PGBM_MOUSE
ID PGBM_MOUSE Reviewed; 3707 AA.
AC Q05793;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Basement membrane-specific heparan sulfate proteoglycan core protein;
DE Short=HSPG;
DE Contains:
DE RecName: Full=Endorepellin;
DE Contains:
DE RecName: Full=LG3 peptide;
DE Flags: Precursor;
GN Name=Hspg2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Melanoma;
RX PubMed=1744087; DOI=10.1016/s0021-9258(18)54445-8;
RA Noonan D.M., Fulle A., Valente P., Cai S., Horigan E., Sasaki M.,
RA Yamada Y., Hassell J.R.;
RT "The complete sequence of perlecan, a basement membrane heparan sulfate
RT proteoglycan, reveals extensive similarity with laminin A chain, low
RT density lipoprotein-receptor, and the neural cell adhesion molecule.";
RL J. Biol. Chem. 266:22939-22947(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 940-1601 AND 1870-2600, AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=2972708; DOI=10.1016/s0021-9258(18)37604-x;
RA Noonan D.M., Horigan E.A., Ledbetter S.R., Vogeli G., Sasaki M., Yamada Y.,
RA Hassell J.R.;
RT "Identification of cDNA clones encoding different domains of the basement
RT membrane heparan sulfate proteoglycan.";
RL J. Biol. Chem. 263:16379-16387(1988).
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=7649154; DOI=10.1111/j.1432-1033.1995.tb20731.x;
RA Schulze B., Mann K., Battistutta R., Wiedemann H., Timpl R.;
RT "Structural properties of recombinant domain III-3 of perlecan containing a
RT globular domain inserted into an epidermal-growth-factor-like motif.";
RL Eur. J. Biochem. 231:551-556(1995).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10545953; DOI=10.1038/15537;
RA Arikawa-Hirasawa E., Watanabe H., Takami H., Hassell J.R., Yamada Y.;
RT "Perlecan is essential for cartilage and cephalic development.";
RL Nat. Genet. 23:354-358(1999).
RN [5]
RP PROTEOLYTIC PROCESSING.
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 [6]
RP INTERACTION WITH VWA1.
RX PubMed=16407285; DOI=10.1074/jbc.m513746200;
RA Allen J.M., Bateman J.F., Hansen U., Wilson R., Bruckner P., Owens R.T.,
RA Sasaki T., Timpl R., Fitzgerald J.;
RT "WARP is a novel multimeric component of the chondrocyte pericellular
RT matrix that interacts with perlecan.";
RL J. Biol. Chem. 281:7341-7349(2006).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18694874; DOI=10.1093/cvr/cvn225;
RA Sasse P., Malan D., Fleischmann M., Roell W., Gustafsson E., Bostani T.,
RA Fan Y., Kolbe T., Breitbach M., Addicks K., Welz A., Brem G., Hescheler J.,
RA Aszodi A., Costell M., Bloch W., Fleischmann B.K.;
RT "Perlecan is critical for heart stability.";
RL Cardiovasc. Res. 80:435-444(2008).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-89; ASN-2336; ASN-3098 AND
RP ASN-3154.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2336 AND ASN-3098.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1761-1858 IN COMPLEX WITH A
RP NIDOGEN FRAGMENT.
RX PubMed=11427896; DOI=10.1038/89683;
RA Hopf M., Gohring W., Ries A., Timpl R., Hohenester E.;
RT "Crystal structure and mutational analysis of a perlecan-binding fragment
RT of nidogen-1.";
RL Nat. Struct. Biol. 8:634-640(2001).
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 (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: Endorepellin in an anti-angiogenic and anti-tumor peptide
CC that inhibits endothelial cell migration, collagen-induced endothelial
CC tube morphogenesis and blood vessel growth in the chorioallantoic
CC membrane. Blocks endothelial cell adhesion to fibronectin and type I
CC collagen. Anti-tumor agent in neovascularization. Interaction with its
CC ligand, integrin alpha2/beta1, is required for the anti-angiogenic
CC properties. Evokes a reduction in phosphorylation of receptor tyrosine
CC kinases via alpha2/beta1 integrin-mediated activation of the tyrosine
CC phosphatase, PTPN6 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The LG3 peptide has anti-angiogenic properties that require
CC binding of calcium ions for full activity. {ECO:0000250}.
CC -!- SUBUNIT: Purified perlecan has a strong tendency to aggregate in dimers
CC or stellate structures. It interacts with other basement membrane
CC components such as laminin, prolargin and collagen type IV. Interacts
CC with COL13A1, FGFBP1 and VWA1. Interacts (via C-terminus) with ECM1
CC (via C-terminus) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane.
