ID TGFB1_HUMAN Reviewed; 390 AA. AC P01137; A8K792; Q9UCG4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 13-SEP-2023, sequence version 3. DT 04-NOV-2026, entry version 284. DE RecName: Full=Transforming growth factor beta-1 proprotein; DE Contains: DE RecName: Full=Latency-associated peptide {ECO:0000305|PubMed:2982829, ECO:0000305|PubMed:3162913, ECO:0000305|PubMed:7737999, ECO:0000305|PubMed:8471846}; DE Short=LAP; DE Contains: DE RecName: Full=Transforming growth factor beta-1 {ECO:0000305|PubMed:2982829, ECO:0000305|PubMed:3162913, ECO:0000305|PubMed:7737999, ECO:0000305|PubMed:8471846}; DE Short=TGF-beta-1; DE Flags: Precursor; GN Name=TGFB1 {ECO:0000312|HGNC:HGNC:11766}; Synonyms=TGFB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3470709; DOI=10.1093/nar/15.7.3188; RA Derynck R., Rhee L., Chen E.Y., van Tilburg A.; RT "Intron-exon structure of the human transforming growth factor-beta RT precursor gene."; RL Nucleic Acids Res. 15:3188-3189(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LEU-10 AND PRO-25. RX PubMed=3861940; DOI=10.1038/316701a0; RA Derynck R., Jarrett J.A., Chen E.Y., Eaton D.H., Bell J.R., Assoian R.K., RA Roberts A.B., Sporn M.B., Goeddel D.V.; RT "Human transforming growth factor-beta complementary DNA sequence and RT expression in normal and transformed cells."; RL Nature 316:701-705(1985). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Duodenum, and Eye; 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 279-390. RC TISSUE=Carcinoma; RA Urushizaki Y., Niitsu Y., Terui T., Koshida Y., Mahara K., Kohgo Y., RA Urushizaki I., Takahashi Y., Ito H.; RT "Cloning and expression of the gene for human transforming growth factor- RT beta in Escherichia coli."; RL Tumor Res. 22:41-55(1987). RN [8] RP PROTEIN SEQUENCE OF 279-329. RC TISSUE=Urinary bladder carcinoma; RX PubMed=8471846; DOI=10.1006/prep.1993.1019; RA Bourdrel L., Lin C.-H., Lauren S.L., Elmore R.H., Sugarman B.J., Hu S., RA Westcott K.R.; RT "Recombinant human transforming growth factor-beta 1: expression by Chinese RT hamster ovary cells, isolation, and characterization."; RL Protein Expr. Purif. 4:130-140(1993). RN [9] RP PROTEIN SEQUENCE OF 279-301. RX PubMed=2982829; DOI=10.1016/s0021-9258(18)89408-x; RA Massague J., Like B.; RT "Cellular receptors for type beta transforming growth factor. Ligand RT binding and affinity labeling in human and rodent cell lines."; RL J. Biol. Chem. 260:2636-2645(1985). RN [10] RP PROTEIN SEQUENCE OF 30-42 AND 279-290, AND GLYCOSYLATION. RX PubMed=3162913; DOI=10.1016/s0021-9258(18)68800-3; RA Miyazono K., Hellman U., Wernstedt C., Heldin C.H.; RT "Latent high molecular weight complex of transforming growth factor beta 1. RT Purification from human platelets and structural characterization."; RL J. Biol. Chem. 263:6407-6415(1988). RN [11] RP PROTEIN SEQUENCE OF 279-283, AND PROTEOLYTIC CLEAVAGE. RX PubMed=7737999; DOI=10.1074/jbc.270.18.10618; RA Dubois C.M., Laprise M.H., Blanchette F., Gentry L.E., Leduc R.; RT "Processing of transforming growth factor beta 1 precursor by human furin RT convertase."; RL J. Biol. Chem. 270:10618-10624(1995). RN [12] RP GLYCOSYLATION. RX PubMed=2493139; DOI=10.1038/338158a0; RA Miyazono K., Heldin C.H.; RT "Role for carbohydrate structures in TGF-beta 1 latency."; RL Nature 338:158-160(1989). RN [13] RP INTERACTION WITH LTBP1. RX PubMed=2022183; DOI=10.1002/j.1460-2075.1991.tb08049.x; RA Miyazono K., Olofsson A., Colosetti P., Heldin C.H.; RT "A role of the latent TGF-beta 1-binding protein in the assembly and RT secretion of TGF-beta 1."; RL EMBO J. 10:1091-1101(1991). RN [14] RP INTERACTION WITH LTBP1, AND MUTAGENESIS OF CYS-33. RX PubMed=8617200; DOI=10.1002/j.1460-2075.1996.tb00355.x; RA Saharinen J., Taipale J., Keski-Oja J.; RT "Association of the small latent transforming growth factor-beta with an RT eight cysteine repeat of its binding protein LTBP-1."; RL EMBO J. 15:245-253(1996). RN [15] RP INTERACTION WITH LTBP1. RX PubMed=8939931; DOI=10.1074/jbc.271.47.29891; RA Gleizes P.E., Beavis R.C., Mazzieri R., Shen B., Rifkin D.B.; RT "Identification and characterization of an eight-cysteine repeat of the RT latent transforming growth factor-beta binding protein-1 that mediates RT bonding to the latent transforming growth factor-beta1."; RL J. Biol. Chem. 271:29891-29896(1996). RN [16] RP REVIEW. RX PubMed=9150447; DOI=10.1038/ki.1997.188; RA Munger J.S., Harpel J.G., Gleizes P.E., Mazzieri R., Nunes I., Rifkin D.B.; RT "Latent transforming growth factor-beta: structural features and mechanisms RT of activation."; RL Kidney Int. 51:1376-1382(1997). RN [17] RP INTERACTION WITH DPT. RX PubMed=9895299; DOI=10.1042/bj3370537; RA Okamoto O., Fujiwara S., Abe M., Sato Y.; RT "Dermatopontin interacts with transforming growth factor beta and enhances RT its biological activity."; RL Biochem. J. 337:537-541(1999). RN [18] RP TISSUE SPECIFICITY. RX PubMed=11746498; DOI=10.1002/jcb.1249; RA Shur I., Lokiec F., Bleiberg I., Benayahu D.; RT "Differential gene expression of cultured human osteoblasts."; RL J. Cell. Biochem. 83:547-553(2001). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [20] RP INTERACTION WITH CD109. RX PubMed=16754747; DOI=10.1096/fj.05-5229fje; RA Finnson K.W., Tam B.Y.Y., Liu K., Marcoux A., Lepage P., Roy S., RA Bizet A.A., Philip A.; RT "Identification of CD109 as part of the TGF-beta receptor system in human RT keratinocytes."; RL FASEB J. 20:1525-1527(2006). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [22] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH ASPN. RX PubMed=17827158; DOI=10.1074/jbc.m700522200; RA Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.; RT "Mechanisms for asporin function and regulation in articular cartilage."; RL J. Biol. Chem. 282:32185-32192(2007). RN [23] RP INTERACTION WITH TGFBR3. RX PubMed=18184661; DOI=10.1074/jbc.m704883200; RA Kirkbride K.C., Townsend T.A., Bruinsma M.W., Barnett J.V., Blobe G.C.; RT "Bone morphogenetic proteins signal through the transforming growth factor- RT beta type III receptor."; RL J. Biol. Chem. 283:7628-7637(2008). RN [24] RP FUNCTION, AND INTERACTION WITH LRRC32. RX PubMed=19750484; DOI=10.1002/eji.200939684; RA Stockis J., Colau D., Coulie P.G., Lucas S.; RT "Membrane protein GARP is a receptor for latent TGF-beta on the surface of RT activated human Treg."; RL Eur. J. Immunol. 