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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; P98160; HS. 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 //