CC -!- TISSUE SPECIFICITY: Found in the basement membranes.
CC -!- PTM: Proteolytic processing produces the C-terminal angiogenic peptide,
CC endorepellin. This peptide can be further processed to produce the LG3
CC peptide (By similarity). {ECO:0000250}.
CC -!- PTM: N- and O-glycosylated; contains 3 heparan sulfate chains. The LG3
CC peptide contains at least three and up to five potential O-
CC glycosylation sites and no N-glycosylation (By similarity).
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: About 40% of perlecan null mice die at 10.5 dpc,
CC the rest die just after birth. Embryonic percelan-null mice exhibit
CC cardiac abnormalities including mechanical instability in the early
CC stages of development (10.5 dpc) with lower amounts of critical
CC basement membrane components, collagen IV and lamanins. Basement
CC membranes are absent in cardiomyocytes whereas adherens junctions
CC formed and matured around 9.5 dpc. Mice also have skeletal dysplasia
CC characterized by micromelia with broad and bowed long bones, narrow
CC thorax and craniofacial abnormalities. Cartilage matrix containd
CC reduced and disorganized collagen fibrils and glycosaminoglycans. In
CC cartilage, proliferation of chondrocytes was reduced and the
CC prehypertrophic zone was diminished. {ECO:0000269|PubMed:10545953,
CC ECO:0000269|PubMed:18694874}.
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DR EMBL; M77174; AAA39911.1; -; mRNA.
DR EMBL; J04054; AAA39899.1; -; mRNA.
DR EMBL; J04055; AAA39912.1; -; mRNA.
DR PIR; S18252; S18252.
DR RefSeq; NP_032331.2; NM_008305.3.
DR PDB; 1GL4; X-ray; 2.00 A; B=1765-1858.
DR PDBsum; 1GL4; -.
DR SMR; Q05793; -.
DR BioGRID; 200461; 16.
DR IntAct; Q05793; 4.
DR MINT; Q05793; -.
DR GlyConnect; 2146; 2 N-Linked glycans (3 sites).
DR GlyGen; Q05793; 13 sites, 2 N-linked glycans (3 sites).
DR iPTMnet; Q05793; -.
DR PhosphoSitePlus; Q05793; -.
DR SwissPalm; Q05793; -.
DR jPOST; Q05793; -.
DR MaxQB; Q05793; -.
DR PeptideAtlas; Q05793; -.
DR PRIDE; Q05793; -.
DR ProteomicsDB; 288180; -.
DR GeneID; 15530; -.
DR KEGG; mmu:15530; -.
DR CTD; 3339; -.
DR MGI; MGI:96257; Hspg2.
DR InParanoid; Q05793; -.
DR OrthoDB; 414294at2759; -.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR Reactome; R-MMU-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR Reactome; R-MMU-2024096; HS-GAG degradation.
DR Reactome; R-MMU-216083; Integrin cell surface interactions.
DR Reactome; R-MMU-3000157; Laminin interactions.
DR Reactome; R-MMU-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-MMU-3000178; ECM proteoglycans.
DR Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR BioGRID-ORCS; 15530; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Hspg2; mouse.
DR EvolutionaryTrace; Q05793; -.
DR PRO; PR:Q05793; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q05793; protein.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:MGI.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:ARUK-UCL.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR CDD; cd00055; EGF_Lam; 8.
DR CDD; cd00110; LamG; 3.
DR CDD; cd00112; LDLa; 4.
DR Gene3D; 2.60.40.10; -; 15.
DR Gene3D; 4.10.400.10; -; 4.
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 Pfam; PF00008; EGF; 2.
DR Pfam; PF07679; I-set; 10.
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; 10.
DR SMART; SM00179; EGF_CA; 4.
DR SMART; SM00180; EGF_Lam; 9.
DR SMART; SM00409; IG; 15.
DR SMART; SM00408; IGc2; 14.
DR SMART; SM00406; IGv; 7.
DR SMART; SM00281; LamB; 3.
DR SMART; SM00282; LamG; 3.
DR SMART; SM00192; LDLa; 4.
DR SMART; SM00200; SEA; 1.
DR SUPFAM; SSF48726; SSF48726; 15.
DR SUPFAM; SSF49899; SSF49899; 3.
DR SUPFAM; SSF57424; SSF57424; 4.
DR PROSITE; PS00022; EGF_1; 8.
DR PROSITE; PS01186; EGF_2; 5.
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; 15.
