HPSE_BOVIN
ID HPSE_BOVIN Reviewed; 545 AA.
AC Q9MYY0;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Heparanase;
DE EC=3.2.1.166;
DE Contains:
DE RecName: Full=Heparanase 8 kDa subunit;
DE Contains:
DE RecName: Full=Heparanase 50 kDa subunit;
DE Flags: Precursor;
GN Name=HPSE;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=11277877; DOI=10.1530/rep.0.1210573;
RA Kizaki K., Nakano H., Nakano H., Takahashi T., Imai K., Hashizume K.;
RT "Expression of heparanase mRNA in bovine placenta during gestation.";
RL Reproduction 121:573-580(2001).
CC -!- FUNCTION: Endoglycosidase that cleaves heparan sulfate proteoglycans
CC (HSPGs) into heparan sulfate side chains and core proteoglycans.
CC Participates in extracellular matrix (ECM) degradation and remodeling.
CC Selectively cleaves the linkage between a glucuronic acid unit and an
CC N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo
CC group. Can also cleave the linkage between a glucuronic acid unit and
CC an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not
CC linkages between a glucuronic acid unit and a 2-O-sulfated iduronic
CC acid moiety. Essentially inactive at neutral pH but becomes active
CC under acidic conditions such as during tumor invasion and in
CC inflammatory processes. Facilitates cell migration associated with
CC metastasis, wound healing and inflammation. Enhances shedding of
CC syndecans. Acts as procoagulant by enhancing the generation of
CC activated factor X/F10 in the presence of tissue factor/TF and
CC activated factor VII/F7. Independent of its enzymatic activity,
CC increases cell adhesion to the extracellular matrix (ECM). Enhances
CC AKT1/PKB phosphorylation, possibly via interaction with a lipid raft-
CC resident receptor. Plays a role in the regulation of osteogenesis.
CC Enhances angiogenesis through up-regulation of SRC-mediated activation
CC of VEGF. Implicated in hair follicle inner root sheath differentiation
CC and hair homeostasis (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan
CC sulfate chains in heparan sulfate proteoglycan.; EC=3.2.1.166;
CC -!- ACTIVITY REGULATION: Inhibited by laminarin sulfate and, to a lower
CC extent, by heparin, sulfamin and EDTA. Activated by calcium and
CC magnesium (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer; heterodimer formation between the 8 kDa and the
CC 50 kDa subunits is required for enzyme activity (By similarity).
CC Interacts with TF; the interaction, inhibited by heparin, enhances the
CC generation of activated factor X and activates coagulation. Interacts
CC with HRG; the interaction is enhanced at acidic pH, partially inhibits
CC binding of HPSE to cell surface receptors and modulates its enzymatic
CC activity. Interacts with SDC1; the interaction enhances the shedding of
CC SDC1. Interacts with HPSE2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Secreted {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Proheparanase is secreted via vesicles of the
CC Golgi. Interacts with cell membrane heparan sulfate proteoglycans
CC (HSPGs). Endocytosed and accumulates in endosomes. Transferred to
CC lysosomes where it is proteolytically cleaved to produce the active
CC enzyme. Under certain stimuli, transferred to the cell surface.
CC Associates with lipid rafts. Colocalizes with SDC1 in
CC endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal
CC vesicles. Heparin retains proheparanase in the extracellular medium (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta and weakly in the
CC kidney, lung, spleen and uterus. {ECO:0000269|PubMed:11277877}.
CC -!- PTM: Proteolytically processed. The cleavage of the 65 kDa form leads
CC to the generation of a linker peptide, and the 8 kDa and the 50 kDa
CC products. The active form, the 8/50 kDa heterodimer, is resistant to
CC degradation. Complete removal of the linker peptide appears to be a
CC prerequisite to the complete activation of the enzyme (By similarity).
CC {ECO:0000250}.
CC -!- PTM: N-glycosylated. Glycosylation of the 50 kDa subunit appears to be
CC essential for its solubility (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 79 family. {ECO:0000305}.
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DR EMBL; AF281160; AAF87301.2; -; mRNA.
DR RefSeq; NP_776507.1; NM_174082.2.
DR AlphaFoldDB; Q9MYY0; -.
DR SMR; Q9MYY0; -.
DR STRING; 9913.ENSBTAP00000007550; -.
DR CAZy; GH79; Glycoside Hydrolase Family 79.
DR PaxDb; Q9MYY0; -.
DR PRIDE; Q9MYY0; -.
DR GeneID; 281230; -.
DR KEGG; bta:281230; -.
DR CTD; 10855; -.
DR eggNOG; ENOG502QQST; Eukaryota.
DR InParanoid; Q9MYY0; -.
DR OrthoDB; 1132327at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030305; F:heparanase activity; ISS:UniProtKB.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IBA:GO_Central.
DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0030200; P:heparan sulfate proteoglycan catabolic process; ISS:UniProtKB.
DR InterPro; IPR005199; Glyco_hydro_79.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF03662; Glyco_hydro_79n; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cell adhesion; Disulfide bond; Glycoprotein; Hydrolase; Lysosome;
KW Magnesium; Membrane; Nucleus; Reference proteome; Secreted; Signal.
FT SIGNAL 1..37
FT /evidence="ECO:0000250"
FT CHAIN 38..111
FT /note="Heparanase 8 kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042256"
FT PROPEP 112..159
FT /note="Linker peptide"
FT /id="PRO_0000042257"
FT CHAIN 160..545
FT /note="Heparanase 50 kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042258"
FT REGION 290..419
FT /note="Required for heterodimerization with the heparanase
FT 8 kDa subunit"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT REGION 529..545
FT /note="Required for transferring proheparanase to the Golgi
FT apparatus, secretion and subsequent enzyme activity and for
FT enhancement of PKB/AKT1 phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT ACT_SITE 227
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT ACT_SITE 345
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 64..66
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 160..164
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 272..282
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 298
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 305
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 350..352
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT BINDING 391..393
FT /ligand="heparan sulfate group"
FT /ligand_id="ChEBI:CHEBI:157750"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT DISULFID 129..181
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
FT DISULFID 439..544
FT /evidence="ECO:0000250|UniProtKB:Q9Y251"
SQ SEQUENCE 545 AA; 61077 MW; FAC4BDFFD855B933 CRC64;
MLACRKPGLR PPLLLLLPLL GPLGPCSPGT PAAAAPADDA AELEFFTERP LHLVSPAFLS
FTIDANLATD PRFFTFLGSS KLRTLARGLA PAYLRFGGNK GDFLIFDPKK EPAFEERSYW
LSQSNQDICK SGSIPSDVEE KLRLEWPFQE QVLLREQYQK KFTNSTYSRS SVDMLYTFAS
CSGLNLIFGV NALLRTTDMH WDSSNAQLLL DYCSSKNYNI SWELGNEPNS FQRKAGIFIN
GRQLGEDFIE FRKLLGKSAF KNAKLYGPDI GQPRRNTVKM LKSFLKAGGE VIDSVTWHHY
YVNGRIATKE DFLNPDILDT FISSVQKTLR IVEKIRPLKK VWLGETSSAF GGGAPFLSNT
FAAGFMWLDK LGLSARMGIE VVMRQVLFGA GNYHLVDGNF EPLPDYWLSL LFKKLVGNKV
LMASVKGPDR SKFRVYLHCT NTKHPRYKEG DLTLYALNLH NVTKHLELPH HLFNKQVDKY
LIKPSGTDGL LSKSVQLNGQ ILKMVDEQTL PALTEKPLHP GSSLGMPPFS YGFFVIRNAK
VAACI
