LTBP4_HUMAN
ID LTBP4_HUMAN Reviewed; 1624 AA.
AC Q8N2S1; O00508; O75412; O75413;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Latent-transforming growth factor beta-binding protein 4;
DE Short=LTBP-4;
DE Flags: Precursor;
GN Name=LTBP4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND VARIANT
RP MET-1141.
RX PubMed=9271198; DOI=10.1016/s0014-5793(97)00685-6;
RA Giltay R., Kostka G., Timpl R.;
RT "Sequence and expression of a novel member (LTBP-4) of the family of latent
RT transforming growth factor-beta binding proteins.";
RL FEBS Lett. 411:164-168(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION
RP WITH LTBP1 AND TGFB1, AND VARIANTS ILE-194; ALA-787; ALA-820 AND MET-1141.
RC TISSUE=Heart;
RX PubMed=9660815; DOI=10.1074/jbc.273.29.18459;
RA Saharinen J., Taipale J., Monni O., Keski-Oja J.;
RT "Identification and characterization of a new latent transforming growth
RT factor-beta-binding protein, LTBP-4.";
RL J. Biol. Chem. 273:18459-18469(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
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 [8]
RP VARIANT URDS GLY-311.
RX PubMed=19836010; DOI=10.1016/j.ajhg.2009.09.013;
RA Urban Z., Hucthagowder V., Schuermann N., Todorovic V., Zilberberg L.,
RA Choi J., Sens C., Brown C.W., Clark R.D., Holland K.E., Marble M.,
RA Sakai L.Y., Dabovic B., Rifkin D.B., Davis E.C.;
RT "Mutations in LTBP4 cause a syndrome of impaired pulmonary,
RT gastrointestinal, genitourinary, musculoskeletal, and dermal development.";
RL Am. J. Hum. Genet. 85:593-605(2009).
RN [9]
RP VARIANTS ILE-194; ALA-787; ALA-820 AND MET-1141, AND INVOLVEMENT IN DMD.
RX PubMed=23440719; DOI=10.1002/ana.23819;
RG United Dystrophinopathy Project;
RA Flanigan K.M., Ceco E., Lamar K.M., Kaminoh Y., Dunn D.M., Mendell J.R.,
RA King W.M., Pestronk A., Florence J.M., Mathews K.D., Finkel R.S.,
RA Swoboda K.J., Gappmaier E., Howard M.T., Day J.W., McDonald C.,
RA McNally E.M., Weiss R.B.;
RT "LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular
RT dystrophy.";
RL Ann. Neurol. 73:481-488(2013).
RN [10]
RP VARIANT MET-1141, AND INVOLVEMENT IN DMD.
RX PubMed=25641372; DOI=10.1002/ana.24370;
RG Cooperative International Neuromuscular Research Group Investigators;
RA Bello L., Kesari A., Gordish-Dressman H., Cnaan A., Morgenroth L.P.,
RA Punetha J., Duong T., Henricson E.K., Pegoraro E., McDonald C.M.,
RA Hoffman E.P.;
RT "Genetic modifiers of ambulation in the Cooperative International
RT Neuromuscular Research Group Duchenne Natural History Study.";
RL Ann. Neurol. 77:684-696(2015).
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:0000250|UniProtKB:Q14766}.
CC -!- SUBUNIT: Forms part of the large latent transforming growth factor beta
CC precursor complex; removal is essential for activation of complex
CC (PubMed:9660815). Interacts with LTBP1 and TGFB1 (PubMed:9660815).
CC Interacts with EFEMP2; this interaction promotes fibrillar deposition
CC of EFEMP2 (PubMed:27339457). {ECO:0000269|PubMed:27339457,
CC ECO:0000269|PubMed:9660815}.
CC -!- INTERACTION:
CC Q8N2S1; O15265: ATXN7; NbExp=2; IntAct=EBI-947718, EBI-708350;
CC Q8N2S1; O00555: CACNA1A; NbExp=2; IntAct=EBI-947718, EBI-766279;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:16157329, ECO:0000269|PubMed:9660815}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=LTBP-4L;
CC IsoId=Q8N2S1-1; Sequence=Displayed;
CC Name=2; Synonyms=LTBP-4S;
CC IsoId=Q8N2S1-2; Sequence=VSP_029364, VSP_029365;
CC Name=3;
CC IsoId=Q8N2S1-3; Sequence=VSP_029363;
CC Name=4;
CC IsoId=Q8N2S1-4; Sequence=VSP_029362, VSP_029366, VSP_029367;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle,
CC pancreas, uterus, and small intestine. Weakly expressed in placenta and
CC lung. {ECO:0000269|PubMed:9271198, ECO:0000269|PubMed:9660815}.
CC -!- DEVELOPMENTAL STAGE: Very low expression in fetal brain, liver, heart,
CC spleen and thymus. {ECO:0000269|PubMed:9660815}.
CC -!- PTM: Contains hydroxylated asparagine residues.
CC {ECO:0000250|UniProtKB:Q14766}.
CC -!- DISEASE: Urban-Rifkin-Davis syndrome (URDS) [MIM:613177]: A syndrome
CC characterized by disrupted pulmonary, gastrointestinal, urinary,
CC musculoskeletal, craniofacial and dermal development. Clinical features
CC include cutis laxa, mild cardiovascular lesions, respiratory distress
CC with cystic and atelectatic changes in the lungs, and diverticulosis,
CC tortuosity and stenosis at various levels of the intestinal tract.
CC Craniofacial features include microretrognathia, flat midface, receding
CC forehead and wide fontanelles. {ECO:0000269|PubMed:19836010}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Duchenne muscular dystrophy (DMD) [MIM:310200]: Most common
CC form of muscular dystrophy; a sex-linked recessive disorder. It
CC typically presents in boys aged 3 to 7 year as proximal muscle weakness
CC causing waddling gait, toe-walking, lordosis, frequent falls, and
CC difficulty in standing up and climbing up stairs. The pelvic girdle is
CC affected first, then the shoulder girdle. Progression is steady and
CC most patients are confined to a wheelchair by age of 10 or 12. Flexion
CC contractures and scoliosis ultimately occur. About 50% of patients have
CC a lower IQ than their genetic expectations would suggest. There is no
CC treatment. {ECO:0000269|PubMed:23440719, ECO:0000269|PubMed:25641372}.
CC Note=The gene represented in this entry may act as a disease modifier.
CC DMD patients homozygous for the IAAM haplotype consisting of Ile-194,
CC Ala-787, Ala-820 and Met-1141 remain ambulatory significantly longer
CC than those heterozygous or homozygous for the VTTT haplotype consisting
CC of Val-194, Thr-787, Thr-820 and Thr-1141. This may be due to increased
CC binding to TGFB1, resulting in TGFB1 sequestration in the extracellular
CC matrix and reduced TGFB1 signaling which has been linked to improved
CC muscle function and regeneration. {ECO:0000269|PubMed:23440719}.
CC -!- SIMILARITY: Belongs to the LTBP family. {ECO:0000305}.
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DR EMBL; Y13622; CAA73944.1; -; mRNA.
DR EMBL; AF051344; AAC39879.2; -; mRNA.
DR EMBL; AF051345; AAC39880.2; -; mRNA.
DR EMBL; AK074499; BAC11024.1; -; mRNA.
DR EMBL; AC010412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS74368.1; -. [Q8N2S1-3]
DR CCDS; CCDS74369.1; -. [Q8N2S1-1]
DR CCDS; CCDS74370.1; -. [Q8N2S1-2]
DR RefSeq; NP_001036009.1; NM_001042544.1. [Q8N2S1-1]
DR RefSeq; NP_001036010.1; NM_001042545.1. [Q8N2S1-2]
DR RefSeq; NP_003564.2; NM_003573.2.
DR AlphaFoldDB; Q8N2S1; -.
DR BioGRID; 114009; 84.
DR IntAct; Q8N2S1; 56.
DR MINT; Q8N2S1; -.
DR STRING; 9606.ENSP00000311905; -.
DR CarbonylDB; Q8N2S1; -.
DR GlyGen; Q8N2S1; 17 sites, 3 O-linked glycans (12 sites).
DR iPTMnet; Q8N2S1; -.
DR PhosphoSitePlus; Q8N2S1; -.
DR BioMuta; LTBP4; -.
DR DMDM; 160410003; -.
DR EPD; Q8N2S1; -.
DR jPOST; Q8N2S1; -.
DR MassIVE; Q8N2S1; -.
DR MaxQB; Q8N2S1; -.
DR PaxDb; Q8N2S1; -.
DR PeptideAtlas; Q8N2S1; -.
DR PRIDE; Q8N2S1; -.
DR ProteomicsDB; 71731; -. [Q8N2S1-1]
DR ProteomicsDB; 71732; -. [Q8N2S1-2]
DR ProteomicsDB; 71733; -. [Q8N2S1-3]
DR ProteomicsDB; 71734; -. [Q8N2S1-4]
DR Antibodypedia; 4199; 85 antibodies from 17 providers.
DR DNASU; 8425; -.
DR Ensembl; ENST00000308370.11; ENSP00000311905.8; ENSG00000090006.18. [Q8N2S1-1]
DR Ensembl; ENST00000396819.8; ENSP00000380031.5; ENSG00000090006.18. [Q8N2S1-2]
DR GeneID; 8425; -.
DR KEGG; hsa:8425; -.
DR MANE-Select; ENST00000396819.8; ENSP00000380031.5; NM_001042545.2; NP_001036010.1. [Q8N2S1-2]
DR UCSC; uc032hxp.2; human. [Q8N2S1-1]
DR CTD; 8425; -.
DR DisGeNET; 8425; -.
DR GeneCards; LTBP4; -.
DR GeneReviews; LTBP4; -.
DR HGNC; HGNC:6717; LTBP4.
DR HPA; ENSG00000090006; Low tissue specificity.
DR MalaCards; LTBP4; -.
DR MIM; 310200; phenotype.
DR MIM; 604710; gene.
DR MIM; 613177; phenotype.
DR neXtProt; NX_Q8N2S1; -.
DR OpenTargets; ENSG00000090006; -.
DR Orphanet; 221145; Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies.
DR Orphanet; 98896; Duchenne muscular dystrophy.
DR PharmGKB; PA30480; -.
DR VEuPathDB; HostDB:ENSG00000090006; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000158234; -.
DR InParanoid; Q8N2S1; -.
DR OMA; LCDQYEG; -.
DR OrthoDB; 1174178at2759; -.
DR PhylomeDB; Q8N2S1; -.
DR TreeFam; TF317514; -.
DR PathwayCommons; Q8N2S1; -.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
DR SignaLink; Q8N2S1; -.
DR BioGRID-ORCS; 8425; 5 hits in 266 CRISPR screens.
DR ChiTaRS; LTBP4; human.
DR GenomeRNAi; 8425; -.
DR Pharos; Q8N2S1; Tbio.
DR PRO; PR:Q8N2S1; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N2S1; protein.
DR Bgee; ENSG00000090006; Expressed in tibial nerve and 175 other tissues.
DR ExpressionAtlas; Q8N2S1; baseline and differential.
DR Genevisible; Q8N2S1; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0001527; C:microfibril; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0005539; F:glycosaminoglycan binding; NAS:UniProtKB.
DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB.
DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:UniProtKB.
DR GO; GO:0005024; F:transforming growth factor beta receptor activity; NAS:UniProtKB.
DR GO; GO:0048251; P:elastic fiber assembly; ISS:UniProtKB.
DR GO; GO:0046879; P:hormone secretion; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; TAS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR Gene3D; 3.90.290.10; -; 4.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR017878; TB_dom.
DR InterPro; IPR036773; TB_dom_sf.
DR Pfam; PF07645; EGF_CA; 17.
DR Pfam; PF12661; hEGF; 1.
DR Pfam; PF00683; TB; 3.
DR SMART; SM00181; EGF; 20.
DR SMART; SM00179; EGF_CA; 19.
DR SUPFAM; SSF57184; SSF57184; 6.
DR SUPFAM; SSF57581; SSF57581; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 14.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 12.
DR PROSITE; PS50026; EGF_3; 15.
DR PROSITE; PS01187; EGF_CA; 17.
