ID LTBP1_HUMAN Reviewed; 1721 AA. AC Q14766; A1L3V1; P22064; Q53SD8; Q53SF3; Q53SG1; Q59HF7; Q8TD95; DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 02-MAR-2010, sequence version 4. DT 22-APR-2020, entry version 194. DE RecName: Full=Latent-transforming growth factor beta-binding protein 1 {ECO:0000303|PubMed:8537398}; DE Short=LTBP-1 {ECO:0000303|PubMed:8537398}; DE AltName: Full=Transforming growth factor beta-1-binding protein 1 {ECO:0000303|PubMed:2350783}; DE Short=TGF-beta1-BP-1 {ECO:0000303|PubMed:2350783}; DE Flags: Precursor; GN Name=LTBP1 {ECO:0000312|HGNC:HGNC:6714}; 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 [MRNA] (ISOFORM SHORT), PARTIAL PROTEIN SEQUENCE, AND RP HYDROXYLATION AT ASN-974 AND ASN-1137. RC TISSUE=Fibroblast, and Platelet; RX PubMed=2350783; DOI=10.1016/0092-8674(90)90069-q; RA Kanzaki T., Olofsson A., Moren A., Wernstedt C., Hellman U., Miyazono K., RA Claesson-Welsh L., Heldin C.-H.; RT "TGF-beta 1 binding protein: a component of the large latent complex of RT TGF-beta 1 with multiple repeat sequences."; RL Cell 61:1051-1061(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RA Kwak J.H., Shin K.Y., Kim S.I.; RT "Major alternative spliced-form of LTBP1 mRNA in human glomerular RT endothelial cell."; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). RC TISSUE=Brain; 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 [GENOMIC DNA] OF 1-346. RC TISSUE=Blood; RX PubMed=8537398; DOI=10.1074/jbc.270.52.31294; RA Olofsson A., Ichijo H., Moren A., ten Dijke P., Miyazono K., Heldin C.-H.; RT "Efficient association of an amino-terminally extended form of human latent RT transforming growth factor-beta binding protein with the extracellular RT matrix."; RL J. Biol. Chem. 270:31294-31297(1995). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 684-875 (ISOFORMS 4 AND 5). RA Suzuki Y., Yamashita R., Shirota M., Sakakibara Y., Chiba J., Nakai K., RA Sugano S.; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION, AND INTERACTION WITH TGFB1. 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 [10] RP FUNCTION, INTERACTION WITH TGFB1, DOMAIN, SUBCELLULAR LOCATION, RP GLYCOSYLATION AT ASN-1366, DISULFIDE BOND, AND MUTAGENESIS OF ASN-1366. 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 [11] RP FUNCTION, INTERACTION WITH TGFB1, DOMAIN, GLYCOSYLATION AT ASN-1366, RP DISULFIDE BOND, AND MUTAGENESIS OF ASN-1366. 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 [12] RP REVIEW. RX PubMed=10743502; DOI=10.1016/s1359-6101(99)00010-6; RA Saharinen J., Hyytiainen M., Taipale J., Keski-Oja J.; RT "Latent transforming growth factor-beta binding proteins (LTBPs) RT -- structural extracellular matrix proteins for targeting TGF-beta RT action."; RL Cytokine Growth Factor Rev. 10:99-117(1999). RN [13] RP REVIEW. RX PubMed=11104663; DOI=10.1042/bj3520601; RA Oklu R., Hesketh R.; RT "The latent transforming growth factor beta binding protein (LTBP) RT family."; RL Biochem. J. 352:601-610(2000). RN [14] RP GLYCOSYLATION AT ASN-1366. RX PubMed=10677208; DOI=10.1021/bi9918285; RA Rudd P.M., Downing A.K., Cadene M., Harvey D.J., Wormald M.R., Weir I., RA Dwek R.A., Rifkin D.B., Gleizes P.E.; RT "Hybrid and complex glycans are linked to the conserved N-glycosylation RT site of the third eight-cysteine domain of LTBP-1 in insect cells."; RL Biochemistry 39:1596-1603(2000). RN [15] RP INTERACTION WITH TGFB1, AND MUTAGENESIS OF 1385-GLU--PRO-1388. RX PubMed=10930463; DOI=10.1091/mbc.11.8.2691; RA Saharinen J., Keski-Oja J.; RT "Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, RT LTBPs, creates a hydrophobic interaction surface for binding of small RT latent TGF-beta."; RL Mol. Biol. Cell 11:2691-2704(2000). RN [16] RP INTERACTION WITH FBN1 AND FBN2. RX PubMed=12429738; DOI=10.1074/jbc.m209256200; RA Isogai Z., Ono R.N., Ushiro S., Keene D.R., Chen Y., Mazzieri R., RA Charbonneau N.L., Reinhardt D.P., Rifkin D.B., Sakai L.Y.; RT "Latent transforming growth factor beta-binding protein 1 interacts with RT fibrillin and is a microfibril-associated protein."; RL J. Biol. Chem. 278:2750-2757(2003). RN [17] RP FUNCTION. RX PubMed=15184403; DOI=10.1083/jcb.200312172; RA Annes J.P., Chen Y., Munger J.S., Rifkin D.B.; RT "Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the RT latent TGF-beta binding protein-1."; RL J. Cell Biol. 165:723-734(2004). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=16157329; DOI=10.1016/j.yexcr.2005.08.008; RA Koli K., Hyytieainen M., Ryynanen M.J., Keski-Oja J.; RT "Sequential deposition of latent TGF-beta binding proteins (LTBPs) during RT formation of the extracellular matrix in human lung fibroblasts."; RL Exp. Cell Res. 310:370-382(2005). RN [19] RP INTERACTION WITH TGFB1, AND MUTAGENESIS OF GLU-1348 AND 1382-ASP--GLU-1385. RX PubMed=15567420; DOI=10.1016/j.jmb.2004.10.039; RA Chen Y., Ali T., Todorovic V., O'leary J.M., Kristina Downing A., RA Rifkin D.B.; RT "Amino acid requirements for formation of the TGF-beta-latent TGF-beta RT binding protein complexes."; RL J. Mol. Biol. 345:175-186(2005). RN [20] RP INTERACTION WITH FBN1, C-TERMINAL REGION DOMAIN, AND TISSUE SPECIFICITY. RX PubMed=17293099; DOI=10.1016/j.matbio.2006.12.006; RA Hirani R., Hanssen E., Gibson M.A.; RT "LTBP-2 specifically interacts with the amino-terminal region of fibrillin- RT 1 and competes with LTBP-1 for binding to this microfibrillar protein."; RL Matrix Biol. 26:213-223(2007). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1597, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [22] RP INTERACTION WITH ADAMTSL2. RX PubMed=18677313; DOI=10.1038/ng.199; RA Le Goff C., Morice-Picard F., Dagoneau N., Wang L.W., Perrot C., Crow Y.J., RA Bauer F., Flori E., Prost-Squarcioni C., Krakow D., Ge G., Greenspan D.S., RA Bonnet D., Le Merrer M., Munnich A., Apte S.S., Cormier-Daire V.; RT "ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS- RT like proteins in TGF-beta bioavailability regulation."; RL Nat. Genet. 40:1119-1123(2008). RN [23] RP FUNCTION, AND INTERACTION WITH TGFB1. 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 [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [25] RP PHOSPHORYLATION AT SER-1414. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [26] RP STRUCTURE BY NMR OF 1340-1412, AND DISULFIDE BONDS. RX PubMed=14607119; DOI=10.1016/j.jmb.2003.09.053; RA Lack J., O'Leary J.M., Knott V., Yuan X., Rifkin D.B., Handford P.A., RA Downing A.K.; RT "Solution structure of the third TB domain from LTBP1 provides insight into RT assembly of the large latent complex that sequesters latent TGF-beta."; RL J. Mol. Biol. 334:281-291(2003). CC -!- FUNCTION: Key regulator of transforming growth factor beta (TGFB1, CC TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in CC a latent state during storage in extracellular space (PubMed:2022183, CC PubMed:8617200, PubMed:8939931). Associates specifically via disulfide CC bonds with the Latency-associated peptide (LAP), which is the CC regulatory chain of TGF-beta, and regulates integrin-dependent CC activation of TGF-beta (PubMed:8617200, PubMed:8939931, CC PubMed:15184403). Outcompeted by LRRC32/GARP for binding to LAP CC regulatory chain of TGF-beta (PubMed:22278742). CC {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:2022183, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200, CC ECO:0000269|PubMed:8939931}. CC -!