ID PGBM_HUMAN Reviewed; 4391 AA.
AC P98160; Q16287; Q5SZI3; Q9H3V5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 27-MAR-2024, entry version 247.
DE RecName: Full=Basement membrane-specific heparan sulfate proteoglycan core protein;
DE Short=HSPG;
DE AltName: Full=Perlecan;
DE Short=PLC;
DE Contains:
DE RecName: Full=Endorepellin;
DE Contains:
DE RecName: Full=LG3 peptide;
DE Flags: Precursor;
GN Name=HSPG2;
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], AND VARIANTS VAL-638; SER-765 AND VAL-1503.
RC TISSUE=Colon, and Skin;
RX PubMed=1569102; DOI=10.1016/s0021-9258(18)42478-7;
RA Murdoch A.D., Dodge G.R., Cohen I., Tuan R.S., Iozzo R.V.;
RT "Primary structure of the human heparan sulfate proteoglycan from basement
RT membrane (HSPG2/perlecan). A chimeric molecule with multiple domains
RT homologous to the low density lipoprotein receptor, laminin, neural cell
RT adhesion molecules, and epidermal growth factor.";
RL J. Biol. Chem. 267:8544-8557(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-638; SER-765; VAL-1503;
RP HIS-2980; GLY-2995; THR-3168 AND GLN-3632.
RX PubMed=1730768; DOI=10.1083/jcb.116.2.559;
RA Kallunki P., Tryggvason K.;
RT "Human basement membrane heparan sulfate proteoglycan core protein: a 467-
RT kD protein containing multiple domains resembling elements of the low
RT density lipoprotein receptor, laminin, neural cell adhesion molecules, and
RT epidermal growth factor.";
RL J. Cell Biol. 116:559-571(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RX PubMed=8234307; DOI=10.1073/pnas.90.21.10404;
RA Cohen I.R., Graessel S., Murdoch A.D., Iozzo R.V.;
RT "Structural characterization of the complete human perlecan gene and its
RT promoter.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10404-10408(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-4391, VARIANTS VAL-638; SER-765 AND
RP VAL-1503, AND VARIANT SJS1 TYR-1532.
RX PubMed=11101850; DOI=10.1038/82638;
RA Nicole S., Davoine C.-S., Topaloglu H., Cattolico L., Barral D.,
RA Beighton P., Ben-Hamida C., Hammouda H., Cruaud C., White P.S., Samson D.,
RA Urtizberea J.A., Lehmann-Horn F., Weissenbach J., Hentati F., Fontaine B.;
RT "Perlecan, the major proteoglycan of basement membranes, is altered in
RT patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia).";
RL Nat. Genet. 26:480-483(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 890-1396.
RC TISSUE=Fibrosarcoma;
RX PubMed=1685141; DOI=10.1016/0888-7543(91)90147-7;
RA Kallunki P., Eddy R.L., Byers M.G., Kestila M., Shows T.B., Tryggvason K.;
RT "Cloning of human heparan sulfate proteoglycan core protein, assignment of
RT the gene (HSPG2) to 1p36.1-->p35 and identification of a BamHI restriction
RT fragment length polymorphism.";
RL Genomics 11:389-396(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1016-1470.
RC TISSUE=Colon;
RX PubMed=1679749; DOI=10.1016/0888-7543(91)90451-j;
RA Dodge G.R., Kovalszky I., Chu M.-L., Hassell J.R., McBride O.W., Yi H.F.,
RA Iozzo R.V.;
RT "Heparan sulfate proteoglycan of human colon: partial molecular cloning,
RT cellular expression, and mapping of the gene (HSPG2) to the short arm of
RT human chromosome 1.";
RL Genomics 10:673-680(1991).
RN [8]
RP PROTEIN SEQUENCE OF 1379-1398 AND 2259-2278.
RX PubMed=2687294; DOI=10.1083/jcb.109.6.3199;
RA Heremans A., van der Schueren B., de Cock B., Paulsson M., Cassiman J.-J.,
RA van den Berghe H., David G.;
RT "Matrix-associated heparan sulfate proteoglycan: core protein-specific
RT monoclonal antibodies decorate the pericellular matrix of connective tissue
RT cells and the stromal side of basement membranes.";
RL J. Cell Biol. 109:3199-3211(1989).
RN [9]
RP PROTEIN SEQUENCE OF 4197-4208, PROTEOLYTIC PROCESSING AT ASN-4196, FUNCTION
RP OF LG3 PEPTIDE, GLYCOSYLATION, AND MUTAGENESIS OF ASP-4197; ASP-4258 AND
RP ASN-4327.
RX PubMed=15591058; DOI=10.1074/jbc.m409841200;
RA Gonzalez E.M., Reed C.C., Bix G., Fu J., Zhang Y., Gopalakrishnan B.,
RA Greenspan D.S., Iozzo R.V.;
RT "BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic
RT C-terminal fragment of perlecan.";
RL J. Biol. Chem. 280:7080-7087(2005).
RN [10]
RP PROTEIN SEQUENCE OF 4197-4203, PROTEOLYTIC PROCESSING AT ASN-4196, AND
RP FUNCTION OF ENDOREPELLIN AND LG3 PEPTIDE.
RX PubMed=12435733; DOI=10.1074/jbc.m210445200;
RA Mongiat M., Sweeney S.M., San Antonio J.D., Fu J., Iozzo R.V.;
RT "Endorepellin, a novel inhibitor of angiogenesis derived from the C
RT terminus of perlecan.";
RL J. Biol. Chem. 278:4238-4249(2003).
RN [11]
RP INTERACTION WITH FGFBP1.
RX PubMed=11148217; DOI=10.1074/jbc.m011493200;
RA Mongiat M., Otto J., Oldershaw R., Ferrer F., Sato J.D., Iozzo R.V.;
RT "Fibroblast growth factor-binding protein is a novel partner for perlecan
RT protein core.";
RL J. Biol. Chem. 276:10263-10271(2001).
RN [12]
RP INVOLVEMENT IN DDSH.
RX PubMed=11279527; DOI=10.1038/86941;
RA Arikawa-Hirasawa E., Wilcox W.R., Le A.H., Silverman N., Govindraj P.,
RA Hassell J.R., Yamada Y.;
RT "Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional
RT null mutations of the perlecan gene.";
RL Nat. Genet. 27:431-434(2001).
