位置:首页 > 蛋白库 > TGFB1_HUMAN
TGFB1_HUMAN
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   03-AUG-2022, entry version 264.
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 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., 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   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   [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-beta
RT   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 osteosarcoma
RT   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., 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   [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 regulated
RT   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., 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   [30]
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   [31]
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   [32]
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   [33]
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   [34]
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   [35]
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   [36]
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   [37]
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   [38]
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   [39]
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   [40] {ECO:0007744|PDB:3KFD}
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 279-390 IN COMPLEX WITH TGFBR1
RP   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 superfamily.";
RL   J. Biol. Chem. 285:14806-14814(2010).
RN   [41] {ECO:0007744|PDB:4KV5}
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 279-390, SUBUNIT, AND DISULFIDE
RP   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   [42] {ECO:0007744|PDB:5FFO}
RP   X-RAY CRYSTALLOGRAPHY (3.49 ANGSTROMS) OF 34-390 IN COMPLEX WITH ITGAV AND
RP   ITGB6, FUNCTION, INTERACTION WITH ITGAV AND ITGB6, SUBUNIT, DISULFIDE BOND,
RP   GLYCOSYLATION AT ASN-82, AND MUTAGENESIS OF GLU-75; LEU-158; LEU-160;
RP   PRO-193; 232-LEU--ILE-236; 234-VAL--ILE-236; ASN-237; ASN-254 AND
RP   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   [43] {ECO:0007744|PDB:5VQP}
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 30-390, SUBUNIT, DISULFIDE BONDS,
RP   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   [44]
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 gene
RT   with genetic susceptibility to osteoporosis in postmenopausal Japanese
RT   women.";
RL   J. Bone Miner. Res. 13:1569-1576(1998).
RN   [45]
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., 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   [46]
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., 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   [47]
RP   VARIANT PRO-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   [48]
RP   CHARACTERIZATION OF VARIANTS CAEND 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   [49]
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   [50]
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., 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:2022183,
CC       PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742,
CC       PubMed:19651619). 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:19750484, PubMed:22278742,
CC       PubMed:19651619). 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: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): integrin-
CC       binding to LAP stabilizes an alternative conformation of the LAP bowtie
CC       tail and results in distortion of the LAP chain and subsequent release
CC       of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once
CC       activated following release of LAP, TGF-beta-1 acts by binding to TGF-
CC       beta receptors (TGFBR1 and TGFBR2), which transduce signal
CC       (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only
CC       has a very localized range of action within cell environment thanks to
CC       fine regulation of its activation by Latency-associated peptide chain
CC       (LAP) and 'milieu molecules' (By similarity). Plays an important role
CC       in bone remodeling: acts as a potent stimulator of osteoblastic bone
CC       formation, causing chemotaxis, proliferation and differentiation in
CC       committed osteoblasts (By similarity). Can promote either T-helper 17
CC       cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a
CC       concentration-dependent manner (By similarity). At high concentrations,
CC       leads to FOXP3-mediated suppression of RORC and down-regulation of IL-
CC       17 expression, favoring Treg cell development (By similarity). At low
CC       concentrations in concert with IL-6 and IL-21, leads to expression of
CC       the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells
CC       (By similarity). Stimulates sustained production of collagen through
CC       the activation of CREB3L1 by regulated intramembrane proteolysis (RIP)
CC       (PubMed:25310401). Mediates SMAD2/3 activation by inducing its
CC       phosphorylation and subsequent translocation to the nucleus
CC       (PubMed:25893292, PubMed:29483653, PubMed:30696809). Can induce
CC       epithelial-to-mesenchymal transition (EMT) and cell migration in
CC       various cell types (PubMed:25893292, PubMed:30696809).
CC       {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:19651619,
CC       ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:20207738,
CC       ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742,
CC       ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:25893292,
CC       ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152,
CC       ECO:0000269|PubMed:29483653, ECO:0000269|PubMed:30696809,
CC       ECO:0000269|PubMed:8617200, 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:9895299, PubMed:16754747, PubMed:17827158). 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:19750484, PubMed:22278742, PubMed:19651619). 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). {ECO:0000250|UniProtKB:P04202,
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=2; IntAct=EBI-779636, EBI-15796956;
CC       P01137; Q14766-1: LTBP1; NbExp=4; IntAct=EBI-779636, EBI-11173861;
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=6; 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; 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:3162913,
CC       PubMed:2493139, PubMed:28117447). 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   -!- POLYMORPHISM: In post-menopausal Japanese women, the frequency of Leu-
CC       10 is higher in subjects with osteoporosis than in controls.
