO:0000250|UniProtKB:P01137}. CC -!- FUNCTION: [Latency-associated peptide]: Required to maintain the CC Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state CC during storage in extracellular matrix (PubMed:29909984). Associates CC non-covalently with TGF-beta-1 and regulates its activation via CC interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and CC LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:29909984). CC Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in CC macrophages and microglia (PubMed:29909984). Interaction with CC LRRC32/GARP controls activation of TGF-beta-1 on the surface of CC activated regulatory T-cells (Tregs) (By similarity). Interaction with CC integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the CC Latency-associated peptide chain and subsequent release of the active CC TGF-beta-1 (PubMed:10025398). {ECO:0000250|UniProtKB:P01137, CC ECO:0000269|PubMed:10025398, ECO:0000269|PubMed:29909984}. CC -!- FUNCTION: [Transforming growth factor beta-1]: Multifunctional protein CC that regulates the growth and differentiation of various cell types and CC is involved in various processes, such as normal development, immune CC function, microglia function and responses to neurodegeneration CC (PubMed:22781750, PubMed:29909984). Activation into mature form follows CC different steps: following cleavage of the proprotein in the Golgi CC apparatus, Latency-associated peptide (LAP) and Transforming growth CC factor beta-1 (TGF-beta-1) chains remain non-covalently linked CC rendering TGF-beta-1 inactive during storage in extracellular matrix CC (By similarity). At the same time, LAP chain interacts with 'milieu CC molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control CC activation of TGF-beta-1 and maintain it in a latent state during CC storage in extracellular milieus (PubMed:29909984). TGF-beta-1 is CC released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin- CC binding to LAP stabilizes an alternative conformation of the LAP bowtie CC tail and results in distortion of the LAP chain and subsequent release CC of the active TGF-beta-1 (By similarity) (PubMed:10025398). Once CC activated following release of LAP, TGF-beta-1 acts by binding to TGF- CC beta receptors (TGFBR1 and TGFBR2), which transduce signal (By CC similarity). While expressed by many cells types, TGF-beta-1 only has a CC very localized range of action within cell environment thanks to fine CC regulation of its activation by Latency-associated peptide chain (LAP) CC and 'milieu molecules' (PubMed:29909984). Plays an important role in CC bone remodeling: acts as a potent stimulator of osteoblastic bone CC formation, causing chemotaxis, proliferation and differentiation in CC committed osteoblasts (PubMed:22781750). Can promote either T-helper 17 CC cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a CC concentration-dependent manner (PubMed:18368049). At high CC concentrations, leads to FOXP3-mediated suppression of RORC and down- CC regulation of IL-17 expression, favoring Treg cell development CC (PubMed:18368049). At low concentrations in concert with IL-6 and IL- CC 21, leads to expression of the IL-17 and IL-23 receptors, favoring CC differentiation to Th17 cells (PubMed:18368049). Stimulates sustained CC production of collagen through the activation of CREB3L1 by regulated CC intramembrane proteolysis (RIP) (By similarity). Mediates SMAD2/3 CC activation by inducing its phosphorylation and subsequent translocation CC to the nucleus. Positively regulates odontoblastic differentiation in CC dental papilla cells, via promotion of IPO7-mediated translocation of CC phosphorylated SMAD2 to the nucleus and subsequent transcription of CC target genes (PubMed:33548622). Can induce epithelial-to-mesenchymal CC transition (EMT) and cell migration in various cell types (By CC similarity). {ECO:0000250|UniProtKB:P01137, CC ECO:0000269|PubMed:10025398, ECO:0000269|PubMed:18368049, CC ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:29909984, CC ECO:0000269|PubMed:33548622}. CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with CC the serine proteases, HTRA1 and HTRA3: the interaction with either CC inhibits TGFB1-mediated signaling and the HTRA protease activity is CC required for this inhibition (PubMed:14973287, PubMed:15206957). May CC interact with THSD4; this interaction may lead to sequestration by FBN1 CC microfibril assembly and attenuation of TGFB signaling CC (PubMed:21880733). Interacts with CD109, DPT and ASPN. Interacts with CC EFEMP2 (By similarity). Interacts with TSKU; the interaction CC contributes to regulation of the hair cycle (PubMed:22995554). CC Interacts with TGFBR3 (By similarity). {ECO:0000250|UniProtKB:P01137, CC ECO:0000269|PubMed:14973287, ECO:0000269|PubMed:15206957, CC ECO:0000269|PubMed:21880733, ECO:0000269|PubMed:22995554}. CC -!