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Identification
HMDB Protein ID HMDBP02807
Secondary Accession Numbers
  • 8313
Name Heparanase
Synonyms
  1. Endo-glucoronidase
  2. Heparanase 50 kDa subunit
  3. Heparanase 8 kDa subunit
  4. Heparanase-1
  5. Hpa1
Gene Name HPSE
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity, acting on glycosyl bonds
Specific 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.
Pathways
  • Glycosaminoglycan degradation
  • Proteoglycans in cancer
Reactions
Heparan sulfate + Water → Heparan sulfate + details
GO Classification
Biological Process
positive regulation of blood coagulation
positive regulation of hair follicle development
positive regulation of osteoblast proliferation
positive regulation vascular endothelial growth factor production
regulation of hair follicle development
vascular wound healing
glycosaminoglycan catabolic process
positive regulation of protein kinase B signaling cascade
carbohydrate metabolic process
cell-matrix adhesion
heparan sulfate proteoglycan catabolic process
Cellular Component
membrane raft
nucleus
lysosomal lumen
extracellular region
lysosomal membrane
Component
membrane
cell part
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
Molecular Function
beta-glucuronidase activity
cation binding
heparanase activity
protein dimerization activity
syndecan binding
Cellular Location
  1. Peripheral membrane protein
  2. Secreted
  3. Lysosome membrane
Gene Properties
Chromosome Location 4
Locus 4q21.3
SNPs HPSE
Gene Sequence
>1632 bp
ATGCTGCTGCGCTCGAAGCCTGCGCTGCCGCCGCCGCTGATGCTGCTGCTCCTGGGGCCG
CTGGGTCCCCTCTCCCCTGGCGCCCTGCCCCGACCTGCGCAAGCACAGGACGTCGTGGAC
CTGGACTTCTTCACCCAGGAGCCGCTGCACCTGGTGAGCCCCTCGTTCCTGTCCGTCACC
ATTGACGCCAACCTGGCCACGGACCCGCGGTTCCTCATCCTCCTGGGTTCTCCAAAGCTT
CGTACCTTGGCCAGAGGCTTGTCTCCTGCGTACCTGAGGTTTGGTGGCACCAAGACAGAC
TTCCTAATTTTCGATCCCAAGAAGGAATCAACCTTTGAAGAGAGAAGTTACTGGCAATCT
CAAGTCAACCAGGATATTTGCAAATATGGATCCATCCCTCCTGATGTGGAGGAGAAGTTA
CGGTTGGAATGGCCCTACCAGGAGCAATTGCTACTCCGAGAACACTACCAGAAAAAGTTC
AAGAACAGCACCTACTCAAGAAGCTCTGTAGATGTGCTATACACTTTTGCAAACTGCTCA
GGACTGGACTTGATCTTTGGCCTAAATGCGTTATTAAGAACAGCAGATTTGCAGTGGAAC
AGTTCTAATGCTCAGTTGCTCCTGGACTACTGCTCTTCCAAGGGGTATAACATTTCTTGG
GAACTAGGCAATGAACCTAACAGTTTCCTTAAGAAGGCTGATATTTTCATCAATGGGTCG
CAGTTAGGAGAAGATTTTATTCAATTGCATAAACTTCTAAGAAAGTCCACCTTCAAAAAT
GCAAAACTCTATGGTCCTGATGTTGGTCAGCCTCGAAGAAAGACGGCTAAGATGCTGAAG
AGCTTCCTGAAGGCTGGTGGAGAAGTGATTGATTCAGTTACATGGCATCACTACTATTTG
AATGGACGGACTGCTACCAAGGAAGATTTTCTAAACCCTGATGTATTGGACATTTTTATT
TCATCTGTGCAAAAAGTTTTCCAGGTGGTTGAGAGCACCAGGCCTGGCAAGAAGGTCTGG
TTAGGAGAAACAAGCTCTGCATATGGAGGCGGAGCGCCCTTGCTATCCGACACCTTTGCA
GCTGGCTTTATGTGGCTGGATAAATTGGGCCTGTCAGCCCGAATGGGAATAGAAGTGGTG
ATGAGGCAAGTATTCTTTGGAGCAGGAAACTACCATTTAGTGGATGAAAACTTCGATCCT
TTACCTGATTATTGGCTATCTCTTCTGTTCAAGAAATTGGTGGGCACCAAGGTGTTAATG
GCAAGCGTGCAAGGTTCAAAGAGAAGGAAGCTTCGAGTATACCTTCATTGCACAAACACT
GACAATCCAAGGTATAAAGAAGGAGATTTAACTCTGTATGCCATAAACCTCCATAATGTC
ACCAAGTACTTGCGGTTACCCTATCCTTTTTCTAACAAGCAAGTGGATAAATACCTTCTA
AGACCTTTGGGACCTCATGGATTACTTTCCAAATCTGTCCAACTCAATGGTCTAACTCTA
AAGATGGTGGATGATCAAACCTTGCCACCTTTAATGGAAAAACCTCTCCGGCCAGGAAGT
TCACTGGGCTTGCCAGCTTTCTCATATAGTTTTTTTGTGATAAGAAATGCCAAAGTTGCT
GCTTGCATCTGA
Protein Properties
Number of Residues 543
Molecular Weight 61148.17
Theoretical pI 9.278
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Heparanase
MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFFTQEPLHLVSPSFLSVT
IDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFLIFDPKKESTFEERSYWQS
QVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKFKNSTYSRSSVDVLYTFANCS
GLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNEPNSFLKKADIFINGS
QLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTAKMLKSFLKAGGEVIDSVTWHHYYL
NGRTATKEDFLNPDVLDIFISSVQKVFQVVESTRPGKKVWLGETSSAYGGGAPLLSDTFA
AGFMWLDKLGLSARMGIEVVMRQVFFGAGNYHLVDENFDPLPDYWLSLLFKKLVGTKVLM
ASVQGSKRRKLRVYLHCTNTDNPRYKEGDLTLYAINLHNVTKYLRLPYPFSNKQVDKYLL
RPLGPHGLLSKSVQLNGLTLKMVDDQTLPPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVA
ACI
GenBank ID Protein 148746204
UniProtKB/Swiss-Prot ID Q9Y251
UniProtKB/Swiss-Prot Entry Name HPSE_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001098540.1
GeneCard ID HPSE
GenAtlas ID HPSE
HGNC ID HGNC:5164
References
General References
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  4. Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics. 2006 Feb;5(2):226-33. Epub 2005 Oct 31. [PubMed:16263699 ]
  5. Kussie PH, Hulmes JD, Ludwig DL, Patel S, Navarro EC, Seddon AP, Giorgio NA, Bohlen P: Cloning and functional expression of a human heparanase gene. Biochem Biophys Res Commun. 1999 Jul 22;261(1):183-7. [PubMed:10405343 ]
  6. Toyoshima M, Nakajima M: Human heparanase. Purification, characterization, cloning, and expression. J Biol Chem. 1999 Aug 20;274(34):24153-60. [PubMed:10446189 ]
  7. 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: Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999 Jul;5(7):793-802. [PubMed:10395325 ]
  8. Hulett MD, Freeman C, Hamdorf BJ, Baker RT, Harris MJ, Parish CR: Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med. 1999 Jul;5(7):803-9. [PubMed:10395326 ]
  9. Dempsey LA, Plummer TB, Coombes SL, Platt JL: Heparanase expression in invasive trophoblasts and acute vascular damage. Glycobiology. 2000 May;10(5):467-75. [PubMed:10764835 ]
  10. Zcharia E, Metzger S, Chajek-Shaul T, Friedmann Y, Pappo O, Aviv A, Elkin M, Pecker I, Peretz T, Vlodavsky I: Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis. J Mammary Gland Biol Neoplasia. 2001 Jul;6(3):311-22. [PubMed:11547900 ]
  11. 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: Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells. Biochem J. 2003 Jul 15;373(Pt 2):423-35. [PubMed:12713442 ]
  12. Hulett MD, Hornby JR, Ohms SJ, Zuegg J, Freeman C, Gready JE, Parish CR: Identification of active-site residues of the pro-metastatic endoglycosidase heparanase. Biochemistry. 2000 Dec 26;39(51):15659-67. [PubMed:11123890 ]
  13. Simizu S, Ishida K, Wierzba MK, Osada H: Secretion of heparanase protein is regulated by glycosylation in human tumor cell lines. J Biol Chem. 2004 Jan 23;279(4):2697-703. Epub 2003 Oct 22. [PubMed:14573609 ]
  14. Gingis-Velitski S, Zetser A, Kaplan V, Ben-Zaken O, Cohen E, Levy-Adam F, Bashenko Y, Flugelman MY, Vlodavsky I, Ilan N: Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans. J Biol Chem. 2004 Oct 15;279(42):44084-92. Epub 2004 Jul 29. [PubMed:15292202 ]
  15. Cohen E, Atzmon R, Vlodavsky I, Ilan N: Heparanase processing by lysosomal/endosomal protein preparation. FEBS Lett. 2005 Apr 25;579(11):2334-8. [PubMed:15848168 ]
  16. Abboud-Jarrous G, Rangini-Guetta Z, Aingorn H, Atzmon R, Elgavish S, Peretz T, Vlodavsky I: Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase. J Biol Chem. 2005 Apr 8;280(14):13568-75. Epub 2005 Jan 19. [PubMed:15659389 ]
  17. Levy-Adam F, Abboud-Jarrous G, Guerrini M, Beccati D, Vlodavsky I, Ilan N: Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase. J Biol Chem. 2005 May 27;280(21):20457-66. Epub 2005 Mar 10. [PubMed:15760902 ]
  18. Chen XP, Liu YB, Rui J, Peng SY, Peng CH, Zhou ZY, Shi LH, Shen HW, Xu B: Heparanase mRNA expression and point mutation in hepatocellular carcinoma. World J Gastroenterol. 2004 Oct 1;10(19):2795-9. [PubMed:15334672 ]