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Q9Y251 (HPSE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Heparanase

EC=3.2.1.166
Alternative name(s):
Endo-glucoronidase
Heparanase-1
Short name=Hpa1

Cleaved into the following 2 chains:

  1. Heparanase 8 kDa subunit
  2. Heparanase 50 kDa subunit
Gene names
Name:HPSE
Synonyms:HEP, HPA, HPA1, HPR1, HPSE1, HSE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length543 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Ref.16 Ref.19 Ref.21 Ref.27 Ref.29 Ref.30 Ref.31 Ref.33 Ref.35 Ref.36 Ref.38 Ref.39

Catalytic activity

Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan. Ref.16 Ref.17 Ref.18 Ref.34 Ref.35 Ref.36

Enzyme regulation

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

Subunit structure

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. Ref.7 Ref.15 Ref.18 Ref.34 Ref.35 Ref.37

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. Ref.6 Ref.15 Ref.17 Ref.22 Ref.23 Ref.24 Ref.25 Ref.31 Ref.38

Tissue specificity

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. Ref.1 Ref.4 Ref.5 Ref.29 Ref.38

Post-translational modification

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.

N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility. Ref.3 Ref.7 Ref.20

Sequence similarities

Belongs to the glycosyl hydrolase 79 family.

Biophysicochemical properties

pH dependence:

Optimum pH is 4-6. Ref.2 Ref.5 Ref.7 Ref.24

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentLysosome
Membrane
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   LigandCalcium
Magnesium
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

cell-matrix adhesion

Inferred from direct assay Ref.19. Source: UniProtKB

glycosaminoglycan catabolic process

Traceable author statement. Source: Reactome

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

heparan sulfate proteoglycan catabolic process

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of blood coagulation

Inferred from direct assay Ref.34. Source: UniProtKB

positive regulation of hair follicle development

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast proliferation

Inferred from direct assay Ref.38. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from direct assay Ref.21. Source: UniProtKB

positive regulation vascular endothelial growth factor production

Inferred from direct assay Ref.27. Source: UniProtKB

proteoglycan metabolic process

Traceable author statement Ref.2. Source: ProtInc

regulation of hair follicle development

Inferred from direct assay Ref.29. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

vascular wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

lysosomal lumen

Traceable author statement. Source: Reactome

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from direct assay Ref.23. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.38. Source: UniProtKB

   Molecular_functionbeta-glucuronidase activity

Traceable author statement Ref.3. Source: ProtInc

heparanase activity

Inferred from direct assay Ref.16. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.22Ref.35Ref.34. Source: UniProtKB

protein dimerization activity

Inferred from direct assay Ref.18. Source: UniProtKB

syndecan binding

Inferred from direct assay Ref.22. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y251-1)

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.
Isoform 2 (identifier: Q9Y251-2)

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.
Isoform 3 (identifier: Q9Y251-3)

Also known as: ex9-10del;

The sequence of this isoform differs from the canonical sequence as follows:
     329-402: Missing.
Isoform 4 (identifier: Q9Y251-4)

Also known as: ex10del;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Ref.7
Chain36 – 10974Heparanase 8 kDa subunit
PRO_0000042260
Propeptide110 – 15748Linker peptide
PRO_0000042261
Chain158 – 543386Heparanase 50 kDa subunit
PRO_0000042262

Regions

Region158 – 1625Heparin/HS-binding
Region270 – 28011Heparin/HS-binding
Region527 – 54317Required for transferring proheparanase to the Golgi apparatus, secretion and subsequent enzyme activity and for enhancement of PKB/AKT1 phosphorylation

Sites

Active site2251Proton donor Potential
Active site3431Nucleophile Potential

Amino acid modifications

Glycosylation1621N-linked (GlcNAc...) Ref.20
Glycosylation1781N-linked (GlcNAc...) Ref.20
Glycosylation2001N-linked (GlcNAc...) Ref.20
Glycosylation2171N-linked (GlcNAc...) Ref.20 Ref.28 Ref.32
Glycosylation2381N-linked (GlcNAc...) Ref.20 Ref.32
Glycosylation4591N-linked (GlcNAc...) Ref.20

Natural variations

Alternative sequence167 – 22559RSSVD…ELGNE → K in isoform 2.
VSP_044537
Alternative sequence329 – 40274Missing in isoform 3.
VSP_044664
Alternative sequence365 – 38016WLDKL…GIEVV → IIGYLFCSRNWWAPRC in isoform 4.
VSP_053730
Alternative sequence381 – 543163Missing in isoform 4.
VSP_053731
Natural variant2601N → S in some hepatocellular carcinoma. Ref.40
VAR_023600
Natural variant3071K → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Corresponds to variant rs11099592 [ dbSNP | Ensembl ].
VAR_068907