RN [13]
RP INTERACTION WITH COL13A1.
RX PubMed=11956183; DOI=10.1074/jbc.m107583200;
RA Tu H., Sasaki T., Snellman A., Gohring W., Pirila P., Timpl R.,
RA Pihlajaniemi T.;
RT "The type XIII collagen ectodomain is a 150-nm rod and capable of binding
RT to fibronectin, nidogen-2, perlecan, and heparin.";
RL J. Biol. Chem. 277:23092-23099(2002).
RN [14]
RP INTERACTION WITH ECM1.
RX PubMed=12604605; DOI=10.1074/jbc.m210529200;
RA Mongiat M., Fu J., Oldershaw R., Greenhalgh R., Gown A.M., Iozzo R.V.;
RT "Perlecan protein core interacts with extracellular matrix protein 1
RT (ECM1), a glycoprotein involved in bone formation and angiogenesis.";
RL J. Biol. Chem. 278:17491-17499(2003).
RN [15]
RP GLYCOSYLATION AT ASN-2121.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1755.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [17]
RP FUNCTION OF ENDOREPELLIN.
RX PubMed=17105986; DOI=10.1093/jnci/djj441;
RA Bix G., Castello R., Burrows M., Zoeller J.J., Weech M., Iozzo R.A.,
RA Cardi C., Thakur M.L., Barker C.A., Camphausen K., Iozzo R.V.;
RT "Endorepellin in vivo: targeting the tumor vasculature and retarding cancer
RT growth and metabolism.";
RL J. Natl. Cancer Inst. 98:1634-1646(2006).
RN [18]
RP FUNCTION OF ENDOREPELLIN, AND IDENTIFICATION OF RECEPTOR.
RX PubMed=18024432; DOI=10.1074/jbc.m708364200;
RA Woodall B.P., Nystroem A., Iozzo R.A., Eble J.A., Niland S., Krieg T.,
RA Eckes B., Pozzi A., Iozzo R.V.;
RT "Integrin alpha2beta1 is the required receptor for endorepellin angiostatic
RT activity.";
RL J. Biol. Chem. 283:2335-2343(2008).
RN [19]
RP FUNCTION.
RX PubMed=19789387; DOI=10.1182/blood-2009-02-207134;
RA Nystrom A., Shaik Z.P., Gullberg D., Krieg T., Eckes B., Zent R., Pozzi A.,
RA Iozzo R.V.;
RT "Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin
RT angiostatic activity.";
RL Blood 114:4897-4906(2009).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-554; ASN-1755; ASN-3072;
RP ASN-3780; ASN-3836 AND ASN-4068.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [21]
RP GLYCOSYLATION AT THR-42, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [22]
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 [23]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION AT SER-4193.
RX PubMed=25326458; DOI=10.1074/mcp.m114.043703;
RA Noborn F., Gomez Toledo A., Sihlbom C., Lengqvist J., Fries E., Kjellen L.,
RA Nilsson J., Larson G.;
RT "Identification of chondroitin sulfate linkage region glycopeptides reveals
RT prohormones as a novel class of proteoglycans.";
RL Mol. Cell. Proteomics 14:41-49(2015).
RN [24]
RP GLYCOSYLATION AT SER-4193.
RX PubMed=32337544; DOI=10.1093/glycob/cwaa039;
RA Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A.,
RA Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D.,
RA Larson G., Salanti A., Clausen T.M.;
RT "An affinity chromatography and glycoproteomics workflow to profile the
RT chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in
RT the placenta and in cancer.";
RL Glycobiology 30:989-1002(2020).
RN [25]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION AT SER-4193.
RX PubMed=36213313; DOI=10.1007/s42485-022-00092-3;
RA Ramarajan M.G., Saraswat M., Budhraja R., Garapati K., Raymond K.,
RA Pandey A.;
RT "Mass spectrometric analysis of chondroitin sulfate-linked peptides.";
RL J. Proteins Proteom. 13:187-203(2022).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 4197-4391, DISULFIDE BOND, AND
RP CALCIUM-BINDING SITES.
RX PubMed=21996443; DOI=10.1016/j.jmb.2011.09.048;
RA Le B.V., Kim H., Choi J., Kim J.H., Hahn M.J., Lee C., Kim K.K.,
RA Hwang H.Y.;
RT "Crystal structure of the LG3 domain of endorepellin, an angiogenesis
RT inhibitor.";
RL J. Mol. Biol. 414:231-242(2011).
CC -!- FUNCTION: Integral component of basement membranes. Component of the
CC glomerular basement membrane (GBM), responsible for the fixed negative
CC electrostatic membrane charge, and which provides a barrier which is
CC both size- and charge-selective. It serves as an attachment substrate
CC for cells. Plays essential roles in vascularization. Critical for
CC normal heart development and for regulating the vascular response to
CC injury. Also required for avascular cartilage development.
CC -!- FUNCTION: [Endorepellin]: Anti-angiogenic and anti-tumor peptide that
CC inhibits endothelial cell migration, collagen-induced endothelial tube
CC morphogenesis and blood vessel growth in the chorioallantoic membrane.
CC Blocks endothelial cell adhesion to fibronectin and type I collagen.
CC Anti-tumor agent in neovascularization. Interaction with its ligand,
CC integrin alpha2/beta1, is required for the anti-angiogenic properties.
CC Evokes a reduction in phosphorylation of receptor tyrosine kinases via
CC alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase,
CC PTPN6.
CC -!- FUNCTION: [LG3 peptide]: Has anti-angiogenic properties that require
CC binding of calcium ions for full activity.
CC -!- SUBUNIT: Has a strong tendency to aggregate in dimers or stellate
CC structures. Interacts with other basement membrane components such as
CC laminin, prolargin and collagen type IV. Interacts with COL13A1
CC (PubMed:11956183). Interacts with FGFBP1 (PubMed:11148217). Interacts
CC with VWA1 (By similarity). Interacts (via C-terminus) with ECM1 (via C-
CC terminus) (PubMed:12604605). Interacts with SVEP1 (By similarity).
