kvarforl
commented
3 years ago Noting that this is an issue in KG2.4.0 as well. Looking more into it now!
Closed amykglen closed 3 years ago
kvarforl
commented
3 years ago Noting that this is an issue in KG2.4.0 as well. Looking more into it now!
kvarforl
commented
3 years ago Okay, I'm pretty sure this issue is stemming from these lines of code:
The name of the node gets set to the short name on L209, which keeps it from getting set to the full name later in the script on L263
I don't have enough knowledge/context to know whether or not this should be changed! I suppose it depends on how often its "better" to use the short name than the recommended name vs how often it causes issues.
I'll leave that determination up to you guys? @amykglen @saramsey
kvarforl
commented
3 years ago match (n) where n.id in ["UniProtKB:P01137", "UniProtKB:P61812", "UniProtKB:P10600"] return n.name, n.full_name
amykglen
commented
3 years ago ah, nice digging! hmm.. so in the screenshot from uniprot.org above, it looks like LAP is the short name for one of the two chains the protein is cleaved into (and the short name of the other chain is "TGF-beta-1"). so why is this protein assigned the short name LAP in the KG2 build process? it looks like short names are only given for the chains it's cleaved into, and not the protein itself?
kvarforl
commented
3 years ago Interesting... it looks like you're right about only the cleaved chains having short names. This is the entry for P01137 in the uniprot_sprot.dat file used for KG2.3.4
ubuntu@ip-172-31-3-188:~$ grep -m 1 -A 20 "AC P01137" kg2-build/uniprotkb/uniprot_sprot.dat
AC P01137; A8K792; Q9UCG4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 12-AUG-2020, entry version 255.
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;
....From the neo4j screenshot above, the node ends up with the full name Transforming growth factor beta-1 {ECO:0000305|PubMed:2982829, ECO:0000305|PubMed:3162913, ECO:0000305|PubMed:7737999, ECO:0000305|PubMed:8471846} (the lowest DE entry that starts with "RecName:"). looking at the code, I would think that the name would end up being TGF-beta-1, the accompanying short name.
I'm scratching my head about how it ends up with the name LAP. I'll try to walk through the code some more and see what I can figure out.
Either way... should we be skipping over the contains sections entirely, since they seem to refer to the chains it's cleaved into instead of the protein the node itself represents?
edeutsch
commented
3 years ago I think UniProtKB has been struggling with this sort of thing for a long time. Many proteins have specific separately identifiable chains, and they're annotated as CHAINs, and the chains can have very different functions and roles and contribute complex final molecules, effectively rising to the level of full proteins in complexes, but there're no separate entries or identifiers for the chains, and so annotation and naming are difficult.
kvarforl
commented
3 years ago Ah, that's good to know! Looking through the same uniprotkb_dat_to_json.py file, I don't think KG2 currently does anything using the FT slots at all. Do you think they should be included somehow, or should we just leave it as is given the lack of identifiers?
saramsey
commented
3 years ago @kvarforl can you please paste the complete record for P01137 (from uniprot_sprot.dat) into the issue here? Thanks.
kvarforl
commented
3 years ago Yes! Fair warning, it is long. Here is the output of grep -m 1 -B 2 -A 1210 "AC P01137" kg2-build/uniprotkb/uniprot_sprot.dat on kg2lindsey:
//
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 02-DEC-2020, entry version 257.
