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Q9Y251

- HPSE_HUMAN

UniProt

Q9Y251 - HPSE_HUMAN

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Protein

Heparanase

Gene

HPSE

Organism
Homo sapiens (Human)
Status
Reviewed - 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.12 Publications

Catalytic activityi

Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan.6 Publications

Enzyme regulationi

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

pH dependencei

Optimum pH is 4-6.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei225 – 2251Proton donorSequence Analysis
Active sitei343 – 3431NucleophileSequence Analysis

GO - Molecular functioni

  1. beta-glucuronidase activity Source: ProtInc
  2. heparanase activity Source: UniProtKB
  3. protein dimerization activity Source: UniProtKB
  4. syndecan binding Source: UniProtKB

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. cell-matrix adhesion Source: UniProtKB
  3. glycosaminoglycan catabolic process Source: Reactome
  4. glycosaminoglycan metabolic process Source: Reactome
  5. heparan sulfate proteoglycan catabolic process Source: UniProtKB
  6. positive regulation of blood coagulation Source: UniProtKB
  7. positive regulation of hair follicle development Source: Ensembl
  8. positive regulation of osteoblast proliferation Source: UniProtKB
  9. positive regulation of protein kinase B signaling Source: UniProtKB
  10. positive regulation vascular endothelial growth factor production Source: UniProtKB
  11. proteoglycan metabolic process Source: ProtInc
  12. regulation of hair follicle development Source: UniProtKB
  13. small molecule metabolic process Source: Reactome
  14. vascular wound healing Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000173083-MONOMER.
ReactomeiREACT_120752. HS-GAG degradation.

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
Heparanase-1
Short name:
Hpa1
Cleaved into the following 2 chains:
Gene namesi
Name:HPSE
Synonyms:HEP, HPA, HPA1, HPR1, HPSE1, HSE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:5164. HPSE.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
  2. intracellular membrane-bounded organelle Source: HPA
  3. lysosomal lumen Source: Reactome
  4. lysosome Source: UniProtKB
  5. membrane raft Source: Ensembl
  6. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561Y → A or 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. 1 Publication
Mutagenesisi156 – 1561Y → V: Normal processing. 1 Publication
Mutagenesisi158 – 1581K → A: No association with GS-modified heparin; when associated with K-158. 1 Publication
Mutagenesisi161 – 1611K → 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. 1 Publication
Mutagenesisi162 – 1621N → 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. 1 Publication
Mutagenesisi178 – 1781N → 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. 1 Publication
Mutagenesisi200 – 2001N → 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. 1 Publication
Mutagenesisi217 – 2171N → 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. 1 Publication
Mutagenesisi225 – 2251E → A: Loss of heparanase activity. No effect on HPSE-mediated cell adhesion. 2 Publications
Mutagenesisi238 – 2381N → 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. 1 Publication
Mutagenesisi343 – 3431E → A: Loss of heparanase activity. 1 Publication
Mutagenesisi367 – 3671D → A: Strong decrease in heparanase activity. 1 Publication
Mutagenesisi378 – 3781E → A: No reduction in heparanase activity.
Mutagenesisi396 – 3961E → A: No reduction in heparanase activity.
Mutagenesisi414 – 4141V → K: Abolishes processing, secretion and enzyme activity. 1 Publication
Mutagenesisi417 – 4171K → E: No effect on processing nor secretion. No enzyme activity detected. 1 Publication
Mutagenesisi459 – 4591N → 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. 1 Publication
Mutagenesisi525 – 5251P → G: No effect on processing nor secretion. No enzyme activity detected. 1 Publication
Mutagenesisi527 – 5271F → R: No effect on processing nor secretion. No enzyme activity detected. 1 Publication
Mutagenesisi528 – 5281S → K: No effect on processing nor secretion. No enzyme activity detected. 1 Publication
Mutagenesisi529 – 5291Y → A: No effect on processing nor secretion. No enzyme activity detected. 1 Publication
Mutagenesisi531 – 5311F → R: Abolishes processing, secretion and enzyme activity. 1 Publication
Mutagenesisi533 – 5331V → R: Abolishes processing, secretion and enzyme activity. 1 Publication
Mutagenesisi534 – 5341I → D: Abolishes processing, secretion and enzyme activity. 1 Publication
Mutagenesisi535 – 5351R → A: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi536 – 5361N → A: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi537 – 5371A → K: Abolishes processing, secretion and enzyme activity. 1 Publication
Mutagenesisi538 – 5381K → A: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi539 – 5391V → A: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi540 – 5401A → K: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi541 – 5411A → K: No effect on processing, secretion nor enzyme activity. 1 Publication
Mutagenesisi542 – 5421C → A: Abolishes processing, secretion and enzyme activity. 1 Publication

