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Protein

Heparanase

Gene

HPSE

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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. 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. Acts as procoagulant by enhancing the generation of activated factor X/F10 in the presence of tissue factor/TF and activated factor VII/F7. Independent of its enzymatic activity, increases cell adhesion to the extracellular matrix (ECM). Enhances AKT1/PKB phosphorylation, possibly via interaction with a lipid raft-resident receptor. Plays a role in the regulation of osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis (By similarity).By similarity

Catalytic activityi

Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan.

Enzyme regulationi

Inhibited by laminarin sulfate and, to a lower extent, by heparin, sulfamin and EDTA. Activated by calcium and magnesium (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei227 – 2271Proton donorSequence analysis
Active sitei345 – 3451NucleophileSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Magnesium

Protein family/group databases

CAZyiGH79. Glycoside Hydrolase Family 79.

Names & Taxonomyi

Protein namesi
Recommended name:
Heparanase (EC:3.2.1.166)
Cleaved into the following 2 chains:
Gene namesi
Name:HPSE
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Lysosome membrane By similarity; Peripheral membrane protein By similarity
  • Secreted By similarity
  • Nucleus By similarity

  • 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).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3737By similarityAdd
BLAST
Chaini38 – 11174Heparanase 8 kDa subunitBy similarityPRO_0000042256Add
BLAST
Propeptidei112 – 15948Linker peptidePRO_0000042257Add
BLAST
Chaini160 – 545386Heparanase 50 kDa subunitBy similarityPRO_0000042258Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence analysis
Glycosylationi219 – 2191N-linked (GlcNAc...)Sequence analysis
Glycosylationi461 – 4611N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and the 8 kDa and the 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 (By similarity).By similarity
N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility (By similarity).By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9MYY0.
PRIDEiQ9MYY0.

Expressioni

Tissue specificityi

Highly expressed in placenta and weakly in the kidney, lung, spleen and uterus.1 Publication

Interactioni

Subunit structurei

Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity (By similarity). Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1. Interacts with HPSE2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007550.

Structurei

3D structure databases

ProteinModelPortaliQ9MYY0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni160 – 1645Heparin/HS-bindingSequence analysis
Regioni272 – 28211Heparin/HS-bindingSequence analysisAdd
BLAST
Regioni529 – 54517Required for transferring proheparanase to the Golgi apparatus, secretion and subsequent enzyme activity and for enhancement of PKB/AKT1 phosphorylationBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the glycosyl hydrolase 79 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHNV. Eukaryota.
ENOG410YDJW. LUCA.
HOGENOMiHOG000007256.
HOVERGENiHBG081606.
InParanoidiQ9MYY0.
KOiK07964.

Family and domain databases

Gene3Di3.20.20.80. 1 hit.
InterProiIPR005199. Glyco_hydro_79.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERiPTHR14363. PTHR14363. 2 hits.
PfamiPF03662. Glyco_hydro_79n. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 2 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9MYY0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLACRKPGLR PPLLLLLPLL GPLGPCSPGT PAAAAPADDA AELEFFTERP
60 70 80 90 100
LHLVSPAFLS FTIDANLATD PRFFTFLGSS KLRTLARGLA PAYLRFGGNK
110 120 130 140 150
GDFLIFDPKK EPAFEERSYW LSQSNQDICK SGSIPSDVEE KLRLEWPFQE
160 170 180 190 200
QVLLREQYQK KFTNSTYSRS SVDMLYTFAS CSGLNLIFGV NALLRTTDMH
210 220 230 240 250
WDSSNAQLLL DYCSSKNYNI SWELGNEPNS FQRKAGIFIN GRQLGEDFIE
260 270 280 290 300
FRKLLGKSAF KNAKLYGPDI GQPRRNTVKM LKSFLKAGGE VIDSVTWHHY
310 320 330 340 350
YVNGRIATKE DFLNPDILDT FISSVQKTLR IVEKIRPLKK VWLGETSSAF
360 370 380 390 400
GGGAPFLSNT FAAGFMWLDK LGLSARMGIE VVMRQVLFGA GNYHLVDGNF
410 420 430 440 450
EPLPDYWLSL LFKKLVGNKV LMASVKGPDR SKFRVYLHCT NTKHPRYKEG
460 470 480 490 500
DLTLYALNLH NVTKHLELPH HLFNKQVDKY LIKPSGTDGL LSKSVQLNGQ
510 520 530 540
ILKMVDEQTL PALTEKPLHP GSSLGMPPFS YGFFVIRNAK VAACI
Length:545
Mass (Da):61,077
Last modified:June 1, 2001 - v2
Checksum:iFAC4BDFFD855B933
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281160 mRNA. Translation: AAF87301.2.
RefSeqiNP_776507.1. NM_174082.2.
UniGeneiBt.8127.

Genome annotation databases

GeneIDi281230.
KEGGibta:281230.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281160 mRNA. Translation: AAF87301.2.
RefSeqiNP_776507.1. NM_174082.2.
UniGeneiBt.8127.

3D structure databases

ProteinModelPortaliQ9MYY0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007550.

Protein family/group databases

CAZyiGH79. Glycoside Hydrolase Family 79.

Proteomic databases

PaxDbiQ9MYY0.
PRIDEiQ9MYY0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281230.
KEGGibta:281230.

Organism-specific databases

CTDi10855.

Phylogenomic databases

eggNOGiENOG410IHNV. Eukaryota.
ENOG410YDJW. LUCA.
HOGENOMiHOG000007256.
HOVERGENiHBG081606.
InParanoidiQ9MYY0.
KOiK07964.

Miscellaneous databases

NextBioi20805277.

Family and domain databases

Gene3Di3.20.20.80. 1 hit.
InterProiIPR005199. Glyco_hydro_79.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERiPTHR14363. PTHR14363. 2 hits.
PfamiPF03662. Glyco_hydro_79n. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 2 hits.
ProtoNetiSearch...

Publicationsi

  1. "Expression of heparanase mRNA in bovine placenta during gestation."
    Kizaki K., Nakano H., Nakano H., Takahashi T., Imai K., Hashizume K.
    Reproduction 121:573-580(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Placenta.

Entry informationi

Entry nameiHPSE_BOVIN
AccessioniPrimary (citable) accession number: Q9MYY0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: June 1, 2001
Last modified: November 11, 2015
This is version 75 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.