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Protein

Heparanase

Gene

Hpse

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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. 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 procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular 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.4 Publications

Catalytic activityi

Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan.2 Publications

Enzyme regulationi

Inhibited by EDTA and activated by calcium and magnesium (By similarity). Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin.By similarity2 Publications

pH dependencei

Optimum pH is 5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei217Proton donorSequence analysis1
Active sitei335NucleophileSequence analysis1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

ReactomeiR-MMU-2024096. HS-GAG degradation.
R-MMU-6798695. Neutrophil degranulation.

Protein family/group databases

CAZyiGH79. Glycoside Hydrolase Family 79.

Names & Taxonomyi

Protein namesi
Recommended name:
Heparanase (EC:3.2.1.166)
Alternative name(s):
Endo-glucoronidase
Cleaved into the following 2 chains:
Gene namesi
Name:Hpse
Synonyms:Hpa
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1343124. Hpse.

Subcellular locationi

GO - Cellular componenti

  • intracellular membrane-bounded organelle Source: MGI
  • lysosomal membrane Source: UniProtKB-SubCell
  • lysosome Source: MGI
  • membrane raft Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • proteinaceous extracellular matrix Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27By similarityAdd BLAST27
ChainiPRO_000004226328 – 101Heparanase 8 kDa subunitAdd BLAST74
PropeptideiPRO_0000042264102 – 149Linker peptideBy similarityAdd BLAST48
ChainiPRO_0000042265150 – 535Heparanase 50 kDa subunitAdd BLAST386

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi154N-linked (GlcNAc...)1 Publication1
Glycosylationi192N-linked (GlcNAc...)Sequence analysis1
Glycosylationi209N-linked (GlcNAc...)Sequence analysis1
Glycosylationi451N-linked (GlcNAc...)Sequence analysis1

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 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.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ6YGZ1.
MaxQBiQ6YGZ1.
PaxDbiQ6YGZ1.
PRIDEiQ6YGZ1.

PTM databases

iPTMnetiQ6YGZ1.
PhosphoSitePlusiQ6YGZ1.

Expressioni

Tissue specificityi

Expressed in skin, mainly in the stratum granulosum and the first layer of the stratum corneum in the upper part of the epidermis. Also detected in hair follicles and in sebaceous glands.2 Publications

Developmental stagei

In 18.5 day embryos, expressed in the peri-chondrium, periosteum and at the chondro-osseus junction of developing bone.1 Publication

Gene expression databases

BgeeiENSMUSG00000035273.
CleanExiMM_HPSE.
ExpressionAtlasiQ6YGZ1. baseline and differential.
GenevisibleiQ6YGZ1. MM.

Interactioni

Subunit structurei

Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity. 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 (By similarity). Interacts with HPSE2 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000044072.

Structurei

3D structure databases

ProteinModelPortaliQ6YGZ1.
SMRiQ6YGZ1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni150 – 154Heparin/HS-bindingBy similarity5
Regioni262 – 272Heparin/HS-bindingBy similarityAdd BLAST11
Regioni280 – 409Required for heterodimerization with the heparanase 8 kDa subunitBy similarityAdd BLAST130
Regioni519 – 535Required for transferring proheparanase to the Golgi apparatus, secretion and subsequent enzyme activity and for enhancement of PKB/AKT1 phosphorylationBy similarityAdd BLAST17

Sequence similaritiesi

Belongs to the glycosyl hydrolase 79 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHNV. Eukaryota.
ENOG410YDJW. LUCA.
GeneTreeiENSGT00390000004874.
HOGENOMiHOG000007256.
HOVERGENiHBG081606.
InParanoidiQ6YGZ1.
KOiK07964.
OMAiKHNSFSH.
OrthoDBiEOG091G05QD.
TreeFamiTF328999.

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.