DR PROSITE; PS51364; TB; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Disulfide bond; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Growth factor binding;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1624
FT /note="Latent-transforming growth factor beta-binding
FT protein 4"
FT /id="PRO_0000310964"
FT DOMAIN 149..181
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 287..339
FT /note="TB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 357..397
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 407..459
FT /note="TB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 545..586
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 587..628
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 629..670
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 671..708
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 710..751
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 752..793
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 834..877
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 878..919
FT /note="EGF-like 10; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 920..960
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1049..1090
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1181..1235
FT /note="TB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 1253..1295
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1296..1337
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1349..1402
FT /note="TB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DOMAIN 1533..1573
FT /note="EGF-like 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1574..1618
FT /note="EGF-like 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 125..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 474..546
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1130..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1446..1524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1149..1170
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1446..1462
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1055
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 153..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 157..169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 171..180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 289..311
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 298..324
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 312..327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 361..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 367..381
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 383..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 409..431
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 418..444
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 432..447
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 433..459
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 549..561
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 556..570
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 572..585
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 591..603
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 598..612
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 614..627
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 633..645
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 640..654
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 656..669
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 675..687
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 682..696
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 698..707
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 714..726
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 721..735
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 737..750
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 756..768
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 763..777
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 779..792
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 838..851
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 845..860
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 862..876
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 882..894
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 888..903
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 905..918
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 924..935
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 930..944
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 946..959
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1053..1065
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1059..1074
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1076..1089
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1183..1206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1193..1218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1193
FT /note="Interchain (with C-33 in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q14766"
FT DISULFID 1207..1223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1208..1235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1218
FT /note="Interchain (with C-33 in TGFB1); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q14766"
FT DISULFID 1257..1270
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1265..1279
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1281..1294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1300..1312
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1307..1321