39:3315-3322(2009). RN [25] RP FUNCTION, INTERACTION WITH LRRC32, AND MUTAGENESIS OF CYS-33. RX PubMed=22278742; DOI=10.1091/mbc.e11-12-1018; RA Wang R., Zhu J., Dong X., Shi M., Lu C., Springer T.A.; RT "GARP regulates the bioavailability and activation of TGFbeta."; RL Mol. Biol. Cell 23:1129-1139(2012). RN [26] RP FUNCTION, AND INTERACTION WITH LRRC32. RX PubMed=19651619; DOI=10.1073/pnas.0901944106; RA Tran D.Q., Andersson J., Wang R., Ramsey H., Unutmaz D., Shevach E.M.; RT "GARP (LRRC32) is essential for the surface expression of latent TGF-beta RT on platelets and activated FOXP3+ regulatory T cells."; RL Proc. Natl. Acad. Sci. U.S.A. 106:13445-13450(2009). RN [27] RP INTERACTION WITH HSP90AB1. RX PubMed=20599762; DOI=10.1016/j.bbrc.2010.06.112; RA Suzuki S., Kulkarni A.B.; RT "Extracellular heat shock protein HSP90beta secreted by MG63 osteosarcoma RT cells inhibits activation of latent TGF-beta1."; RL Biochem. Biophys. Res. Commun. 398:525-531(2010). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [29] RP FUNCTION. RX PubMed=25310401; DOI=10.1371/journal.pone.0108528; RA Chen Q., Lee C.E., Denard B., Ye J.; RT "Sustained induction of collagen synthesis by TGF-beta requires regulated RT intramembrane proteolysis of CREB3L1."; RL PLoS ONE 9:E108528-E108528(2014). RN [30] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [31] RP INTERACTION WITH EFEMP2. RX PubMed=27339457; DOI=10.1016/j.matbio.2016.06.003; RA Sasaki T., Hanisch F.G., Deutzmann R., Sakai L.Y., Sakuma T., Miyamoto T., RA Yamamoto T., Hannappel E., Chu M.L., Lanig H., von der Mark K.; RT "Functional consequence of fibulin-4 missense mutations associated with RT vascular and skeletal abnormalities and cutis laxa."; RL Matrix Biol. 56:132-149(2016). RN [32] RP FUNCTION. RX PubMed=25893292; DOI=10.1038/onc.2015.100; RA Hwangbo C., Tae N., Lee S., Kim O., Park O.K., Kim J., Kwon S.H., Lee J.H.; RT "Syntenin regulates TGF-beta1-induced Smad activation and the epithelial- RT to-mesenchymal transition by inhibiting caveolin-mediated TGF-beta type I RT receptor internalization."; RL Oncogene 35:389-401(2016). RN [33] RP INTERACTION WITH PSG9. RX PubMed=27389696; DOI=10.1371/journal.pone.0158050; RA Jones K., Ballesteros A., Mentink-Kane M., Warren J., Rattila S., RA Malech H., Kang E., Dveksler G.; RT "PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF- RT beta1 Pathway."; RL PLoS ONE 11:e0158050-e0158050(2016). RN [34] RP REVIEW. RX PubMed=27252363; DOI=10.1101/cshperspect.a021907; RA Robertson I.B., Rifkin D.B.; RT "Regulation of the bioavailability of TGF-beta and TGF-beta-related RT proteins."; RL Cold Spring Harb. Perspect. Biol. 8:0-0(2016). RN [35] 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 [36] RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN IBDIMDE, VARIANTS IBDIMDE RP CYS-45; CYS-110 AND ARG-387, AND CHARACTERIZATION OF VARIANTS IBDIMDE RP CYS-45; CYS-110 AND ARG-387. RX PubMed=29483653; DOI=10.1038/s41588-018-0063-6; RA Kotlarz D., Marquardt B., Baroey T., Lee W.S., Konnikova L., Hollizeck S., RA Magg T., Lehle A.S., Walz C., Borggraefe I., Hauck F., Bufler P., Conca R., RA Wall S.M., Schumacher E.M., Misceo D., Frengen E., Bentsen B.S., RA Uhlig H.H., Hopfner K.P., Muise A.M., Snapper S.B., Stroemme P., Klein C.; RT "Human TGF-beta1 deficiency causes severe inflammatory bowel disease and RT encephalopathy."; RL Nat. Genet. 50:344-348(2018). RN [37] RP FUNCTION. RX PubMed=30696809; DOI=10.1038/s41419-019-1308-8; RA Kim J.H., Ham S., Lee Y., Suh G.Y., Lee Y.S.; RT "TTC3 contributes to TGF-beta1-induced epithelial-mesenchymal transition RT and myofibroblast differentiation, potentially through SMURF2 RT ubiquitylation and degradation."; RL Cell Death Dis. 10:92-92(2019). RN [38] RP STRUCTURE BY NMR OF 279-390. RX PubMed=8424942; DOI=10.1021/bi00055a021; RA Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., RA Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., RA Torchia D.A.; RT "Transforming growth factor beta 1: NMR signal assignments of the RT recombinant protein expressed and isotopically enriched using Chinese RT hamster ovary cells."; RL Biochemistry 32:1152-1163(1993). RN [39] RP STRUCTURE BY NMR OF 279-390. RX PubMed=8424943; DOI=10.1021/bi00055a022; RA Archer S.J., Bax A., Roberts A.B., Sporn M.B., Ogawa Y., Piez K.A., RA Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., RA Torchia D.A.; RT "Transforming growth factor beta 1: secondary structure as determined by RT heteronuclear magnetic resonance spectroscopy."; RL Biochemistry 32:1164-1171(1993). RN [40] RP STRUCTURE BY NMR OF 279-390. RX PubMed=8679613; DOI=10.1021/bi9604946; RA Hinck A.P., Archer S.J., Qian S.W., Roberts A.B., Sporn M.B., RA Weatherbee J.A., Tsang M.L.-S., Lucas R., Zheng B.-L., Wenker J., RA Torchia D.A.; RT "Transforming growth factor beta 1: three-dimensional structure in solution RT and comparison with the X-ray structure of transforming growth factor beta RT 2."; RL Biochemistry 35:8517-8534(1996). RN [41] {ECO:0007744|PDB:3KFD} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH TGFBR1 AND TGFBR2, FUNCTION, SUBUNIT, RP AND DISULFIDE BONDS. RX PubMed=20207738; DOI=10.1074/jbc.m109.079921; RA Radaev S., Zou Z., Huang T., Lafer E.M., Hinck A.P., Sun P.D.; RT "Ternary complex of transforming growth factor-beta1 reveals isoform- RT specific ligand recognition and receptor recruitment in the superfamily."; RL J. Biol. Chem. 285:14806-14814(2010). RN [42] {ECO:0007744|PDB:4KV5} RP X-RAY CRYSTALLOGRAPHY, SUBUNIT, AND DISULFIDE BONDS. RX PubMed=25209176; DOI=10.1002/pro.2548; RA Moulin A., Mathieu M., Lawrence C., Bigelow R., Levine M., Hamel C., RA Marquette J.P., Le Parc J., Loux C., Ferrari P., Capdevila C., Dumas J., RA Dumas B., Rak A., Bird J., Qiu H., Pan C.Q., Edmunds T., Wei R.R.; RT "Structures of a pan-specific antagonist antibody complexed to different RT isoforms of TGFbeta reveal structural plasticity of antibody-antigen RT interactions."; RL Protein Sci. 23:1698-1707(2014). RN [43] {ECO:0007744|PDB:5FFO} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ITGAV AND ITGB6, FUNCTION, RP INTERACTION WITH ITGAV AND ITGB6, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT RP ASN-82, AND MUTAGENESIS OF GLU-75; LEU-158; LEU-160; PRO-193; RP 232-LEU--ILE-236; 234-VAL--ILE-236; ASN-237; ASN-254 AND 257-PHE--LEU-260. RX PubMed=28117447; DOI=10.1038/nature21035; RA Dong X., Zhao B., Iacob R.E., Zhu J., Koksal A.C., Lu C., Engen J.R., RA Springer T.A.; RT "Force interacts with macromolecular structure in activation of TGF-beta."; RL Nature 542:55-59(2017). RN [44] {ECO:0007744|PDB:5VQP} RP X-RAY CRYSTALLOGRAPHY, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF RP ARG-278. RX PubMed=29109152; DOI=10.1074/jbc.m117.809657; RA Zhao B., Xu S., Dong X., Lu C., Springer T.A.; RT "Prodomain-growth factor swapping in the structure of pro-TGF-beta1."; RL J. Biol. Chem. 293:1579-1589(2018). RN [45] RP VARIANT LEU-10. RX PubMed=9783545; DOI=10.1359/jbmr.1998.13.10.1569; RA Yamada Y., Miyauchi A., Goto J., Takagi Y., Okuizumi H., Kanematsu M., RA Hase M., Takai H., Harada A., Ikeda K.; RT "Association of a polymorphism of the transforming growth factor-beta1 gene RT with genetic susceptibility to osteoporosis in postmenopausal Japanese RT women."; RL J. Bone Miner. Res. 13:1569-1576(1998). RN [46] RP VARIANTS CAEND1 CYS-218; HIS-218 AND ARG-225. RX PubMed=10973241; DOI=10.1038/79128; RA Kinoshita A., Saito T., Tomita H., Makita Y., Yoshida K., Ghadami M., RA Yamada K., Kondo S., Ikegawa S., Nishimura G., Fukushima Y., Nakagomi T., RA Saito H., Sugimoto T., Kamegaya M., Hisa K., Murray J.C., Taniguchi N., RA Niikawa N., Yoshiura K.; RT "Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease."; RL Nat. Genet. 26:19-20(2000). RN [47] RP VARIANTS CAEND1 HIS-81; CYS-218 AND ARG-225. RX PubMed=11062463; DOI=10.1038/81563; RA Janssens K., Gershoni-Baruch R., Guanabens N., Migone N., Ralston S., RA Bonduelle M., Lissens W., Van Maldergem L., Vanhoenacker F., Verbruggen L., RA Van Hul W.; RT "Mutations in the gene encoding the latency-associated peptide of TGF-beta RT 1 cause Camurati-Engelmann disease."; RL Nat. Genet. 26:273-275(2000). RN [48] RP VARIANT LEU-10. RX PubMed=12202987; DOI=10.1007/s100380200069; RA Watanabe Y., Kinoshita A., Yamada T., Ohta T., Kishino T., Matsumoto N., RA Ishikawa M., Niikawa N., Yoshiura K.; RT "A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types RT of variations in genes for transforming growth factor-beta1 (TGF-beta1) and RT its signaling pathway."; RL J. Hum. Genet. 47:478-483(2002). RN [49] RP CHARACTERIZATION OF VARIANTS CAEND1 HIS-81; CYS-218; ASP-222 AND ARG-225. RX PubMed=12493741; DOI=10.1074/jbc.m208857200; RA Janssens K., ten Dijke P., Ralston S.H., Bergmann C., Van Hul W.; RT "Transforming growth factor-beta-1 mutations in Camurati-Engelmann disease RT lead to increased signaling by altering either activation or secretion of RT the mutant protein."; RL J. Biol. Chem. 278:7718-7724(2003). RN [50] RP CHARACTERIZATION OF VARIANT CAEND1 CYS-218. RX PubMed=12843182; DOI=10.1210/jc.2002-020564; RA McGowan N.W., MacPherson H., Janssens K., Van Hul W., Frith J.C., RA Fraser W.D., Ralston S.H., Helfrich M.H.; RT "A mutation affecting the latency-associated peptide of TGFbeta1 in RT Camurati-Engelmann disease enhances osteoclast formation in vitro."; RL J. Clin. Endocrinol. Metab. 88:3321-3326(2003). RN [51] RP VARIANTS CAEND1 GLY-223 AND ARG-223. RX PubMed=15103729; DOI=10.1002/ajmg.a.20671; RA Kinoshita A., Fukumaki Y., Shirahama S., Miyahara A., Nishimura G., RA Haga N., Namba A., Ueda H., Hayashi H., Ikegawa S., Seidel J., Niikawa N., RA Yoshiura K.; RT "TGFB1 mutations in four new families with Camurati-Engelmann disease: RT confirmation of independently arising LAP-domain-specific mutations."; RL Am. J. Med. Genet. 127A:104-107(2004). 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:0000269|PubMed:29109152, CC ECO:0000303|PubMed:27252363}. 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:28117447). 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:19651619, CC PubMed:19750484, PubMed:2022183, PubMed:22278742, PubMed:8617200, CC PubMed:8939931). Interaction with LRRC33/NRROS regulates activation of CC TGF-beta-1 in macrophages and microglia (Probable). Interaction with CC LRRC32/GARP controls activation of TGF-beta-1 on the surface of CC activated regulatory T-cells (Tregs) (PubMed:19651619, PubMed:19750484, CC PubMed:22278742). Interaction with integrins (ITGAV:ITGB6 or CC ITGAV:ITGB8) results in distortion of the Latency-associated peptide CC chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, CC PubMed:28117447). {ECO:0000269|PubMed:19651619, CC ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:2022183, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447, CC ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931, CC ECO:0000305|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 (By CC similarity). Activation into mature form follows different steps: CC following cleavage of the proprotein in the Golgi apparatus, Latency- CC associated peptide (LAP) and Transforming growth factor beta-1 (TGF- CC beta-1) chains remain non-covalently linked rendering TGF-beta-1 CC inactive during storage in extracellular matrix (PubMed:29109152). At CC the same time, LAP chain interacts with 'milieu molecules', such as CC LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF- CC beta-1 and maintain it in a latent state during storage in CC extracellular milieus (PubMed:19651619, PubMed:19750484, CC PubMed:2022183, PubMed:22278742, PubMed:8617200, PubMed:8939931). TGF- CC beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): CC integrin-binding to LAP stabilizes an alternative conformation of the CC LAP bowtie tail and results in distortion of the LAP chain and CC subsequent release of the active TGF-beta-1 (PubMed:22278742, CC PubMed:28117447). Once activated following release of LAP, TGF-beta-1 CC acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which CC transduce signal (PubMed:20207738). While expressed by many cells CC types, TGF-beta-1 only has a very localized range of action within cell CC environment thanks to fine regulation of its activation by Latency- CC associated peptide chain (LAP) and 'milieu molecules' (By similarity). CC Plays an important role in bone remodeling: acts as a potent stimulator CC of osteoblastic bone formation, causing chemotaxis, proliferation and CC differentiation in committed osteoblasts (By similarity). Can promote CC either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage CC differentiation in a concentration-dependent manner (By similarity). At CC high concentrations, leads to FOXP3-mediated suppression of RORC and CC down-regulation of IL-17 expression, favoring Treg cell development (By CC similarity). At low concentrations in concert with IL-6 and IL-21, CC leads to expression of the IL-17 and IL-23 receptors, favoring CC differentiation to Th17 cells (By similarity). Stimulates sustained CC production of collagen through the activation of CREB3L1 by regulated CC intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 CC activation by inducing its phosphorylation and subsequent translocation CC to the nucleus (PubMed:25893292, PubMed:29483653, PubMed:30696809). CC Positively regulates odontoblastic differentiation in dental papilla CC cells, via promotion of IPO7-mediated translocation of phosphorylated CC SMAD2 to the nucleus and subsequent transcription of target genes (By CC similarity). Can induce epithelial-to-mesenchymal transition (EMT) and CC cell migration in various cell types (PubMed:25893292, CC PubMed:30696809). {ECO:0000250|UniProtKB:P04202, CC ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, CC ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:2022183, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25310401, CC ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:28117447, CC ECO:0000269|PubMed:29109152, ECO:0000269|PubMed:29483653, CC ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:8617200, CC ECO:0000269|PubMed:8939931}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:20207738, PubMed:25209176, CC PubMed:28117447, PubMed:29109152). Interacts with the serine proteases, CC HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated CC signaling and the HTRA protease activity is required for this CC inhibition (By similarity). May interact with THSD4; this interaction CC may lead to sequestration by FBN1 microfibril assembly and attenuation CC of TGFB signaling (By similarity). Interacts with CD109, DPT and ASPN CC (PubMed:16754747, PubMed:17827158, PubMed:9895299). Interacts with CC EFEMP2 (PubMed:27339457). Interacts with TSKU; the interaction CC contributes to regulation of the hair cycle (By similarity). CC {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:16754747, CC ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:20207738, CC ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:27339457, CC ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152, CC ECO:0000269|PubMed:9895299}. CC -!- SUBUNIT: [Latency-associated peptide]: Homodimer; disulfide-linked CC (PubMed:28117447, PubMed:29109152). Interacts with transforming growth CC factor beta-1 (TGF-beta-1) chain; interaction is non-covalent and CC maintains TGF-beta-1 in a latent state; each latency-associated peptide CC (LAP) monomer interacts with TGF-beta-1 in the other monomer CC (PubMed:29109152). Interacts with LTBP1; leading to regulation of TGF- CC beta-1 activation (PubMed:2022183, PubMed:8617200, PubMed:8939931). CC Interacts with LRRC32/GARP; leading to regulation of TGF-beta-1 CC activation on the surface of activated regulatory T-cells (Tregs) CC (PubMed:19651619, PubMed:19750484, PubMed:22278742). Interacts with CC LRRC33/NRROS; leading to regulation of TGF-beta-1 in macrophages and CC microglia (Probable). Interacts (via cell attachment site) with CC integrins ITGAV and ITGB6 (ITGAV:ITGB6), leading to release of the CC active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Interacts with CC NREP; the interaction results in a decrease in TGFB1 autoinduction (By CC similarity). Interacts with HSP90AB1; inhibits latent TGFB1 activation CC (PubMed:20599762). Interact with PSG9; leading to TGFB1 activation CC (PubMed:27389696). Interacts with TGFBR3 (PubMed:18184661). CC {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:18184661, CC ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, CC ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:20599762, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25209176, CC ECO:0000269|PubMed:27389696, ECO:0000269|PubMed:28117447, CC ECO:0000269|PubMed:29109152, ECO:0000269|PubMed:8617200, CC ECO:0000269|PubMed:8939931, ECO:0000305|PubMed:29909984}. CC -!- SUBUNIT: [Transforming growth factor beta-1]: Homodimer; disulfide- CC linked (PubMed:20207738, PubMed:25209176, PubMed:28117447, CC PubMed:29109152). Interacts with TGF-beta receptors (TGFBR1 and CC TGFBR2), leading to signal transduction (PubMed:20207738). CC {ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:25209176, CC ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152}. CC -!- INTERACTION: CC P01137; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-779636, EBI-10173507; CC P01137; P05067: APP; NbExp=3; IntAct=EBI-779636, EBI-77613; CC P01137; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-779636, EBI-744545; CC P01137; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-779636, EBI-3867333; CC P01137; Q14689: DIP2A; NbExp=2; IntAct=EBI-779636, EBI-2564275; CC P01137; P17813: ENG; NbExp=2; IntAct=EBI-779636, EBI-2834630; CC P01137; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-779636, EBI-11977403; CC P01137; Q12841: FSTL1; NbExp=2; IntAct=EBI-779636, EBI-2349801; CC P01137; P49639: HOXA1; NbExp=3; IntAct=EBI-779636, EBI-740785; CC P01137; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-779636, EBI-11959885; CC P01137; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-779636, EBI-11749135; CC P01137; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-779636, EBI-10171774; CC P01137; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-779636, EBI-10302392; CC P01137; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-779636, EBI-11962058; CC P01137; Q5T751: LCE1C; NbExp=3; IntAct=EBI-779636, EBI-12224199; CC P01137; Q5T752: LCE1D; NbExp=3; IntAct=EBI-779636, EBI-11741311; CC P01137; O14633: LCE2B; NbExp=3; IntAct=EBI-779636, EBI-11478468; CC P01137; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-779636, EBI-11973993; CC P01137; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-779636, EBI-9394625; CC