Experimental info

Mutagenesis1561Y → 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. Ref.25
Mutagenesis1561Y → V: Normal processing. Ref.25
Mutagenesis1581K → A: No association with GS-modified heparin; when associated with K-158. Ref.26
Mutagenesis1611K → 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. Ref.26
Mutagenesis1621N → 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. Ref.20
Mutagenesis1781N → 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. Ref.20
Mutagenesis2001N → 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. Ref.20
Mutagenesis2171N → 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. Ref.20
Mutagenesis2251E → A: Loss of heparanase activity. No effect on HPSE-mediated cell adhesion. Ref.14 Ref.19
Mutagenesis2381N → 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. Ref.20
Mutagenesis3431E → A: Loss of heparanase activity. Ref.14
Mutagenesis3671D → A: Strong decrease in heparanase activity. Ref.14
Mutagenesis3781E → A: No reduction in heparanase activity.
Mutagenesis3961E → A: No reduction in heparanase activity.
Mutagenesis4141V → K: Abolishes processing, secretion and enzyme activity. Ref.31
Mutagenesis4171K → E: No effect on processing nor secretion. No enzyme activity detected. Ref.31
Mutagenesis4591N → 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. Ref.20
Mutagenesis5251P → G: No effect on processing nor secretion. No enzyme activity detected. Ref.31
Mutagenesis5271F → R: No effect on processing nor secretion. No enzyme activity detected. Ref.31
Mutagenesis5281S → K: No effect on processing nor secretion. No enzyme activity detected. Ref.31
Mutagenesis5291Y → A: No effect on processing nor secretion. No enzyme activity detected. Ref.31
Mutagenesis5311F → R: Abolishes processing, secretion and enzyme activity. Ref.31
Mutagenesis5331V → R: Abolishes processing, secretion and enzyme activity. Ref.31
Mutagenesis5341I → D: Abolishes processing, secretion and enzyme activity. Ref.31
Mutagenesis5351R → A: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5361N → A: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5371A → K: Abolishes processing, secretion and enzyme activity. Ref.31
Mutagenesis5381K → A: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5391V → A: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5401A → K: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5411A → K: No effect on processing, secretion nor enzyme activity. Ref.31
Mutagenesis5421C → A: Abolishes processing, secretion and enzyme activity. Ref.31
Sequence conflict131L → LL in AAD54516. Ref.5
Sequence conflict361Q → QQ in AAD54516. Ref.5
Sequence conflict2911D → G in BAD96706. Ref.11

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: A990F5AFD639CA1A

FASTA54361,149
        10         20         30         40         50         60 
MLLRSKPALP PPLMLLLLGP LGPLSPGALP RPAQAQDVVD LDFFTQEPLH LVSPSFLSVT 

        70         80         90        100        110        120 
IDANLATDPR FLILLGSPKL RTLARGLSPA YLRFGGTKTD FLIFDPKKES TFEERSYWQS 

       130        140        150        160        170        180 
QVNQDICKYG SIPPDVEEKL RLEWPYQEQL LLREHYQKKF KNSTYSRSSV DVLYTFANCS 

       190        200        210        220        230        240 
GLDLIFGLNA LLRTADLQWN SSNAQLLLDY CSSKGYNISW ELGNEPNSFL KKADIFINGS 

       250        260        270        280        290        300 
QLGEDFIQLH KLLRKSTFKN AKLYGPDVGQ PRRKTAKMLK SFLKAGGEVI DSVTWHHYYL 

       310        320        330        340        350        360 
NGRTATKEDF LNPDVLDIFI SSVQKVFQVV ESTRPGKKVW LGETSSAYGG GAPLLSDTFA 

       370        380        390        400        410        420 
AGFMWLDKLG LSARMGIEVV MRQVFFGAGN YHLVDENFDP LPDYWLSLLF KKLVGTKVLM 

       430        440        450        460        470        480 
ASVQGSKRRK LRVYLHCTNT DNPRYKEGDL TLYAINLHNV TKYLRLPYPF SNKQVDKYLL 

       490        500        510        520        530        540 
RPLGPHGLLS KSVQLNGLTL KMVDDQTLPP LMEKPLRPGS SLGLPAFSYS FFVIRNAKVA 


ACI 

« Hide

Isoform 2 (55 kDa) (splice 5) [UniParc].

Checksum: DCF33CD4B2BC3A43
Show »

FASTA48554,734
Isoform 3 (ex9-10del) [UniParc].