- SUBUNIT: Interacts with TGFB1; associates via disulfide bonds with the CC Latency-associated peptide chain (LAP) regulatory chain of TGFB1, CC leading to regulate activation of TGF-beta-1 (PubMed:10930463, CC PubMed:2022183, PubMed:8617200, PubMed:15567420, PubMed:8939931, CC PubMed:22278742). LTBP1 does not bind directly to TGF-beta-1, the CC active chain of TGFB1 (PubMed:10930463). Interacts (via C-terminal CC domain) with FBN1 (via N-terminal domain) (PubMed:12429738, CC PubMed:17293099). Interacts with FBN2 (PubMed:12429738). Interacts with CC ADAMTSL2 (PubMed:18677313). {ECO:0000269|PubMed:10930463, CC ECO:0000269|PubMed:12429738, ECO:0000269|PubMed:15567420, CC ECO:0000269|PubMed:17293099, ECO:0000269|PubMed:18677313, CC ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, CC ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}. CC -!- INTERACTION: CC Q14766-2; P35555: FBN1; NbExp=2; IntAct=EBI-11173832, EBI-2505934; CC Q14766-1; P01137: TGFB1; NbExp=4; IntAct=EBI-11173861, EBI-779636; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16157329}. Secreted, CC extracellular space, extracellular matrix {ECO:0000269|PubMed:16157329, CC ECO:0000269|PubMed:8617200}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=Long; Synonyms=LTBP-1L; CC IsoId=Q14766-1; Sequence=Displayed; CC Name=Short; Synonyms=LTBP-1S; CC IsoId=Q14766-2, P22064-1; CC Sequence=VSP_036963, VSP_036964; CC Name=3; CC IsoId=Q14766-3; Sequence=VSP_036963, VSP_036964, VSP_036965; CC Name=4; CC IsoId=Q14766-4; Sequence=VSP_040125; CC Name=5; CC IsoId=Q14766-5; Sequence=VSP_036963, VSP_036964, VSP_040125; CC -!- TISSUE SPECIFICITY: Expressed in the aorta (at protein level) CC (PubMed:17293099). Isoform Long: Expressed in fibroblasts CC (PubMed:17293099). {ECO:0000269|PubMed:17293099}. CC -!- DOMAIN: The 8-Cys3 region in the third TB domain mediates the CC interchain disulfide bond interaction with the Latency-associated CC peptide chain (LAP) regulatory chain of TGFB1. CC {ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}. CC -!- PTM: Contains hydroxylated asparagine residues. CC {ECO:0000269|PubMed:2350783}. CC -!- PTM: Isoform Short N-terminus is blocked. {ECO:0000269|PubMed:2350783}. CC -!- PTM: Two intrachain disulfide bonds from the TB3 domain are rearranged CC upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, CC anchoring it to the extracellular matrix. CC {ECO:0000269|PubMed:14607119}. CC -!- SIMILARITY: Belongs to the LTBP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92038.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M34057; AAA61160.1; -; mRNA. DR EMBL; AF489528; AAM03124.1; -; mRNA. DR EMBL; AB208801; BAD92038.1; ALT_INIT; mRNA. DR EMBL; AC019195; AAY14953.1; -; Genomic_DNA. DR EMBL; AC019127; AAY24260.1; -; Genomic_DNA. DR EMBL; AC020594; AAY15036.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00437.1; -; Genomic_DNA. DR EMBL; BC130289; AAI30290.1; -; mRNA. DR EMBL; L48925; AAA96327.1; -; Genomic_DNA. DR EMBL; BP291349; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS33177.2; -. [Q14766-1] DR CCDS; CCDS33178.2; -. [Q14766-2] DR CCDS; CCDS54345.1; -. [Q14766-3] DR PIR; A35626; A35626. DR RefSeq; NP_000618.3; NM_000627.3. DR RefSeq; NP_001159736.1; NM_001166264.1. DR RefSeq; NP_001159737.1; NM_001166265.1. DR RefSeq; NP_001159738.1; NM_001166266.1. DR RefSeq; NP_996826.2; NM_206943.2. DR RefSeq; XP_011531155.1; XM_011532853.2. [Q14766-4] DR PDB; 1KSQ; NMR; -; A=1340-1412. DR PDBsum; 1KSQ; -. DR SMR; Q14766; -. DR BioGrid; 110230; 47. DR DIP; DIP-50011N; -. DR IntAct; Q14766; 33. DR MINT; Q14766; -. DR STRING; 9606.ENSP00000386043; -. DR GlyConnect; 329; -. DR iPTMnet; Q14766; -. DR PhosphoSitePlus; Q14766; -. DR UniCarbKB; Q14766; -. DR BioMuta; LTBP1; -. DR DMDM; 290457687; -. DR EPD; Q14766; -. DR jPOST; Q14766; -. DR MassIVE; Q14766; -. DR MaxQB; Q14766; -. DR PaxDb; Q14766; -. DR PeptideAtlas; Q14766; -. DR PRIDE; Q14766; -. DR ProteomicsDB; 60159; -. [Q14766-1] DR ProteomicsDB; 60160; -. [Q14766-2] DR ProteomicsDB; 60161; -. [Q14766-3] DR ProteomicsDB; 60162; -. [Q14766-4] DR ProteomicsDB; 60163; -. [Q14766-5] DR Antibodypedia; 1284; 204 antibodies. DR Ensembl; ENST00000404525; ENSP00000385359; ENSG00000049323. [Q14766-3] DR Ensembl; ENST00000404816; ENSP00000386043; ENSG00000049323. [Q14766-1] DR Ensembl; ENST00000407925; ENSP00000384091; ENSG00000049323. [Q14766-2] DR GeneID; 4052; -. DR KEGG; hsa:4052; -. DR UCSC; uc002rou.4; human. [Q14766-1] DR CTD; 4052; -. DR DisGeNET; 4052; -. DR GeneCards; LTBP1; -. DR HGNC; HGNC:6714; LTBP1. DR HPA; ENSG00000049323; Low tissue specificity. DR MIM; 150390; gene. DR neXtProt; NX_Q14766; -. DR OpenTargets; ENSG00000049323; -. DR PharmGKB; PA30477; -. DR eggNOG; KOG1217; Eukaryota. DR eggNOG; ENOG410Z7XK; LUCA. DR GeneTree; ENSGT00940000155823; -. DR InParanoid; Q14766; -. DR KO; K19559; -. DR OMA; PQFPGIV; -. DR OrthoDB; 1174178at2759; -. DR PhylomeDB; Q14766; -. DR TreeFam; TF317514; -. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SIGNOR; Q14766; -. DR ChiTaRS; LTBP1; human. DR EvolutionaryTrace; Q14766; -. DR GeneWiki; LTBP1_(gene); -. DR GenomeRNAi; 4052; -. DR Pharos; Q14766; Tbio. DR PRO; PR:Q14766; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q14766; protein. DR Bgee; ENSG00000049323; Expressed in descending thoracic aorta and 240 other tissues. DR ExpressionAtlas; Q14766; baseline and differential. DR Genevisible; Q14766; HS. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0001527; C:microfibril; IDA:AgBase. DR GO; GO:0032991; C:protein-containing complex; IDA:AgBase. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0050436; F:microfibril binding; IDA:AgBase. DR GO; GO:0050431; F:transforming growth factor beta binding; IPI:UniProtKB. DR GO; GO:0005024; F:transforming growth factor beta-activated receptor activity; NAS:UniProtKB. DR GO; GO:0035904; P:aorta development; IEA:Ensembl. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0060976; P:coronary vasculature development; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:1901388; P:regulation of transforming growth factor beta activation; IDA:UniProtKB. DR GO; GO:0035583; P:sequestering of TGFbeta in extracellular matrix; IDA:UniProtKB. DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl. DR Gene3D; 3.90.290.10; -; 4. DR InterPro; IPR026823; cEGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR017878; TB_dom. DR InterPro; IPR036773; TB_dom_sf. DR Pfam; PF12662; cEGF; 1. DR Pfam; PF07645; EGF_CA; 13. DR Pfam; PF00683; TB; 4. DR SMART; SM00181; EGF; 18. DR SMART; SM00179; EGF_CA; 16. DR SUPFAM; SSF57184; SSF57184; 5. DR SUPFAM; SSF57581; SSF57581; 4. DR PROSITE; PS00010; ASX_HYDROXYL; 13. DR PROSITE; PS00022; EGF_1; 2. DR PROSITE; PS01186; EGF_2; 11. DR PROSITE; PS50026; EGF_3; 14. DR PROSITE; PS01187; EGF_CA; 15. DR PROSITE; PS51364; TB; 4. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disulfide bond; EGF-like domain; Extracellular matrix; Glycoprotein; KW Growth factor binding; Hydroxylation; Phosphoprotein; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..1721 FT /note="Latent-transforming growth factor beta-binding FT protein 1" FT /id="PRO_0000007635" FT DOMAIN 187..219 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 399..431 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 557..609 FT /note="TB 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DOMAIN 626..663 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 677..729 FT /note="TB 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DOMAIN 873..910 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 915..956 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 957..997 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 998..1037 FT /note="EGF-like 7; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1038..1078 FT /note="EGF-like 8; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1079..1119 FT /note="EGF-like 9; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1120..1160 FT /note="EGF-like 10; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1161..1201 FT /note="EGF-like 11; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1202..1243 FT /note="EGF-like 12; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1244..1281 FT /note="EGF-like 13; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1286..1328 FT /note="EGF-like 14; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1347..1401 FT /note="TB 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DOMAIN 1424..1466 FT /note="EGF-like 15; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1467..1503 FT /note="EGF-like 16; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1524..1577 FT /note="TB 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DOMAIN 1621..1657 FT /note="EGF-like 17" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1662..1706 FT /note="EGF-like 18; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 1344..1411 FT /note="8-Cys3 region" FT /evidence="ECO:0000269|PubMed:8617200, FT ECO:0000269|PubMed:8939931" FT REGION 1507..1721 FT /note="C-terminal domain" FT /evidence="ECO:0000269|PubMed:17293099" FT MOTIF 1174..1176 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT COMPBIAS 100..130 FT /note="Pro-rich" FT MOD_RES 974 FT /note="(3R)-3-hydroxyasparagine" FT /evidence="ECO:0000269|PubMed:2350783" FT MOD_RES 1137 FT /note="(3R)-3-hydroxyasparagine" FT /evidence="ECO:0000269|PubMed:2350783" FT MOD_RES 1414 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 1597 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18088087" FT MOD_RES 1616 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CG19" FT CARBOHYD 347 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 378 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 424 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 620 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1197 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1250 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1366 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10677208, FT ECO:0000269|PubMed:8617200" FT /id="CAR_000184" FT DISULFID 191..201 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 195..207 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 209..218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 403..413 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 407..419 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 421..430 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 559..581 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 568..594 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 582..597 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 630..641 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 636..650 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 652..665 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 679..702 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 689..714 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 703..717 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 704..729 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 877..889 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 884..898 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 900..913 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 919..931 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 926..940 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 942..955 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 961..972 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 967..981 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 984..996 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1002..1013 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1008..1022 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1025..1036 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1042..1053 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1048..1062 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1064..1077 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1083..1094 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1089..1103 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1105..1118 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1124..1135 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1130..1144 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1146..1159 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1165..1177 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1172..1186 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1188..1200 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1206..1218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1212..1227 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1229..1242 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1248..1260 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1254..1269 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1349..1372 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697, FT ECO:0000269|PubMed:14607119" FT DISULFID 1359..1384 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697, FT ECO:0000269|PubMed:14607119" FT DISULFID 1359 FT /note="Interchain (with C-33 in TGFB1); in linked form" FT /evidence="ECO:0000305|PubMed:14607119" FT DISULFID 1373..1389 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697, FT ECO:0000269|PubMed:14607119" FT DISULFID 1374..1401 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697, FT ECO:0000269|PubMed:14607119" FT DISULFID 1384 FT /note="Interchain (with C-33 in TGFB1); in linked form" FT /evidence="ECO:0000305|PubMed:14607119" FT DISULFID 1471..1482 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1477..1491 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1526..1550 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 1536..1562 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 1551..1565 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 1552..1577 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697" FT DISULFID 1625..1636 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1631..1645 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1666..1681 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1676..1690 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 1692..1705 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT VAR_SEQ 1..326 FT /note="Missing (in isoform Short, isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2350783, ECO:0000303|Ref.2, FT ECO:0000303|Ref.3, ECO:0000303|Ref.8" FT /id="VSP_036963" FT VAR_SEQ 327..345 FT /note="EGSFPLRYVQDQVAAPFQL -> MDTKLMCLLFFFSLPPLLV (in FT isoform Short, isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2350783, ECO:0000303|Ref.2, FT ECO:0000303|Ref.3, ECO:0000303|Ref.8" FT /id="VSP_036964" FT VAR_SEQ 724..776 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_036965" FT VAR_SEQ 839..840 FT /note="PV -> PGI (in isoform 4 and isoform 5)" FT /evidence="ECO:0000303|Ref.8" FT /id="VSP_040125" FT MUTAGEN 1348 FT /note="E->A: Abolishes interaction with the Latency- FT associated peptide chain (LAP) regulatory chain of TGFB1; FT when associated with 1382-A--A-1385." FT /evidence="ECO:0000269|PubMed:15567420" FT MUTAGEN 1366 FT /note="N->A,Q: Abolishes N-glycosylation at this site FT without affecting ability to interact with the Latency- FT associated peptide chain (LAP) regulatory chain of TGFB1." FT /evidence="ECO:0000269|PubMed:8617200, FT ECO:0000269|PubMed:8939931" FT MUTAGEN 1382..1385 