CC {ECO:0000250|UniProtKB:Q05793, ECO:0000269|PubMed:11148217,
CC ECO:0000269|PubMed:11956183, ECO:0000269|PubMed:12604605}.
CC -!- INTERACTION:
CC P98160; P35968: KDR; NbExp=5; IntAct=EBI-947664, EBI-1005487;
CC PRO_0000391621; P17948-2: FLT1; NbExp=2; IntAct=EBI-6896259, EBI-6530464;
CC PRO_0000391621; P35968: KDR; NbExp=2; IntAct=EBI-6896259, EBI-1005487;
CC PRO_0000391622; P17948-2: FLT1; NbExp=2; IntAct=EBI-6896607, EBI-6530464;
CC PRO_0000391622; P35968: KDR; NbExp=2; IntAct=EBI-6896607, EBI-1005487;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane. Secreted {ECO:0000269|PubMed:25326458,
CC ECO:0000269|PubMed:36213313}.
CC -!- TISSUE SPECIFICITY: Detected in cerebrospinal fluid, fibroblasts and
CC urine (at protein level). {ECO:0000269|PubMed:25326458,
CC ECO:0000269|PubMed:36213313}.
CC -!- PTM: Proteolytic processing produces the C-terminal angiogenic peptide,
CC endorepellin. This peptide can be further processed to produce the LG3
CC peptide. {ECO:0000269|PubMed:12435733, ECO:0000269|PubMed:15591058}.
CC -!- PTM: O-glycosylated with core 1 or possibly core 8 glycans. Contains
CC three heparan sulfate chains. Also contains chondroitin sulfate.
CC {ECO:0000269|PubMed:15591058, ECO:0000269|PubMed:22171320,
CC ECO:0000269|PubMed:25326458}.
CC -!- DISEASE: Schwartz-Jampel syndrome (SJS1) [MIM:255800]: Rare autosomal
CC recessive disorder characterized by permanent myotonia (prolonged
CC failure of muscle relaxation) and skeletal dysplasia, resulting in
CC reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular
CC epiphyses. {ECO:0000269|PubMed:11101850}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Dyssegmental dysplasia Silverman-Handmaker type (DDSH)
CC [MIM:224410]: The dyssegmental dysplasias are rare, autosomal recessive
CC skeletal dysplasias with anisospondyly and micromelia. There are two
CC recognized types: the severe, lethal DDSH and the milder Rolland-
CC Desbuquois form. Individuals with DDSH also have a flat face,
CC micrognathia, cleft palate and reduced joint mobility, and frequently
CC have an encephalocoele. The endochondral growth plate is short, the
CC calcospherites (which are spherical calcium-phosphorus crystals
CC produced by hypertrophic chondrocytes) are unfused, and there is mucoid
CC degeneration of the resting cartilage. {ECO:0000269|PubMed:11279527}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [LG3 peptide]: Has been found in the urine of patients
CC with end-stage renal disease and in the amniotic fluid of pregnant
CC women with premature rupture of fetal membranes.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40890/HSPG2";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Perlecan entry;
CC URL="https://en.wikipedia.org/wiki/Perlecan";
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DR EMBL; M85289; AAA52700.1; -; mRNA.
DR EMBL; X62515; CAA44373.1; -; mRNA.
DR EMBL; AL590556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L22078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445795; CAC18534.1; -; Genomic_DNA.
DR EMBL; S76436; AAB21121.2; -; mRNA.
DR EMBL; M64283; AAA52699.1; -; mRNA.
DR CCDS; CCDS30625.1; -.
DR PIR; A38096; A38096.
DR RefSeq; NP_001278789.1; NM_001291860.1.
DR RefSeq; NP_005520.4; NM_005529.6.
DR PDB; 3SH4; X-ray; 1.50 A; A=4197-4391.
DR PDB; 3SH5; X-ray; 2.80 A; A=4197-4391.
DR PDBsum; 3SH4; -.
DR PDBsum; 3SH5; -.
DR SMR; P98160; -.
DR BioGRID; 109571; 92.
DR IntAct; P98160; 39.
DR MINT; P98160; -.
DR STRING; 9606.ENSP00000363827; -.
DR DrugBank; DB00039; Palifermin.
DR UniLectin; P98160; -.
DR CarbonylDB; P98160; -.
DR GlyConnect; 653; 43 N-Linked glycans (5 sites), 4 O-Linked glycans (3 sites).
DR GlyCosmos; P98160; 53 sites, 53 glycans.
DR GlyGen; P98160; 76 sites, 43 N-linked glycans (5 sites), 11 O-linked glycans (57 sites).
DR iPTMnet; P98160; -.
DR PhosphoSitePlus; P98160; -.
DR SwissPalm; P98160; -.
DR BioMuta; HSPG2; -.
DR DMDM; 317373536; -.
DR DOSAC-COBS-2DPAGE; P98160; -.
DR EPD; P98160; -.
DR jPOST; P98160; -.
DR MassIVE; P98160; -.
DR MaxQB; P98160; -.
DR PaxDb; 9606-ENSP00000363827; -.
DR PeptideAtlas; P98160; -.
DR ProteomicsDB; 57796; -.
DR Pumba; P98160; -.
DR Antibodypedia; 980; 517 antibodies from 30 providers.
DR DNASU; 3339; -.
DR Ensembl; ENST00000374695.8; ENSP00000363827.3; ENSG00000142798.20.
DR GeneID; 3339; -.
DR KEGG; hsa:3339; -.
DR MANE-Select; ENST00000374695.8; ENSP00000363827.3; NM_005529.7; NP_005520.4.
DR UCSC; uc001bfj.4; human.
DR AGR; HGNC:5273; -.
DR CTD; 3339; -.
DR DisGeNET; 3339; -.
DR GeneCards; HSPG2; -.
DR HGNC; HGNC:5273; HSPG2.
DR HPA; ENSG00000142798; Low tissue specificity.
DR MalaCards; HSPG2; -.
DR MIM; 142461; gene.
DR MIM; 224410; phenotype.
DR MIM; 255800; phenotype.
DR neXtProt; NX_P98160; -.
DR OpenTargets; ENSG00000142798; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR Orphanet; 1865; Dyssegmental dysplasia, Silverman-Handmaker type.