P01137; Q5TA77: LCE3B; NbExp=3; IntAct=EBI-779636, EBI-11974495; CC P01137; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-779636, EBI-6658837; CC P01137; O60711: LPXN; NbExp=3; IntAct=EBI-779636, EBI-744222; CC P01137; Q14392: LRRC32; NbExp=7; IntAct=EBI-779636, EBI-15796956; CC P01137; Q14766-1: LTBP1; NbExp=4; IntAct=EBI-779636, EBI-11173861; CC P01137; Q8N2S1-1: LTBP4; NbExp=2; IntAct=EBI-779636, EBI-22016567; CC P01137; P50222: MEOX2; NbExp=3; IntAct=EBI-779636, EBI-748397; CC P01137; P07237: P4HB; NbExp=3; IntAct=EBI-779636, EBI-395883; CC P01137; Q12837: POU4F2; NbExp=3; IntAct=EBI-779636, EBI-17236143; CC P01137; P11464: PSG1; NbExp=3; IntAct=EBI-779636, EBI-716740; CC P01137; P01137: TGFB1; NbExp=2; IntAct=EBI-779636, EBI-779636; CC P01137; P36897: TGFBR1; NbExp=2; IntAct=EBI-779636, EBI-1027557; CC P01137; P37173: TGFBR2; NbExp=11; IntAct=EBI-779636, EBI-296151; CC P01137; Q03167: TGFBR3; NbExp=2; IntAct=EBI-779636, EBI-2852679; CC P01137; P07996: THBS1; NbExp=2; IntAct=EBI-779636, EBI-2530274; CC P01137; P22105: TNXB; NbExp=3; IntAct=EBI-779636, EBI-2821024; CC P01137; Q90998: TGFBR3; Xeno; NbExp=2; IntAct=EBI-779636, EBI-6620843; CC PRO_0000033762; P11464: PSG1; NbExp=2; IntAct=EBI-15487336, EBI-716740; CC -!- SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted, CC extracellular space, extracellular matrix CC {ECO:0000269|PubMed:17827158}. CC -!- SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted CC {ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:29483653}. CC -!- TISSUE SPECIFICITY: Highly expressed in bone (PubMed:11746498, CC PubMed:17827158). Abundantly expressed in articular cartilage and CC chondrocytes and is increased in osteoarthritis (OA) (PubMed:11746498, CC PubMed:17827158). Colocalizes with ASPN in chondrocytes within OA CC lesions of articular cartilage (PubMed:17827158). CC {ECO:0000269|PubMed:11746498, ECO:0000269|PubMed:17827158}. 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) CC (PubMed:28117447). The motif locates to a long loop in the arm domain CC called the bowtie tail (PubMed:28117447). Integrin-binding stabilizes CC an alternative conformation of the bowtie tail (PubMed:28117447). CC 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 (PubMed:28117447). CC {ECO:0000269|PubMed:28117447}. 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:0000269|PubMed:7737999}. CC -!- PTM: [Latency-associated peptide]: N-glycosylated (PubMed:2493139, CC PubMed:28117447, PubMed:3162913). Deglycosylation leads to activation CC of Transforming growth factor beta-1 (TGF-beta-1); mechanisms CC triggering deglycosylation-driven activation of TGF-beta-1 are however CC unclear (PubMed:2493139). {ECO:0000269|PubMed:2493139, CC ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:3162913}. CC -!- DISEASE: Camurati-Engelmann disease 1 (CAEND1) [MIM:131300]: A form of CC Camurati-Engelmann disease, an autosomal dominant disorder CC characterized by hyperostosis and sclerosis of the diaphyses of long CC bones. Sclerotic changes at the skull base may also be present. The CC disease typically presents in childhood with pain, muscular weakness, CC and waddling gait. Systemic manifestations such as anemia, leukopenia, CC and hepatosplenomegaly may also occur. {ECO:0000269|PubMed:10973241, CC ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:12493741, CC ECO:0000269|PubMed:12843182, ECO:0000269|PubMed:15103729}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Inflammatory bowel disease, immunodeficiency, and CC encephalopathy (IBDIMDE) [MIM:618213]: An autosomal recessive disorder CC characterized by severe infantile inflammatory bowel disease CC manifesting as bloody diarrhea and failure to thrive, global CC developmental delay, epilepsy, brain atrophy and encephalopathy. CC Affected individuals suffer from recurrent infections associated with CC impaired T-cell response to stimulation and decreased T-cell subsets, CC including regulatory and helper T cells. {ECO:0000269|PubMed:29483653}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: TGF-beta-1 is inactivated by fresolimumab (also named CC GC1008), a monoclonal-neutralizing antibody. CC {ECO:0000269|PubMed:25209176}. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=TGF beta-1 entry; CC URL="https://en.wikipedia.org/wiki/TGF_beta_1"; 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; X05839; CAA29283.1; -; Genomic_DNA. DR EMBL; X05840; CAA29283.1; JOINED; Genomic_DNA. DR EMBL; X05843; CAA29283.1; JOINED; Genomic_DNA. DR EMBL; X05844; CAA29283.1; JOINED; Genomic_DNA. DR EMBL; X05849; CAA29283.1; JOINED; Genomic_DNA. DR EMBL; X05850; CAA29283.1; JOINED; Genomic_DNA. DR EMBL; X02812; CAA26580.1; -; mRNA. DR EMBL; BT007245; AAP35909.1; -; mRNA. DR EMBL; AK291907; BAF84596.1; -; mRNA. DR EMBL; CH471126; EAW57032.1; -; Genomic_DNA. DR EMBL; BC001180; AAH01180.1; -; mRNA. DR EMBL; BC000125; AAH00125.1; -; mRNA. DR EMBL; BC022242; AAH22242.1; -; mRNA. DR EMBL; M38449; AAA36735.1; -; mRNA. DR CCDS; CCDS33031.1; -. DR PIR; A27513; WFHU2. DR RefSeq; NP_000651.3; NM_000660.7. DR PDB; 13FJ; X-ray; 2.75 A; A/B=279-390. DR PDB; 1KLA; NMR; -; A/B=279-390. DR PDB; 1KLC; NMR; -; A/B=279-390. DR PDB; 1KLD; NMR; -; A/B=279-390. DR PDB; 3KFD; X-ray; 3.00 A; A/B/C/D=279-390. DR PDB; 4KV5; X-ray; 3.00 A; A/B/C/D=279-390. DR PDB; 5FFO; X-ray; 3.49 A; C/D/G/H=34-390. DR PDB; 5VQP; X-ray; 2.90 A; A=30-390. DR PDB; 6GFF; X-ray; 3.10 A; A/C/E/G=30-278, B/D/F/H=279-390. DR PDB; 6OM2; X-ray; 2.77 A; E/F=242-252. DR PDB; 6P7J; X-ray; 3.50 A; A=30-278. DR PDB; 7Y1R; EM; 4.01 A; A/B=30-390. DR PDB; 7Y1T; EM; 3.24 A; D=30-390. DR PDB; 8C7H; EM; 2.70 A; A/C=30-278, B/D=279-390. DR PDB; 8REW; EM; 2.98 A; A/B/C/D=1-390. DR PDB; 8UDZ; X-ray; 2.21 A; A/B=30-390. DR PDB; 8VSC; EM; 3.00 A; A/B=1-390. DR PDB; 8VSD; EM; 3.20 A; E/F=30-390. DR PDB; 9FDY; EM; 3.40 A; A/B=279-390. DR PDB; 9FKP; EM; 3.72 A; A/B=279-390. DR PDB; 9VJJ; X-ray; 2.48 A; A/B=30-390. DR AlphaFoldDB; P01137; -. DR EMDB; EMD-16460; -. DR EMDB; EMD-19110; -. DR EMDB; EMD-33571; -. DR EMDB; EMD-33572; -. DR EMDB; EMD-33573; -. DR EMDB; EMD-43493; -. DR EMDB; EMD-43494; -. DR EMDB; EMD-50326; -. DR EMDB; EMD-50333; -. DR EMDB; EMD-50524; -. DR SASBDB; P01137; -. DR SMR; P01137; -. DR BioGRID; 112898; 367. DR ComplexPortal; CPX-529; TGF-beta-1-TGFR complex. DR ComplexPortal; CPX-602; TGF-beta-1 complex. DR CORUM; P01137; -. DR DIP; DIP-5934N; -. DR FunCoup; P01137; 1355. DR IntAct; P01137; 137. DR NDEx; IQUERY-CP-TGFB1; 111 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000221930; -. DR BindingDB; P01137; -. DR ChEMBL; CHEMBL1795178; -. DR DrugBank; DB12953; Disitertide. DR DrugBank; DB10770; Foreskin fibroblast (neonatal). DR DrugBank; DB10772; Foreskin keratinocyte (neonatal). DR DrugBank; DB11911; Galunisertib. DR DrugBank; DB14740; Hyaluronidase. DR DrugBank; DB06205; Hyaluronidase (human recombinant). DR DrugBank; DB00070; Hyaluronidase (ovine). DR DrugBank; DB04951; Pirfenidone. DR DrugBank; DB01162; Terazosin. DR DrugBank; DB06004; TG-C. DR GlyConnect; P01137; 1 N-Linked glycan (1 site). DR GlyCosmos; P01137; 3 sites, 10 glycans. DR GlyGen; P01137; 4 sites, 14 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P01137; -. DR PhosphoSitePlus; P01137; -. DR BioMuta; TGFB1; -. DR DMDM; 135674; -. DR OGP; P01137; -. DR jPOST; P01137; -. DR MassIVE; P01137; -. DR PaxDb; 9606-ENSP00000221930; -. DR PeptideAtlas; P01137; -. DR ProteomicsDB; 51337; -. DR Pumba; P01137; -. DR ABCD; P01137; 13 sequenced antibodies. DR CPTC; P01137; 1 antibody. DR DNASU; 7040; -. DR Ensembl; ENST00000221930.6; ENSP00000221930.4; ENSG00000105329.12. DR GeneID; 7040; -. DR KEGG; hsa:7040; -. DR MANE-Select; ENST00000221930.6; ENSP00000221930.4; NM_000660.7; NP_000651.3. DR UCSC; uc002oqh.4; human. DR AGR; HGNC:11766; -. DR ClinPGx; PA350; -. DR CTD; 7040; -. DR DisGeNET; 7040; -. DR GeneCards; TGFB1; -. DR GeneReviews; TGFB1; -. DR HGNC; HGNC:11766; TGFB1. DR MalaCards; TGFB1; -. DR MIM; 131300; phenotype. DR MIM; 190180; gene. DR MIM; 618213; phenotype. DR OpenTargets; ENSG00000105329; -. DR Orphanet; 1328; Camurati-Engelmann disease. DR Orphanet; 586; Cystic fibrosis. DR Orphanet; 565788; Infantile inflammatory bowel disease with neurological involvement. DR eggNOG; KOG3900; Eukaryota. DR GeneTree; ENSGT00940000160457; -. DR HOGENOM; CLU_039840_0_0_1; -. DR InParanoid; P01137; -. DR OMA; AAPDEIC; -. DR OrthoDB; 8863549at2759; -. DR PAN-GO; P01137; 6 GO annotations based on evolutionary models. DR PhylomeDB; P01137; -. DR PathwayCommons; P01137; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-168277; Influenza Virus Induced Apoptosis. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition). DR Reactome; R-HSA-3000170; Syndecan interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR Reactome; R-HSA-3304356; SMAD2/3 Phosphorylation Motif Mutants in Cancer. DR Reactome; R-HSA-3642279; TGFBR2 MSI Frameshift Mutants in Cancer. DR Reactome; R-HSA-3645790; TGFBR2 Kinase Domain Mutants in Cancer. DR Reactome; R-HSA-3656532; TGFBR1 KD Mutants in Cancer. DR Reactome; R-HSA-3656535; TGFBR1 LBD Mutants in Cancer. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-5689603; UCH proteinases. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-8941855; RUNX3 regulates CDKN1A transcription. DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity. DR Reactome; R-HSA-8951936; RUNX3 regulates p14-ARF. DR Reactome; R-HSA-9839389; TGFBR3 regulates TGF-beta signaling. DR SignaLink; P01137; -. DR SIGNOR; P01137; -. DR Agora; ENSG00000105329; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 7040; 11 hits in 1160 CRISPR screens. DR ChiTaRS; TGFB1; human. DR EvolutionaryTrace; P01137; -. DR GeneWiki; TGF_beta_1; -. DR GenomeRNAi; 7040; -. DR Pharos; P01137; Tbio. DR PRO; PR:P01137; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P01137; protein. DR ExpressionAtlas; P01137; baseline and differential. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IMP:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0099126; C:transforming growth factor beta complex; TAS:GO_Central. DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IMP:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IMP:AgBase. DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL. DR GO; GO:0034714; F:type III transforming growth factor beta receptor binding; IMP:AgBase. DR GO; GO:0002460; P:adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; IEA:Ensembl. DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL. DR GO; GO:0006754; P:ATP biosynthetic process; IDA:BHF-UCL. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0045216; P:cell-cell junction organization; IDA:BHF-UCL. DR GO; GO:1905641; P:cellular response to acetaldehyde; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IMP:BHF-UCL. 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; IEA:Ensembl. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IMP:BHF-UCL. 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:BHF-UCL. DR GO; GO:0002062; P:chondrocyte differentiation; IDA:UniProtKB. DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; TAS:BHF-UCL. DR GO; GO:0050832; P:defense response to fungus; IEA:Ensembl. DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl. DR GO; GO:1990402; P:embryonic liver development; ISS:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB. DR GO; GO:0085029; P:extracellular matrix assembly; IDA:BHF-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0060364; P:frontal suture morphogenesis; IEA:Ensembl. DR GO; GO:0007507; P:heart development; ISS:BHF-UCL. DR GO; GO:0003179; P:heart valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IDA:UniProtKB. DR GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0048535; P:lymph node development; ISS:UniProtKB. DR GO; GO:0010742; P:macrophage derived foam cell differentiation; IC:BHF-UCL. DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:UniProtKB. DR GO; GO:0001763; P:morphogenesis of a branching structure; IEA:Ensembl. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR GO; GO:0036446; P:myofibroblast differentiation; NAS:BHF-UCL. DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:BHF-UCL. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:HGNC-UCL. DR GO; GO:0045596; P:negative regulation of cell differentiation; IEP:CACAO. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0010716; P:negative regulation of extracellular matrix disassembly; TAS:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:1900126; P:negative regulation of hyaluronan biosynthetic process; IDA:UniProtKB. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl. DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:DFLAT. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:ARUK-UCL. DR GO; GO:0034125; P:negative regulation of MyD88-dependent toll-like receptor signaling pathway; IDA:UniProt. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:UniProtKB. DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IDA:ARUK-UCL. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0050765; P:negative regulation of phagocytosis; IEA:Ensembl. DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IDA:UniProtKB. DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl. DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL. DR GO; GO:0021915; P:neural tube development; ISS:BHF-UCL. DR GO; GO:0071895; P:odontoblast differentiation; ISS:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl. DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IDA:BHF-UCL. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:BHF-UCL. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:CACAO. DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IMP:BHF-UCL. DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:BHF-UCL. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:HGNC-UCL. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0031536; P:positive regulation of exit from mitosis; IEA:Ensembl. DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; ISS:BHF-UCL. DR GO; GO:0010763; P:positive regulation of fibroblast migration; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:BHF-UCL. 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; IMP:BHF-UCL. DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IDA:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL. DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IGI:BHF-UCL. DR GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:2000636; P:positive regulation of primary miRNA processing; IDA:BHF-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:BHF-UCL. DR GO; GO:0051247; P:positive regulation of protein metabolic process; IDA:BHF-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; IDA:ARUK-UCL. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IEA:Ensembl. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:ARUK-UCL. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:BHF-UCL. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; TAS:BHF-UCL. DR GO; GO:0043117; P:positive regulation of vascular permeability; IDA:UniProtKB. DR GO; GO:1904018; P:positive regulation of vasculature development; IDA:BHF-UCL. DR GO; GO:0006611; P:protein export from nucleus; IDA:BHF-UCL. DR GO; GO:0032801; P:receptor catabolic process; IDA:BHF-UCL. DR GO; GO:0060312; P:regulation of blood vessel remodeling; TAS:BHF-UCL. DR GO; GO:0030334; P:regulation of cell migration; TAS:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0032667; P:regulation of interleukin-23 production; IEA:Ensembl. DR GO; GO:0042306; P:regulation of protein import into nucleus; ISS:UniProtKB. DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISS:UniProtKB. DR GO; GO:0045066; P:regulatory T cell differentiation; IDA:UniProt. DR GO; GO:0070723; P:response to cholesterol; IDA:BHF-UCL. DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL. 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; IDA:BHF-UCL. 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; IEP:BHF-UCL. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007435; P:salivary gland morphogenesis; IEP:BHF-UCL. DR GO; GO:0002040; P:sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl. DR GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR CDD; cd19384; TGF_beta_TGFB1; 1. DR DisProt; DP01252; -. 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 IDEAL; IID00534; -. 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. PE 1: Evidence at protein level; KW 3D-structure; Cleavage on pair of basic residues; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Extracellular matrix; Glycoprotein; Growth factor; Mitogen; KW Proteomics identification; Reference proteome; Secreted; Signal. FT SIGNAL 1..29 FT /evidence="ECO:0000269|PubMed:3162913" FT CHAIN 30..278 FT /note="Latency-associated peptide" FT /evidence="ECO:0000305|PubMed:2982829, FT ECO:0000305|PubMed:3162913, ECO:0000305|PubMed:7737999, FT ECO:0000305|PubMed:8471846" FT /id="PRO_0000033762" FT CHAIN 279..390 FT /note="Transforming growth factor beta-1" FT /evidence="ECO:0000305|PubMed:2982829, FT ECO:0000305|PubMed:3162913, ECO:0000305|PubMed:7737999, FT ECO:0000305|PubMed:8471846" FT /id="PRO_0000033763" 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:0000269|PubMed:28117447" FT MOTIF 244..246 FT /note="Cell attachment site" FT /evidence="ECO:0000269|PubMed:28117447" FT SITE 278..279 FT /note="Cleavage; by FURIN" FT /evidence="ECO:0000269|PubMed:7737999" FT CARBOHYD 82 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:28117447, FT ECO:0007744|PDB:5FFO" 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:0000305|PubMed:22278742" FT DISULFID 223 FT /note="Interchain (with C-225)" FT /evidence="ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 225 FT /note="Interchain (with C-223)" FT /evidence="ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 285..294 FT /evidence="ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3KFD, FT ECO:0007744|PDB:4KV5, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 293..356 FT /evidence="ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3KFD, FT ECO:0007744|PDB:4KV5, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 322..387 FT /evidence="ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3KFD, FT ECO:0007744|PDB:4KV5, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 326..389 FT /evidence="ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152, ECO:0007744|PDB:3KFD, FT ECO:0007744|PDB:4KV5, ECO:0007744|PDB:5FFO, FT ECO:0007744|PDB:5VQP" FT DISULFID 355 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447, FT ECO:0007744|PDB:3KFD, ECO:0007744|PDB:4KV5, FT ECO:0007744|PDB:5FFO" FT VARIANT 10 FT /note="P -> L (associated with lower bone mineral density FT and higher frequency of vertebral fractures in Japanese FT post-menopausal