HPSE
entrez
10855
canonical
uniprot
Q9Y251
canonical
ensembl
ENSG00000173083
resolver
ensp
ENSP00000308107
resolver
ensp
ENSP00000384262
resolver
ensp
ENSP00000421365
resolver
ensp
ENSP00000423265
resolver
genesymbol
HPSE
resolver
genesymbol_syn
HEP
resolver
genesymbol_syn
HPA
resolver
genesymbol_syn
HPA1
resolver
genesymbol_syn
HPR1
resolver
genesymbol_syn
HPSE1
resolver
genesymbol_syn
HSE1
resolver
hgnc
HGNC:5164
resolver
uniprot
A9JIG7
resolver
uniprot
C7F7I3
resolver
uniprot
C7F7I4
resolver
uniprot
E9PCA9
resolver
uniprot
E9PGR1
resolver
uniprot
Q53GE5
resolver
uniprot
Q9UL39
resolver
uniprot_entry
HPSE_HUMAN
resolver
uniprot_sec
A9JIG7
resolver
uniprot_sec
C7F7I3
resolver
uniprot_sec
C7F7I4
resolver
uniprot_sec
E9PCA9
resolver
uniprot_sec
E9PGR1
resolver
uniprot_sec
Q53GE5
resolver
uniprot_sec
Q9UL39
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFFTQEPLHLVSPSFLSVTIDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFLIFDPKKESTFEERSYWQSQVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKFKNSTYSRSSVDVLYTFANCSGLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNEPNSFLKKADIFINGSQLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTAKMLKSFLKAGGEVIDSVTWHHYYLNGRTATKEDFLNPDVLDIFISSVQKVFQVVESTRPGKKVWLGETSSAYGGGAPLLSDTFAAGFMWLDKLGLSARMGIEVVMRQVFFGAGNYHLVDENFDPLPDYWLSLLFKKLVGTKVLMASVQGSKRRKLRVYLHCTNTDNPRYKEGDLTLYAINLHNVTKYLRLPYPFSNKQVDKYLLRPLGPHGLLSKSVQLNGLTLKMVDDQTLPPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVAACI
uniprot
proteins
ec_number
3.2.1.166
uniprot
proteins
function
FUNCTION: Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as a procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis. {ECO:0000269|PubMed:12213822, ECO:0000269|PubMed:12773484, ECO:0000269|PubMed:15044433, ECO:0000269|PubMed:16452201, ECO:0000269|PubMed:18557927, ECO:0000269|PubMed:18798279, ECO:0000269|PubMed:19244131, ECO:0000269|PubMed:20097882, ECO:0000269|PubMed:20181948, ECO:0000269|PubMed:20309870, ECO:0000269|PubMed:20561914, ECO:0000269|PubMed:21131364}.
uniprot
proteins
mass_dalton
61149
uniprot
proteins
mutagenesis
MUTAGEN 156; /note="Y->A,E: Alteration of the correct processing of heparanase which results in the cleavage at an upstream site in the linker peptide and no activation of proheparanase."; /evidence="ECO:0000269|PubMed:15659389"; MUTAGEN 156; /note="Y->V: Normal processing."; /evidence="ECO:0000269|PubMed:15659389"; MUTAGEN 158; /note="K->A: No association with GS-modified heparin; when associated with K-158."; /evidence="ECO:0000269|PubMed:15760902"; MUTAGEN 161; /note="K->A: Two-fold increase in the level of secretion upon addition of GS-modified heparin. No association with GS-modified heparin; when associated with K-161."; /evidence="ECO:0000269|PubMed:15760902"; MUTAGEN 162; /note="N->Q: Faster electrophoretic migration typical of a size reduction and important decrease of secretion. Larger size reduction; when associated with Q-178; Q-200; Q-217; Q-238 and Q-459."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 178; /note="N->Q: Faster electrophoretic migration typical of a size reduction and important decrease of secretion. Larger size reduction; when associated with Q-162; Q-200; Q-217; Q-238 and Q-459."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 200; /note="N->Q: Faster electrophoretic migration typical of a size reduction and partial decrease in secretion. Larger size reduction; when associated with Q-162; Q-178; Q-217; Q-238 and Q-459."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 217; /note="N->Q: Faster electrophoretic migration typical of a size reduction and partial decrease in secretion. Larger size reduction; when associated with Q-162; Q-178; Q-200; Q-238 and Q-459."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 225; /note="E->A: Loss of heparanase activity. No effect on HPSE-mediated cell adhesion."; /evidence="ECO:0000269|PubMed:11123890, ECO:0000269|PubMed:12773484"; MUTAGEN 238; /note="N->Q: Faster electrophoretic migration typical of a size reduction. Larger size reduction and important decrease of secretion; when associated with Q-162; Q-178; Q-200; Q-217 and Q-459."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 343; /note="E->A: Loss of heparanase activity."; /evidence="ECO:0000269|PubMed:11123890"; MUTAGEN 367; /note="D->A: Strong decrease in heparanase activity."; /evidence="ECO:0000269|PubMed:11123890"; MUTAGEN 378; /note="E->A: No reduction in heparanase activity."; MUTAGEN 396; /note="E->A: No reduction in heparanase activity."; MUTAGEN 414; /note="V->K: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 417; /note="K->E: No effect on processing nor secretion. No enzyme activity detected."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 459; /note="N->Q: Faster electrophoretic migration typical of a size reduction. Larger size reduction and important decrease of secretion; when associated with Q-162; Q-178; Q-200; Q-217 and Q-238."; /evidence="ECO:0000269|PubMed:14573609"; MUTAGEN 525; /note="P->G: No effect on processing nor secretion. No enzyme activity detected."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 527; /note="F->R: No effect on processing nor secretion. No enzyme activity detected."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 528; /note="S->K: No effect on processing nor secretion. No enzyme activity detected."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 529; /note="Y->A: No effect on processing nor secretion. No enzyme activity detected."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 531; /note="F->R: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 533; /note="V->R: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 534; /note="I->D: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 535; /note="R->A: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 536; /note="N->A: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 537; /note="A->K: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 538; /note="K->A: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 539; /note="V->A: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 540; /note="A->K: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 541; /note="A->K: No effect on processing, secretion nor enzyme activity."; /evidence="ECO:0000269|PubMed:19244131"; MUTAGEN 542; /note="C->A: Abolishes processing, secretion and enzyme activity."; /evidence="ECO:0000269|PubMed:19244131
uniprot
proteins
post_translational_modification
PTM: Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme. {ECO:0000269|PubMed:10395325, ECO:0000269|PubMed:11973358, ECO:0000269|PubMed:12441129, ECO:0000269|PubMed:15126626, ECO:0000269|PubMed:15659389, ECO:0000269|PubMed:15848168}.; PTM: N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility. {ECO:0000269|PubMed:10395325, ECO:0000269|PubMed:12713442, ECO:0000269|PubMed:14573609, ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:19159218}.
uniprot
proteins
protein_family
Glycosyl hydrolase 79 family
uniprot
proteins
pubmed
10395325
uniprot
proteins
pubmed
10395326
uniprot
proteins
pubmed
10405343
uniprot
proteins
pubmed
10446189
uniprot
proteins
pubmed
10764835
uniprot
proteins
pubmed
11123890
uniprot
proteins
pubmed
11547900
uniprot
proteins
pubmed
11973358
uniprot
proteins
pubmed
12213822
uniprot
proteins
pubmed
12441129
uniprot
proteins
pubmed
12713442
uniprot
proteins
pubmed
12773484
uniprot
proteins
pubmed
12927802
uniprot
proteins
pubmed
14573609
uniprot
proteins
pubmed
15044433
uniprot
proteins
pubmed
15126626
uniprot
proteins
pubmed
15292202
uniprot
proteins
pubmed
15334672
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15659389
uniprot
proteins
pubmed
15760902
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15848168
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16452201
uniprot
proteins
pubmed
17208203
uniprot
proteins
pubmed
18557927
uniprot
proteins
pubmed
18798279
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19244131
uniprot
proteins
pubmed
20097882
uniprot
proteins
pubmed
20181948
uniprot
proteins
pubmed
20309870
uniprot
proteins
pubmed
20561914
uniprot
proteins
pubmed
20576607
uniprot
proteins
pubmed
20634491
uniprot
proteins
pubmed
21131364
uniprot
proteins
pubmed
26575439
uniprot
proteins
pubmed
26733221
uniprot
proteins
pubmed
28581485
uniprot
proteins
sequence_length
543
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane; Peripheral membrane protein. Secreted. Nucleus. Note=Proheparanase is secreted via vesicles of the Golgi. Interacts with cell membrane heparan sulfate proteoglycans (HSPGs). Endocytosed and accumulates in endosomes. Transferred to lysosomes where it is proteolytically cleaved to produce the active enzyme. Under certain stimuli, transferred to the cell surface. Associates with lipid rafts. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium (By similarity). {ECO:0000250}.
uniprot
proteins