Q6YGZ1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRLLLLWLW GPLGALAQGA PAGTAPTDDV VDLEFYTKRP LRSVSPSFLS
60 70 80 90 100
ITIDASLATD PRFLTFLGSP RLRALARGLS PAYLRFGGTK TDFLIFDPDK
110 120 130 140 150
EPTSEERSYW KSQVNHDICR SEPVSAAVLR KLQVEWPFQE LLLLREQYQK
160 170 180 190 200
EFKNSTYSRS SVDMLYSFAK CSGLDLIFGL NALLRTPDLR WNSSNAQLLL
210 220 230 240 250
DYCSSKGYNI SWELGNEPNS FWKKAHILID GLQLGEDFVE LHKLLQRSAF
260 270 280 290 300
QNAKLYGPDI GQPRGKTVKL LRSFLKAGGE VIDSLTWHHY YLNGRIATKE
310 320 330 340 350
DFLSSDVLDT FILSVQKILK VTKEITPGKK VWLGETSSAY GGGAPLLSNT
360 370 380 390 400
FAAGFMWLDK LGLSAQMGIE VVMRQVFFGA GNYHLVDENF EPLPDYWLSL
410 420 430 440 450
LFKKLVGPRV LLSRVKGPDR SKLRVYLHCT NVYHPRYQEG DLTLYVLNLH
460 470 480 490 500
NVTKHLKVPP PLFRKPVDTY LLKPSGPDGL LSKSVQLNGQ ILKMVDEQTL
510 520 530
PALTEKPLPA GSALSLPAFS YGFFVIRNAK IAACI
Length:535
Mass (Da):60,066
Last modified:July 27, 2011 - v3
Checksum:i6E73A8302FB8A0DF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti206K → R in AAN41636 (PubMed:12837765).Curated1
Sequence conflicti212W → S in AAN41636 (PubMed:12837765).Curated1
Sequence conflicti230 – 232DGL → NGS in AAN41636 (PubMed:12837765).Curated3
Sequence conflicti335E → K in AAN41636 (PubMed:12837765).Curated1
Sequence conflicti342G → A in AAN41636 (PubMed:12837765).Curated1
Sequence conflicti455H → Y in AAN41636 (PubMed:12837765).Curated1
Sequence conflicti531I → V in AAN41636 (PubMed:12837765).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF359507 mRNA. Translation: AAQ15188.1.
AY077467 mRNA. Translation: AAL76083.1.
AY151051 mRNA. Translation: AAN41636.1.
AK040471 mRNA. Translation: BAC30600.1.
AK154628 mRNA. Translation: BAE32725.1.
BC138782 mRNA. Translation: AAI38783.1.
BC138784 mRNA. Translation: AAI38785.1.
CCDSiCCDS19466.1.
RefSeqiNP_690016.1. NM_152803.5.
UniGeneiMm.265786.

Genome annotation databases

EnsembliENSMUST00000045617; ENSMUSP00000044072; ENSMUSG00000035273.
GeneIDi15442.
KEGGimmu:15442.
UCSCiuc008yhw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF359507 mRNA. Translation: AAQ15188.1.
AY077467 mRNA. Translation: AAL76083.1.
AY151051 mRNA. Translation: AAN41636.1.
AK040471 mRNA. Translation: BAC30600.1.
AK154628 mRNA. Translation: BAE32725.1.
BC138782 mRNA. Translation: AAI38783.1.
BC138784 mRNA. Translation: AAI38785.1.
CCDSiCCDS19466.1.
RefSeqiNP_690016.1. NM_152803.5.
UniGeneiMm.265786.

3D structure databases

ProteinModelPortaliQ6YGZ1.
SMRiQ6YGZ1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000044072.

Protein family/group databases

CAZyiGH79. Glycoside Hydrolase Family 79.

PTM databases

iPTMnetiQ6YGZ1.
PhosphoSitePlusiQ6YGZ1.

Proteomic databases

EPDiQ6YGZ1.
MaxQBiQ6YGZ1.
PaxDbiQ6YGZ1.
PRIDEiQ6YGZ1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000045617; ENSMUSP00000044072; ENSMUSG00000035273.
GeneIDi15442.
KEGGimmu:15442.
UCSCiuc008yhw.1. mouse.

Organism-specific databases

CTDi10855.
MGIiMGI:1343124. Hpse.

Phylogenomic databases

eggNOGiENOG410IHNV. Eukaryota.
ENOG410YDJW. LUCA.
GeneTreeiENSGT00390000004874.
HOGENOMiHOG000007256.
HOVERGENiHBG081606.
InParanoidiQ6YGZ1.
KOiK07964.
OMAiKHNSFSH.
OrthoDBiEOG091G05QD.
TreeFamiTF328999.

Enzyme and pathway databases

ReactomeiR-MMU-2024096. HS-GAG degradation.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiHpse. mouse.
PROiQ6YGZ1.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035273.
CleanExiMM_HPSE.
ExpressionAtlasiQ6YGZ1. baseline and differential.
GenevisibleiQ6YGZ1. MM.

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...

Entry informationi

Entry nameiHPSE_MOUSE
AccessioniPrimary (citable) accession number: Q6YGZ1
Secondary accession number(s): B2RS99, Q8K3K3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.