Checksum: F0E4853CC0CF0D88
Show »

FASTA46953,161
Isoform 4 (ex10del) [UniParc].

Checksum: 913407210F45CF1E
Show »

FASTA38042,791

References

« Hide 'large scale' references
[1]"Cloning and functional expression of a human heparanase gene."
Kussie P.H., Hulmes J.D., Ludwig D.L., Patel S., Navarro E.C., Seddon A.P., Giorgio N.A., Bohlen P.
Biochem. Biophys. Res. Commun. 261:183-187(1999) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Human heparanase is localized within lysosomes in a stable form."
Goldshmidt O., Nadav L., Aingorn H., Irit C., Feinstein N., Ilan N., Zamir E., Geiger B., Vlodavsky I., Katz B.Z.
Exp. Cell Res. 281:50-62(2002) [PubMed] [Europe PMC] [Abstract]
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]"Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans."
Gingis-Velitski S., Zetser A., Kaplan V., Ben-Zaken O., Cohen E., Levy-Adam F., Bashenko Y., Flugelman M.Y., Vlodavsky I., Ilan N.
J. Biol. Chem. 279:44084-44092(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"Processing and activation of latent heparanase occurs in lysosomes."
Zetser A., Levy-Adam F., Kaplan V., Gingis-Velitski S., Bashenko Y., Schubert S., Flugelman M.Y., Vlodavsky I., Ilan N.
J. Cell Sci. 117:2249-2258(2004) [PubMed] [Europe PMC] [Abstract]
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]"Heparanase in primary human osteoblasts."
Smith P.N., Freeman C., Yu D., Chen M., Gatenby P.A., Parish C.R., Li R.W.
J. Orthop. Res. 28:1315-1322(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3602.1. [Q9Y251-1]
CCDS54774.1. [Q9Y251-3]
CCDS56337.1. [Q9Y251-2]
RefSeqNP_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]
UniGeneHs.44227.

3D structure databases

ProteinModelPortalQ9Y251.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116066. 1 interaction.
STRING9606.ENSP00000308107.

Chemistry

ChEMBLCHEMBL3921.
DrugBankDB01109. Heparin.

Protein family/group databases

CAZyGH79. Glycoside Hydrolase Family 79.

PTM databases

PhosphoSiteQ9Y251.

Polymorphism databases

DMDM296434532.

Proteomic databases

MaxQBQ9Y251.
PaxDbQ9Y251.
PRIDEQ9Y251.

Protocols and materials databases

DNASU10855.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311412; ENSP00000308107; ENSG00000173083. [Q9Y251-1]
ENST00000405413; ENSP00000384262; ENSG00000173083. [Q9Y251-1]
ENST00000509906; ENSP00000421038; ENSG00000173083. [Q9Y251-4]
ENST00000512196; ENSP00000423265; ENSG00000173083. [Q9Y251-3]
ENST00000513463; ENSP00000421365; ENSG00000173083. [Q9Y251-2]
GeneID10855.
KEGGhsa:10855.
UCSCuc003hoj.4. human. [Q9Y251-1]

Organism-specific databases

CTD10855.
GeneCardsGC04M084213.
HGNCHGNC:5164. HPSE.
HPACAB009813.
HPA055344.
MIM604724. gene.
neXtProtNX_Q9Y251.
PharmGKBPA29435.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72789.
HOGENOMHOG000007256.
HOVERGENHBG081606.
InParanoidQ9Y251.
KOK07964.
OMAEWPFQEQ.
OrthoDBEOG7BZVRW.
PhylomeDBQ9Y251.
TreeFamTF328999.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000173083-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ9Y251.
BgeeQ9Y251.
CleanExHS_HPSE.
GenevestigatorQ9Y251.

Family and domain databases

Gene3D3.20.20.80. 1 hit.
InterProIPR005199. Glyco_hydro_79.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERPTHR14363. PTHR14363. 1 hit.
PfamPF03662. Glyco_hydro_79n. 1 hit.
[Graphical view]
SUPFAMSSF51445. SSF51445. 2 hits.
ProtoNetSearch...

Other

GeneWikiHeparanase.
GenomeRNAi10855.
NextBio35483544.
PROQ9Y251.
SOURCESearch...

Entry information

Entry nameHPSE_HUMAN
AccessionPrimary (citable) accession number: Q9Y251
Secondary accession number(s): A9JIG7 expand/collapse secondary AC list , C7F7I3, C7F7I4, E9PCA9, E9PGR1, Q53GE5, Q9UL39
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries