| IED ID | IndEnz0002000448 |
| Enzyme Type ID | protease000448 |
| Protein Name |
Basement membrane-specific heparan sulfate proteoglycan core protein HSPG Cleaved into: Endorepellin; LG3 peptide |
| Gene Name | Hspg2 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MGQRAVGSLLLGLLLHARLLAVTHGLRAYDGLSLPEDTETVTASRYGWTYSYLSDDEDLLADDASGDGLGSGDVGSGDFQMVYFRALVNFTRSIEYSPQLEDASAKEFREVSEAVVEKLEPEYRKIPGDQIVSVVFIKELDGWVFVELDVGSEGNADGSQIQEVLHTVVSSGSIGPYVTSPWGFKFRRLGTVPQFPRVCTETEFACHSYNECVALEYRCDRRPDCRDMSDELNCEEPVPELSSSTPAVGKVSPLPLWPEAATTPPPPVTHGPQFLLPSVPGPSACGPQEASCHSGHCIPRDYLCDGQEDCRDGSDELGCASPPPCEPNEFACENGHCALKLWRCDGDFDCEDRTDEANCSVKQPGEVCGPTHFQCVSTNRCIPASFHCDEESDCPDRSDEFGCMPPQVVTPPQQSIQASRGQTVTFTCVATGVPTPIINWRLNWGHIPAHPRVTMTSEGGRGTLIIRDVKEADQGAYTCEAMNSRGMVFGIPDGVLELVPQRGPCPDGHFYLEDSASCLPCFCFGVTNVCQSSLRFRDQIRLSFDQPNDFKGVNVTMPSQPGVPPLSSTQLQIDPALQEFQLVDLSRRFLVHDAFWALPKQFLGNKVDSYGGFLRYKVRYELARGMLEPVQKPDVILVGAGYRLHSRGHTPTHPGTLNQRQVQLSEEHWVHESGRPVQRAEMLQALASLEAVLLQTVYNTKMASVGLSDIVMDTTVTHTTIHGRAHSVEECRCPIGYSGLSCESCDAHFTRVPGGPYLGTCSGCNCNGHASSCDPVYGHCLNCQHNTEGPQCDKCKPGFFGDATKATATACRPCPCPYIDASRRFSDTCFLDTDGQATCDACAPGYTGRRCESCAPGYEGNPIQPGGKCRPTTQEIVRCDERGSLGTSGETCRCKNNVVGRLCNECSDGSFHLSKQNPDGCLKCFCMGVSRQCSSSSWSRAQVLGASEQPSQFSLSNAAGTHTTSEGVSSPAPGELSFSSFHNLLSEPYFWSLPASFRGDKVTSYGGELRFTVMQRPRPSSAPLHRQPLVVLQGNNIVLEHHASRDPSPGQPSNFIVPFQEQAWQRPDGQPATREHLLMALAGIDALLIQASYTQQPAESRLSGISMDVAVPENTGQDSAREVEQCTCPPGYRGPSCQDCDTGYTRVPSGLYLGTCERCNCHGHSETCEPETGACQSCQHHTEGASCEQCQPGYYGDAQRGTPQDCQPCPCYGAPAAGQAAHTCFLDTDGHPTCDSCSPGHSGRHCERCAPGYYGNPSQGQPCHRDGQVPEVLGCGCDPHGSISSQCDAAGQCQCKAQVEGRSCSHCRPHHFHLSASNPEGCLPCFCMGVTQQCASSSYSRQLISTHFAPGDFQGFALVNPQRNSQLTGGFTVEPVHDGARLSFSNFAHLGQESFYWQLPEIYQGDKVAAYGGKLRYTLSYTAGPQGSPLLDPDIQITGNNIMLVASQPALQGPERRSYEIIFREEFWRRPDGQPATREHLLMALADLDELLVRATFSSVPRAASISAVSLEGAQPGPSSGPRALEVEECRCPPGYVGLSCQDCAPGYTRTGSGLYLGQCELCECNGHSDLCHPETGACSRCQHNTAGEFCELCATGYYGDATAGTPEDCQPCACPLTNPENMFSRTCESLGAGGYRCTACEPGYTGQYCEQCAPGYEGDPNVQGGRCQPLTKESLEVQIHPSRSVVPQGGPHSLRCQVSGSPPHYFYWSREDGRPLPSSAQQRHQGSELHFPSVQPSDAGVYICTCRNLIHTSNSRAELLVAEAPSKPIMVTVEEQRSQSVRPGADVTFICTAKSKSPAYTLVWTRLHNGKLPSRAMDFNGILTIRNVQPSDAGTYVCTGSNMFAMDQGTATLHVQVSGTSTAPVASIHPPQLTVQPGQQAEFRCSATGNPTPMLEWIGGPSGQLPAKAQIHNGILRLPAIEPSDQGQYLCRALSSAGQHVARAMLQVHGGSGPRVQVSPERTQVHEGRTVRLYCRAAGVPSASITWRKEGGSLPFRHQAHGSRLRLHHMSVADSGEYVCRANNNIDAQETSIMISVSPSTNSPPAPASPAPIRIESSSSRVAEGQTLDLNCVVPGHAHAQVTWHKRGGSLPTHHQTHGSRLRLYQVSSADSGEYVCSVLSSSGPLEASVLVSITPAAANVHIPGVVPPIRIETSSSRVAEGQTLDLSCVVPGQAHAQVTWHKRGGSLPAGHQVHGHMLRLNRVSPADSGEYSCQVTGSSGTLEASVLVTIEASEPSPIPAPGLAQPVYIESSSSHLTEGQTVDLKCVVPGQAHAQVTWHKRGSSLPARHQTHGSLLRLYQLSPADSGEYVCQVAGSSHPEHEASFKLTVPSSQNSSFRLRSPVISIEPPSSTVQQGQDASFKCLIHEGAMPIKVEWKIRDQELEDNVHISPNGSIITIVAPGPATMEPTACVASNVYGMAQSVVNLSVHGPPTVSVLPEGPVHVKMGKDITLECISSGEPRSSPRWTRLGIPVKLEPRMFGLMNSHAMLKIASVKPSDAGTYVCQAQNALGTAQKQVELIVDTGTVAPGTPQVQVEESELTLEAGHTATLHCSATGNPPPTIHWSKLRAPLPWQHRIEGNTLVIPRVAQQDSGQYICNATNSAGHTEATVVLHVESPPYATIIPEHTSAQPGNLVQLQCLAHGTPPLTYQWSLVGGVLPEKAVVRNQLLRLEPTVPEDSGRYRCQVSNRVGSAEAFAQVLVQGSSSNLPDTSIPGGSTPTVQVTPQLETRNIGASVEFHCAVPNERGTHLRWLKEGGQLPPGHSVQDGVLRIQNLDQNCQGTYVCQAHGPWGQAQATAQLIVQALPSVLINVRTSVHSVVVGHSVEFECLALGDPKPQVTWSKVGGHLRPGIVQSGTIIRIAHVELADAGQYRCAATNAAGTTQSHVLLLVQALPQISTPPEIRVPAGSAAVFPCMASGYPTPAITWSKVDGDLPPDSRLENNMLMLPSVRPEDAGTYVCTATNRQGKVKAFAYLQVPERVIPYFTQTPYSFLPLPTIKDAYRKFEIKITFRPDSADGMLLYNGQKRSPTNLANRQPDFISFGLVGGRPEFRFDAGSGMATIRHPTPLALGQFHTVTLLRSLTQGSLIVGNLAPVNGTSQGKFQGLDLNEELYLGGYPDYGAIPKAGLSSGFVGCVRELRIQGEEIVFHDVNLTTHGISHCPTCQDRPCQNGGQCQDSESSSYTCVCPAGFTAAAVNIRKPCTATPSLWADATCVNRPDGRGYTCRCHLGRSGVRCEEGVTVTTPSMSGAGSYLALPALTNTHHELRLDVEFKPLEPNGILLFSGGKSGPVEDFVSLAMVGGHLEFRYELGSGLAVLRSHEPLALGRWHRVSAERLNKDGSLRVDGGRPVLRSSPGKSQGLNLHTLLYLGGVEPSVQLSPATNMSAHFHGCVGEVSVNGKRLDLTYSFLGSQGVGQCYDSSPCERQPCRNGATCMPAGEYEFQCLCQDGFKGDLCEHEENPCQLHEPCLNGGTCRGARCLCLPGFSGPRCQQGAGYGVVESDWHPEGSGGNDAPGQYGAYFYDNGFLGLPGNSFSRSLPEVPETIEFEVRTSTADGLLLWQGVVREASRSKDFISLGLQDGHLVFSYQLGSGEARLVSGDPINDGEWHRITALREGQRGSIQVDGEDLVTGRSPGPNVAVNTKDIIYIGGAPDVATLTRGKFSSGITGCIKNLVLHTARPGAPPPQPLDLQHRAQAGANTRPCPS |
| Enzyme Length | 3707 |
| Uniprot Accession Number | Q05793 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (By similarity). {ECO:0000250}.; FUNCTION: Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6 (By similarity). {ECO:0000250}.; FUNCTION: The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (8); Chain (3); Compositional bias (1); Disulfide bond (69); Domain (41); Glycosylation (13); Helix (2); Metal binding (4); Region (4); Sequence conflict (2); Signal peptide (1); Site (1) |
| Keywords | 3D-structure;Angiogenesis;Basement membrane;Calcium;Direct protein sequencing;Disulfide bond;EGF-like domain;Extracellular matrix;Glycoprotein;Heparan sulfate;Immunoglobulin domain;Laminin EGF-like domain;Metal-binding;Proteoglycan;Reference proteome;Repeat;Secreted;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix, basement membrane. |
| Modified Residue | |
| Post Translational Modification | PTM: Proteolytic processing produces the C-terminal angiogenic peptide, endorepellin. This peptide can be further processed to produce the LG3 peptide (By similarity). {ECO:0000250}.; PTM: N- and O-glycosylated; contains 3 heparan sulfate chains. The LG3 peptide contains at least three and up to five potential O-glycosylation sites and no N-glycosylation (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..21; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 1GL4; |
