LTBP3_HUMAN
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 03-AUG-2022, entry version 184.
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; 45.
DR IntAct; Q9NS15; 12.
DR MINT; Q9NS15; -.
DR STRING; 9606.ENSP00000301873; -.
DR GlyGen; Q9NS15; 10 sites, 2 O-linked glycans (4 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; Q9NS15; -.
DR PeptideAtlas; Q9NS15; -.
DR PRIDE; Q9NS15; -.
DR ProteomicsDB; 82461; -. [Q9NS15-1]
DR ProteomicsDB; 82462; -. [Q9NS15-2]
DR Antibodypedia; 70903; 9 antibodies from 9 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 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; PCGPGKG; -.
DR OrthoDB; 1174178at2759; -.
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; 81 hits in 1078 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 189 other tissues.
DR ExpressionAtlas; Q9NS15; baseline and differential.
DR Genevisible; Q9NS15; HS.
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:0048251; P:elastic fiber assembly; IBA:GO_Central.
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 Gene3D; 3.90.290.10; -; 4.
DR InterPro; IPR026823; cEGF.
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; PF12662; cEGF; 2.
DR Pfam; PF07645; EGF_CA; 9.
DR Pfam; PF00683; TB; 4.
DR SMART; SM00181; EGF; 15.
DR SMART; SM00179; EGF_CA; 14.
DR SUPFAM; SSF57184; SSF57184; 4.
DR SUPFAM; SSF57581; SSF57581; 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.
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; unknown pathological
FT significance; no effect on TGF-beta secretion;
FT 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
