ID TGFB1_HUMAN Reviewed; 390 AA. AC P01137; A8K792; Q9UCG4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 2. DT 13-FEB-2019, entry version 243. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 PRO-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., RA Assoian R.K., 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 RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT factor-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., RA Hu S., Westcott K.R.; RT "Recombinant human transforming growth factor-beta 1: expression by RT Chinese 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; 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; RA Miyazono K., Hellman U., Wernstedt C., Heldin C.H.; RT "Latent high molecular weight complex of transforming growth factor RT beta 1. Purification from human platelets and structural RT characterization."; RL J. Biol. Chem. 263:6407-6415(1988). RN [11] RP PROTEIN SEQUENCE OF 279-283, AND PROTEOLYTIC CLEAVAGE. RX PubMed=7737999; 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 RT furin 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; 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; RA Saharinen J., Taipale J., Keski-Oja J.; RT "Association of the small latent transforming growth factor-beta with RT an 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; RA Gleizes P.E., Beavis R.C., Mazzieri R., Shen B., Rifkin D.B.; RT "Identification and characterization of an eight-cysteine repeat of RT the latent transforming growth factor-beta binding protein-1 that RT mediates 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., RA Rifkin D.B.; RT "Latent transforming growth factor-beta: structural features and RT mechanisms 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 RT enhances 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., RA Moore R.J., 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 RT human 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 RT cartilage."; RL J. Biol. Chem. 282:32185-32192(2007). RN [23] 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 RT surface of activated human Treg."; RL Eur. J. Immunol. 39:3315-3322(2009). RN [24] 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 [25] 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- RT beta on platelets and activated FOXP3+ regulatory T cells."; RL Proc. Natl. Acad. Sci. U.S.A. 106:13445-13450(2009). RN [26] 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 RT osteosarcoma cells inhibits activation of latent TGF-beta1."; RL Biochem. Biophys. Res. Commun. 398:525-531(2010). RN [27] 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., RA Buerckstuemmer T., 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 [28] 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 RT regulated intramembrane proteolysis of CREB3L1."; RL PLoS ONE 9:E108528-E108528(2014). RN [29] 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., RA Ayoub D., 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 [30] 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., RA Lee J.H.; RT "Syntenin regulates TGF-beta1-induced Smad activation and the RT epithelial-to-mesenchymal transition by inhibiting caveolin-mediated RT TGF-beta type I receptor internalization."; RL Oncogene 35:389-401(2016). RN [31] 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 [32] 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., RA Rossi D.J., 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 [33] 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 [34] 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 RT by heteronuclear magnetic resonance spectroscopy."; RL Biochemistry 32:1164-1171(1993). RN [35] 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 RT solution and comparison with the X-ray structure of transforming RT growth factor beta 2."; RL Biochemistry 35:8517-8534(1996). RN [36] {ECO:0000244|PDB:3KFD} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 279-390 IN COMPLEX WITH RP TGFBR1 AND TGFBR2, FUNCTION, SUBUNIT, 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 RT superfamily."; RL J. Biol. Chem. 285:14806-14814(2010). RN [37] {ECO:0000244|PDB:4KV5} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 279-390, SUBUNIT, AND RP 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., RA Dumas J., Dumas B., Rak A., Bird J., Qiu H., Pan C.Q., Edmunds T., RA Wei R.R.; RT "Structures of a pan-specific antagonist antibody complexed to RT different isoforms of TGFbeta reveal structural plasticity of RT antibody-antigen interactions."; RL Protein Sci. 23:1698-1707(2014). RN [38] {ECO:0000244|PDB:5FFO} RP X-RAY CRYSTALLOGRAPHY (3.49 ANGSTROMS) OF 34-390 IN COMPLEX WITH ITGAV RP AND ITGB6, FUNCTION, INTERACTION WITH ITGAV AND ITGB6, SUBUNIT, RP DISULFIDE BOND, GLYCOSYLATION AT ASN-82, AND MUTAGENESIS OF GLU-75; RP LEU-158; LEU-160; PRO-193; 232-LEU--ILE-236; 234-VAL--ILE-236; RP 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- RT beta."; RL Nature 542:55-59(2017). RN [39] {ECO:0000244|PDB:5VQP} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 30-390, SUBUNIT, DISULFIDE RP BONDS, AND MUTAGENESIS OF 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 [40] RP VARIANT PRO-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 RT gene with genetic susceptibility to osteoporosis in postmenopausal RT Japanese women."; RL J. Bone Miner. Res. 13:1569-1576(1998). RN [41] RP VARIANTS CAEND 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., RA Nakagomi T., Saito H., Sugimoto T., Kamegaya M., Hisa K., Murray J.C., RA Taniguchi N., Niikawa N., Yoshiura K.; RT "Domain-specific mutations in TGFB1 result in Camurati-Engelmann RT disease."; RL Nat. Genet. 26:19-20(2000). RN [42] RP VARIANTS CAEND 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., RA Verbruggen L., Van Hul W.; RT "Mutations in the gene encoding the latency-associated peptide of TGF- RT beta 1 cause Camurati-Engelmann disease."; RL Nat. Genet. 26:273-275(2000). RN [43] RP VARIANT PRO-10. RX PubMed=12202987; DOI=10.1007/s100380200069; RA Watanabe Y., Kinoshita A., Yamada T., Ohta T., Kishino T., RA Matsumoto N., Ishikawa M., Niikawa N., Yoshiura K.; RT "A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other RT types of variations in genes for transforming growth factor-beta1 RT (TGF-beta1) and its signaling pathway."; RL J. Hum. Genet. 47:478-483(2002). RN [44] RP CHARACTERIZATION OF VARIANTS CAEND HIS-81; CYS-218; ASP-222 AND RP 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 RT disease lead to increased signaling by altering either activation or RT secretion of the mutant protein."; RL J. Biol. Chem. 278:7718-7724(2003). RN [45] RP CHARACTERIZATION OF VARIANT CAEND 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 [46] RP VARIANTS CAEND 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., RA Niikawa N., 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 CC of the Latency-associated peptide (LAP) and Transforming growth CC factor beta-1 (TGF-beta-1) chains, which constitute the regulatory CC and active subunit of TGF-beta-1, respectively. CC {ECO:0000269|PubMed:29109152, 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 CC state during storage in extracellular matrix (PubMed:28117447). CC Associates non-covalently with TGF-beta-1 and regulates its CC activation via interaction with 'milieu molecules', such as LTBP1, CC LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta- CC 1 (PubMed:2022183, PubMed:8617200, PubMed:8939931, CC PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction CC with LRRC33/NRROS regulates activation of TGF-beta-1 in CC macrophages and microglia (Probable). Interaction with LRRC32/GARP CC controls activation of TGF-beta-1 on the surface of activated CC regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, CC PubMed:19651619). Interaction with integrins (ITGAV:ITGB6 or CC ITGAV:ITGB8) results in distortion of the Latency-associated CC peptide chain and subsequent release of the active TGF-beta-1 CC (PubMed:22278742, 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 CC protein that regulates the growth and differentiation of various CC cell types and is involved in various processes, such as normal CC development, immune function, microglia function and responses to CC neurodegeneration (By similarity). Activation into mature form CC follows different steps: following cleavage of the proprotein in CC the Golgi apparatus, Latency-associated peptide (LAP) and CC Transforming growth factor beta-1 (TGF-beta-1) chains remain non- CC covalently linked rendering TGF-beta-1 inactive during storage in CC extracellular matrix (PubMed:29109152). At the same time, LAP CC chain interacts with 'milieu molecules', such as LTBP1, CC LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 CC and maintain it in a latent state during storage in extracellular CC milieus (PubMed:2022183, PubMed:8617200, PubMed:8939931, CC PubMed:19750484, PubMed:22278742, PubMed:19651619). TGF-beta-1 is CC released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): CC integrin-binding to LAP stabilizes an alternative conformation of CC the 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- CC beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), CC which transduce signal (PubMed:20207738). While expressed by many CC cells types, TGF-beta-1 only has a very localized range of action CC within cell environment thanks to fine regulation of its CC activation by Latency-associated peptide chain (LAP) and 'milieu CC molecules' (By similarity). Plays an important role in bone CC remodeling: acts as a potent stimulator of osteoblastic bone CC formation, causing chemotaxis, proliferation and differentiation CC in committed osteoblasts (By similarity). Can promote either T- CC helper 17 cells (Th17) or regulatory T-cells (Treg) lineage CC differentiation in a concentration-dependent manner (By CC similarity). At high concentrations, leads to FOXP3-mediated CC suppression of RORC and down-regulation of IL-17 expression, CC favoring Treg cell development (By similarity). At low CC concentrations in concert with IL-6 and IL-21, leads to expression CC of the IL-17 and IL-23 receptors, favoring differentiation to Th17 CC cells (By similarity). Stimulates sustained production of collagen CC through the activation of CREB3L1 by regulated intramembrane CC proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation CC by inducing its phosphorylation and subsequent translocation to CC the nucleus (PubMed:25893292). Can induce epithelial-to- CC mesenchymal transition (EMT) and cell migration in various cell CC types (PubMed:25893292). {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:8617200, CC ECO:0000269|PubMed:8939931}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:20207738, CC PubMed:25209176, PubMed:28117447, PubMed:29109152). Interacts with CC the serine proteases, HTRA1 and HTRA3: the interaction with either CC inhibits TGFB1-mediated signaling. The HTRA protease activity is CC required for this inhibition (By similarity). May interact with CC THSD4; this interaction may lead to sequestration by FBN1 CC microfibril assembly and attenuation of TGFB signaling (By CC similarity). Interacts with CD109, DPT and ASPN (PubMed:9895299, CC PubMed:16754747, PubMed:17827158). Latency-associated peptide: CC Homodimer; disulfide-linked (PubMed:28117447, PubMed:29109152). CC Latency-associated peptide: 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 CC peptide (LAP) monomer interacts with TGF-beta-1 in the other CC monomer (PubMed:29109152). Latency-associated peptide: Interacts CC with LTBP1; leading to regulate activation of TGF-beta-1 CC (PubMed:2022183, PubMed:8617200, PubMed:8939931). Latency- CC associated peptide: Interacts with LRRC32/GARP; leading to CC regulate activation of TGF-beta-1 on the surface of activated CC regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, CC PubMed:19651619). Interacts with LRRC33/NRROS; leading to regulate CC activation of TGF-beta-1 in macrophages and microglia (Probable). CC Latency-associated peptide: Interacts (via cell attachment site) CC with integrins ITGAV and ITGB6 (ITGAV:ITGB6), leading to release CC of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). CC Latency-associated peptide: Interacts with NREP; the interaction CC results in a decrease in TGFB1 autoinduction (By similarity). CC Latency-associated peptide: Interacts with HSP90AB1; inhibits CC latent TGFB1 activation (PubMed:20599762). Transforming growth CC factor beta-1: Homodimer; disulfide-linked (PubMed:20207738, CC PubMed:25209176, PubMed:28117447, PubMed:29109152). Transforming CC growth factor beta-1: Interacts with TGF-beta receptors (TGFBR1 CC and TGFBR2), leading to signal transduction (PubMed:20207738). CC {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:16754747, CC ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:19651619, CC ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:20207738, CC ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:20599762, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25209176, CC ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152, CC ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931, CC ECO:0000269|PubMed:9895299, ECO:0000305|PubMed:29909984}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-779636, EBI-779636; CC P05067:APP; NbExp=3; IntAct=EBI-779636, EBI-77613; CC Q14689:DIP2A; NbExp=2; IntAct=EBI-779636, EBI-2564275; CC P17813:ENG; NbExp=2; IntAct=EBI-779636, EBI-2834630; CC Q12841:FSTL1; NbExp=2; IntAct=EBI-779636, EBI-2349801; CC Q14766-1:LTBP1; NbExp=4; IntAct=EBI-779636, EBI-11173861; CC P50222:MEOX2; NbExp=3; IntAct=EBI-779636, EBI-748397; CC P11464:PSG1; NbExp=3; IntAct=EBI-779636, EBI-716740; CC P36897:TGFBR1; NbExp=2; IntAct=EBI-779636, EBI-1027557; CC P37173:TGFBR2; NbExp=6; IntAct=EBI-779636, EBI-296151; CC Q03167:TGFBR3; NbExp=2; IntAct=EBI-779636, EBI-2852679; CC Q90998:TGFBR3 (xeno); NbExp=2; IntAct=EBI-779636, EBI-6620843; CC P07996:THBS1; NbExp=2; IntAct=EBI-779636, EBI-2530274; 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}. 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) CC (PubMed:11746498, PubMed:17827158). Colocalizes with ASPN in CC chondrocytes within OA lesions of articular cartilage CC (PubMed:17827158). {ECO:0000269|PubMed:11746498, CC ECO:0000269|PubMed:17827158}. CC -!- DOMAIN: Latency-associated peptide: The 'straitjacket' and 'arm' CC domains encircle the Transforming growth factor beta-1 (TGF-beta- CC 1) monomers and are fastened together by strong bonding between CC Lys-56 and 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 CC domain called the bowtie tail (PubMed:28117447). Integrin-binding CC stabilizes an alternative conformation of the bowtie tail CC (PubMed:28117447). Activation by integrin requires force CC application by the actin cytoskeleton, which is resisted by the CC 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or CC LRRC33/NRROS), resulting in distortion of the prodomain and CC 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- CC associated peptide (LAP) chains, which remain non-covalently CC linked, rendering TGF-beta-1 inactive. CC {ECO:0000269|PubMed:7737999}. CC -!- PTM: Latency-associated peptide: N-glycosylated (PubMed:3162913, CC PubMed:2493139, PubMed:28117447). Deglycosylation leads to CC activation of Transforming growth factor beta-1 (TGF-beta-1); CC mechanisms triggering deglycosylation-driven activation of TGF- CC beta-1 are however unclear (PubMed:2493139). CC {ECO:0000269|PubMed:2493139, ECO:0000269|PubMed:28117447, CC ECO:0000269|PubMed:3162913}. CC -!- POLYMORPHISM: In post-menopausal Japanese women, the frequency of CC Leu-10 is higher in subjects with osteoporosis than in controls. CC {ECO:0000269|PubMed:9783545}. CC -!- DISEASE: Camurati-Engelmann disease (CAEND) [MIM:131300]: An CC autosomal dominant disorder characterized by hyperostosis and CC sclerosis of the diaphyses of long bones. The disease typically CC presents in early childhood with pain, muscular weakness and CC waddling gait, and in some cases other features such as CC exophthalmos, facial paralysis, hearing difficulties and loss of CC vision. {ECO:0000269|PubMed:10973241, ECO:0000269|PubMed:11062463, CC ECO:0000269|PubMed:12493741, ECO:0000269|PubMed:12843182, CC ECO:0000269|PubMed:15103729}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: TGF-beta-1 is inactivated by fresolimumab (also CC named 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_000660.6. DR UniGene; Hs.645227; -. 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 PDBsum; 1KLA; -. DR PDBsum; 1KLC; -. DR PDBsum; 1KLD; -. DR PDBsum; 3KFD; -. DR PDBsum; 4KV5; -. DR PDBsum; 5FFO; -. DR PDBsum; 5VQP; -. DR ProteinModelPortal; P01137; -. DR SMR; P01137; -. DR BioGrid; 112898; 225. 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 IntAct; P01137; 84. DR MINT; P01137; -. DR STRING; 9606.ENSP00000221930; -. DR BindingDB; P01137; -. DR ChEMBL; CHEMBL1795178; -. DR DrugBank; DB00070; Hyaluronidase. DR DrugBank; DB06205; Hyaluronidase (Human Recombinant). DR GlyConnect; 1835; -. DR iPTMnet; P01137; -. DR PhosphoSitePlus; P01137; -. DR BioMuta; TGFB1; -. DR DMDM; 135674; -. DR OGP; P01137; -. DR EPD; P01137; -. DR jPOST; P01137; -. DR MaxQB; P01137; -. DR PaxDb; P01137; -. DR PeptideAtlas; P01137; -. DR PRIDE; P01137; -. DR ProteomicsDB; 51337; -. DR DNASU; 7040; -. DR Ensembl; ENST00000221930; ENSP00000221930; ENSG00000105329. DR GeneID; 7040; -. DR KEGG; hsa:7040; -. DR UCSC; uc002oqh.4; human. DR CTD; 7040; -. DR DisGeNET; 7040; -. DR EuPathDB; HostDB:ENSG00000105329.9; -. DR GeneCards; TGFB1; -. DR GeneReviews; TGFB1; -. DR H-InvDB; HIX0015152; -. DR HGNC; HGNC:11766; TGFB1. DR HPA; CAB000361; -. DR HPA; CAB073543; -. DR MalaCards; TGFB1; -. DR MIM; 131300; phenotype. DR MIM; 190180; gene. DR neXtProt; NX_P01137; -. DR Orphanet; 1328; Camurati-Engelmann disease. DR Orphanet; 586; Cystic fibrosis. DR PharmGKB; PA350; -. DR eggNOG; KOG3900; Eukaryota. DR eggNOG; ENOG410XT8Z; LUCA. DR HOGENOM; HOG000290198; -. DR HOVERGEN; HBG074115; -. DR InParanoid; P01137; -. DR KO; K13375; -. DR OrthoDB; 853728at2759; -. DR PhylomeDB; P01137; -. DR TreeFam; TF318514; -. 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-3315487; SMAD2/3 MH2 Domain 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 SignaLink; P01137; -. DR SIGNOR; P01137; -. DR ChiTaRS; TGFB1; human. DR EvolutionaryTrace; P01137; -. DR GeneWiki; TGF_beta_1; -. DR GenomeRNAi; 7040; -. DR PRO; PR:P01137; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000105329; Expressed in 170 organ(s), highest expression level in leukocyte. DR ExpressionAtlas; P01137; baseline and differential. DR Genevisible; P01137; HS. 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:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; 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:0003823; F:antigen binding; IPI:UniProtKB. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl. DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central. 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:0007568; P:aging; 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:0060751; P:branch elongation involved in mammary gland duct branching; IEA:Ensembl. DR GO; GO:0007050; P:cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0016477; P:cell migration; IDA:UniProtKB. DR GO; GO:0045216; P:cell-cell junction organization; IDA:BHF-UCL. DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. 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:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB. 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:0007182; P:common-partner SMAD protein phosphorylation; IDA:UniProtKB. DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; TAS:BHF-UCL. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0009817; P:defense response to fungus, incompatible interaction; 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:0007492; P:endoderm development; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB. DR GO; GO:0019049; P:evasion or tolerance of host defenses by virus; IDA:BHF-UCL. 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:0008354; P:germ cell migration; 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:0006954; P:inflammatory response; IDA:UniProtKB. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB. 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:0060744; P:mammary gland branching involved in thelarche; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB. DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:UniProtKB. DR GO; GO:0007093; P:mitotic cell cycle checkpoint; IDA:BHF-UCL. DR GO; GO:0032943; P:mononuclear cell proliferation; IEA:Ensembl. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl. 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. 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:0022408; P:negative regulation of cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0045918; P:negative regulation of cytolysis; IDA:ARUK-UCL. 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; IC: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:0060965; P:negative regulation of gene silencing by miRNA; IGI: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:0045930; P:negative regulation of mitotic cell cycle; IDA:BHF-UCL. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:UniProtKB. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl. DR GO; GO:0050765; P:negative regulation of phagocytosis; IEA:Ensembl. DR GO; GO:1903799; P:negative regulation of production of miRNAs involved in gene silencing by miRNA; IGI:BHF-UCL. DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IDA:UniProtKB. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL. 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:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome. 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:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl. DR GO; GO:0043932; P:ossification involved in bone remodeling; IEP:BHF-UCL. DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl. DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB. DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IDA:BHF-UCL. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0030501; P:positive regulation of bone mineralization; IEP:BHF-UCL. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IEA:Ensembl. DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0071158; P:positive regulation of cell cycle arrest; IEA:Ensembl. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. 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:0032270; P:positive regulation of cellular protein metabolic process; IDA: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: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; IC:BHF-UCL. DR GO; GO:0010763; P:positive regulation of fibroblast migration; IDA:BHF-UCL. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0035066; P:positive regulation of histone acetylation; IEA:Ensembl. DR GO; GO:0031065; P:positive regulation of histone deacetylation; IEA:Ensembl. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IDA:MGI. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL. DR GO; GO:0014008; P:positive regulation of microglia differentiation; ISS:UniProtKB. DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; IEA:Ensembl. DR GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; IDA:BHF-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl. DR GO; GO:0042482; P:positive regulation of odontogenesis; IEA:Ensembl. DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:BHF-UCL. DR GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:1903800; P:positive regulation of production of miRNAs involved in gene silencing by miRNA; IDA:BHF-UCL. DR GO; GO:0031334; P:positive regulation of protein complex assembly; IDA:BHF-UCL. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:BHF-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:BHF-UCL. DR GO; GO:1903911; P:positive regulation of receptor clustering; IEA:Ensembl. 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:BHF-UCL. DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IEA:Ensembl. 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:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. 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:0006611; P:protein export from nucleus; IDA:UniProtKB. DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0032801; P:receptor catabolic process; IDA:BHF-UCL. DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0051098; P:regulation of binding; ISS:UniProtKB. DR GO; GO:0060312; P:regulation of blood vessel remodeling; NAS:BHF-UCL. DR GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0061035; P:regulation of cartilage development; IEA:Ensembl. 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:0051101; P:regulation of DNA binding; ISS:UniProtKB. DR GO; GO:0032667; P:regulation of interleukin-23 production; IEA:Ensembl. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0042306; P:regulation of protein import into nucleus; ISS:UniProtKB. DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; IDA:UniProtKB. DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl. DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISS:UniProtKB. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0045066; P:regulatory T cell differentiation; IEA:Ensembl. 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:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; 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:0007435; P:salivary gland morphogenesis; IEP:BHF-UCL. DR GO; GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL. DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central. DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl. DR GO; GO:0002513; P:tolerance induction to self antigen; IEA:Ensembl. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:1905313; P:transforming growth factor beta receptor signaling pathway involved in heart development; ISS: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 Gene3D; 2.10.90.10; -; 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-rel. DR InterPro; IPR003939; TGFb1. DR InterPro; IPR017948; TGFb_CS. DR PANTHER; PTHR11848; PTHR11848; 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; SSF57501; 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; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Extracellular matrix; Glycoprotein; Growth factor; Mitogen; KW Polymorphism; Reference proteome; Secreted; Signal. FT SIGNAL 1 29 {ECO:0000269|PubMed:3162913}. FT CHAIN 30 278 Latency-associated peptide. FT {ECO:0000305|PubMed:2982829, FT ECO:0000305|PubMed:3162913, FT ECO:0000305|PubMed:7737999, FT ECO:0000305|PubMed:8471846}. FT /FTId=PRO_0000033762. FT CHAIN 279 390 Transforming growth factor beta-1. FT {ECO:0000305|PubMed:2982829, FT ECO:0000305|PubMed:3162913, FT ECO:0000305|PubMed:7737999, FT ECO:0000305|PubMed:8471846}. FT /FTId=PRO_0000033763. FT REGION 30 74 Straightjacket domain. FT {ECO:0000250|UniProtKB:P07200}. FT REGION 75 271 Arm domain. FT {ECO:0000250|UniProtKB:P07200}. FT REGION 226 252 Bowtie tail. FT {ECO:0000269|PubMed:28117447}. FT MOTIF 244 246 Cell attachment site. FT {ECO:0000269|PubMed:28117447}. FT SITE 278 279 Cleavage; by FURIN. FT {ECO:0000269|PubMed:7737999}. FT CARBOHYD 82 82 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:5FFO, FT ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:28117447}. FT CARBOHYD 136 136 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 176 176 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 33 33 Interchain (with C-1359 or C-1384 in FT LTBP1); in inactive form. FT {ECO:0000305|PubMed:22278742}. FT DISULFID 223 223 Interchain (with C-225). FT {ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 225 225 Interchain (with C-223). FT {ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 285 294 {ECO:0000244|PDB:3KFD, FT ECO:0000244|PDB:4KV5, FT ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 293 356 {ECO:0000244|PDB:3KFD, FT ECO:0000244|PDB:4KV5, FT ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 322 387 {ECO:0000244|PDB:3KFD, FT ECO:0000244|PDB:4KV5, FT ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 326 389 {ECO:0000244|PDB:3KFD, FT ECO:0000244|PDB:4KV5, FT ECO:0000244|PDB:5FFO, FT ECO:0000244|PDB:5VQP, FT ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, FT ECO:0000269|PubMed:28117447, FT ECO:0000269|PubMed:29109152}. FT DISULFID 355 355 Interchain. {ECO:0000244|PDB:3KFD, FT ECO:0000244|PDB:4KV5, FT ECO:0000244|PDB:5FFO, FT ECO:0000269|PubMed:20207738, FT ECO:0000269|PubMed:25209176, FT ECO:0000269|PubMed:28117447}. FT VARIANT 10 10 L -> P (associated with higher bone FT mineral density and lower frequency of FT vertebral fractures in Japanese post- FT menopausal women; dbSNP:rs1800470). FT {ECO:0000269|PubMed:12202987, FT ECO:0000269|PubMed:3861940, FT ECO:0000269|PubMed:9783545}. FT /FTId=VAR_016171. FT VARIANT 25 25 R -> P (in dbSNP:rs1800471). FT {ECO:0000269|PubMed:3861940}. FT /FTId=VAR_016172. FT VARIANT 81 81 Y -> H (in CAEND; leads to TGF-beta-1 FT intracellular accumulation). FT {ECO:0000269|PubMed:11062463, FT ECO:0000269|PubMed:12493741}. FT /FTId=VAR_017607. FT VARIANT 218 218 R -> C (in CAEND; higher levels of active FT TGF-beta-1 in the culture medium; FT enhances osteoclast formation in vitro). FT {ECO:0000269|PubMed:10973241, FT ECO:0000269|PubMed:11062463, FT ECO:0000269|PubMed:12493741, FT ECO:0000269|PubMed:12843182}. FT /FTId=VAR_017608. FT VARIANT 218 218 R -> H (in CAEND). FT {ECO:0000269|PubMed:10973241}. FT /FTId=VAR_017609. FT VARIANT 222 222 H -> D (in CAEND; sporadic case; higher FT levels of active TGF-beta-1 in the FT culture medium). FT {ECO:0000269|PubMed:12493741}. FT /FTId=VAR_017610. FT VARIANT 223 223 C -> G (in CAEND). FT {ECO:0000269|PubMed:15103729}. FT /FTId=VAR_067303. FT VARIANT 223 223 C -> R (in CAEND). FT {ECO:0000269|PubMed:15103729}. FT /FTId=VAR_067304. FT VARIANT 225 225 C -> R (in CAEND; higher levels of active FT TGF-beta-1 in the culture medium). FT {ECO:0000269|PubMed:10973241, FT ECO:0000269|PubMed:11062463, FT ECO:0000269|PubMed:12493741}. FT /FTId=VAR_017611. FT VARIANT 263 263 T -> I (in dbSNP:rs1800472). FT /FTId=VAR_016173. FT MUTAGEN 33 33 C->S: Abolishes interchain disulfide bond FT with LTBP1 and/or LRRC32, and subsequent FT regulation of activation of TGF-beta-1. FT {ECO:0000269|PubMed:22278742, FT ECO:0000269|PubMed:8617200}. FT MUTAGEN 75 75 E->A: Does not affect integrin-binding or FT activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 158 158 L->A: Does not affect integrin-binding or FT activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 160 160 L->A,R: Does not affect integrin-binding FT or activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 193 193 P->A,R: Does not affect integrin-binding FT or activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 232 236 LQVDI->GQGDG: Strongly inhibits integrin- FT binding and activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 234 236 VDI->GDG: Strongly inhibits integrin- FT binding and activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 237 237 N->A: Does not affect integrin-binding or FT activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 254 254 N->A: Does not affect integrin-binding or FT activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 257 260 FLLL->GLLG: Strongly inhibits integrin- FT binding and activation of TGF-beta-1. FT {ECO:0000269|PubMed:28117447}. FT MUTAGEN 278 278 R->A: Prevents cleavage and subsequent FT maturation of the protein. Generated in FT order to mimic the structure of the FT Transforming growth factor beta-1 FT proprotein. FT {ECO:0000269|PubMed:29109152}. FT CONFLICT 159 159 R -> RR (in Ref. 2; CAA26580). FT {ECO:0000305}. FT HELIX 33 57 {ECO:0000244|PDB:5VQP}. FT STRAND 70 72 {ECO:0000244|PDB:5FFO}. FT HELIX 75 85 {ECO:0000244|PDB:5VQP}. FT STRAND 107 112 {ECO:0000244|PDB:5VQP}. FT TURN 123 126 {ECO:0000244|PDB:5VQP}. FT STRAND 130 136 {ECO:0000244|PDB:5VQP}. FT HELIX 137 143 {ECO:0000244|PDB:5VQP}. FT STRAND 144 146 {ECO:0000244|PDB:5FFO}. FT HELIX 147 149 {ECO:0000244|PDB:5VQP}. FT STRAND 150 159 {ECO:0000244|PDB:5VQP}. FT STRAND 166 174 {ECO:0000244|PDB:5VQP}. FT TURN 175 177 {ECO:0000244|PDB:5VQP}. FT STRAND 178 187 {ECO:0000244|PDB:5VQP}. FT STRAND 194 199 {ECO:0000244|PDB:5VQP}. FT HELIX 201 209 {ECO:0000244|PDB:5VQP}. FT STRAND 213 228 {ECO:0000244|PDB:5VQP}. FT STRAND 231 238 {ECO:0000244|PDB:5VQP}. FT STRAND 242 244 {ECO:0000244|PDB:5FFO}. FT TURN 245 247 {ECO:0000244|PDB:5VQP}. FT STRAND 251 254 {ECO:0000244|PDB:5VQP}. FT STRAND 257 262 {ECO:0000244|PDB:5VQP}. FT HELIX 265 268 {ECO:0000244|PDB:5VQP}. FT TURN 282 284 {ECO:0000244|PDB:1KLC}. FT HELIX 285 288 {ECO:0000244|PDB:5VQP}. FT STRAND 290 301 {ECO:0000244|PDB:5VQP}. FT TURN 302 305 {ECO:0000244|PDB:5VQP}. FT STRAND 311 313 {ECO:0000244|PDB:5VQP}. FT STRAND 315 323 {ECO:0000244|PDB:5VQP}. FT STRAND 330 332 {ECO:0000244|PDB:3KFD}. FT HELIX 335 346 {ECO:0000244|PDB:3KFD}. FT STRAND 347 349 {ECO:0000244|PDB:3KFD}. FT STRAND 350 353 {ECO:0000244|PDB:5FFO}. FT STRAND 355 370 {ECO:0000244|PDB:5VQP}. FT STRAND 373 390 {ECO:0000244|PDB:5VQP}. SQ SEQUENCE 390 AA; 44341 MW; 75391614250288FE CRC64; MPPSGLRLLL 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 //