women; dbSNP:rs1800470)" FT /evidence="ECO:0000269|PubMed:12202987, FT ECO:0000269|PubMed:3861940, ECO:0000269|PubMed:9783545" FT /id="VAR_016171" FT VARIANT 25 FT /note="R -> P (in dbSNP:rs1800471)" FT /evidence="ECO:0000269|PubMed:3861940" FT /id="VAR_016172" FT VARIANT 45 FT /note="R -> C (in IBDIMDE; decreased TGFB1-mediated FT activation of SMAD signaling; reduced levels of secreted FT TGFB1; dbSNP:rs1555755308)" FT /evidence="ECO:0000269|PubMed:29483653" FT /id="VAR_081584" FT VARIANT 81 FT /note="Y -> H (in CAEND1; leads to TGF-beta-1 intracellular FT accumulation; dbSNP:rs111033611)" FT /evidence="ECO:0000269|PubMed:11062463, FT ECO:0000269|PubMed:12493741" FT /id="VAR_017607" FT VARIANT 110 FT /note="R -> C (in IBDIMDE; decreased TGFB1-mediated FT activation of SMAD signaling; reduced levels of secreted FT TGFB1; dbSNP:rs1555755242)" FT /evidence="ECO:0000269|PubMed:29483653" FT /id="VAR_081585" FT VARIANT 218 FT /note="R -> C (in CAEND1; higher levels of active FT TGF-beta-1 in the culture medium; enhances osteoclast FT formation in vitro; dbSNP:rs104894721)" FT /evidence="ECO:0000269|PubMed:10973241, FT ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:12493741, FT ECO:0000269|PubMed:12843182" FT /id="VAR_017608" FT VARIANT 218 FT /note="R -> H (in CAEND1; dbSNP:rs104894720)" FT /evidence="ECO:0000269|PubMed:10973241" FT /id="VAR_017609" FT VARIANT 222 FT /note="H -> D (in CAEND1; sporadic case; higher levels of FT active TGF-beta-1 in the culture medium; FT dbSNP:rs281865485)" FT /evidence="ECO:0000269|PubMed:12493741" FT /id="VAR_017610" FT VARIANT 223 FT /note="C -> G (in CAEND1; dbSNP:rs104894722)" FT /evidence="ECO:0000269|PubMed:15103729" FT /id="VAR_067303" FT VARIANT 223 FT /note="C -> R (in CAEND1; dbSNP:rs104894722)" FT /evidence="ECO:0000269|PubMed:15103729" FT /id="VAR_067304" FT VARIANT 225 FT /note="C -> R (in CAEND1; higher levels of active FT TGF-beta-1 in the culture medium; dbSNP:rs104894719)" FT /evidence="ECO:0000269|PubMed:10973241, FT ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:12493741" FT /id="VAR_017611" FT VARIANT 263 FT /note="T -> I (in dbSNP:rs1800472)" FT /id="VAR_016173" FT VARIANT 387 FT /note="C -> R (in IBDIMDE; loss of TGFB1-mediated FT activation of SMAD signaling; mutant TGFB1 is not secreted; FT dbSNP:rs1336387628)" FT /evidence="ECO:0000269|PubMed:29483653" FT /id="VAR_081586" FT MUTAGEN 33 FT /note="C->S: Abolishes interchain disulfide bond with LTBP1 FT and/or LRRC32, and subsequent regulation of activation of FT TGF-beta-1." FT /evidence="ECO:0000269|PubMed:22278742, FT ECO:0000269|PubMed:8617200" FT MUTAGEN 75 FT /note="E->A: Does not affect integrin-binding or activation FT of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 158 FT /note="L->A: Does not affect integrin-binding or activation FT of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 160 FT /note="L->A,R: Does not affect integrin-binding or FT activation of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 193 FT /note="P->A,R: Does not affect integrin-binding or FT activation of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 232..236 FT /note="LQVDI->GQGDG: Strongly inhibits integrin-binding and FT activation of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 234..236 FT /note="VDI->GDG: Strongly inhibits integrin-binding and FT activation of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 237 FT /note="N->A: Does not affect integrin-binding or activation FT of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 254 FT /note="N->A: Does not affect integrin-binding or activation FT of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 257..260 FT /note="FLLL->GLLG: Strongly inhibits integrin-binding and FT activation of TGF-beta-1." FT /evidence="ECO:0000269|PubMed:28117447" FT MUTAGEN 278 FT /note="R->A: Prevents cleavage and subsequent maturation of FT the protein. Generated in order to mimic the structure of FT the Transforming growth factor beta-1 proprotein." FT /evidence="ECO:0000269|PubMed:29109152" FT CONFLICT 159 FT /note="R -> RR (in Ref. 2; CAA26580)" FT /evidence="ECO:0000305" FT HELIX 38..56 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:9VJJ" FT HELIX 75..85 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 106..112 FT /evidence="ECO:0007829|PDB:8UDZ" FT TURN 116..119 FT /evidence="ECO:0007829|PDB:6GFF" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:8UDZ" FT TURN 123..126 FT /evidence="ECO:0007829|PDB:5VQP" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 147..149 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 150..157 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 184..187 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 196..199 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 201..207 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 214..221 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 224..230 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:5FFO" FT STRAND 245..248 FT /evidence="ECO:0007829|PDB:6OM2" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:5VQP" FT STRAND 257..262 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 265..268 FT /evidence="ECO:0007829|PDB:9VJJ" FT HELIX 282..288 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 302..306 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:9VJJ" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:8UDZ" FT HELIX 329..331 FT /evidence="ECO:0007829|PDB:8REW" FT TURN 337..340 FT /evidence="ECO:0007829|PDB:8C7H" FT TURN 344..346 FT /evidence="ECO:0007829|PDB:8UDZ" FT TURN 348..350 FT /evidence="ECO:0007829|PDB:8REW" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:8REW" FT STRAND 356..370 FT /evidence="ECO:0007829|PDB:8UDZ" FT STRAND 373..389 FT /evidence="ECO:0007829|PDB:8UDZ" SQ SEQUENCE 390 AA; 44325 MW; 71785979662FC4BE CRC64; MPPSGLRLLP LLLPLLWLLV LTPGRPAAGL STCKTIDMEL VKRKRIEAIR GQILSKLRLA SPPSQGEVPP GPLPEAVLAL YNSTRDRVAG ESAEPEPEPE ADYYAKEVTR VLMVETHNEI YDKFKQSTHS IYMFFNTSEL REAVPEPVLL SRAELRLLRL KLKVEQHVEL YQKYSNNSWR YLSNRLLAPS DSPEWLSFDV TGVVRQWLSR GGEIEGFRLS AHCSCDSRDN TLQVDINGFT TGRRGDLATI HGMNRPFLLL MATPLERAQH LQSSRHRRAL DTNYCFSSTE KNCCVRQLYI DFRKDLGWKW IHEPKGYHAN FCLGPCPYIW SLDTQYSKVL ALYNQHNPGA SAAPCCVPQA LEPLPIVYYV GRKPKVEQLS NMIVRSCKCS //