LTBP2_HUMAN
ID LTBP2_HUMAN Reviewed; 1821 AA.
AC Q14767; Q99907; Q9NS51;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Latent-transforming growth factor beta-binding protein 2;
DE Short=LTBP-2;
DE Flags: Precursor;
GN Name=LTBP2; Synonyms=C14orf141, LTBP3;
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], COMPLEX FORMATION WITH TGFB1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Foreskin fibroblast;
RX PubMed=7798248; DOI=10.1016/s0021-9258(18)31659-4;
RA Moren A., Olofsson A., Stenman G., Sahlin P., Kanzaki T.,
RA Claesson-Welsh L., ten Dijke P., Miyazono K., Heldin C.;
RT "Identification and characterization of LTBP-2, a novel latent transforming
RT growth factor-beta-binding protein.";
RL J. Biol. Chem. 269:32469-32478(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8697098; DOI=10.1016/1357-2725(95)00167-0;
RA Bashir M.M., Han M.-D., Abrams W.R., Tucker T., Ma R.-I., Gibson M.,
RA Ritty T., Mecham R., Rosenbloom J.;
RT "Analysis of the human gene encoding latent transforming growth factor-
RT beta-binding protein-2.";
RL Int. J. Biochem. Cell Biol. 28:531-542(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP LACK OF INTERACTION WITH TGFB1, AND MUTAGENESIS OF 1449-ASP-LEU-1450.
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 [5]
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 [6]
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 [7]
RP INTERACTION WITH FBN1, GLYCOSYLATION, TISSUE SPECIFICITY, AND C-TERMINAL
RP REGION DOMAIN.
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 [8]
RP INVOLVEMENT IN GLC3D.
RX PubMed=19361779; DOI=10.1016/j.ajhg.2009.03.017;
RA Ali M., McKibbin M., Booth A., Parry D.A., Jain P., Riazuddin S.A.,
RA Hejtmancik J.F., Khan S.N., Firasat S., Shires M., Gilmour D.F., Towns K.,
RA Murphy A.L., Azmanov D., Tournev I., Cherninkova S., Jafri H., Raashid Y.,
RA Toomes C., Craig J., Mackey D.A., Kalaydjieva L., Riazuddin S.,
RA Inglehearn C.F.;
RT "Null mutations in LTBP2 cause primary congenital glaucoma.";
RL Am. J. Hum. Genet. 84:664-671(2009).
RN [9]
RP INVOLVEMENT IN MSPKA.
RX PubMed=20617341; DOI=10.1007/s00439-010-0858-8;
RA Kumar A., Duvvari M.R., Prabhakaran V.C., Shetty J.S., Murthy G.J.,
RA Blanton S.H.;
RT "A homozygous mutation in LTBP2 causes isolated microspherophakia.";
RL Hum. Genet. 128:365-371(2010).
RN [10]
RP HEPARIN-BINDING REGIONS, AND INTERACTION WITH SDC4.
RX PubMed=20382221; DOI=10.1016/j.matbio.2010.03.005;
RA Parsi M.K., Adams J.R., Whitelock J., Gibson M.A.;
RT "LTBP-2 has multiple heparin/heparan sulfate binding sites.";
RL Matrix Biol. 29:393-401(2010).
RN [11]
RP VARIANT WMS3 MET-1177.
RX PubMed=22539340; DOI=10.1002/humu.22105;
RA Haji-Seyed-Javadi R., Jelodari-Mamaghani S., Paylakhi S.H., Yazdani S.,
RA Nilforushan N., Fan J.B., Klotzle B., Mahmoudi M.J., Ebrahimian M.J.,
RA Chelich N., Taghiabadi E., Kamyab K., Boileau C., Paisan-Ruiz C.,
RA Ronaghi M., Elahi E.;
RT "LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome
RT and affect disruptions in the extracellular matrix.";
RL Hum. Mutat. 33:1182-1187(2012).
CC -!- FUNCTION: May play an integral structural role in elastic-fiber
CC architectural organization and/or assembly.
CC {ECO:0000303|PubMed:10743502, ECO:0000303|PubMed:11104663}.
CC -!- SUBUNIT: Forms part of the large latent transforming growth factor beta
CC precursor complex; removal is essential for activation of complex
CC (PubMed:7798248). Interacts with SDC4 (PubMed:20382221). Interacts (via
CC C-terminal domain) with FBN1 (via N-terminal domain) in a Ca(+2)-
CC dependent manner (PubMed:17293099). {ECO:0000269|PubMed:17293099,
CC ECO:0000269|PubMed:20382221, ECO:0000269|PubMed:7798248}.
CC -!- INTERACTION:
CC Q14767; Q9UBX5: FBLN5; NbExp=2; IntAct=EBI-1546118, EBI-947897;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:7798248}.
CC -!- TISSUE SPECIFICITY: Expressed in the aorta (at protein level).
CC Expressed in lung, weakly expressed in heart, placenta, liver and
CC skeletal muscle. {ECO:0000269|PubMed:17293099,
CC ECO:0000269|PubMed:7798248}.
CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:17293099}.
CC -!- PTM: Contains hydroxylated asparagine residues.
CC {ECO:0000250|UniProtKB:Q14766}.
CC -!- DISEASE: Glaucoma 3, primary congenital, D (GLC3D) [MIM:613086]: An
CC autosomal recessive form of primary congenital glaucoma (PCG). PCG is
CC characterized by marked increase of intraocular pressure at birth or
CC early childhood, large ocular globes (buphthalmos) and corneal edema.
CC It results from developmental defects of the trabecular meshwork and
CC anterior chamber angle of the eye that prevent adequate drainage of
CC aqueous humor. {ECO:0000269|PubMed:19361779}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Microspherophakia and/or megalocornea, with ectopia lentis and
CC with or without secondary glaucoma (MSPKA) [MIM:251750]: A rare disease
CC characterized by smaller and more spherical lenses than normal
CC bilaterally, an increased anteroposterior thickness of the lens, and
CC highly myopic eyes. Lens dislocation or subluxation may occur, leading
CC to defective accommodation. {ECO:0000269|PubMed:20617341}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Weill-Marchesani syndrome 3 (WMS3) [MIM:614819]: A rare
CC connective tissue disorder characterized by short stature,
CC brachydactyly, joint stiffness, and eye abnormalities including
CC microspherophakia, ectopia lentis, severe myopia and glaucoma.
CC {ECO:0000269|PubMed:22539340}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LTBP family. {ECO:0000305}.
CC -!- CAUTION: A publication reported that a complex is formed with TGFB1
CC (PubMed:7798248). According to another report, there is no association
CC with TGFB1 (PubMed:10930463). {ECO:0000269|PubMed:10930463,
CC ECO:0000269|PubMed:7798248}.
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DR EMBL; Z37976; CAA86030.1; -; mRNA.
DR EMBL; S82451; AAB37459.1; -; mRNA.
DR EMBL; AC013451; AAF87081.1; -; Genomic_DNA.
DR CCDS; CCDS9831.1; -.
DR PIR; A55494; A55494.
DR RefSeq; NP_000419.1; NM_000428.2.
DR AlphaFoldDB; Q14767; -.
DR BioGRID; 110231; 95.
DR IntAct; Q14767; 3.
DR MINT; Q14767; -.
DR STRING; 9606.ENSP00000261978; -.
DR GlyConnect; 1448; 16 N-Linked glycans (3 sites).
DR GlyGen; Q14767; 28 sites, 15 N-linked glycans (3 sites), 6 O-linked glycans (19 sites).
DR iPTMnet; Q14767; -.
DR PhosphoSitePlus; Q14767; -.
DR SwissPalm; Q14767; -.
DR BioMuta; LTBP2; -.