DR Orphanet; 800; Schwartz-Jampel syndrome.
DR PharmGKB; PA29537; -.
DR VEuPathDB; HostDB:ENSG00000142798; -.
DR eggNOG; KOG3509; Eukaryota.
DR GeneTree; ENSGT00940000156670; -.
DR HOGENOM; CLU_000078_1_0_1; -.
DR InParanoid; P98160; -.
DR OMA; ISCFCAG; -.
DR OrthoDB; 2877710at2759; -.
DR PhylomeDB; P98160; -.
DR TreeFam; TF326548; -.
DR PathwayCommons; P98160; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR Reactome; R-HSA-3000157; Laminin interactions.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type.
DR Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD.
DR Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2.
DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
DR Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P98160; -.
DR SIGNOR; P98160; -.
DR BioGRID-ORCS; 3339; 9 hits in 1151 CRISPR screens.
DR ChiTaRS; HSPG2; human.
DR GeneWiki; Perlecan; -.
DR GenomeRNAi; 3339; -.
DR Pharos; P98160; Tbio.
DR PRO; PR:P98160; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P98160; Protein.
DR Bgee; ENSG00000142798; Expressed in saphenous vein and 193 other cell types or tissues.
DR ExpressionAtlas; P98160; baseline and differential.
DR Genevisible; P98160; HS.
DR GO; GO:0005604; C:basement membrane; TAS:ARUK-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098797; C:plasma membrane protein complex; TAS:ARUK-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0070052; F:collagen V binding; IEA:Ensembl.
DR GO; GO:0030021; F:extracellular matrix structural constituent conferring compression resistance; ISS:BHF-UCL.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; TAS:ARUK-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; TAS:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; TAS:ARUK-UCL.
DR GO; GO:0072359; P:circulatory system development; TAS:ARUK-UCL.
DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:ARUK-UCL.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ARUK-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; TAS:ARUK-UCL.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:ARUK-UCL.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR CDD; cd00054; EGF_CA; 4.
DR CDD; cd00055; EGF_Lam; 8.
DR CDD; cd00096; Ig; 6.
DR CDD; cd05743; Ig_Perlecan_like; 1.
DR CDD; cd05754; IgI_Perlecan_like; 1.
DR CDD; cd00110; LamG; 3.
DR CDD; cd00112; LDLa; 4.
DR Gene3D; 2.60.120.200; -; 3.
DR Gene3D; 2.60.40.10; Immunoglobulins; 22.
DR Gene3D; 2.10.25.10; Laminin; 10.
DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 4.
DR Gene3D; 2.170.300.10; Tie2 ligand-binding domain superfamily; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR001791; Laminin_G.
DR InterPro; IPR000034; Laminin_IV.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR000082; SEA_dom.
DR PANTHER; PTHR45080; CONTACTIN 5; 1.
DR PANTHER; PTHR45080:SF32; MYOTILIN; 1.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF07679; I-set; 8.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF13927; Ig_3; 13.
DR Pfam; PF00052; Laminin_B; 3.
DR Pfam; PF00053; Laminin_EGF; 9.
DR Pfam; PF00054; Laminin_G_1; 3.
DR Pfam; PF00057; Ldl_recept_a; 4.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 11.
DR SMART; SM00179; EGF_CA; 5.
DR SMART; SM00180; EGF_Lam; 9.
DR SMART; SM00409; IG; 22.
DR SMART; SM00408; IGc2; 22.
DR SMART; SM00406; IGv; 8.
DR SMART; SM00281; LamB; 3.
DR SMART; SM00282; LamG; 3.
DR SMART; SM00192; LDLa; 4.
DR SMART; SM00200; SEA; 1.
DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 3.
DR SUPFAM; SSF57196; EGF/Laminin; 8.
DR SUPFAM; SSF48726; Immunoglobulin; 22.
DR SUPFAM; SSF57424; LDL receptor-like module; 4.
DR PROSITE; PS00022; EGF_1; 9.
DR PROSITE; PS01186; EGF_2; 6.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS01248; EGF_LAM_1; 11.
DR PROSITE; PS50027; EGF_LAM_2; 8.
DR PROSITE; PS50835; IG_LIKE; 22.
DR PROSITE; PS50025; LAM_G_DOMAIN; 3.
DR PROSITE; PS51115; LAMININ_IVA; 3.
DR PROSITE; PS01209; LDLRA_1; 4.
DR PROSITE; PS50068; LDLRA_2; 4.
