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   27-MAR-2024, entry version 200.
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; 96.
DR   IntAct; Q14767; 3.
DR   MINT; Q14767; -.
DR   STRING; 9606.ENSP00000261978; -.
DR   GlyConnect; 1448; 16 N-Linked glycans (3 sites).
DR   GlyCosmos; Q14767; 28 sites, 21 glycans.
DR   GlyGen; Q14767; 41 sites, 15 N-linked glycans (3 sites), 8 O-linked glycans (32 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; 9606-ENSP00000261978; -.
DR   PeptideAtlas; Q14767; -.
DR   ProteomicsDB; 60164; -.
DR   Antibodypedia; 157; 140 antibodies from 23 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   AGR; HGNC:6715; -.
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; ADPPHCA; -.
DR   OrthoDB; 354414at2759; -.
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 1138 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 198 other cell types or tissues.
DR   ExpressionAtlas; Q14767; baseline and differential.
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   CDD; cd00054; EGF_CA; 13.
DR   Gene3D; 2.10.25.10; Laminin; 19.
DR   Gene3D; 3.90.290.10; TGF-beta binding (TB) domain; 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   PANTHER; PTHR24034; EGF-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR24034:SF166; VACUOLAR-SORTING RECEPTOR 1; 1.
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; SSF57196; EGF/Laminin; 6.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 5.
DR   SUPFAM; SSF57581; TB module/8-cys domain; 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.
DR   Genevisible; Q14767; HS.
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
//