Organism-specific databases

PharmGKBiPA29435.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 35351 PublicationAdd
BLAST
Chaini36 – 10974Heparanase 8 kDa subunitPRO_0000042260Add
BLAST
Propeptidei110 – 15748Linker peptide3 PublicationsPRO_0000042261Add
BLAST
Chaini158 – 543386Heparanase 50 kDa subunitPRO_0000042262Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi162 – 1621N-linked (GlcNAc...)1 Publication
Glycosylationi178 – 1781N-linked (GlcNAc...)1 Publication
Glycosylationi200 – 2001N-linked (GlcNAc...)1 Publication
Glycosylationi217 – 2171N-linked (GlcNAc...)3 Publications
Glycosylationi238 – 2381N-linked (GlcNAc...)2 Publications
Glycosylationi459 – 4591N-linked (GlcNAc...)1 Publication

Post-translational modificationi

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.6 Publications
N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.5 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9Y251.
PaxDbiQ9Y251.
PRIDEiQ9Y251.

PTM databases

PhosphoSiteiQ9Y251.

Expressioni

Tissue specificityi

Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle's and Huxley's layers of inner the root sheath (IRS) at anagen phase.5 Publications

Gene expression databases

BgeeiQ9Y251.
CleanExiHS_HPSE.
ExpressionAtlasiQ9Y251. baseline and differential.
GenevestigatoriQ9Y251.

Organism-specific databases

HPAiCAB009813.
HPA055344.

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. Interacts with HPSE2.5 Publications

Protein-protein interaction databases

BioGridi116066. 1 interaction.
STRINGi9606.ENSP00000308107.

Structurei

3D structure databases

ProteinModelPortaliQ9Y251.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni158 – 1625Heparin/HS-binding
Regioni270 – 28011Heparin/HS-bindingAdd
BLAST
Regioni527 – 54317Required for transferring proheparanase to the Golgi apparatus, secretion and subsequent enzyme activity and for enhancement of PKB/AKT1 phosphorylationAdd
BLAST

Sequence similaritiesi

Belongs to the glycosyl hydrolase 79 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG72789.
GeneTreeiENSGT00390000004874.
HOGENOMiHOG000007256.
HOVERGENiHBG081606.
InParanoidiQ9Y251.
KOiK07964.
OMAiEWPFQEQ.
OrthoDBiEOG7BZVRW.
PhylomeDBiQ9Y251.
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. 1 hit.
PfamiPF03662. Glyco_hydro_79n. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 2 hits.

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9Y251-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLLRSKPALP PPLMLLLLGP LGPLSPGALP RPAQAQDVVD LDFFTQEPLH
60 70 80 90 100
LVSPSFLSVT IDANLATDPR FLILLGSPKL RTLARGLSPA YLRFGGTKTD
110 120 130 140 150
FLIFDPKKES TFEERSYWQS QVNQDICKYG SIPPDVEEKL RLEWPYQEQL
160 170 180 190 200
LLREHYQKKF KNSTYSRSSV DVLYTFANCS GLDLIFGLNA LLRTADLQWN
210 220 230 240 250
SSNAQLLLDY CSSKGYNISW ELGNEPNSFL KKADIFINGS QLGEDFIQLH
260 270 280 290 300
KLLRKSTFKN AKLYGPDVGQ PRRKTAKMLK SFLKAGGEVI DSVTWHHYYL
310 320 330 340 350
NGRTATKEDF LNPDVLDIFI SSVQKVFQVV ESTRPGKKVW LGETSSAYGG
360 370 380 390 400
GAPLLSDTFA AGFMWLDKLG LSARMGIEVV MRQVFFGAGN YHLVDENFDP
410 420 430 440 450
LPDYWLSLLF KKLVGTKVLM ASVQGSKRRK LRVYLHCTNT DNPRYKEGDL
460 470 480 490 500
TLYAINLHNV TKYLRLPYPF SNKQVDKYLL RPLGPHGLLS KSVQLNGLTL
510 520 530 540
KMVDDQTLPP LMEKPLRPGS SLGLPAFSYS FFVIRNAKVA ACI
Length:543
Mass (Da):61,149
Last modified:May 18, 2010 - v2
Checksum:iA990F5AFD639CA1A
GO
Isoform 2 (identifier: Q9Y251-2) [UniParc]FASTAAdd to Basket

Also known as: 55 kDa, splice 5

The sequence of this isoform differs from the canonical sequence as follows:
     167-225: RSSVDVLYTFANCSGLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNE → K

Note: Escapes proteolytic cleavage, devoid of HS degradation activity.