DR PROSITE; PS50024; SEA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Basement membrane; Calcium;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW EGF-like domain; Extracellular matrix; Glycoprotein; Heparan sulfate;
KW Immunoglobulin domain; Laminin EGF-like domain; Metal-binding;
KW Proteoglycan; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..4391
FT /note="Basement membrane-specific heparan sulfate
FT proteoglycan core protein"
FT /id="PRO_0000026696"
FT CHAIN 3687..4391
FT /note="Endorepellin"
FT /id="PRO_0000391621"
FT CHAIN 4197..4391
FT /note="LG3 peptide"
FT /id="PRO_0000391622"
FT DOMAIN 80..191
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT DOMAIN 198..235
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 284..320
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 324..360
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 367..404
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 405..504
FT /note="Ig-like C2-type 1"
FT DOMAIN 521..530
FT /note="Laminin EGF-like 1; first part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 538..730
FT /note="Laminin IV type A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00458"
FT DOMAIN 731..763
FT /note="Laminin EGF-like 1; second part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 764..813
FT /note="Laminin EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 814..871
FT /note="Laminin EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 879..923
FT /note="Laminin EGF-like 4; truncated"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 924..933
FT /note="Laminin EGF-like 5; first part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 941..1125
FT /note="Laminin IV type A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00458"
FT DOMAIN 1126..1158
FT /note="Laminin EGF-like 5; second part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1159..1208
FT /note="Laminin EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1209..1265
FT /note="Laminin EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1275..1324
FT /note="Laminin EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1325..1334
FT /note="Laminin EGF-like 9; first part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1344..1529
FT /note="Laminin IV type A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00458"
FT DOMAIN 1530..1562
FT /note="Laminin EGF-like 9; second part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1563..1612
FT /note="Laminin EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1613..1670
FT /note="Laminin EGF-like 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 1677..1771
FT /note="Ig-like C2-type 2"
FT DOMAIN 1772..1865
FT /note="Ig-like C2-type 3"
FT DOMAIN 1866..1955
FT /note="Ig-like C2-type 4"
FT DOMAIN 1956..2051
FT /note="Ig-like C2-type 5"
FT DOMAIN 2052..2151
FT /note="Ig-like C2-type 6"
FT DOMAIN 2152..2244
FT /note="Ig-like C2-type 7"
FT DOMAIN 2245..2340
FT /note="Ig-like C2-type 8"
FT DOMAIN 2341..2436
FT /note="Ig-like C2-type 9"
FT DOMAIN 2437..2533
FT /note="Ig-like C2-type 10"
FT DOMAIN 2534..2629
FT /note="Ig-like C2-type 11"
FT DOMAIN 2630..2726
FT /note="Ig-like C2-type 12"
FT DOMAIN 2727..2826
FT /note="Ig-like C2-type 13"
FT DOMAIN 2827..2924
FT /note="Ig-like C2-type 14"
FT DOMAIN 2925..3021
FT /note="Ig-like C2-type 15"
FT DOMAIN 3022..3112
FT /note="Ig-like C2-type 16"
FT DOMAIN 3113..3211
FT /note="Ig-like C2-type 17"
FT DOMAIN 3212..3298
FT /note="Ig-like C2-type 18"
FT DOMAIN 3299..3399
FT /note="Ig-like C2-type 19"
FT DOMAIN 3400..3488
FT /note="Ig-like C2-type 20"
FT DOMAIN 3489..3574
FT /note="Ig-like C2-type 21"
FT DOMAIN 3575..3662
FT /note="Ig-like C2-type 22"
FT DOMAIN 3663..3843
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 3844..3881
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3884..3922
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3928..4103
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 4104..4141
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4143..4176
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4201..4389
FT /note="Laminin G-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT REGION 2994..3014
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4149..4151
FT /note="Mediates motor neuron attachment"
FT /evidence="ECO:0000255"
FT REGION 4299..4301
FT /note="Mediates motor neuron attachment"
FT /evidence="ECO:0000255"
FT REGION 4364..4391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 4258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 4275
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 4325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 4327
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT SITE 4196..4197
FT /note="Cleavage; by BMP1"
FT CARBOHYD 42
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 65
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 1755
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 2121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519"
FT CARBOHYD 2995
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3072
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3780
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3836
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3933
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4068
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 4179
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4193