FT /note="DNCE->ANCA: Abolishes interaction with the Latency- FT associated peptide chain (LAP) regulatory chain of TGFB1; FT when associated with A-1348." FT /evidence="ECO:0000269|PubMed:15567420" FT MUTAGEN 1385..1388 FT /note="EIFP->DL: Loss of binding to TGFB1." FT /evidence="ECO:0000269|PubMed:10930463" FT CONFLICT 50 FT /note="R -> AS (in Ref. 7; AAA96327)" FT /evidence="ECO:0000305" FT CONFLICT 691 FT /note="H -> Y (in Ref. 1; AAA61160)" FT /evidence="ECO:0000305" FT CONFLICT 694 FT /note="S -> P (in Ref. 8; BP291349)" FT /evidence="ECO:0000305" FT CONFLICT 710 FT /note="Missing (in Ref. 1; AAA61160 and 2; AAM03124)" FT /evidence="ECO:0000305" FT CONFLICT 744 FT /note="R -> M (in Ref. 8; BP291349)" FT /evidence="ECO:0000305" FT CONFLICT 792..794 FT /note="PGV -> ARS (in Ref. 1; AAA61160 and 2; AAM03124)" FT /evidence="ECO:0000305" FT CONFLICT 831 FT /note="T -> A (in Ref. 1; AAA61160)" FT /evidence="ECO:0000305" FT CONFLICT 1378 FT /note="V -> A (in Ref. 1; AAA61160, 2; AAM03124, 3; FT BAD92038, 5; EAX00437 and 6; AAI30290)" FT /evidence="ECO:0000305" FT CONFLICT 1648 FT /note="F -> L (in Ref. 1; AAA61160 and 2; AAM03124)" FT /evidence="ECO:0000305" FT CONFLICT 1661 FT /note="V -> F (in Ref. 1; AAA61160)" FT /evidence="ECO:0000305" FT STRAND 1340..1342 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1346..1353 FT /evidence="ECO:0000244|PDB:1KSQ" FT TURN 1355..1358 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1366..1368 FT /evidence="ECO:0000244|PDB:1KSQ" FT HELIX 1369..1374 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1378..1382 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1385..1388 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1392..1394 FT /evidence="ECO:0000244|PDB:1KSQ" FT HELIX 1395..1400 FT /evidence="ECO:0000244|PDB:1KSQ" FT STRAND 1408..1410 FT /evidence="ECO:0000244|PDB:1KSQ" SQ SEQUENCE 1721 AA; 186796 MW; 432489CAC3023754 CRC64; MAGAWLRWGL LLWAGLLASS AHGRLRRITY VVHPGPGLAA GALPLSGPPR SRTFNVALNA RYSRSSAAAG APSRASPGVP SERTRRTSKP GGAALQGLRP PPPPPPEPAR PAVPGGQLHP NPGGHPAAAP FTKQGRQVVR SKVPQETQSG GGSRLQVHQK QQLQGVNVCG GRCCHGWSKA PGSQRCTKPS CVPPCQNGGM CLRPQLCVCK PGTKGKACET IAAQDTSSPV FGGQSPGAAS SWGPPEQAAK HTSSKKADTL PRVSPVAQMT LTLKPKPSVG LPQQIHSQVT PLSSQSVVIH HGQTQEYVLK PKYFPAQKGI SGEQSTEGSF PLRYVQDQVA APFQLSNHTG RIKVVFTPSI CKVTCTKGSC QNSCEKGNTT TLISENGHAA DTLTATNFRV VICHLPCMNG GQCSSRDKCQ CPPNFTGKLC QIPVHGASVP KLYQHSQQPG KALGTHVIHS THTLPLTVTS QQGVKVKFPP NIVNIHVKHP PEASVQIHQV SRIDGPTGQK TKEAQPGQSQ VSYQGLPVQK TQTIHSTYSH QQVIPHVYPV AAKTQLGRCF QETIGSQCGK ALPGLSKQED CCGTVGTSWG FNKCQKCPKK PSYHGYNQMM ECLPGYKRVN NTFCQDINEC QLQGVCPNGE CLNTMGSYRC TCKIGFGPDP TFSSCVPDPP VISEEKGPCY RLVSSGRQCM HPLSVHLTKQ LCCCSVGKAW GPHCEKCPLP GTAAFKEICP GGMGYTVSGV HRRRPIHHHV GKGPVFVKPK NTQPVAKSTH PPPLPAKEEP VEALTFSREH GPGVAEPEVA TAPPEKEIPS LDQEKTKLEP GQPQLSPGIS TIHLHPQFPV VIEKTSPPVP VEVAPEASTS SASQVIAPTQ VTEINECTVN PDICGAGHCI NLPVRYTCIC YEGYRFSEQQ RKCVDIDECT QVQHLCSQGR CENTEGSFLC ICPAGFMASE EGTNCIDVDE CLRPDVCGEG HCVNTVGAFR CEYCDSGYRM TQRGRCEDID ECLNPSTCPD EQCVNSPGSY QCVPCTEGFR GWNGQCLDVD ECLEPNVCAN GDCSNLEGSY MCSCHKGYTR TPDHKHCRDI DECQQGNLCV NGQCKNTEGS FRCTCGQGYQ LSAAKDQCED IDECQHRHLC AHGQCRNTEG SFQCVCDQGY RASGLGDHCE DINECLEDKS VCQRGDCINT AGSYDCTCPD GFQLDDNKTC QDINECEHPG LCGPQGECLN TEGSFHCVCQ QGFSISADGR TCEDIDECVN NTVCDSHGFC DNTAGSFRCL CYQGFQAPQD GQGCVDVNEC ELLSGVCGEA FCENVEGSFL CVCADENQEY SPMTGQCRSR TSTDLDVDVD QPKEEKKECY YNLNDASLCD NVLAPNVTKQ ECCCTSGVGW GDNCEIFPCP VLGTAEFTEM CPKGKGFVPA GESSSEAGGE NYKDADECLL FGQEICKNGF CLNTRPGYEC YCKQGTYYDP VKLQCFDMDE CQDPSSCIDG QCVNTEGSYN CFCTHPMVLD ASEKRCIRPA ESNEQIEETD VYQDLCWEHL SDEYVCSRPL VGKQTTYTEC CCLYGEAWGM QCALCPLKDS DDYAQLCNIP VTGRRQPYGR DALVDFSEQY TPEADPYFIQ DRFLNSFEEL QAEECGILNG CENGRCVRVQ EGYTCDCFDG YHLDTAKMTC VDVNECDELN NRMSLCKNAK CINTDGSYKC LCLPGYVPSD KPNYCTPLNT ALNLEKDSDL E //