Show »
Length:485
Mass (Da):54,734
Checksum:iDCF33CD4B2BC3A43
GO
Isoform 3 (identifier: Q9Y251-3) [UniParc]FASTAAdd to Basket

Also known as: ex9-10del

The sequence of this isoform differs from the canonical sequence as follows:
     329-402: Missing.

Show »
Length:469
Mass (Da):53,161
Checksum:iF0E4853CC0CF0D88
GO
Isoform 4 (identifier: Q9Y251-4) [UniParc]FASTAAdd to Basket

Also known as: ex10del

The sequence of this isoform differs from the canonical sequence as follows:
     365-380: WLDKLGLSARMGIEVV → IIGYLFCSRNWWAPRC
     381-543: Missing.

Show »
Length:380
Mass (Da):42,791
Checksum:i913407210F45CF1E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131L → LL in AAD54516. (PubMed:10764835)Curated
Sequence conflicti36 – 361Q → QQ in AAD54516. (PubMed:10764835)Curated
Sequence conflicti291 – 2911D → G in BAD96706. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti260 – 2601N → S in some hepatocellular carcinoma. 1 Publication
VAR_023600
Natural varianti307 – 3071K → R.10 Publications
Corresponds to variant rs11099592 [ dbSNP | Ensembl ].
VAR_068907

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei167 – 22559RSSVD…ELGNE → K in isoform 2. 1 PublicationVSP_044537Add
BLAST
Alternative sequencei329 – 40274Missing in isoform 3. 1 PublicationVSP_044664Add
BLAST
Alternative sequencei365 – 38016WLDKL…GIEVV → IIGYLFCSRNWWAPRC in isoform 4. 1 PublicationVSP_053730Add
BLAST
Alternative sequencei381 – 543163Missing in isoform 4. 1 PublicationVSP_053731Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152376 mRNA. Translation: AAD45669.1.
AF155510 mRNA. Translation: AAD54941.1.
AF144325 mRNA. Translation: AAD41342.1.
AF165154 mRNA. Translation: AAD45379.1.
AF084467 mRNA. Translation: AAD54516.1.
AM419200 mRNA. Translation: CAL91960.1.
AY948074 mRNA. Translation: AAX47106.1.
GQ337901 mRNA. Translation: ACT98237.1.
GQ337902 mRNA. Translation: ACT98238.1.
AK222986 mRNA. Translation: BAD96706.1.
AC114781 Genomic DNA. No translation available.
BC051321 mRNA. Translation: AAH51321.1.
CCDSiCCDS3602.1. [Q9Y251-1]
CCDS54774.1. [Q9Y251-3]
CCDS56337.1. [Q9Y251-2]
RefSeqiNP_001092010.1. NM_001098540.2. [Q9Y251-1]
NP_001159970.1. NM_001166498.2. [Q9Y251-3]
NP_001186759.1. NM_001199830.1. [Q9Y251-2]
NP_006656.2. NM_006665.5. [Q9Y251-1]
UniGeneiHs.44227.

Genome annotation databases

EnsembliENST00000311412; ENSP00000308107; ENSG00000173083. [Q9Y251-1]
ENST00000405413; ENSP00000384262; ENSG00000173083. [Q9Y251-1]
ENST00000509906; ENSP00000421038; ENSG00000173083. [Q9Y251-4]
ENST00000512196; ENSP00000423265; ENSG00000173083. [Q9Y251-3]
ENST00000513463; ENSP00000421365; ENSG00000173083. [Q9Y251-2]
GeneIDi10855.
KEGGihsa:10855.
UCSCiuc003hoj.4. human. [Q9Y251-1]

Polymorphism databases

DMDMi296434532.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152376 mRNA. Translation: AAD45669.1 .
AF155510 mRNA. Translation: AAD54941.1 .
AF144325 mRNA. Translation: AAD41342.1 .
AF165154 mRNA. Translation: AAD45379.1 .
AF084467 mRNA. Translation: AAD54516.1 .
AM419200 mRNA. Translation: CAL91960.1 .
AY948074 mRNA. Translation: AAX47106.1 .
GQ337901 mRNA. Translation: ACT98237.1 .
GQ337902 mRNA. Translation: ACT98238.1 .
AK222986 mRNA. Translation: BAD96706.1 .
AC114781 Genomic DNA. No translation available.
BC051321 mRNA. Translation: AAH51321.1 .
CCDSi CCDS3602.1. [Q9Y251-1 ]
CCDS54774.1. [Q9Y251-3 ]
CCDS56337.1. [Q9Y251-2 ]
RefSeqi NP_001092010.1. NM_001098540.2. [Q9Y251-1 ]
NP_001159970.1. NM_001166498.2. [Q9Y251-3 ]
NP_001186759.1. NM_001199830.1. [Q9Y251-2 ]
NP_006656.2. NM_006665.5. [Q9Y251-1 ]
UniGenei Hs.44227.

3D structure databases

ProteinModelPortali Q9Y251.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116066. 1 interaction.
STRINGi 9606.ENSP00000308107.

Chemistry

BindingDBi Q9Y251.
ChEMBLi CHEMBL3921.
DrugBanki DB06779. Dalteparin.
DB01109. Heparin.

Protein family/group databases

CAZyi GH79. Glycoside Hydrolase Family 79.

PTM databases

PhosphoSitei Q9Y251.

Polymorphism databases

DMDMi 296434532.

Proteomic databases

MaxQBi Q9Y251.
PaxDbi Q9Y251.
PRIDEi Q9Y251.

Protocols and materials databases

DNASUi 10855.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000311412 ; ENSP00000308107 ; ENSG00000173083 . [Q9Y251-1 ]
ENST00000405413 ; ENSP00000384262 ; ENSG00000173083 . [Q9Y251-1 ]
ENST00000509906 ; ENSP00000421038 ; ENSG00000173083 . [Q9Y251-4 ]
ENST00000512196 ; ENSP00000423265 ; ENSG00000173083 . [Q9Y251-3 ]
ENST00000513463 ; ENSP00000421365 ; ENSG00000173083 . [Q9Y251-2 ]
GeneIDi 10855.
KEGGi hsa:10855.
UCSCi uc003hoj.4. human. [Q9Y251-1 ]

Organism-specific databases

CTDi 10855.
GeneCardsi GC04M084213.
HGNCi HGNC:5164. HPSE.
HPAi CAB009813.
HPA055344.
MIMi 604724. gene.
neXtProti NX_Q9Y251.
PharmGKBi PA29435.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG72789.
GeneTreei ENSGT00390000004874.
HOGENOMi HOG000007256.
HOVERGENi HBG081606.
InParanoidi Q9Y251.
KOi K07964.
OMAi EWPFQEQ.
OrthoDBi EOG7BZVRW.
PhylomeDBi Q9Y251.
TreeFami TF328999.

Enzyme and pathway databases

BioCyci MetaCyc:ENSG00000173083-MONOMER.
Reactomei REACT_120752. HS-GAG degradation.

Miscellaneous databases

GeneWikii Heparanase.
GenomeRNAii 10855.
NextBioi 35483544.
PROi Q9Y251.
SOURCEi Search...

Gene expression databases

Bgeei Q9Y251.
CleanExi HS_HPSE.
ExpressionAtlasi Q9Y251. baseline and differential.
Genevestigatori Q9Y251.