- SUBUNIT: [Latency-associated peptide]: Homodimer; disulfide-linked (By CC similarity). Interacts with transforming growth factor beta-1 (TGF- CC beta-1) chain; interaction is non-covalent and maintains TGF-beta-1 in CC a latent state; each latency-associated peptide (LAP) monomer interacts CC with TGF-beta-1 in the other monomer (By similarity). Interacts with CC LTBP1; leading to regulation of TGF-beta-1 activation (By similarity). CC Interacts with LRRC32/GARP; leading to regulation of TGF-beta-1 CC activation on the surface of activated regulatory T-cells (Tregs) (By CC similarity). Interacts with LRRC33/NRROS; leading to regulation of TGF- CC beta-1 activation in macrophages and microglia (PubMed:29909984). CC Interacts (via cell attachment site) with integrins ITGAV and ITGB6 CC (ITGAV:ITGB6), leading to release of the active TGF-beta-1 CC (PubMed:10025398). Interacts with NREP; the interaction results in a CC decrease in TGFB1 autoinduction (PubMed:14985127). Interacts with CC HSP90AB1; inhibits latent TGFB1 activation. CC {ECO:0000250|UniProtKB:P01137, ECO:0000269|PubMed:10025398, CC ECO:0000269|PubMed:14985127, ECO:0000269|PubMed:29909984}. CC -!- SUBUNIT: [Transforming growth factor beta-1]: Homodimer; disulfide- CC linked. Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading CC to signal transduction. {ECO:0000250|UniProtKB:P01137}. CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted, CC extracellular space, extracellular matrix CC {ECO:0000250|UniProtKB:P01137}. CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted CC {ECO:0000250|UniProtKB:P01137}. CC -!- TISSUE SPECIFICITY: Expressed in cardiomyocytes (PubMed:26858265). CC Weakly expressed in the mammary glands, with a slight increase of CC expression following onset of involution (PubMed:19745830). CC {ECO:0000269|PubMed:19745830, ECO:0000269|PubMed:26858265}. CC -!- DOMAIN: [Latency-associated peptide]: The 'straitjacket' and 'arm' CC domains encircle the Transforming growth factor beta-1 (TGF-beta-1) CC monomers and are fastened together by strong bonding between Lys-56 and CC Tyr-103/Tyr-104. {ECO:0000250|UniProtKB:P07200}. CC -!- DOMAIN: [Latency-associated peptide]: The cell attachment site motif CC mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif CC locates to a long loop in the arm domain called the bowtie tail. CC Integrin-binding stabilizes an alternative conformation of the bowtie CC tail. Activation by integrin requires force application by the actin CC cytoskeleton, which is resisted by the 'milieu molecules' (such as CC LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the CC prodomain and release of the active TGF-beta-1. CC {ECO:0000250|UniProtKB:P01137}. CC -!- PTM: Transforming growth factor beta-1 proprotein: The precursor CC proprotein is cleaved in the Golgi apparatus by FURIN to form CC Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated CC peptide (LAP) chains, which remain non-covalently linked, rendering CC TGF-beta-1 inactive. {ECO:0000250|UniProtKB:P01137}. CC -!- PTM: [Latency-associated peptide]: N-glycosylated. Deglycosylation CC leads to activation of Transforming growth factor beta-1 (TGF-beta-1); CC mechanisms triggering deglycosylation-driven activation of TGF-beta-1 CC are however unclear. {ECO:0000250|UniProtKB:P01137}. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M13177; AAA40423.1; -; mRNA. DR EMBL; L42462; AAB00138.1; -; Genomic_DNA. DR EMBL; L42456; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; L42457; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; L42458; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; L42459; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; L42460; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; L42461; AAB00138.1; JOINED; Genomic_DNA. DR EMBL; AJ009862; CAA08900.1; -; mRNA. DR EMBL; BC013738; AAH13738.1; -; mRNA. DR CCDS; CCDS20993.1; -. DR PIR; A01396; WFMS2. DR RefSeq; NP_035707.1; NM_011577.2. DR PDB; 8REX; EM; 3.00 A; A/B/C/D=1-390. DR AlphaFoldDB; P04202; -. DR EMDB; EMD-19111; -. DR SMR; P04202; -. DR BioGRID; 204157; 6. DR ComplexPortal; CPX-821; TGF-beta-1 complex. DR ComplexPortal; CPX-823; TGF-beta-1-TGFR complex. DR DIP; DIP-48640N; -. DR FunCoup; P04202; 1059. DR IntAct; P04202; 1. DR STRING; 10090.ENSMUSP00000002678; -. DR ChEMBL; CHEMBL4295696; -. DR GlyCosmos; P04202; 3 sites, No reported glycans. DR GlyGen; P04202; 3 sites, 1 N-linked glycan (2 sites). DR iPTMnet; P04202; -. DR PhosphoSitePlus; P04202; -. DR CPTAC; non-CPTAC-3952; -. DR jPOST; P04202; -. DR PaxDb; 10090-ENSMUSP00000002678; -. DR PeptideAtlas; P04202; -. DR ProteomicsDB; 263039; -. DR Pumba; P04202; -. DR Antibodypedia; 4372; 1846 antibodies from 46 providers. DR DNASU; 21803; -. DR Ensembl; ENSMUST00000002678.10; ENSMUSP00000002678.10; ENSMUSG00000002603.16. DR GeneID; 21803; -. DR KEGG; mmu:21803; -. DR UCSC; uc009ftq.1; mouse. DR AGR; MGI:98725; -. DR CTD; 7040; -. DR MGI; MGI:98725; Tgfb1. DR VEuPathDB; HostDB:ENSMUSG00000002603; -. DR eggNOG; KOG3900; Eukaryota. DR GeneTree; ENSGT00940000160457; -. DR HOGENOM; CLU_039840_0_0_1; -. DR InParanoid; P04202; -. DR OMA; SHNCCLK; -. DR OrthoDB; 8863549at2759; -. DR PhylomeDB; P04202; -. DR Reactome; R-MMU-114608; Platelet degranulation. DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres. DR Reactome; R-MMU-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-MMU-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition). DR Reactome; R-MMU-3000170; Syndecan interactions. DR Reactome; R-MMU-8941855; RUNX3 regulates CDKN1A transcription. DR Reactome; R-MMU-8941858; Regulation of RUNX3 expression and activity. DR Reactome; R-MMU-8951936; RUNX3 regulates p14-ARF. DR Reactome; R-MMU-9839389; TGFBR3 regulates TGF-beta signaling. DR BioGRID-ORCS; 21803; 2 hits in 119 CRISPR screens. DR PRO; PR:P04202; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P04202; protein. DR Bgee; ENSMUSG00000002603; Expressed in molar tooth and 218 other cell types or tissues. DR ExpressionAtlas; P04202; baseline and differential. DR GO; GO:0030424; C:axon; ISO:GO_Central. DR GO; GO:0072562; C:blood microparticle; ISS:AgBase. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0031012; C:extracellular matrix; IDA:MGI. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0005902; C:microvillus; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0030141; C:secretory granule; ISO:GO_Central. DR GO; GO:0099126; C:transforming growth factor beta complex; ISO:GO_Central. DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; ISO:GO_Central. DR GO; GO:0005125; F:cytokine activity; ISO:GO_Central. DR GO; GO:0035800; F:deubiquitinase activator activity; ISO:GO_Central. DR GO; GO:0019899; F:enzyme binding; ISO:GO_Central. DR GO; GO:0008083; F:growth factor activity; ISO:GO_Central. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central. DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:MGI. DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISS:AgBase. DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISS:UniProtKB. DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; ISS:AgBase. DR GO; GO:0002460; P:adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; IDA:BHF-UCL. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:MGI. DR GO; GO:0031100; P:animal organ regeneration; ISO:GO_Central. DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL. DR GO; GO:0006754; P:ATP biosynthetic process; ISS:UniProtKB. DR GO; GO:0060751; P:branch elongation involved in mammary gland duct branching; IMP:MGI. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; ISO:GO_Central. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI. DR GO; GO:0002362; P:CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment; TAS:UniProtKB. DR GO; GO:0001775; P:cell activation; IDA:MGI. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0000902; P:cell morphogenesis; IDA:MGI. DR GO; GO:0008283; P:cell population proliferation; IDA:MGI. DR GO; GO:0045216; P:cell-cell junction organization; ISS:UniProtKB. DR GO; GO:1905641; P:cellular response to acetaldehyde; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:GO_Central. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI. DR GO; GO:0071456; P:cellular response to hypoxia; ISO:GO_Central. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEA:Ensembl. DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:MGI. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:GO_Central. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:MGI. DR GO; GO:0098586; P:cellular response to virus; IDA:MGI. DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0002069; P:columnar/cuboidal epithelial cell maturation; IMP:MGI. DR GO; GO:0061448; P:connective tissue development; IGI:MGI. DR GO; GO:0006952; P:defense response; TAS:MGI. DR GO; GO:0050832; P:defense response to fungus; ISO:GO_Central. DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl. DR GO; GO:1990402; P:embryonic liver development; IMP:BHF-UCL. DR GO; GO:0007492; P:endoderm development; IDA:MGI. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB. DR GO; GO:0085029; P:extracellular matrix assembly; IDA:BHF-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:0060325; P:face morphogenesis; IEP:UniProtKB. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0060364; P:frontal suture morphogenesis; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IDA:MGI. DR GO; GO:0008354; P:germ cell migration; IDA:MGI. DR GO; GO:0007507; P:heart development; IMP:BHF-UCL. DR GO; GO:0003179; P:heart valve morphogenesis; IMP:BHF-UCL. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:UniProtKB. DR GO; GO:0030214; P:hyaluronan catabolic process; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IMP:MGI. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:MGI. DR GO; GO:0070306; P:lens fiber cell differentiation; IMP:MGI. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IDA:MGI. DR GO; GO:0048535; P:lymph node development; IMP:MGI. DR GO; GO:0060744; P:mammary gland branching involved in thelarche; IMP:MGI. DR GO; GO:0030879; P:mammary gland development; IDA:MGI. DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS:UniProtKB. DR GO; GO:0032943; P:mononuclear cell proliferation; IMP:MGI. DR GO; GO:0001763; P:morphogenesis of a branching structure; ISO:GO_Central. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:MGI. DR GO; GO:0042552; P:myelination; ISO:GO_Central. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IMP:MGI. DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IMP:BHF-UCL. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISS:UniProtKB. DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL. DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; ISS:UniProtKB. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IDA:UniProtKB. DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; ISS:AgBase. DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:GO_Central. DR GO; GO:0034125; P:negative regulation of MyD88-dependent toll-like receptor signaling pathway; ISO:GO_Central. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB. DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISO:GO_Central. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; ISO:GO_Central. DR GO; GO:0030279; P:negative regulation of ossification; IDA:MGI. DR GO; GO:0050765; P:negative regulation of phagocytosis; ISO:GO_Central. DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISO:GO_Central. DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; ISO:GO_Central. DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; ISS:UniProtKB. DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:MGI. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0001843; P:neural tube closure; IMP:BHF-UCL. DR GO; GO:0021915; P:neural tube development; IMP:BHF-UCL. DR GO; GO:0051402; P:neuron apoptotic process; IDA:MGI. DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI. DR GO; GO:0071895; P:odontoblast differentiation; IMP:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0014003; P:oligodendrocyte development; IMP:CACAO. DR GO; GO:0030316; P:osteoclast differentiation; IDA:MGI. DR GO; GO:0006796; P:phosphate-containing compound metabolic process; ISS:UniProtKB. DR GO; GO:0055091; P:phospholipid homeostasis; IDA:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:GO_Central. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISS:UniProtKB. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISO:GO_Central. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:GO_Central. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:GO_Central. DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISO:GO_Central. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:GO_Central. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:GO_Central. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:GO_Central. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0031536; P:positive regulation of exit from mitosis; ISO:GO_Central. DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IDA:BHF-UCL. DR GO; GO:0010763; P:positive regulation of fibroblast migration; IMP:MGI. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:GO_Central. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:GO_Central. DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; ISS:AgBase. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:GO_Central. DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; ISO:GO_Central. DR GO; GO:0014008; P:positive regulation of microglia differentiation; IMP:UniProtKB. DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:GO_Central. DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; ISO:GO_Central. DR GO; GO:0042482; P:positive regulation of odontogenesis; IDA:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:GO_Central. DR GO; GO:2000636; P:positive regulation of primary miRNA processing; ISO:GO_Central. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:AgBase. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IGI:MGI. DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISS:UniProtKB. DR GO; GO:0050714; P:positive regulation of protein secretion; ISS:UniProtKB. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:UniProtKB. DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; ISO:GO_Central. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:UniProtKB. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:MGI. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:GO_Central. DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:GO_Central. DR GO; GO:1904018; P:positive regulation of vasculature development; ISO:GO_Central. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:GO_Central. DR GO; GO:0006611; P:protein export from nucleus; ISO:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI. DR GO; GO:0032801; P:receptor catabolic process; ISS:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IGI:MGI. DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IGI:MGI. DR GO; GO:0061035; P:regulation of cartilage development; IDA:MGI. DR GO; GO:0032829; P:regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; TAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI. DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI. DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI. DR GO; GO:0032667; P:regulation of interleukin-23 production; IDA:UniProtKB. DR GO; GO:0042306; P:regulation of protein import into nucleus; IDA:MGI. DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IGI:MGI. DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:MGI. DR GO; GO:0016202; P:regulation of striated muscle tissue development; IDA:MGI. DR GO; GO:0045066; P:regulatory T cell differentiation; IDA:MGI. DR GO; GO:0070723; P:response to cholesterol; ISS:UniProtKB. DR GO; GO:0032355; P:response to estradiol; ISS:UniProtKB. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl. DR GO; GO:0034616; P:response to laminar fluid shear stress; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB. DR GO; GO:1902074; P:response to salt; IEA:Ensembl. DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; ISS:AgBase. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IDA:MGI. DR GO; GO:0007435; P:salivary gland morphogenesis; ISS:AgBase. DR GO; GO:0007519; P:skeletal muscle tissue development; TAS:MGI. DR GO; GO:0001501; P:skeletal system development; TAS:MGI. DR GO; GO:0002040; P:sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0043129; P:surfactant homeostasis; IDA:MGI. DR GO; GO:0042110; P:T cell activation; IDA:MGI. DR GO; GO:0030217; P:T cell differentiation; IMP:MGI. DR GO; GO:0043029; P:T cell homeostasis; IMP:MGI. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; TAS:UniProtKB. DR GO; GO:0002513; P:tolerance induction to self antigen; IMP:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; IMP:BHF-UCL. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR CDD; cd19384; TGF_beta_TGFB1; 1. DR FunFam; 2.10.90.10:FF:000004; Transforming growth factor beta; 1. DR FunFam; 2.60.120.970:FF:000010; Transforming growth factor beta; 1. DR Gene3D; 2.60.120.970; -; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR001839; TGF-b_C. DR InterPro; IPR001111; TGF-b_propeptide. DR InterPro; IPR016319; TGF-beta. DR InterPro; IPR015615; TGF-beta-like. DR InterPro; IPR003939; TGFb1. DR InterPro; IPR017948; TGFb_CS. DR PANTHER; PTHR11848; TGF-BETA FAMILY; 1. DR PANTHER; PTHR11848:SF125; TRANSFORMING GROWTH FACTOR BETA-1 PROPROTEIN; 1. DR Pfam; PF00019; TGF_beta; 1. DR Pfam; PF00688; TGFb_propeptide; 1. DR PIRSF; PIRSF001787; TGF-beta; 1. DR PRINTS; PR01423; TGFBETA. DR PRINTS; PR01424; TGFBETA1. DR SMART; SM00204; TGFB; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR PROSITE; PS00250; TGF_BETA_1; 1. DR PROSITE; PS51362; TGF_BETA_2; 1. DR PDBsum; 8REX; -. PE 1: Evidence at protein level; KW 3D-structure; Cleavage on pair of basic residues; Disulfide bond; KW Extracellular matrix; Glycoprotein; Growth factor; Mitogen; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..29 FT /evidence="ECO:0000250|UniProtKB:P01137" FT CHAIN 30..278 FT /note="Latency-associated peptide" FT /evidence="ECO:0000250|UniProtKB:P01137" FT /id="PRO_0000033766" FT CHAIN 279..390 FT /note="Transforming growth factor beta-1" FT /evidence="ECO:0000250|UniProtKB:P01137" FT /id="PRO_0000033767" FT REGION 30..74 FT /note="Straightjacket domain" FT /evidence="ECO:0000250|UniProtKB:P07200" FT REGION 75..271 FT /note="Arm domain" FT /evidence="ECO:0000250|UniProtKB:P07200" FT REGION 226..252 FT /note="Bowtie tail" FT /evidence="ECO:0000250|UniProtKB:P01137" FT MOTIF 244..246 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT SITE 278..279 FT /note="Cleavage; by FURIN" FT /evidence="ECO:0000250|UniProtKB:P01137" FT CARBOHYD 82 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 136 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 176 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 33 FT /note="Interchain (with C-1359 or C-1384 in LTBP1); in FT inactive form" FT /evidence="ECO:0000250|UniProtKB:P07200" FT DISULFID 223 FT /note="Interchain (with C-225)" FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 225 FT /note="Interchain (with C-223)" FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 285..294 FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 293..356 FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 322..387 FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 326..389 FT /evidence="ECO:0000250|UniProtKB:P01137" FT DISULFID 355 FT /note="Interchain" FT /evidence="ECO:0000250|UniProtKB:P01137" FT HELIX 38..56 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 75..85 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 106..112 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 122..124 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 129..136 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 147..149 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 150..156 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:8REX" FT TURN 174..177 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 185..187 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 201..208 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 212..221 FT /evidence="ECO:0007829|PDB:8REX" FT TURN 237..239 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 257..262 FT /evidence="ECO:0007829|PDB:8REX" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 282..286 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 291..295 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:8REX" FT TURN 302..305 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 310..313 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:8REX" FT TURN 329..331 FT /evidence="ECO:0007829|PDB:8REX" FT HELIX 341..345 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 348..353 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 356..370 FT /evidence="ECO:0007829|PDB:8REX" FT STRAND 373..389 FT /evidence="ECO:0007829|PDB:8REX" SQ SEQUENCE 390 AA; 44310 MW; 4381A51B711D689E CRC64; MPPSGLRLLP LLLPLPWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESADPEPEPE ADYYAKEVTR VLMVDRNNAI YEKTKDISHS IYMFFNTSDI REAVPEPPLL SRAELRLQRL KSSVEQHVEL YQKYSNNSWR YLGNRLLTPT DTPEWLSFDV TGVVRQWLNQ GDGIQGFRFS AHCSCDSKDN KLHVEINGIS PKRRGDLGTI HDMNRPFLLL MATPLERAQH LHSSRHRRAL DTNYCFSSTE KNCCVRQLYI DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SASPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS //