ID   LTBP3_HUMAN             Reviewed;        1303 AA.
AC   Q9NS15; O15107; Q96HB9; Q9H7K2; Q9UFN4;
DT   16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 4.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Latent-transforming growth factor beta-binding protein 3;
DE            Short=LTBP-3;
DE   Flags: Precursor;
GN   Name=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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=12154076; DOI=10.1242/jcs.115.17.3457;
RA   Penttinen C., Saharinen J., Weikkolainen K., Hyytiainen M., Keski-Oja J.;
RT   "Secretion of human latent TGF-beta-binding protein-3 (LTBP-3) is dependent
RT   on co-expression of TGF-beta.";
RL   J. Cell Sci. 115:3457-3468(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Spleen;
RA   Ohara O., Nagase T., Kikuno R., Okumura K.;
RT   "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 394-573.
RC   TISSUE=Liver;
RX   PubMed=9620332; DOI=10.1002/hep.510270619;
RA   Michel K., Roth S., Trautwein C., Gong W., Flemming P., Gressner A.M.;
RT   "Analysis of the expression pattern of the latent transforming growth
RT   factor beta binding protein isoforms in normal and diseased human liver
RT   reveals a new splice variant missing the proteinase-sensitive hinge
RT   region.";
RL   Hepatology 27:1592-1599(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 514-1303 (ISOFORM 2).
RC   TISSUE=Colon;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 793-1303.
RC   TISSUE=Uterus;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   INTERACTION WITH TGFB1.
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   [7]
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   [8]
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   [9]
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   [10]
RP   INTERACTION WITH EFEMP2.
RX   PubMed=27339457; DOI=10.1016/j.matbio.2016.06.003;
RA   Sasaki T., Hanisch F.G., Deutzmann R., Sakai L.Y., Sakuma T., Miyamoto T.,
RA   Yamamoto T., Hannappel E., Chu M.L., Lanig H., von der Mark K.;
RT   "Functional consequence of fibulin-4 missense mutations associated with
RT   vascular and skeletal abnormalities and cutis laxa.";
RL   Matrix Biol. 56:132-149(2016).
RN   [11]
RP   INVOLVEMENT IN DASS.
RX   PubMed=19344874; DOI=10.1016/j.ajhg.2009.03.007;
RA   Noor A., Windpassinger C., Vitcu I., Orlic M., Rafiq M.A., Khalid M.,
RA   Malik M.N., Ayub M., Alman B., Vincent J.B.;
RT   "Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-
RT   beta binding protein 3.";
RL   Am. J. Hum. Genet. 84:519-523(2009).
RN   [12]
RP   INVOLVEMENT IN GPHYSD3, VARIANT GPHYSD3 CYS-696, AND CHARACTERIZATION OF
RP   VARIANT GPHYSD3 CYS-696.
RX   PubMed=27068007; DOI=10.1136/jmedgenet-2015-103647;
RA   McInerney-Leo A.M., Le Goff C., Leo P.J., Kenna T.J., Keith P.,
RA   Harris J.E., Steer R., Bole-Feysot C., Nitschke P., Kielty C., Brown M.A.,
RA   Zankl A., Duncan E.L., Cormier-Daire V.;
RT   "Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia.";
RL   J. Med. Genet. 53:457-464(2016).
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. Associates
CC       specifically via disulfide bonds with the Latency-associated peptide
CC       (LAP), which is the regulatory chain of TGF-beta, and regulates
CC       integrin-dependent activation of TGF-beta.
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       Interacts with EFEMP2 (PubMed:27339457). {ECO:0000269|PubMed:10930463,
CC       ECO:0000269|PubMed:27339457}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12154076}. Secreted,
CC       extracellular space, extracellular matrix
CC       {ECO:0000269|PubMed:16157329}. Note=Secretion occurs after coexpression
CC       with TGFB1 and requires complexing with 'Cys-33' of the TGFB1
CC       propeptide. {ECO:0000269|PubMed:12154076}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NS15-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NS15-2; Sequence=VSP_009241;
CC   -!- TISSUE SPECIFICITY: Isoform 2: Expressed prominently in heart, skeletal
CC       muscle, prostate, testis, small intestine and ovary (PubMed:12154076).
CC       Isoform 1: Strongly expressed in pancreas and liver (PubMed:12154076).
CC       {ECO:0000269|PubMed:12154076}.
CC   -!- PTM: Contains hydroxylated asparagine residues.
CC       {ECO:0000250|UniProtKB:Q14766}.
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:0000250|UniProtKB:Q14766}.
CC   -!- DISEASE: Dental anomalies and short stature (DASS) [MIM:601216]: A
CC       disorder characterized by hypoplastic amelogenesis imperfecta,
CC       significant short stature, brachyolmia-like anomalies including
CC       platyspondyly with short pedicles, narrow intervertebral and
CC       interpedicular distances, rectangular-shaped vertebrae with posterior
CC       scalloping and herniation of the nuclei, and broad femoral necks.
CC       Dental anomalies include widely spaced, small, yellow teeth,
CC       oligodontia, and severely reduced to absent enamel.
CC       {ECO:0000269|PubMed:19344874}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Geleophysic dysplasia 3 (GPHYSD3) [MIM:617809]: A form of
CC       geleophysic dysplasia, a rare skeletal disease characterized by severe
CC       short stature, short hands and feet, and joint limitations. Radiologic
CC       features include delayed bone age, cone-shaped epiphyses, shortened
CC       long tubular bones, and ovoid vertebral bodies. Affected individuals
CC       have characteristic facial features including a 'happy' face with full
CC       cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin
CC       upper lip. Other distinctive features include skin thickening,
CC       progressive cardiac valvular thickening often leading to an early
CC       death, toe walking, tracheal stenosis, respiratory insufficiency, and
CC       lysosomal-like storage vacuoles in various tissues. GPHYSD3 inheritance
CC       is autosomal dominant. {ECO:0000269|PubMed:27068007}. Note=The disease
CC       is caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the LTBP family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB15767.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF135960; AAF62352.3; -; mRNA.
DR   EMBL; AK024477; BAB15767.1; ALT_INIT; mRNA.
DR   EMBL; AF011407; AAB64201.1; -; mRNA.
DR   EMBL; BC008761; AAH08761.2; -; mRNA.
DR   EMBL; AL117551; CAB55988.1; -; mRNA.
DR   CCDS; CCDS44647.1; -. [Q9NS15-1]
DR   CCDS; CCDS8103.1; -. [Q9NS15-2]
DR   PIR; T17298; T17298.
DR   RefSeq; NP_001123616.1; NM_001130144.2. [Q9NS15-1]
DR   RefSeq; NP_001157738.1; NM_001164266.1.
DR   RefSeq; NP_066548.2; NM_021070.4. [Q9NS15-2]
DR   AlphaFoldDB; Q9NS15; -.
DR   BioGRID; 110232; 49.
DR   IntAct; Q9NS15; 13.
DR   MINT; Q9NS15; -.
DR   STRING; 9606.ENSP00000301873; -.
DR   GlyCosmos; Q9NS15; 9 sites, 2 glycans.
DR   GlyGen; Q9NS15; 23 sites, 4 O-linked glycans (17 sites).
DR   iPTMnet; Q9NS15; -.
DR   PhosphoSitePlus; Q9NS15; -.
DR   BioMuta; LTBP3; -.
DR   DMDM; 116242623; -.
DR   EPD; Q9NS15; -.
DR   jPOST; Q9NS15; -.
DR   MassIVE; Q9NS15; -.
DR   MaxQB; Q9NS15; -.
DR   PaxDb; 9606-ENSP00000301873; -.
DR   PeptideAtlas; Q9NS15; -.
DR   ProteomicsDB; 82461; -. [Q9NS15-1]
DR   ProteomicsDB; 82462; -. [Q9NS15-2]
DR   Antibodypedia; 70903; 14 antibodies from 10 providers.
DR   DNASU; 4054; -.
DR   Ensembl; ENST00000301873.11; ENSP00000301873.5; ENSG00000168056.18. [Q9NS15-1]
DR   Ensembl; ENST00000322147.8; ENSP00000326647.4; ENSG00000168056.18. [Q9NS15-2]
DR   GeneID; 4054; -.
DR   KEGG; hsa:4054; -.
DR   MANE-Select; ENST00000301873.11; ENSP00000301873.5; NM_001130144.3; NP_001123616.1.
DR   UCSC; uc001oei.4; human. [Q9NS15-1]
DR   AGR; HGNC:6716; -.
DR   CTD; 4054; -.
DR   DisGeNET; 4054; -.
DR   GeneCards; LTBP3; -.
DR   GeneReviews; LTBP3; -.
DR   HGNC; HGNC:6716; LTBP3.
DR   HPA; ENSG00000168056; Low tissue specificity.
DR   MalaCards; LTBP3; -.
DR   MIM; 601216; phenotype.
DR   MIM; 602090; gene.
DR   MIM; 617809; phenotype.
DR   neXtProt; NX_Q9NS15; -.
DR   OpenTargets; ENSG00000168056; -.
DR   Orphanet; 969; Acromicric dysplasia.
DR   Orphanet; 2899; Brachyolmia-amelogenesis imperfecta syndrome.
DR   Orphanet; 2623; Geleophysic dysplasia.
DR   Orphanet; 2227; NON RARE IN EUROPE: Hypodontia.
DR   PharmGKB; PA30479; -.
DR   VEuPathDB; HostDB:ENSG00000168056; -.
DR   eggNOG; KOG1217; Eukaryota.
DR   GeneTree; ENSGT00940000160285; -.
DR   InParanoid; Q9NS15; -.
DR   OMA; CRDSCHH; -.
DR   OrthoDB; 354414at2759; -.
DR   PhylomeDB; Q9NS15; -.
DR   TreeFam; TF317514; -.
DR   PathwayCommons; Q9NS15; -.
DR   Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR   Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
DR   SignaLink; Q9NS15; -.
DR   BioGRID-ORCS; 4054; 83 hits in 1157 CRISPR screens.
DR   ChiTaRS; LTBP3; human.
DR   GeneWiki; LTBP3; -.
DR   GenomeRNAi; 4054; -.
DR   Pharos; Q9NS15; Tbio.
DR   PRO; PR:Q9NS15; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9NS15; Protein.
DR   Bgee; ENSG00000168056; Expressed in descending thoracic aorta and 191 other cell types or tissues.
DR   ExpressionAtlas; Q9NS15; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0050431; F:transforming growth factor beta binding; IPI:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR   GO; GO:0060349; P:bone morphogenesis; IEA:Ensembl.
DR   GO; GO:0046849; P:bone remodeling; IEA:Ensembl.
DR   GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0060430; P:lung saccule development; IEA:Ensembl.
DR   GO; GO:0030502; P:negative regulation of bone mineralization; IEA:Ensembl.
DR   GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR   GO; GO:2000741; P:positive regulation of mesenchymal stem cell differentiation; IMP:UniProtKB.
DR   GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IMP:UniProtKB.
DR   GO; GO:0036363; P:transforming growth factor beta activation; IMP:UniProtKB.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR   CDD; cd00054; EGF_CA; 11.
DR   Gene3D; 2.10.25.10; Laminin; 15.
DR   Gene3D; 3.90.290.10; TGF-beta binding (TB) domain; 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   PANTHER; PTHR24040:SF13; FIBROPELLIN-1; 1.
DR   PANTHER; PTHR24040; LAMININ G-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF12662; cEGF; 1.
DR   Pfam; PF07645; EGF_CA; 10.
DR   Pfam; PF12661; hEGF; 2.
DR   Pfam; PF00683; TB; 4.
DR   SMART; SM00181; EGF; 15.
DR   SMART; SM00179; EGF_CA; 14.
DR   SUPFAM; SSF57196; EGF/Laminin; 4.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 4.
DR   SUPFAM; SSF57581; TB module/8-cys domain; 4.
DR   PROSITE; PS00010; ASX_HYDROXYL; 11.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 8.
DR   PROSITE; PS50026; EGF_3; 13.
DR   PROSITE; PS01187; EGF_CA; 12.
DR   PROSITE; PS51364; TB; 4.
DR   Genevisible; Q9NS15; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Amelogenesis imperfecta; Disease variant;
KW   Disulfide bond; Dwarfism; EGF-like domain; Extracellular matrix;
KW   Glycoprotein; Growth factor binding; Reference proteome; Repeat; Secreted;
KW   Signal.
FT   SIGNAL          1..43
FT                   /evidence="ECO:0000255"
FT   CHAIN           44..1303
FT                   /note="Latent-transforming growth factor beta-binding
FT                   protein 3"
FT                   /id="PRO_0000007646"
FT   DOMAIN          109..141
FT                   /note="EGF-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          277..331
FT                   /note="TB 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DOMAIN          355..395
FT                   /note="EGF-like 2; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          403..455
FT                   /note="TB 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DOMAIN          574..615
FT                   /note="EGF-like 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          616..659
FT                   /note="EGF-like 4; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          660..702
FT                   /note="EGF-like 5; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          744..784
FT                   /note="EGF-like 6; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          785..825
FT                   /note="EGF-like 7; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          826..865
FT                   /note="EGF-like 8; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          866..908
FT                   /note="EGF-like 9; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          917..971
FT                   /note="TB 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DOMAIN          993..1035
FT                   /note="EGF-like 10; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1036..1076
FT                   /note="EGF-like 11; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1082..1122
FT                   /note="EGF-like 12; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1136..1186
FT                   /note="TB 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DOMAIN          1254..1298
FT                   /note="EGF-like 13; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REGION          247..282
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          478..552
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1188..1219
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        487..501
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        517..534
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        89
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        349
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        845
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        936
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1275
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        113..123
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        117..129
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        131..140
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        279..303
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        289..316
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        304..319
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        359..370
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        365..379
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        381..394
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        405..428
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        415..440
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        429..443
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        430..455
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        578..590
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        585..599
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        601..614
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        620..632
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        625..641
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        664..676
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        670..685
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        687..701
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        748..759
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        754..768
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        770..783
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        789..800
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        795..809
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        811..824
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        830..841
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        836..850
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        852..864
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        870..883
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        877..892
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        894..907
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        919..942
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        929..954
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        929
FT                   /note="Interchain (with C-33 in TGFB1); in linked form"
FT                   /evidence="ECO:0000250|UniProtKB:Q14766"
FT   DISULFID        943..959
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        944..971
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        954
FT                   /note="Interchain (with C-33 in TGFB1); in linked form"
FT                   /evidence="ECO:0000250|UniProtKB:Q14766"
FT   DISULFID        997..1010
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1005..1019
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1021..1034
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1040..1051
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1046..1060
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1062..1075
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1086..1097
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1092..1106
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1108..1121
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1138..1162
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        1148..1174
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        1163..1177
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        1164..1186
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT   DISULFID        1258..1273
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1268..1282
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   VAR_SEQ         1082..1128
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_009241"
FT   VARIANT         696
FT                   /note="S -> C (in GPHYSD3; uncertain significance; no
FT                   effect on TGF-beta secretion; dbSNP:rs1554974135)"
FT                   /evidence="ECO:0000269|PubMed:27068007"
FT                   /id="VAR_080565"
FT   CONFLICT        35
FT                   /note="Missing (in Ref. 2; BAB15767)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        477
FT                   /note="D -> H (in Ref. 3; AAB64201)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1303 AA;  139359 MW;  3BC6B1EE19198414 CRC64;
     MPGPRGAAGG LAPEMRGAGA AGLLALLLLL LLLLLGLGGR VEGGPAGERG AGGGGALARE
     RFKVVFAPVI CKRTCLKGQC RDSCQQGSNM TLIGENGHST DTLTGSGFRV VVCPLPCMNG
     GQCSSRNQCL CPPDFTGRFC QVPAGGAGGG TGGSGPGLSR TGALSTGALP PLAPEGDSVA
     SKHAIYAVQV IADPPGPGEG PPAQHAAFLV PLGPGQISAE VQAPPPVVNV RVHHPPEASV
     QVHRIESSNA ESAAPSQHLL PHPKPSHPRP PTQKPLGRCF QDTLPKQPCG SNPLPGLTKQ
     EDCCGSIGTA WGQSKCHKCP QLQYTGVQKP GPVRGEVGAD CPQGYKRLNS THCQDINECA
     MPGVCRHGDC LNNPGSYRCV CPPGHSLGPS RTQCIADKPE EKSLCFRLVS PEHQCQHPLT
     TRLTRQLCCC SVGKAWGARC QRCPTDGTAA FKEICPAGKG YHILTSHQTL TIQGESDFSL
     FLHPDGPPKP QQLPESPSQA PPPEDTEEER GVTTDSPVSE ERSVQQSHPT ATTTPARPYP
     ELISRPSPPT MRWFLPDLPP SRSAVEIAPT QVTETDECRL NQNICGHGEC VPGPPDYSCH
     CNPGYRSHPQ HRYCVDVNEC EAEPCGPGRG ICMNTGGSYN CHCNRGYRLH VGAGGRSCVD
     LNECAKPHLC GDGGFCINFP GHYKCNCYPG YRLKASRPPV CEDIDECRDP SSCPDGKCEN
     KPGSFKCIAC QPGYRSQGGG ACRDVNECAE GSPCSPGWCE NLPGSFRCTC AQGYAPAPDG
     RSCLDVDECE AGDVCDNGIC SNTPGSFQCQ CLSGYHLSRD RSHCEDIDEC DFPAACIGGD
     CINTNGSYRC LCPQGHRLVG GRKCQDIDEC SQDPSLCLPH GACKNLQGSY VCVCDEGFTP
     TQDQHGCEEV EQPHHKKECY LNFDDTVFCD SVLATNVTQQ ECCCSLGAGW GDHCEIYPCP
     VYSSAEFHSL CPDGKGYTQD NNIVNYGIPA HRDIDECMLF GSEICKEGKC VNTQPGYECY
     CKQGFYYDGN LLECVDVDEC LDESNCRNGV CENTRGGYRC ACTPPAEYSP AQRQCLSPEE
     MDVDECQDPA ACRPGRCVNL PGSYRCECRP PWVPGPSGRD CQLPESPAER APERRDVCWS
     QRGEDGMCAG PLAGPALTFD DCCCRQGRGW GAQCRPCPPR GAGSHCPTSQ SESNSFWDTS
     PLLLGKPPRD EDSSEEDSDE CRCVSGRCVP RPGGAVCECP GGFQLDASRA RCVDIDECRE
     LNQRGLLCKS ERCVNTSGSF RCVCKAGFAR SRPHGACVPQ RRR
//