DR DMDM; 296439311; -.
DR EPD; Q14767; -.
DR jPOST; Q14767; -.
DR MassIVE; Q14767; -.
DR PaxDb; Q14767; -.
DR PeptideAtlas; Q14767; -.
DR PRIDE; Q14767; -.
DR ProteomicsDB; 60164; -.
DR Antibodypedia; 157; 130 antibodies from 24 providers.
DR DNASU; 4053; -.
DR Ensembl; ENST00000261978.9; ENSP00000261978.4; ENSG00000119681.12.
DR GeneID; 4053; -.
DR KEGG; hsa:4053; -.
DR MANE-Select; ENST00000261978.9; ENSP00000261978.4; NM_000428.3; NP_000419.1.
DR UCSC; uc001xqa.4; human.
DR CTD; 4053; -.
DR DisGeNET; 4053; -.
DR GeneCards; LTBP2; -.
DR GeneReviews; LTBP2; -.
DR HGNC; HGNC:6715; LTBP2.
DR HPA; ENSG00000119681; Low tissue specificity.
DR MalaCards; LTBP2; -.
DR MIM; 251750; phenotype.
DR MIM; 602091; gene.
DR MIM; 613086; phenotype.
DR MIM; 614819; phenotype.
DR neXtProt; NX_Q14767; -.
DR OpenTargets; ENSG00000119681; -.
DR Orphanet; 98976; Congenital glaucoma.
DR Orphanet; 238763; Glaucoma secondary to spherophakia/ectopia lentis and megalocornea.
DR Orphanet; 3449; Weill-Marchesani syndrome.
DR PharmGKB; PA164741922; -.
DR VEuPathDB; HostDB:ENSG00000119681; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000160884; -.
DR HOGENOM; CLU_001884_1_0_1; -.
DR InParanoid; Q14767; -.
DR OMA; GNGHEHT; -.
DR OrthoDB; 1174178at2759; -.
DR PhylomeDB; Q14767; -.
DR PathwayCommons; Q14767; -.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
DR SignaLink; Q14767; -.
DR SIGNOR; Q14767; -.
DR BioGRID-ORCS; 4053; 14 hits in 1062 CRISPR screens.
DR ChiTaRS; LTBP2; human.
DR GeneWiki; LTBP2; -.
DR GenomeRNAi; 4053; -.
DR Pharos; Q14767; Tbio.
DR PRO; PR:Q14767; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q14767; protein.
DR Bgee; ENSG00000119681; Expressed in descending thoracic aorta and 196 other tissues.
DR ExpressionAtlas; Q14767; baseline and differential.
DR Genevisible; Q14767; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019838; F:growth factor binding; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0050436; F:microfibril binding; IBA:GO_Central.
DR GO; GO:0009306; P:protein secretion; TAS:ProtInc.
DR GO; GO:0006605; P:protein targeting; TAS:ProtInc.
DR GO; GO:0097435; P:supramolecular fiber organization; IMP:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
DR Gene3D; 3.90.290.10; -; 4.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
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; PF00008; EGF; 1.
DR Pfam; PF07645; EGF_CA; 17.
DR Pfam; PF00683; TB; 4.
DR SMART; SM00181; EGF; 20.
DR SMART; SM00179; EGF_CA; 18.
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; 15.
DR PROSITE; PS01187; EGF_CA; 16.
DR PROSITE; PS51364; TB; 4.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Dwarfism; EGF-like domain;
KW Extracellular matrix; Glaucoma; Glycoprotein; Growth factor binding;
KW Heparin-binding; Hydroxylation; Phosphoprotein; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..35
FT /evidence="ECO:0000250|UniProtKB:O35806"
FT CHAIN 36..1821
FT /note="Latent-transforming growth factor beta-binding
FT protein 2"
FT /id="PRO_0000007643"
FT DOMAIN 187..219
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 396..428
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 552..604
FT /note="TB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 622..662
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 672..724
FT /note="TB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 844..886
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 887..929
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 930..969
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 970..1009
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1010..1050
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1051..1092
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1093..1134
FT /note="EGF-like 10; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1135..1175
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1176..1217
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1218..1258
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1259..1302
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1303..1344
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1345..1387
FT /note="EGF-like 16; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1411..1463
FT /note="TB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 1485..1527
FT /note="EGF-like 17; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1528..1567
FT /note="EGF-like 18; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1584..1636
FT /note="TB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 1733..1773
FT /note="EGF-like 19; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1774..1818
FT /note="EGF-like 20; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 38..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 94..115
FT /note="Heparin-binding"
FT REGION 229..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 232..249
FT /note="Heparin-binding"
FT REGION 510..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 744..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1639..1821
FT /note="C-terminal domain"
FT /evidence="ECO:0000269|PubMed:17293099"
FT MOTIF 375..377
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 110..132
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 344..354
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08999"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 811
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 400..410
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 404..416
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 418..427
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 554..576
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 563..589
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 577..592
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 626..637
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 632..646
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 648..661
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 674..696
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 683..709
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 697..712
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 698..724
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 848..861
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 856..870
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 872..885
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 891..902
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 896..911
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 913..928
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 934..945
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 940..954
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 956..968
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 974..985
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 980..994
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 997..1008
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1014..1025
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1020..1034
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1036..1049
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1055..1066
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1061..1075
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1078..1091
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1097..1108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1103..1117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1120..1133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1139..1151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1146..1160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1162..1174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1180..1192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1186..1201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1203..1216
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1222..1233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1228..1242
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1244..1257
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1263..1276
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1271..1285
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1289..1301
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1307..1319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1313..1328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1330..1343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1349..1361
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1356..1370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1372..1386
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1413..1436
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1423..1448
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1437..1451
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1438..1463
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1489..1502
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1497..1511
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1513..1526
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1532..1542
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1537..1551
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1553..1566
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1586..1609
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1595..1621
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1610..1624
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1611..1636
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1737..1748
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1743..1757
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1759..1772
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1778..1793
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1788..1802
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1804..1817
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VARIANT 37
FT /note="R -> M (in dbSNP:rs934996)"
FT /id="VAR_059270"
FT VARIANT 319
FT /note="P -> Q (in dbSNP:rs2304707)"
FT /id="VAR_055752"
FT VARIANT 591
FT /note="P -> S (in dbSNP:rs2196862)"
FT /id="VAR_060337"
FT VARIANT 1177
FT /note="V -> M (in WMS3; dbSNP:rs137854856)"
FT /evidence="ECO:0000269|PubMed:22539340"
FT /id="VAR_068647"
FT MUTAGEN 1449..1450
FT /note="DL->EIFP: Gain-of-function. Forms a complex with
FT TGFB1."
FT /evidence="ECO:0000269|PubMed:10930463"
FT CONFLICT 897
FT /note="K -> Q (in Ref. 1; CAA86030)"
FT /evidence="ECO:0000305"
FT CONFLICT 1443
FT /note="S -> T (in Ref. 1; CAA86030)"
FT /evidence="ECO:0000305"
FT CONFLICT 1615
FT /note="E -> K (in Ref. 1; CAA86030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1821 AA; 195052 MW; 3D6952B39885E1A6 CRC64;
MRPRTKARSP GRALRNPWRG FLPLTLALFV GAGHAQRDPV GRYEPAGGDA NRLRRPGGSY
PAAAAAKVYS LFREQDAPVA GLQPVERAQP GWGSPRRPTE AEARRPSRAQ QSRRVQPPAQ
TRRSTPLGQQ QPAPRTRAAP ALPRLGTPQR SGAAPPTPPR GRLTGRNVCG GQCCPGWTTA
NSTNHCIKPV CEPPCQNRGS CSRPQLCVCR SGFRGARCEE VIPDEEFDPQ NSRLAPRRWA
ERSPNLRRSS AAGEGTLARA QPPAPQSPPA PQSPPAGTLS GLSQTHPSQQ HVGLSRTVRL
HPTATASSQL SSNALPPGPG LEQRDGTQQA VPLEHPSSPW GLNLTEKIKK IKIVFTPTIC
KQTCARGHCA NSCERGDTTT LYSQGGHGHD PKSGFRIYFC QIPCLNGGRC IGRDECWCPA
NSTGKFCHLP IPQPDREPPG RGSRPRALLE APLKQSTFTL PLSNQLASVN PSLVKVHIHH
PPEASVQIHQ VAQVRGGVEE ALVENSVETR PPPWLPASPG HSLWDSNNIP ARSGEPPRPL
PPAAPRPRGL LGRCYLNTVN GQCANPLLEL TTQEDCCGSV GAFWGVTLCA PCPPRPASPV
IENGQLECPQ GYKRLNLTHC QDINECLTLG LCKDAECVNT RGSYLCTCRP GLMLDPSRSR
CVSDKAISML QGLCYRSLGP GTCTLPLAQR ITKQICCCSR VGKAWGSECE KCPLPGTEAF
REICPAGHGY TYASSDIRLS MRKAEEEELA RPPREQGQRS SGALPGPAER QPLRVVTDTW
LEAGTIPDKG DSQAGQVTTS VTHAPAWVTG NATTPPMPEQ GIAEIQEEQV TPSTDVLVTL
STPGIDRCAA GATNVCGPGT CVNLPDGYRC VCSPGYQLHP SQAYCTDDNE CLRDPCKGKG
RCINRVGSYS CFCYPGYTLA TSGATQECQD INECEQPGVC SGGQCTNTEG SYHCECDQGY
IMVRKGHCQD INECRHPGTC PDGRCVNSPG SYTCLACEEG YRGQSGSCVD VNECLTPGVC
AHGKCTNLEG SFRCSCEQGY EVTSDEKGCQ DVDECASRAS CPTGLCLNTE GSFACSACEN
GYWVNEDGTA CEDLDECAFP GVCPSGVCTN TAGSFSCKDC DGGYRPSPLG DSCEDVDECE
DPQSSCLGGE CKNTVGSYQC LCPQGFQLAN GTVCEDVNEC MGEEHCAPHG ECLNSHGSFF
CLCAPGFVSA EGGTSCQDVD ECATTDPCVG GHCVNTEGSF NCLCETGFQP SPESGECVDI
DECEDYGDPV CGTWKCENSP GSYRCVLGCQ PGFHMAPNGD CIDIDECAND TMCGSHGFCD
NTDGSFRCLC DQGFEISPSG WDCVDVNECE LMLAVCGAAL CENVEGSFLC LCASDLEEYD
AQEGHCRPRG AGGQSMSEAP TGDHAPAPTR MDCYSGQKGH APCSSVLGRN TTQAECCCTQ
GASWGDACDL CPSEDSAEFS EICPSGKGYI PVEGAWTFGQ TMYTDADECV IFGPGLCPNG
RCLNTVPGYV CLCNPGFHYD ASHKKCEDHD ECQDLACENG ECVNTEGSFH CFCSPPLTLD
LSQQRCMNST SSTEDLPDHD IHMDICWKKV TNDVCSEPLR GHRTTYTECC CQDGEAWSQQ
CALCPPRSSE VYAQLCNVAR IEAEREAGVH FRPGYEYGPG PDDLHYSIYG PDGAPFYNYL
GPEDTVPEPA FPNTAGHSAD RTPILESPLQ PSELQPHYVA SHPEPPAGFE GLQAEECGIL
NGCENGRCVR VREGYTCDCF EGFQLDAAHM ACVDVNECDD LNGPAVLCVH GYCENTEGSY
RCHCSPGYVA EAGPPHCTAK E