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; Disulfide bond; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Heparan sulfate; Immunoglobulin domain;
KW Laminin EGF-like domain; Metal-binding; Proteoglycan; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..3707
FT /note="Basement membrane-specific heparan sulfate
FT proteoglycan core protein"
FT /id="PRO_0000026697"
FT CHAIN 3008..3707
FT /note="Endorepellin"
FT /id="PRO_0000391623"
FT CHAIN 3514..3707
FT /note="LG3 peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000391624"
FT DOMAIN 80..191
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT DOMAIN 195..234
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 281..319
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 320..359
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 360..403
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 404..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..1954
FT /note="Ig-like C2-type 4"
FT DOMAIN 1955..2049
FT /note="Ig-like C2-type 5"
FT DOMAIN 2050..2148
FT /note="Ig-like C2-type 6"
FT DOMAIN 2149..2244
FT /note="Ig-like C2-type 7"
FT DOMAIN 2245..2343
FT /note="Ig-like C2-type 8"
FT DOMAIN 2344..2436
FT /note="Ig-like C2-type 9"
FT DOMAIN 2437..2532
FT /note="Ig-like C2-type 10"
FT DOMAIN 2533..2619
FT /note="Ig-like C2-type 11"
FT DOMAIN 2620..2720
FT /note="Ig-like C2-type 12"
FT DOMAIN 2721..2809
FT /note="Ig-like C2-type 13"
FT DOMAIN 2810..2895
FT /note="Ig-like C2-type 14"
FT DOMAIN 2896..2980
FT /note="Ig-like C2-type 15"
FT DOMAIN 2984..3162
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 3163..3241
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3245..3425
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 3518..3705
FT /note="Laminin G-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT REGION 1713..1733
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2039..2061
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3615..3617
FT /note="Mediates motor neuron attachment"
FT /evidence="ECO:0000255"
FT REGION 3680..3707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1716..1733
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3574
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 3591
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 3641
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 3643
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT SITE 3513..3514
FT /note="Cleavage; by BMP1"
FT /evidence="ECO:0000250"
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:0000269|PubMed:19656770"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 2394
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3098
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 3154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 3385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 428..479
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 1792..1839
FT DISULFID 1886..1932
FT /evidence="ECO:0000250"
FT DISULFID 1976..2021
FT /evidence="ECO:0000250"
FT DISULFID 2073..2118
FT /evidence="ECO:0000250"
FT DISULFID 2170..2215
FT /evidence="ECO:0000250"
FT DISULFID 2268..2313
FT /evidence="ECO:0000250"
FT DISULFID 2365..2413
FT /evidence="ECO:0000250"
FT DISULFID 2456..2506
FT /evidence="ECO:0000250"
FT DISULFID 2554..2599
FT /evidence="ECO:0000250"
FT DISULFID 2641..2686
FT /evidence="ECO:0000250"
FT DISULFID 2831..2876
FT /evidence="ECO:0000250"
FT DISULFID 2917..2962
FT /evidence="ECO:0000250"
FT DISULFID 3137..3163
FT /evidence="ECO:0000250"
FT DISULFID 3166..3177
FT /evidence="ECO:0000250"
FT DISULFID 3171..3187
FT /evidence="ECO:0000250"
FT DISULFID 3204..3216
FT /evidence="ECO:0000250"
FT DISULFID 3229..3238
FT /evidence="ECO:0000250"
FT DISULFID 3393..3419
FT /evidence="ECO:0000250"
FT DISULFID 3425..3436
FT /evidence="ECO:0000250"
FT DISULFID 3430..3446
FT /evidence="ECO:0000250"
FT DISULFID 3448..3457
FT /evidence="ECO:0000250"
FT DISULFID 3464..3476
FT /evidence="ECO:0000250"
FT DISULFID 3470..3481
FT /evidence="ECO:0000250"
FT DISULFID 3483..3492
FT /evidence="ECO:0000250"
FT DISULFID 3671..3705
FT /evidence="ECO:0000250"
FT CONFLICT 1192
FT /note="P -> T (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1227
FT /note="D -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 1770..1774
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1779..1782
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1788..1799
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1802..1807
FT /evidence="ECO:0007829|PDB:1GL4"
FT HELIX 1808..1810
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1817..1820
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1823..1826
FT /evidence="ECO:0007829|PDB:1GL4"
FT HELIX 1831..1833
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1835..1842
FT /evidence="ECO:0007829|PDB:1GL4"
FT STRAND 1847..1856
FT /evidence="ECO:0007829|PDB:1GL4"
SQ SEQUENCE 3707 AA; 398294 MW; D41D2A2EBA65C80B CRC64;
MGQRAVGSLL LGLLLHARLL AVTHGLRAYD GLSLPEDTET VTASRYGWTY SYLSDDEDLL
ADDASGDGLG SGDVGSGDFQ MVYFRALVNF TRSIEYSPQL EDASAKEFRE VSEAVVEKLE
PEYRKIPGDQ IVSVVFIKEL DGWVFVELDV GSEGNADGSQ IQEVLHTVVS SGSIGPYVTS
PWGFKFRRLG TVPQFPRVCT ETEFACHSYN ECVALEYRCD RRPDCRDMSD ELNCEEPVPE
LSSSTPAVGK VSPLPLWPEA ATTPPPPVTH GPQFLLPSVP GPSACGPQEA SCHSGHCIPR
DYLCDGQEDC RDGSDELGCA SPPPCEPNEF ACENGHCALK LWRCDGDFDC EDRTDEANCS
VKQPGEVCGP THFQCVSTNR CIPASFHCDE ESDCPDRSDE FGCMPPQVVT PPQQSIQASR
GQTVTFTCVA TGVPTPIINW RLNWGHIPAH PRVTMTSEGG RGTLIIRDVK EADQGAYTCE
AMNSRGMVFG IPDGVLELVP QRGPCPDGHF YLEDSASCLP CFCFGVTNVC QSSLRFRDQI
RLSFDQPNDF KGVNVTMPSQ PGVPPLSSTQ LQIDPALQEF QLVDLSRRFL VHDAFWALPK
QFLGNKVDSY GGFLRYKVRY ELARGMLEPV QKPDVILVGA GYRLHSRGHT PTHPGTLNQR
QVQLSEEHWV HESGRPVQRA EMLQALASLE AVLLQTVYNT KMASVGLSDI VMDTTVTHTT
IHGRAHSVEE CRCPIGYSGL SCESCDAHFT RVPGGPYLGT CSGCNCNGHA SSCDPVYGHC
LNCQHNTEGP QCDKCKPGFF GDATKATATA CRPCPCPYID ASRRFSDTCF LDTDGQATCD
ACAPGYTGRR CESCAPGYEG NPIQPGGKCR PTTQEIVRCD ERGSLGTSGE TCRCKNNVVG
RLCNECSDGS FHLSKQNPDG CLKCFCMGVS RQCSSSSWSR AQVLGASEQP SQFSLSNAAG