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000269|PubMed:25326458,
FT ECO:0000269|PubMed:32337544, ECO:0000269|PubMed:36213313"
FT DISULFID 199..212
FT /evidence="ECO:0000250"
FT DISULFID 206..225
FT /evidence="ECO:0000250"
FT DISULFID 219..234
FT /evidence="ECO:0000250"
FT DISULFID 285..297
FT /evidence="ECO:0000250"
FT DISULFID 292..310
FT /evidence="ECO:0000250"
FT DISULFID 304..319
FT /evidence="ECO:0000250"
FT DISULFID 325..337
FT /evidence="ECO:0000250"
FT DISULFID 332..350
FT /evidence="ECO:0000250"
FT DISULFID 344..359
FT /evidence="ECO:0000250"
FT DISULFID 368..381
FT /evidence="ECO:0000250"
FT DISULFID 375..394
FT /evidence="ECO:0000250"
FT DISULFID 388..403
FT /evidence="ECO:0000250"
FT DISULFID 764..773
FT /evidence="ECO:0000250"
FT DISULFID 766..780
FT /evidence="ECO:0000250"
FT DISULFID 783..792
FT /evidence="ECO:0000250"
FT DISULFID 795..811
FT /evidence="ECO:0000250"
FT DISULFID 814..829
FT /evidence="ECO:0000250"
FT DISULFID 816..839
FT /evidence="ECO:0000250"
FT DISULFID 842..851
FT /evidence="ECO:0000250"
FT DISULFID 854..869
FT /evidence="ECO:0000250"
FT DISULFID 879..892
FT /evidence="ECO:0000250"
FT DISULFID 894..903
FT /evidence="ECO:0000250"
FT DISULFID 906..921
FT /evidence="ECO:0000250"
FT DISULFID 1159..1168
FT /evidence="ECO:0000250"
FT DISULFID 1161..1175
FT /evidence="ECO:0000250"
FT DISULFID 1178..1187
FT /evidence="ECO:0000250"
FT DISULFID 1190..1206
FT /evidence="ECO:0000250"
FT DISULFID 1209..1224
FT /evidence="ECO:0000250"
FT DISULFID 1211..1234
FT /evidence="ECO:0000250"
FT DISULFID 1237..1246
FT /evidence="ECO:0000250"
FT DISULFID 1249..1263
FT /evidence="ECO:0000250"
FT DISULFID 1275..1287
FT /evidence="ECO:0000250"
FT DISULFID 1277..1293
FT /evidence="ECO:0000250"
FT DISULFID 1295..1304
FT /evidence="ECO:0000250"
FT DISULFID 1307..1322
FT /evidence="ECO:0000250"
FT DISULFID 1563..1572
FT /evidence="ECO:0000250"
FT DISULFID 1565..1579
FT /evidence="ECO:0000250"
FT DISULFID 1582..1591
FT /evidence="ECO:0000250"
FT DISULFID 1594..1610
FT /evidence="ECO:0000250"
FT DISULFID 1613..1628
FT /evidence="ECO:0000250"
FT DISULFID 1615..1638
FT /evidence="ECO:0000250"
FT DISULFID 1641..1650
FT /evidence="ECO:0000250"
FT DISULFID 1653..1668
FT /evidence="ECO:0000250"
FT DISULFID 3819..3845
FT /evidence="ECO:0000250"
FT DISULFID 3848..3859
FT /evidence="ECO:0000250"
FT DISULFID 3853..3869
FT /evidence="ECO:0000250"
FT DISULFID 3871..3880
FT /evidence="ECO:0000250"
FT DISULFID 3888..3899
FT /evidence="ECO:0000250"
FT DISULFID 3893..3910
FT /evidence="ECO:0000250"
FT DISULFID 3912..3921
FT /evidence="ECO:0000250"
FT DISULFID 4076..4102
FT /evidence="ECO:0000250"
FT DISULFID 4108..4119
FT /evidence="ECO:0000250"
FT DISULFID 4113..4129
FT /evidence="ECO:0000250"
FT DISULFID 4131..4140
FT /evidence="ECO:0000250"
FT DISULFID 4147..4159
FT /evidence="ECO:0000250"
FT DISULFID 4153..4164
FT /evidence="ECO:0000250"
FT DISULFID 4166..4175
FT /evidence="ECO:0000250"
FT DISULFID 4355..4389
FT /evidence="ECO:0000269|PubMed:21996443"
FT VARIANT 68
FT /note="D -> E (in dbSNP:rs1869780)"
FT /id="VAR_047979"
FT VARIANT 303
FT /note="L -> H (in dbSNP:rs17460381)"
FT /id="VAR_057051"
FT VARIANT 638
FT /note="M -> V (in dbSNP:rs1874792)"
FT /evidence="ECO:0000269|PubMed:11101850,
FT ECO:0000269|PubMed:1569102, ECO:0000269|PubMed:1730768"
FT /id="VAR_047980"
FT VARIANT 765
FT /note="N -> S (in dbSNP:rs989994)"
FT /evidence="ECO:0000269|PubMed:11101850,
FT ECO:0000269|PubMed:1569102, ECO:0000269|PubMed:1730768"
FT /id="VAR_047981"
FT VARIANT 1186
FT /note="R -> Q (in dbSNP:rs2229481)"
FT /id="VAR_047982"
FT VARIANT 1323
FT /note="L -> V (in dbSNP:rs10917058)"
FT /id="VAR_057052"
FT VARIANT 1503
FT /note="A -> V (in dbSNP:rs897471)"
FT /evidence="ECO:0000269|PubMed:11101850,
FT ECO:0000269|PubMed:1569102, ECO:0000269|PubMed:1730768"
FT /id="VAR_047983"
FT VARIANT 1532
FT /note="C -> Y (in SJS1; dbSNP:rs137853248)"
FT /evidence="ECO:0000269|PubMed:11101850"
FT /id="VAR_014122"
FT VARIANT 1758
FT /note="R -> Q (in dbSNP:rs2229483)"
FT /id="VAR_047984"
FT VARIANT 1919
FT /note="R -> C (in dbSNP:rs2229474)"
FT /id="VAR_047985"
FT VARIANT 1967
FT /note="V -> I (in dbSNP:rs2229475)"
FT /id="VAR_047986"
FT VARIANT 2980
FT /note="L -> H (in dbSNP:rs2229489)"
FT /evidence="ECO:0000269|PubMed:1730768"
FT /id="VAR_047987"
FT VARIANT 2981
FT /note="V -> I (in dbSNP:rs2229490)"
FT /id="VAR_047988"
FT VARIANT 2995
FT /note="S -> G (in dbSNP:rs2229491)"
FT /evidence="ECO:0000269|PubMed:1730768"
FT /id="VAR_047989"
FT VARIANT 3168
FT /note="A -> T (in dbSNP:rs2228349)"
FT /evidence="ECO:0000269|PubMed:1730768"
FT /id="VAR_047990"
FT VARIANT 3256
FT /note="H -> Y (in dbSNP:rs2291827)"
FT /id="VAR_047991"
FT VARIANT 3530
FT /note="R -> W (in dbSNP:rs2270699)"
FT /id="VAR_047992"
FT VARIANT 3632
FT /note="R -> Q (in dbSNP:rs2229493)"
FT /evidence="ECO:0000269|PubMed:1730768"
FT /id="VAR_047993"
FT VARIANT 3640
FT /note="V -> I (in dbSNP:rs17459097)"
FT /id="VAR_047994"
FT VARIANT 4331
FT /note="S -> N (in dbSNP:rs3736360)"
FT /id="VAR_047995"
FT MUTAGEN 4197
FT /note="D->I: Abolishes BMP1-mediated cleavage of
FT endorepellin."
FT /evidence="ECO:0000269|PubMed:15591058"
FT MUTAGEN 4258
FT /note="D->A: Retains proper folding. Reduced calcium ion
FT binding."
FT /evidence="ECO:0000269|PubMed:15591058"
FT MUTAGEN 4327
FT /note="N->A: Retains proper folding. Reduced calcium ion
FT binding."
FT /evidence="ECO:0000269|PubMed:15591058"
FT CONFLICT 6
FT /note="A -> P (in Ref. 2; CAA44373 and 1; AAA52700)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="D -> Y (in Ref. 1; AAA52700)"
FT /evidence="ECO:0000305"
FT CONFLICT 435..437
FT /note="TPI -> APFL (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="H -> Q (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="R -> RA (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 793
FT /note="N -> K (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 890..891
FT /note="EA -> RT (in Ref. 6; AAB21121)"
FT /evidence="ECO:0000305"
FT CONFLICT 909
FT /note="G -> R (in Ref. 2; CAA44373 and 6; AAB21121)"
FT /evidence="ECO:0000305"
FT CONFLICT 1102
FT /note="V -> L (in Ref. 6; AAB21121)"
FT /evidence="ECO:0000305"
FT CONFLICT 1133
FT /note="R -> L (in Ref. 6; AAB21121)"
FT /evidence="ECO:0000305"
FT CONFLICT 1222
FT /note="H -> L (in Ref. 6; AAB21121)"
FT /evidence="ECO:0000305"
FT CONFLICT 1406
FT /note="D -> G (in Ref. 7; AAA52699)"
FT /evidence="ECO:0000305"
FT CONFLICT 1410
FT /note="A -> G (in Ref. 7; AAA52699)"
FT /evidence="ECO:0000305"
FT CONFLICT 1466..1470
FT /note="EFWRR -> LNLRQ (in Ref. 7; AAA52699)"
FT /evidence="ECO:0000305"
FT CONFLICT 1703..1704
FT /note="SP -> RG (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 1753
FT /note="Q -> R (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 2038
FT /note="I -> M (in Ref. 1; AAA52700)"
FT /evidence="ECO:0000305"
FT CONFLICT 2050
FT /note="P -> Q (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 2052
FT /note="P -> G (in Ref. 1; AAA52700)"
FT /evidence="ECO:0000305"
FT CONFLICT 2093
FT /note="P -> H (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 2627
FT /note="S -> R (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 2770
FT /note="H -> Y (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 3241
FT /note="P -> R (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 3427
FT /note="R -> Q (in Ref. 1; AAA52700)"
FT /evidence="ECO:0000305"
FT CONFLICT 4004
FT /note="S -> T (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 4135
FT /note="F -> I (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT CONFLICT 4332
FT /note="V -> I (in Ref. 2; CAA44373)"
FT /evidence="ECO:0000305"
FT TURN 4199..4202
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4203..4214
FT /evidence="ECO:0007829|PDB:3SH4"
FT HELIX 4216..4219
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4228..4236
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4239..4246
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4259..4265
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4268..4274
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4279..4283
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4290..4292
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4294..4301
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4304..4309
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4315..4318
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4320..4322
FT /evidence="ECO:0007829|PDB:3SH5"
FT STRAND 4332..4335
FT /evidence="ECO:0007829|PDB:3SH4"
FT HELIX 4340..4343
FT /evidence="ECO:0007829|PDB:3SH4"
FT TURN 4344..4346
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4353..4363
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4366..4368
FT /evidence="ECO:0007829|PDB:3SH5"
FT TURN 4376..4378
FT /evidence="ECO:0007829|PDB:3SH4"
FT STRAND 4381..4388
FT /evidence="ECO:0007829|PDB:3SH4"
SQ SEQUENCE 4391 AA; 468830 MW; C587660E24C83324 CRC64;
MGWRAAGALL LALLLHGRLL AVTHGLRAYD GLSLPEDIET VTASQMRWTH SYLSDDEDML
ADSISGDDLG SGDLGSGDFQ MVYFRALVNF TRSIEYSPQL EDAGSREFRE VSEAVVDTLE
SEYLKIPGDQ VVSVVFIKEL DGWVFVELDV GSEGNADGAQ IQEMLLRVIS SGSVASYVTS
PQGFQFRRLG TVPQFPRACT EAEFACHSYN ECVALEYRCD RRPDCRDMSD ELNCEEPVLG
ISPTFSLLVE TTSLPPRPET TIMRQPPVTH APQPLLPGSV RPLPCGPQEA ACRNGHCIPR
DYLCDGQEDC EDGSDELDCG PPPPCEPNEF PCGNGHCALK LWRCDGDFDC EDRTDEANCP
TKRPEEVCGP TQFRCVSTNM CIPASFHCDE ESDCPDRSDE FGCMPPQVVT PPRESIQASR
GQTVTFTCVA IGVPTPIINW RLNWGHIPSH PRVTVTSEGG RGTLIIRDVK ESDQGAYTCE
AMNARGMVFG IPDGVLELVP QRGPCPDGHF YLEHSAACLP CFCFGITSVC QSTRRFRDQI
RLRFDQPDDF KGVNVTMPAQ PGTPPLSSTQ LQIDPSLHEF QLVDLSRRFL VHDSFWALPE