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1323..1336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1351..1375
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1361..1387
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1376..1390
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1377..1402
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00697"
FT DISULFID 1537..1548
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1543..1557
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1559..1572
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1578..1593
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1588..1602
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1604..1617
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..902
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029362"
FT VAR_SEQ 1..68
FT /note="MPRPGTSGRRPLLLVLLLPLFAAATSAASPSPSPSQVVEVPGVPSRPASVAV
FT CRCCPGQTSRRSRCIR -> MGDVKALLFVVAARARRLGGAAASESLAVSE (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:9271198"
FT /id="VSP_029363"
FT VAR_SEQ 1..67
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9660815"
FT /id="VSP_029364"
FT VAR_SEQ 68..151
FT /note="RAFCRVRSCQPKKCAGPQRCLNPVPAVPSPSPSVRKRQVSLNWQPLTLQEAR
FT ALLKRRRPRGPGGRGLLRRRPPQRAPAGKAPV -> MAGGVRLLWVSLLVLLAQLGPQP
FT GLGRLGERLRVRFTPVVCGLRCVHGPTGSRCTPTCAPRNATSVDSGAPGGAAPGGPGFR
FT AF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9660815"
FT /id="VSP_029365"
FT VAR_SEQ 903..919
FT /note="CTCAPGYRPGPRGASCL -> MLGGAGGGPGLRTPCPA (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029366"
FT VAR_SEQ 1007..1092
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029367"
FT VARIANT 194
FT /note="V -> I (in dbSNP:rs2303729)"
FT /evidence="ECO:0000269|PubMed:23440719,
FT ECO:0000269|PubMed:9660815"
FT /id="VAR_037119"
FT VARIANT 311
FT /note="C -> G (in URDS; dbSNP:rs267607229)"
FT /evidence="ECO:0000269|PubMed:19836010"
FT /id="VAR_064153"
FT VARIANT 635
FT /note="R -> G (in dbSNP:rs33937741)"
FT /id="VAR_037120"
FT VARIANT 679
FT /note="P -> A (in dbSNP:rs34299942)"
FT /id="VAR_037121"
FT VARIANT 787
FT /note="T -> A (in dbSNP:rs1131620)"
FT /evidence="ECO:0000269|PubMed:23440719,
FT ECO:0000269|PubMed:9660815"
FT /id="VAR_037122"
FT VARIANT 820
FT /note="T -> A (in dbSNP:rs1051303)"
FT /evidence="ECO:0000269|PubMed:23440719,
FT ECO:0000269|PubMed:9660815"
FT /id="VAR_037123"
FT VARIANT 1141
FT /note="T -> M (in dbSNP:rs10880)"
FT /evidence="ECO:0000269|PubMed:23440719,
FT ECO:0000269|PubMed:9271198, ECO:0000269|PubMed:9660815"
FT /id="VAR_037124"
FT CONFLICT 170
FT /note="L -> F (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="T -> A (in Ref. 3; BAC11024)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="L -> F (in Ref. 2; AAC39879/AAC39880)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="A -> G (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 974
FT /note="G -> R (in Ref. 3; BAC11024)"
FT /evidence="ECO:0000305"
FT CONFLICT 1139
FT /note="A -> V (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1142
FT /note="F -> S (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1151
FT /note="A -> V (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1165
FT /note="P -> S (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1169..1170
FT /note="ST -> RK (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1173
FT /note="Q -> K (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1180
FT /note="R -> C (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
FT CONFLICT 1402
FT /note="C -> R (in Ref. 3; BAC11024)"
FT /evidence="ECO:0000305"
FT CONFLICT 1512
FT /note="P -> S (in Ref. 3; BAC11024)"
FT /evidence="ECO:0000305"
FT CONFLICT 1546
FT /note="G -> D (in Ref. 1; CAA73944)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1624 AA; 173435 MW; 75682D1F6E40657A CRC64;
MPRPGTSGRR PLLLVLLLPL FAAATSAASP SPSPSQVVEV PGVPSRPASV AVCRCCPGQT
SRRSRCIRAF CRVRSCQPKK CAGPQRCLNP VPAVPSPSPS VRKRQVSLNW QPLTLQEARA
LLKRRRPRGP GGRGLLRRRP PQRAPAGKAP VLCPLICHNG GVCVKPDRCL CPPDFAGKFC
QLHSSGARPP APAVPGLTRS VYTMPLANHR DDEHGVASMV SVHVEHPQEA SVVVHQVERV
SGPWEEADAE AVARAEAAAR AEAAAPYTVL AQSAPREDGY SDASGFGYCF RELRGGECAS
PLPGLRTQEV CCRGAGLAWG VHDCQLCSER LGNSERVSAP DGPCPTGFER VNGSCEDVDE
CATGGRCQHG ECANTRGGYT CVCPDGFLLD SSRSSCISQH VISEAKGPCF RVLRDGGCSL
PILRNITKQI CCCSRVGKAW GRGCQLCPPF GSEGFREICP AGPGYHYSAS DLRYNTRPLG
QEPPRVSLSQ PRTLPATSRP SAGFLPTHRL EPRPEPRPDP RPGPELPLPS IPAWTGPEIP
ESGPSSGMCQ RNPQVCGPGR CISRPSGYTC ACDSGFRLSP QGTRCIDVDE CRRVPPPCAP
GRCENSPGSF RCVCGPGFRA GPRAAECLDV DECHRVPPPC DLGRCENTPG SFLCVCPAGY
QAAPHGASCQ DVDECTQSPG LCGRGACKNL PGSFRCVCPA GFRGSACEED VDECAQEPPP
CGPGRCDNTA GSFHCACPAG FRSRGPGAPC QDVDECARSP PPCTYGRCEN TEGSFQCVCP
MGFQPNTAGS ECEDVDECEN HLACPGQECV NSPGSFQCRT CPSGHHLHRG RCTDVDECSS
GAPPCGPHGH CTNTEGSFRC SCAPGYRAPS GRPGPCADVN ECLEGDFCFP HGECLNTDGS
FACTCAPGYR PGPRGASCLD VDECSEEDLC QSGICTNTDG SFECICPPGH RAGPDLASCL
DVDECRERGP ALCGSQRCEN SPGSYRCVRD CDPGYHAGPE GTCDDVDECQ EYGPEICGAQ
RCENTPGSYR CTPACDPGYQ PTPGGGCQDV DECRNRSFCG AHAVCQNLPG SFQCLCDQGY
EGARDGRHCV DVNECETLQG VCGAALCENV EGSFLCVCPN SPEEFDPMTG RCVPPRTSAG
TFPGSQPQAP ASPVLPARPP PPPLPRRPST PRQGPVGSGR RECYFDTAAP DACDNILARN
VTWQECCCTV GEGWGSGCRI QQCPGTETAE YQSLCPHGRG YLAPSGDLSL RRDVDECQLF
RDQVCKSGVC VNTAPGYSCY CSNGYYYHTQ RLECIDNDEC ADEEPACEGG RCVNTVGSYH
CTCEPPLVLD GSQRRCVSNE SQSLDDNLGV CWQEVGADLV CSHPRLDRQA TYTECCCLYG
EAWGMDCALC PAQDSDDFEA LCNVLRPPAY SPPRPGGFGL PYEYGPDLGP PYQGLPYGPE
LYPPPALPYD PYPPPPGPFA RREAPYGAPR FDMPDFEDDG GPYGESEAPA PPGPGTRWPY
RSRDTRRSFP EPEEPPEGGS YAGSLAEPYE ELEAEECGIL DGCTNGRCVR VPEGFTCRCF
DGYRLDMTRM ACVDINECDE AEAASPLCVN ARCLNTDGSF RCICRPGFAP THQPHHCAPA
RPRA