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;
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 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 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 [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., 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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38] {ECO:0000244|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 [39] {ECO:0000244|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 [40] {ECO:0000244|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 [41] {ECO:0000244|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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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. The HTRA protease activity is required for this inhibition
CC (By similarity). May interact with THSD4; this interaction may lead to
CC sequestration by FBN1 microfibril assembly and attenuation of TGFB
CC signaling (By similarity). Interacts with CD109, DPT and ASPN
CC (PubMed:9895299, PubMed:16754747, PubMed:17827158). Latency-associated
CC peptide: Homodimer; disulfide-linked (PubMed:28117447,
CC PubMed:29109152). Latency-associated peptide: Interacts with
CC Transforming growth factor beta-1 (TGF-beta-1) chain; interaction is
CC non-covalent and maintains (TGF-beta-1) in a latent state; each
CC Latency-associated peptide (LAP) monomer interacts with TGF-beta-1 in
CC the other monomer (PubMed:29109152). Latency-associated peptide:
CC Interacts with LTBP1; leading to regulate activation of TGF-beta-1
CC (PubMed:2022183, PubMed:8617200, PubMed:8939931). Latency-associated
CC peptide: Interacts with LRRC32/GARP; leading to regulate activation of
CC TGF-beta-1 on the surface of activated regulatory T-cells (Tregs)
CC (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interacts with
CC LRRC33/NRROS; leading to regulate activation of TGF-beta-1 in
CC macrophages and microglia (Probable). Latency-associated peptide:
CC Interacts (via cell attachment site) with integrins ITGAV and ITGB6
CC (ITGAV:ITGB6), leading to release of the active TGF-beta-1
CC (PubMed:22278742, PubMed:28117447). Latency-associated peptide:
CC Interacts with NREP; the interaction results in a decrease in TGFB1
CC autoinduction (By similarity). Latency-associated peptide: Interacts
CC with HSP90AB1; inhibits latent TGFB1 activation (PubMed:20599762).
CC Transforming growth factor beta-1: Homodimer; disulfide-linked
CC (PubMed:20207738, PubMed:25209176, PubMed:28117447, PubMed:29109152).
CC Transforming growth factor beta-1: Interacts with TGF-beta receptors
CC (TGFBR1 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 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; 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 mutations 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 mutations 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 ---------------------------------------------------------------------------
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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 SASBDB; P01137; -.
DR SMR; P01137; -.
DR BioGRID; 112898; 249.
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; 95.
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.
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 DNASU; 7040; -.
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 HGNC; HGNC:11766; TGFB1.
DR HPA; ENSG00000105329; Low tissue specificity.
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; 2 hits in 850 CRISPR screens.
DR ChiTaRS; TGFB1; human.
DR EvolutionaryTrace; P01137; -.
DR GeneWiki; TGF_beta_1; -.
DR GenomeRNAi; 7040; -.
DR Pharos; P01137; Tchem.
DR PRO; PR:P01137; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; P01137; protein.
DR Bgee; ENSG00000105329; Expressed in granulocyte and 181 other tissues.
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: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:0007050; P:cell cycle arrest; IDA:BHF-UCL.
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:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
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:0050900; P:leukocyte migration; TAS:Reactome.
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:0007093; P:mitotic cell cycle checkpoint; IDA:BHF-UCL.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:BHF-UCL.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:HGNC-UCL.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IEP:CACAO.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO: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: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:1902894; P:negative regulation of pri-miRNA transcription by RNA polymerase II; NAS:BHF-UCL.
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: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: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: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:0002576; P:platelet degranulation; TAS:Reactome.
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: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: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: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: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: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:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-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; ISS:UniProtKB.
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 mutation; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Growth factor; Mitogen; Polymorphism;
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:0000244|PDB:5FFO,
FT ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:28117447"
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:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 225
FT /note="Interchain (with C-223)"
FT /evidence="ECO:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 285..294
FT /evidence="ECO:0000244|PDB:3KFD, ECO:0000244|PDB:4KV5,
FT ECO:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:25209176,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 293..356
FT /evidence="ECO:0000244|PDB:3KFD, ECO:0000244|PDB:4KV5,
FT ECO:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:25209176,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 322..387
FT /evidence="ECO:0000244|PDB:3KFD, ECO:0000244|PDB:4KV5,
FT ECO:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:25209176,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 326..389
FT /evidence="ECO:0000244|PDB:3KFD, ECO:0000244|PDB:4KV5,
FT ECO:0000244|PDB:5FFO, ECO:0000244|PDB:5VQP,
FT ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:25209176,
FT ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152"
FT DISULFID 355
FT /note="Interchain"
FT /evidence="ECO:0000244|PDB:3KFD, ECO:0000244|PDB:4KV5,
FT ECO:0000244|PDB:5FFO, ECO:0000269|PubMed:20207738,
FT ECO:0000269|PubMed:25209176, ECO:0000269|PubMed:28117447"
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 secreated
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 secreated
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:0000244|PDB:5VQP"
FT STRAND 70..72
FT /evidence="ECO:0000244|PDB:5FFO"
FT HELIX 75..85
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 107..112
FT /evidence="ECO:0000244|PDB:5VQP"
FT TURN 123..126
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 130..136
FT /evidence="ECO:0000244|PDB:5VQP"
FT HELIX 137..143
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 144..146
FT /evidence="ECO:0000244|PDB:5FFO"
FT HELIX 147..149
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 150..159
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 166..174
FT /evidence="ECO:0000244|PDB:5VQP"
FT TURN 175..177
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 178..187
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 194..199
FT /evidence="ECO:0000244|PDB:5VQP"
FT HELIX 201..209
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 213..228
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 231..238
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 242..244
FT /evidence="ECO:0000244|PDB:5FFO"
FT STRAND 245..248
FT /evidence="ECO:0000244|PDB:6OM2"
FT STRAND 251..254
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 257..262
FT /evidence="ECO:0000244|PDB:5VQP"
FT HELIX 265..268
FT /evidence="ECO:0000244|PDB:5VQP"
FT TURN 282..284
FT /evidence="ECO:0000244|PDB:1KLC"
FT HELIX 285..288
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 290..301
FT /evidence="ECO:0000244|PDB:5VQP"
FT TURN 302..305
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 311..313
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 315..323
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 330..332
FT /evidence="ECO:0000244|PDB:3KFD"
FT HELIX 335..346
FT /evidence="ECO:0000244|PDB:3KFD"
FT STRAND 347..349
FT /evidence="ECO:0000244|PDB:3KFD"
FT STRAND 350..353
FT /evidence="ECO:0000244|PDB:5FFO"
FT STRAND 355..370
FT /evidence="ECO:0000244|PDB:5VQP"
FT STRAND 373..390
FT /evidence="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
//
Hi @kvarforl I made a file issue1160.dat out of that UniProtKB dat record, and ran it like this:
python uniprotkb_dat_to_json.py --test issue1160.dat issue1160.jsonand I got an assertion error:
Traceback (most recent call last):
File "uniprotkb_dat_to_json.py", line 305, in <module>
test_mode)
File "uniprotkb_dat_to_json.py", line 65, in parse_records_from_uniprot_dat
assert organism is not None
AssertionErrorI commented out the assertion and committed it; did I do the right thing?
kvarforl
commented
3 years ago hmmm, good question! I didn't add that assertion, or use the 'organism' field at all in my most recent edits to uniprotkb_dat_to_json.py, and I also didn't run into that issue when I built kg2.5.1 earlier in January. I'll look into it more in just a second!
saramsey
commented
3 years ago OK, no rush.
saramsey
commented
3 years ago fixed in code; ready for testing in the next KG2 build
kvarforl
commented
3 years ago Ah this fell all the way off of my radar. Thanks for the fix Steve! looks better in kg2.5.2
match (n) where n.id in ["UniProtKB:P01137", "UniProtKB:P61812", "UniProtKB:P10600"] return n.id, n.name, n.synonym[0], n.iri| n.id | n.name | n.synonym[0] | n.iri |
|---|---|---|---|
| "UniProtKB:P01137" | "TGFB1" | "TGFB1" | "https://identifiers.org/uniprot:P01137" |
| "UniProtKB:P61812" | "TGFB2" | "TGFB2" | "https://identifiers.org/uniprot:P61812" |
| "UniProtKB:P10600" | "TGFB3" | "TGFB3" | "https://identifiers.org/uniprot:P10600" |
while looking into #1159, I noticed that these three nodes in KG2.3.4 have the name "LAP", but the first item in their
synonymfields is TGFB_, which seemed slightly odd. then I noticed that if you click on their IRIs, uniprot.org seems to suggest that their names shouldn't be LAP, but instead something like "TGFB1", "TGFB2", and "TGFB3", respectively?here's an example for UniProtKB:P01137:
https://www.uniprot.org/uniprot/P01137