QFLGNKVDSY GGSLRYNVRY ELARGMLEPV QRPDVVLMGA GYRLLSRGHT PTQPGALNQR
QVQFSEEHWV HESGRPVQRA ELLQVLQSLE AVLIQTVYNT KMASVGLSDI AMDTTVTHAT
SHGRAHSVEE CRCPIGYSGL SCESCDAHFT RVPGGPYLGT CSGCNCNGHA SSCDPVYGHC
LNCQHNTEGP QCNKCKAGFF GDAMKATATS CRPCPCPYID ASRRFSDTCF LDTDGQATCD
ACAPGYTGRR CESCAPGYEG NPIQPGGKCR PVNQEIVRCD ERGSMGTSGE ACRCKNNVVG
RLCNECADGS FHLSTRNPDG CLKCFCMGVS RHCTSSSWSR AQLHGASEEP GHFSLTNAAS
THTTNEGIFS PTPGELGFSS FHRLLSGPYF WSLPSRFLGD KVTSYGGELR FTVTQRSQPG
STPLHGQPLV VLQGNNIILE HHVAQEPSPG QPSTFIVPFR EQAWQRPDGQ PATREHLLMA
LAGIDTLLIR ASYAQQPAES RVSGISMDVA VPEETGQDPA LEVEQCSCPP GYRGPSCQDC
DTGYTRTPSG LYLGTCERCS CHGHSEACEP ETGACQGCQH HTEGPRCEQC QPGYYGDAQR
GTPQDCQLCP CYGDPAAGQA AHTCFLDTDG HPTCDACSPG HSGRHCERCA PGYYGNPSQG
QPCQRDSQVP GPIGCNCDPQ GSVSSQCDAA GQCQCKAQVE GLTCSHCRPH HFHLSASNPD
GCLPCFCMGI TQQCASSAYT RHLISTHFAP GDFQGFALVN PQRNSRLTGE FTVEPVPEGA
QLSFGNFAQL GHESFYWQLP ETYQGDKVAA YGGKLRYTLS YTAGPQGSPL SDPDVQITGN
NIMLVASQPA LQGPERRSYE IMFREEFWRR PDGQPATREH LLMALADLDE LLIRATFSSV
PLAASISAVS LEVAQPGPSN RPRALEVEEC RCPPGYIGLS CQDCAPGYTR TGSGLYLGHC
ELCECNGHSD LCHPETGACS QCQHNAAGEF CELCAPGYYG DATAGTPEDC QPCACPLTNP
ENMFSRTCES LGAGGYRCTA CEPGYTGQYC EQCGPGYVGN PSVQGGQCLP ETNQAPLVVE
VHPARSIVPQ GGSHSLRCQV SGSPPHYFYW SREDGRPVPS GTQQRHQGSE LHFPSVQPSD
AGVYICTCRN LHQSNTSRAE LLVTEAPSKP ITVTVEEQRS QSVRPGADVT FICTAKSKSP
AYTLVWTRLH NGKLPTRAMD FNGILTIRNV QLSDAGTYVC TGSNMFAMDQ GTATLHVQAS
GTLSAPVVSI HPPQLTVQPG QLAEFRCSAT GSPTPTLEWT GGPGGQLPAK AQIHGGILRL
PAVEPTDQAQ YLCRAHSSAG QQVARAVLHV HGGGGPRVQV SPERTQVHAG RTVRLYCRAA
GVPSATITWR KEGGSLPPQA RSERTDIATL LIPAITTADA GFYLCVATSP AGTAQARIQV
VVLSASDASP PPVKIESSSP SVTEGQTLDL NCVVAGSAHA QVTWYRRGGS LPPHTQVHGS
RLRLPQVSPA DSGEYVCRVE NGSGPKEASI TVSVLHGTHS GPSYTPVPGS TRPIRIEPSS
SHVAEGQTLD LNCVVPGQAH AQVTWHKRGG SLPARHQTHG SLLRLHQVTP ADSGEYVCHV
VGTSGPLEAS VLVTIEASVI PGPIPPVRIE SSSSTVAEGQ TLDLSCVVAG QAHAQVTWYK
RGGSLPARHQ VRGSRLYIFQ ASPADAGQYV CRASNGMEAS ITVTVTGTQG ANLAYPAGST
QPIRIEPSSS QVAEGQTLDL NCVVPGQSHA QVTWHKRGGS LPVRHQTHGS LLRLYQASPA
DSGEYVCRVL GSSVPLEASV LVTIEPAGSV PALGVTPTVR IESSSSQVAE GQTLDLNCLV
AGQAHAQVTW HKRGGSLPAR HQVHGSRLRL LQVTPADSGE YVCRVVGSSG TQEASVLVTI
QQRLSGSHSQ GVAYPVRIES SSASLANGHT LDLNCLVASQ APHTITWYKR GGSLPSRHQI
VGSRLRIPQV TPADSGEYVC HVSNGAGSRE TSLIVTIQGS GSSHVPSVSP PIRIESSSPT
VVEGQTLDLN CVVARQPQAI ITWYKRGGSL PSRHQTHGSH LRLHQMSVAD SGEYVCRANN
NIDALEASIV ISVSPSAGSP SAPGSSMPIR IESSSSHVAE GETLDLNCVV PGQAHAQVTW
HKRGGSLPSH HQTRGSRLRL HHVSPADSGE YVCRVMGSSG PLEASVLVTI EASGSSAVHV
PAPGGAPPIR IEPSSSRVAE GQTLDLKCVV PGQAHAQVTW HKRGGNLPAR HQVHGPLLRL
NQVSPADSGE YSCQVTGSSG TLEASVLVTI EPSSPGPIPA PGLAQPIYIE ASSSHVTEGQ
TLDLNCVVPG QAHAQVTWYK RGGSLPARHQ THGSQLRLHL VSPADSGEYV CRAASGPGPE
QEASFTVTVP PSEGSSYRLR SPVISIDPPS STVQQGQDAS FKCLIHDGAA PISLEWKTRN
QELEDNVHIS PNGSIITIVG TRPSNHGTYR CVASNAYGVA QSVVNLSVHG PPTVSVLPEG
PVWVKVGKAV TLECVSAGEP RSSARWTRIS STPAKLEQRT YGLMDSHAVL QISSAKPSDA
GTYVCLAQNA LGTAQKQVEV IVDTGAMAPG APQVQAEEAE LTVEAGHTAT LRCSATGSPA
PTIHWSKLRS PLPWQHRLEG DTLIIPRVAQ QDSGQYICNA TSPAGHAEAT IILHVESPPY
ATTVPEHASV QAGETVQLQC LAHGTPPLTF QWSRVGSSLP GRATARNELL HFERAAPEDS
GRYRCRVTNK VGSAEAFAQL LVQGPPGSLP ATSIPAGSTP TVQVTPQLET KSIGASVEFH
CAVPSDRGTQ LRWFKEGGQL PPGHSVQDGV LRIQNLDQSC QGTYICQAHG PWGKAQASAQ
LVIQALPSVL INIRTSVQTV VVGHAVEFEC LALGDPKPQV TWSKVGGHLR PGIVQSGGVV
RIAHVELADA GQYRCTATNA AGTTQSHVLL LVQALPQISM PQEVRVPAGS AAVFPCIASG
YPTPDISWSK LDGSLPPDSR LENNMLMLPS VRPQDAGTYV CTATNRQGKV KAFAHLQVPE
RVVPYFTQTP YSFLPLPTIK DAYRKFEIKI TFRPDSADGM LLYNGQKRVP GSPTNLANRQ
PDFISFGLVG GRPEFRFDAG SGMATIRHPT PLALGHFHTV TLLRSLTQGS LIVGDLAPVN
GTSQGKFQGL DLNEELYLGG YPDYGAIPKA GLSSGFIGCV RELRIQGEEI VFHDLNLTAH
GISHCPTCRD RPCQNGGQCH DSESSSYVCV CPAGFTGSRC EHSQALHCHP EACGPDATCV
NRPDGRGYTC RCHLGRSGLR CEEGVTVTTP SLSGAGSYLA LPALTNTHHE LRLDVEFKPL
APDGVLLFSG GKSGPVEDFV SLAMVGGHLE FRYELGSGLA VLRSAEPLAL GRWHRVSAER
LNKDGSLRVN GGRPVLRSSP GKSQGLNLHT LLYLGGVEPS VPLSPATNMS AHFRGCVGEV
SVNGKRLDLT YSFLGSQGIG QCYDSSPCER QPCQHGATCM PAGEYEFQCL CRDGFKGDLC
EHEENPCQLR EPCLHGGTCQ GTRCLCLPGF SGPRCQQGSG HGIAESDWHL EGSGGNDAPG
QYGAYFHDDG FLAFPGHVFS RSLPEVPETI ELEVRTSTAS GLLLWQGVEV GEAGQGKDFI
SLGLQDGHLV FRYQLGSGEA RLVSEDPIND GEWHRVTALR EGRRGSIQVD GEELVSGRSP
GPNVAVNAKG SVYIGGAPDV ATLTGGRFSS GITGCVKNLV LHSARPGAPP PQPLDLQHRA
QAGANTRPCP S
//