THTTSEGVSS PAPGELSFSS FHNLLSEPYF WSLPASFRGD KVTSYGGELR FTVMQRPRPS
SAPLHRQPLV VLQGNNIVLE HHASRDPSPG QPSNFIVPFQ EQAWQRPDGQ PATREHLLMA
LAGIDALLIQ ASYTQQPAES RLSGISMDVA VPENTGQDSA REVEQCTCPP GYRGPSCQDC
DTGYTRVPSG LYLGTCERCN CHGHSETCEP ETGACQSCQH HTEGASCEQC QPGYYGDAQR
GTPQDCQPCP CYGAPAAGQA AHTCFLDTDG HPTCDSCSPG HSGRHCERCA PGYYGNPSQG
QPCHRDGQVP EVLGCGCDPH GSISSQCDAA GQCQCKAQVE GRSCSHCRPH HFHLSASNPE
GCLPCFCMGV TQQCASSSYS RQLISTHFAP GDFQGFALVN PQRNSQLTGG FTVEPVHDGA
RLSFSNFAHL GQESFYWQLP EIYQGDKVAA YGGKLRYTLS YTAGPQGSPL LDPDIQITGN
NIMLVASQPA LQGPERRSYE IIFREEFWRR PDGQPATREH LLMALADLDE LLVRATFSSV
PRAASISAVS LEGAQPGPSS GPRALEVEEC RCPPGYVGLS CQDCAPGYTR TGSGLYLGQC
ELCECNGHSD LCHPETGACS RCQHNTAGEF CELCATGYYG DATAGTPEDC QPCACPLTNP
ENMFSRTCES LGAGGYRCTA CEPGYTGQYC EQCAPGYEGD PNVQGGRCQP LTKESLEVQI
HPSRSVVPQG GPHSLRCQVS GSPPHYFYWS REDGRPLPSS AQQRHQGSEL HFPSVQPSDA
GVYICTCRNL IHTSNSRAEL LVAEAPSKPI MVTVEEQRSQ SVRPGADVTF ICTAKSKSPA
YTLVWTRLHN GKLPSRAMDF NGILTIRNVQ PSDAGTYVCT GSNMFAMDQG TATLHVQVSG
TSTAPVASIH PPQLTVQPGQ QAEFRCSATG NPTPMLEWIG GPSGQLPAKA QIHNGILRLP
AIEPSDQGQY LCRALSSAGQ HVARAMLQVH GGSGPRVQVS PERTQVHEGR TVRLYCRAAG
VPSASITWRK EGGSLPFRHQ AHGSRLRLHH MSVADSGEYV CRANNNIDAQ ETSIMISVSP
STNSPPAPAS PAPIRIESSS SRVAEGQTLD LNCVVPGHAH AQVTWHKRGG SLPTHHQTHG
SRLRLYQVSS ADSGEYVCSV LSSSGPLEAS VLVSITPAAA NVHIPGVVPP IRIETSSSRV
AEGQTLDLSC VVPGQAHAQV TWHKRGGSLP AGHQVHGHML RLNRVSPADS GEYSCQVTGS
SGTLEASVLV TIEASEPSPI PAPGLAQPVY IESSSSHLTE GQTVDLKCVV PGQAHAQVTW
HKRGSSLPAR HQTHGSLLRL YQLSPADSGE YVCQVAGSSH PEHEASFKLT VPSSQNSSFR
LRSPVISIEP PSSTVQQGQD ASFKCLIHEG AMPIKVEWKI RDQELEDNVH ISPNGSIITI
VAPGPATMEP TACVASNVYG MAQSVVNLSV HGPPTVSVLP EGPVHVKMGK DITLECISSG
EPRSSPRWTR LGIPVKLEPR MFGLMNSHAM LKIASVKPSD AGTYVCQAQN ALGTAQKQVE
LIVDTGTVAP GTPQVQVEES ELTLEAGHTA TLHCSATGNP PPTIHWSKLR APLPWQHRIE
GNTLVIPRVA QQDSGQYICN ATNSAGHTEA TVVLHVESPP YATIIPEHTS AQPGNLVQLQ
CLAHGTPPLT YQWSLVGGVL PEKAVVRNQL LRLEPTVPED SGRYRCQVSN RVGSAEAFAQ
VLVQGSSSNL PDTSIPGGST PTVQVTPQLE TRNIGASVEF HCAVPNERGT HLRWLKEGGQ
LPPGHSVQDG VLRIQNLDQN CQGTYVCQAH GPWGQAQATA QLIVQALPSV LINVRTSVHS
VVVGHSVEFE CLALGDPKPQ VTWSKVGGHL RPGIVQSGTI IRIAHVELAD AGQYRCAATN
AAGTTQSHVL LLVQALPQIS TPPEIRVPAG SAAVFPCMAS GYPTPAITWS KVDGDLPPDS
RLENNMLMLP SVRPEDAGTY VCTATNRQGK VKAFAYLQVP ERVIPYFTQT PYSFLPLPTI
KDAYRKFEIK ITFRPDSADG MLLYNGQKRS PTNLANRQPD FISFGLVGGR PEFRFDAGSG
MATIRHPTPL ALGQFHTVTL LRSLTQGSLI VGNLAPVNGT SQGKFQGLDL NEELYLGGYP
DYGAIPKAGL SSGFVGCVRE LRIQGEEIVF HDVNLTTHGI SHCPTCQDRP CQNGGQCQDS
ESSSYTCVCP AGFTAAAVNI RKPCTATPSL WADATCVNRP DGRGYTCRCH LGRSGVRCEE
GVTVTTPSMS GAGSYLALPA LTNTHHELRL DVEFKPLEPN GILLFSGGKS GPVEDFVSLA
MVGGHLEFRY ELGSGLAVLR SHEPLALGRW HRVSAERLNK DGSLRVDGGR PVLRSSPGKS
QGLNLHTLLY LGGVEPSVQL SPATNMSAHF HGCVGEVSVN GKRLDLTYSF LGSQGVGQCY
DSSPCERQPC RNGATCMPAG EYEFQCLCQD GFKGDLCEHE ENPCQLHEPC LNGGTCRGAR
CLCLPGFSGP RCQQGAGYGV VESDWHPEGS GGNDAPGQYG AYFYDNGFLG LPGNSFSRSL
PEVPETIEFE VRTSTADGLL LWQGVVREAS RSKDFISLGL QDGHLVFSYQ LGSGEARLVS
GDPINDGEWH RITALREGQR GSIQVDGEDL VTGRSPGPNV AVNTKDIIYI GGAPDVATLT
RGKFSSGITG CIKNLVLHTA RPGAPPPQPL DLQHRAQAGA NTRPCPS