| Mapped Pubmed ID | 10352025; 10433923; 10579711; 10579729; 10600481; 10918573; 11084655; 11259264; 11279527; 11357198; 11400157; 11493006; 11564885; 11574465; 11771669; 11787818; 11802174; 11973346; 12015298; 12122449; 12142349; 12192060; 12242711; 12243745; 12466851; 12514129; 12520002; 12571105; 12588956; 12682087; 12761845; 12814946; 12818570; 12904583; 1383086; 14610273; 14656929; 14739157; 15186747; 15214943; 15258195; 15280392; 15377789; 15381701; 15657057; 15668394; 15878328; 15895400; 15928325; 16024816; 16098969; 16100707; 16141072; 16219760; 16439479; 16498405; 16554364; 16615898; 16750824; 16785251; 1685141; 1686572; 16873583; 16880404; 16956876; 17023412; 17095659; 17213231; 17411441; 17525255; 17608588; 17767158; 17948866; 17959718; 17967808; 17997086; 18024432; 18040286; 18267097; 18314316; 18356808; 18448648; 18559345; 18570250; 18586242; 18589009; 18596265; 18647752; 18676816; 18757743; 18799693; 18816447; 19056886; 19373938; 19587446; 19783738; 19789387; 19924818; 20072119; 20089971; 20114047; 20237296; 20514525; 20541011; 20684947; 20814969; 20858856; 20970343; 21067603; 21085708; 21289070; 21289173; 21350012; 21452199; 21677750; 21747167; 21839920; 21850672; 21903675; 21924961; 22072575; 22159717; 22222602; 22244880; 22266517; 22274697; 22281059; 22421594; 22449950; 22613833; 22753893; 22767514; 22952693; 23104139; 23217742; 23281850; 23320101; 23339896; 23493297; 23509775; 23509972; 23658023; 23722005; 24006456; 24058167; 24115222; 24559672; 24798737; 24858854; 24983472; 25158168; 25179606; 25646087; 25808553; 26024086; 26056142; 26116392; 26319110; 26428891; 26636652; 26993635; 27098652; 27377666; 27578148; 27613501; 27829154; 27856617; 28011632; 28071719; 28714851; 28760865; 29743679; 29773865; 30042881; 30089653; 30149005; 30228991; 30456378; 30563944; 30814516; 30883226; 30993430; 31112136; 31541017; 3159725; 31600777; 31715337; 32013135; 32201365; 32205445; 32220631; 32381549; 32514132; 32523119; 32673396; 32913205; 33144400; 33875569; 3665768; 7670489; 7945186; 8027524; 8231112; 8914972; 8951060; 9142982; 9337134; 9486530; 9524110; 9788974; 9915576; |
| Motif | |
| Gene Encoded By | |
| Mass | 398,294 |
| Kinetics | |
| Metal Binding | METAL 3574; /note=Calcium; /evidence=ECO:0000250; METAL 3591; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000250; METAL 3641; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000250; METAL 3643; /note=Calcium; /evidence=ECO:0000250 |
| Rhea ID | |
| Cross Reference Brenda |