Family and domain databases

Gene3Di 3.20.20.80. 1 hit.
InterProi IPR005199. Glyco_hydro_79.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view ]
PANTHERi PTHR14363. PTHR14363. 1 hit.
Pfami PF03662. Glyco_hydro_79n. 1 hit.
[Graphical view ]
SUPFAMi SSF51445. SSF51445. 2 hits.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-307, TISSUE SPECIFICITY.
    Tissue: Placenta.
  2. "Human heparanase. Purification, characterization, cloning, and expression."
    Toyoshima M., Nakajima M.
    J. Biol. Chem. 274:24153-24160(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, PROTEIN SEQUENCE OF 158-168; 326-337 AND 447-491, VARIANT ARG-307.
    Tissue: Embryonic fibroblast.
  3. "Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis."
    Vlodavsky I., Friedmann Y., Elkin M., Aingorn H., Atzmon R., Ishai-Michaeli R., Bitan M., Pappo O., Peretz T., Michal I., Spector L., Pecker I.
    Nat. Med. 5:793-802(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, PROTEOLYTIC PROCESSING, VARIANT ARG-307.
  4. "Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis."
    Hulett M.D., Freeman C., Hamdorf B.J., Baker R.T., Harris M.J., Parish C.R.
    Nat. Med. 5:803-809(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, PROTEIN SEQUENCE OF 158-174; 263-272; 326-337; 433-436; 438-443; 466-468 AND 478-483, VARIANT ARG-307.
    Tissue: Placenta.
  5. "Heparanase expression in invasive trophoblasts and acute vascular damage."
    Dempsey L.A., Plummer T.B., Coombes S.L., Platt J.L.
    Glycobiology 10:467-475(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT ARG-307.
    Tissue: Placenta.
  6. "Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis."
    Zcharia E., Metzger S., Chajek-Shaul T., Friedmann Y., Pappo O., Aviv A., Elkin M., Pecker I., Peretz T., Vlodavsky I.
    J. Mammary Gland Biol. Neoplasia 6:311-322(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
  7. "Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells."
    McKenzie E., Young K., Hircock M., Bennett J., Bhaman M., Felix R., Turner P., Stamps A., McMillan D., Saville G., Ng S., Mason S., Snell D., Schofield D., Gong H., Townsend R., Gallagher J., Page M., Parekh R., Stubberfield C.
    Biochem. J. 373:423-435(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 36-41 AND 158-163, SUBUNIT, GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES.
    Tissue: Placenta.
  8. "Cloning, expression, and characterization of an alternatively spliced variant of human heparanase."
    Nasser N.J., Avivi A., Shushy M., Vlodavsky I., Nevo E.
    Biochem. Biophys. Res. Commun. 354:33-38(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, VARIANT ARG-307.
    Tissue: Kidney.
  9. "Cloned heparanase from MCF-7 cells."
    Pinhal M.A., Semedo P.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-307.
  10. "Two new transcript variants of Homo sapiens heparanase (HPSE)."
    Jin S., Yu L., Gong F.
    Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), VARIANT ARG-307.
  11. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
    Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-307.
    Tissue: Small intestine.
  12. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  13. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-307.
    Tissue: Pancreas.
  14. "Identification of active-site residues of the pro-metastatic endoglycosidase heparanase."
    Hulett M.D., Hornby J.R., Ohms S.J., Zuegg J., Freeman C., Gready J.E., Parish C.R.
    Biochemistry 39:15659-15667(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-225; GLU-343 AND ASP-367.
  15. Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, INTERACTION WITH SDC1.
  16. "Structural recognition by recombinant human heparanase that plays critical roles in tumor metastasis. Hierarchical sulfate groups with different effects and the essential target disulfated trisaccharide sequence."
    Okada Y., Yamada S., Toyoshima M., Dong J., Nakajima M., Sugahara K.
    J. Biol. Chem. 277:42488-42495(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  17. "Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts."
    Nadav L., Eldor A., Yacoby-Zeevi O., Zamir E., Pecker I., Ilan N., Geiger B., Vlodavsky I., Katz B.Z.
    J. Cell Sci. 115:2179-2187(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, ENZYME ACTIVITY, SUBCELLULAR LOCATION.
  18. "Heterodimer formation is essential for heparanase enzymatic activity."
    Levy-Adam F., Miao H.Q., Heinrikson R.L., Vlodavsky I., Ilan N.
    Biochem. Biophys. Res. Commun. 308:885-891(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: HETERODIMERIZATION, ENZYME ACTIVITY.
  19. "Heparanase mediates cell adhesion independent of its enzymatic activity."
    Goldshmidt O., Zcharia E., Cohen M., Aingorn H., Cohen I., Nadav L., Katz B.Z., Geiger B., Vlodavsky I.
    FASEB J. 17:1015-1025(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-225.
  20. "Secretion of heparanase protein is regulated by glycosylation in human tumor cell lines."
    Simizu S., Ishida K., Wierzba M.K., Osada H.
    J. Biol. Chem. 279:2697-2703(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-162; ASN-178; ASN-200; ASN-217; ASN-238 AND ASN-459, MUTAGENESIS OF ASN-162; ASN-178; ASN-200; ASN-217; ASN-238 AND ASN-459.
  21. "Heparanase induces endothelial cell migration via protein kinase B/Akt activation."
    Gingis-Velitski S., Zetser A., Flugelman M.Y., Vlodavsky I., Ilan N.
    J. Biol. Chem. 279:23536-23541(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. Cited for: SUBCELLULAR LOCATION.
  23. Cited for: PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
  24. "Heparanase processing by lysosomal/endosomal protein preparation."
    Cohen E., Atzmon R., Vlodavsky I., Ilan N.
    FEBS Lett. 579:2334-2338(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
  25. "Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase."
    Abboud-Jarrous G., Rangini-Guetta Z., Aingorn H., Atzmon R., Elgavish S., Peretz T., Vlodavsky I.
    J. Biol. Chem. 280:13568-13575(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF TYR-156.
  26. "Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase."
    Levy-Adam F., Abboud-Jarrous G., Guerrini M., Beccati D., Vlodavsky I., Ilan N.
    J. Biol. Chem. 280:20457-20466(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEPARIN/HS-BINDING DOMAINS, MUTAGENESIS OF LYS-158 AND LYS-161.
  27. "Heparanase induces vascular endothelial growth factor expression: correlation with p38 phosphorylation levels and Src activation."
    Zetser A., Bashenko Y., Edovitsky E., Levy-Adam F., Vlodavsky I., Ilan N.
    Cancer Res. 66:1455-1463(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  28. "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
    Lewandrowski U., Moebius J., Walter U., Sickmann A.
    Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-217.
    Tissue: Platelet.
  29. "Heparanase 1: a key participant of inner root sheath differentiation program and hair follicle homeostasis."
    Malgouries S., Donovan M., Thibaut S., Bernard B.A.
    Exp. Dermatol. 17:1017-1023(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, FUNCTION.
  30. "Heparanase induces VEGF C and facilitates tumor lymphangiogenesis."
    Cohen-Kaplan V., Naroditsky I., Zetser A., Ilan N., Vlodavsky I., Doweck I.
    Int. J. Cancer 123:2566-2573(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  31. "Structure-function approach identifies a COOH-terminal domain that mediates heparanase signaling."
    Fux L., Feibish N., Cohen-Kaplan V., Gingis-Velitski S., Feld S., Geffen C., Vlodavsky I., Ilan N.
    Cancer Res. 69:1758-1767(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF THE C-TERMINAL DOMAIN, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-414; LYS-417; PRO-525; PHE-527; SER-528; TYR-529; PHE-531; VAL-533; ILE-534; ARG-535; ASN-536; ALA-537; LYS-538; VAL-539; ALA-540; ALA-541 AND CYS-542.
  32. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-217 AND ASN-238.
    Tissue: Liver.
  33. "Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis."
    Purushothaman A., Uyama T., Kobayashi F., Yamada S., Sugahara K., Rapraeger A.C., Sanderson R.D.
    Blood 115:2449-2457(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  34. "Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII."
    Nadir Y., Brenner B., Fux L., Shafat I., Attias J., Vlodavsky I.
    Haematologica 95:1927-1934(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TF, ENZYME ACTIVITY.
  35. "Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions."
    Poon I.K., Yee D.Y., Jones A.L., Wood R.J., Davis D.S., Freeman C., Parish C.R., Hulett M.D.
    Int. J. Biochem. Cell Biol. 42:1507-1516(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HRG, ENZYME ACTIVITY, FUNCTION.
  36. "Unraveling the specificity of heparanase utilizing synthetic substrates."
    Peterson S.B., Liu J.
    J. Biol. Chem. 285:14504-14513(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  37. "Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity."
    Levy-Adam F., Feld S., Cohen-Kaplan V., Shteingauz A., Gross M., Arvatz G., Naroditsky I., Ilan N., Doweck I., Vlodavsky I.
    J. Biol. Chem. 285:28010-28019(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HPSE2.
  38. Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  39. "Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity."
    Ramani V.C., Yang Y., Ren Y., Nan L., Sanderson R.D.
    J. Biol. Chem. 286:6490-6499(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  40. "Heparanase mRNA expression and point mutation in hepatocellular carcinoma."
    Chen X.P., Liu Y.B., Rui J., Peng S.Y., Peng C.H., Zhou Z.Y., Shi L.H., Shen H.W., Xu B.
    World J. Gastroenterol. 10:2795-2799(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SER-260.

Entry informationi

Entry nameiHPSE_HUMAN
AccessioniPrimary (citable) accession number: Q9Y251
Secondary accession number(s): A9JIG7
, C7F7I3, C7F7I4, E9PCA9, E9PGR1, Q53GE5, Q9UL39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 18, 2010
Last modified: November 26, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

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