CC       {ECO:0000269|PubMed:9783545}.
CC   -!- DISEASE: Camurati-Engelmann disease (CAEND) [MIM:131300]: An autosomal
CC       dominant disorder characterized by hyperostosis and sclerosis of the
CC       diaphyses of long bones. The disease typically presents in early
CC       childhood with pain, muscular weakness and waddling gait, and in some
CC       cases other features such as exophthalmos, facial paralysis, hearing
CC       difficulties and loss of vision. {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_000660.6.
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; 6OM2; X-ray; 2.77 A; E/F=242-252.
DR   PDB; 6P7J; X-ray; 3.50 A; A=30-278.
DR   PDBsum; 1KLA; -.
DR   PDBsum; 1KLC; -.
DR   PDBsum; 1KLD; -.
DR   PDBsum; 3KFD; -.
DR   PDBsum; 4KV5; -.
DR   PDBsum; 5FFO; -.
DR   PDBsum; 5VQP; -.
DR   PDBsum; 6OM2; -.
DR   PDBsum; 6P7J; -.
DR   AlphaFoldDB; P01137; -.
DR   SASBDB; P01137; -.
DR   SMR; P01137; -.
DR   BioGRID; 112898; 355.
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; 96.
DR   MINT; P01137; -.
DR   STRING; 9606.ENSP00000221930; -.
DR   BindingDB; P01137; -.
DR   ChEMBL; CHEMBL1795178; -.
DR   DrugBank; DB10770; Foreskin fibroblast (neonatal).
DR   DrugBank; DB10772; Foreskin keratinocyte (neonatal).
DR   DrugBank; DB14740; Hyaluronidase.
DR   DrugBank; DB06205; Hyaluronidase (human recombinant).
DR   DrugBank; DB00070; Hyaluronidase (ovine).
DR   DrugBank; DB01162; Terazosin.
DR   GlyConnect; 1835; 1 N-Linked glycan (1 site).
DR   GlyGen; P01137; 3 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; P01137; -.
DR   PhosphoSitePlus; P01137; -.
DR   BioMuta; TGFB1; -.
DR   DMDM; 135674; -.
DR   OGP; P01137; -.
DR   EPD; P01137; -.
DR   jPOST; P01137; -.
DR   MassIVE; P01137; -.
DR   MaxQB; P01137; -.
DR   PaxDb; P01137; -.
DR   PeptideAtlas; P01137; -.
DR   PRIDE; P01137; -.
DR   ProteomicsDB; 51337; -.
DR   ABCD; P01137; 10 sequenced antibodies.
DR   CPTC; P01137; 1 antibody.
DR   DNASU; 7040; -.
DR   GeneID; 7040; -.
DR   KEGG; hsa:7040; -.
DR   UCSC; uc002oqh.4; human.
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   neXtProt; NX_P01137; -.
DR   Orphanet; 1328; Camurati-Engelmann disease.
DR   Orphanet; 586; Cystic fibrosis.
DR   Orphanet; 565788; Infantile inflammatory bowel disease with neurological involvement.
DR   PharmGKB; PA350; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   HOGENOM; CLU_039840_0_0_1; -.
DR   InParanoid; P01137; -.
DR   OrthoDB; 853728at2759; -.
DR   PhylomeDB; P01137; -.
DR   TreeFam; TF318514; -.
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   SignaLink; P01137; -.
DR   SIGNOR; P01137; -.
DR   BioGRID-ORCS; 7040; 10 hits in 1079 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; Unplaced.
DR   RNAct; P01137; protein.
DR   Genevisible; P01137; HS.
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: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; IPI:ComplexPortal.
DR   GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; IPI:ComplexPortal.
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: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:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0006754; P:ATP biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0030509; P:BMP signaling pathway; 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: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:1990402; P:embryonic liver development; ISS:BHF-UCL.
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:0085029; P:extracellular matrix assembly; IDA:BHF-UCL.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
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:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
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:0000165; P:MAPK cascade; IMP:UniProtKB.
DR   GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:UniProtKB.
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: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:1900126; P:negative regulation of hyaluronan biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:DFLAT.
DR   GO; GO:1903799; P:negative regulation of miRNA maturation; IGI:BHF-UCL.
DR   GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:ARUK-UCL.
DR   GO; GO:0060965; P:negative regulation of miRNA-mediated gene silencing; IGI:BHF-UCL.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:UniProtKB.
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:0048642; P:negative regulation of skeletal muscle tissue development; IDA:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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:0043932; P:ossification involved in bone remodeling; IEP:BHF-UCL.
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: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: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: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: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: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: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:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
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:1903800; P:positive regulation of miRNA maturation; IDA:BHF-UCL.
DR   GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR   GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; IDA:BHF-UCL.
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: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:0051247; P:positive regulation of protein metabolic process; IDA:BHF-UCL.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
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:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL.
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: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; IDA:ComplexPortal.
DR   GO; GO:0032801; P:receptor catabolic process; IDA:BHF-UCL.
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: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: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: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:0070723; P:response to cholesterol; IDA:BHF-UCL.
DR   GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL.
DR   GO; GO:0032570; P:response to progesterone; IDA:BHF-UCL.
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: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:0001570; P:vasculogenesis; ISS:BHF-UCL.
DR   GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR   DisProt; DP01252; -.
DR   Gene3D; 2.10.90.10; -; 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-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;
KW   Direct protein sequencing; Disease variant; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Growth factor; Mitogen;
KW   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="L -> P (associated with higher bone mineral density
FT                   and lower 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)"
FT                   /evidence="ECO:0000269|PubMed:29483653"
FT                   /id="VAR_081584"
FT   VARIANT         81
FT                   /note="Y -> H (in CAEND; leads to TGF-beta-1 intracellular
FT                   accumulation)"
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)"
FT                   /evidence="ECO:0000269|PubMed:29483653"
FT                   /id="VAR_081585"
FT   VARIANT         218
FT                   /note="R -> C (in CAEND; higher levels of active TGF-beta-1
FT                   in the culture medium; enhances osteoclast formation in
FT                   vitro)"
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 CAEND)"
FT                   /evidence="ECO:0000269|PubMed:10973241"
FT                   /id="VAR_017609"
FT   VARIANT         222
FT                   /note="H -> D (in CAEND; sporadic case; higher levels of
FT                   active TGF-beta-1 in the culture medium)"
FT                   /evidence="ECO:0000269|PubMed:12493741"
FT                   /id="VAR_017610"
FT   VARIANT         223
FT                   /note="C -> G (in CAEND)"
FT                   /evidence="ECO:0000269|PubMed:15103729"
FT                   /id="VAR_067303"
FT   VARIANT         223
FT                   /note="C -> R (in CAEND)"
FT                   /evidence="ECO:0000269|PubMed:15103729"
FT                   /id="VAR_067304"
FT   VARIANT         225
FT                   /note="C -> R (in CAEND; higher levels of active TGF-beta-1
FT                   in the culture medium)"
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
FT                   secreted)"
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           33..57
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          70..72
FT                   /evidence="ECO:0007829|PDB:5FFO"
FT   HELIX           75..85
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          107..112
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   TURN            123..126
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          130..136
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   HELIX           137..143
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          144..146
FT                   /evidence="ECO:0007829|PDB:5FFO"
FT   HELIX           147..149
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          150..159
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          166..174
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   TURN            175..177
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          178..187
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          194..199
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   HELIX           201..209
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          213..228
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          231..238
FT                   /evidence="ECO:0007829|PDB:5VQP"
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:5VQP"
FT   HELIX           265..268
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   TURN            282..284
FT                   /evidence="ECO:0007829|PDB:1KLC"
FT   HELIX           285..288
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          290..301
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   TURN            302..305
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          311..313
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          315..323
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          330..332
FT                   /evidence="ECO:0007829|PDB:3KFD"
FT   HELIX           335..346
FT                   /evidence="ECO:0007829|PDB:3KFD"
FT   STRAND          347..349
FT                   /evidence="ECO:0007829|PDB:3KFD"
FT   STRAND          350..353
FT                   /evidence="ECO:0007829|PDB:5FFO"
FT   STRAND          355..370
FT                   /evidence="ECO:0007829|PDB:5VQP"
FT   STRAND          373..390
FT                   /evidence="ECO:0007829|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
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024