title: Cloning, expression, and characterization of an alternatively spliced variant of human heparanase.
abstract: Heparanase is an endoglycosidase that cleaves heparan sulfate in the extracellular matrix (ECM) and hence participates in ECM degradation and remodeling. Heparanase is involved in fundamental biological processes such as cancer metastasis, angiogenesis, and inflammation. Alternative splicing in the coding region of human heparanase was not reported. Here, we report the cloning of a splice variant of human heparanase that lacks exon 5 and is missing 174 bp compared to the wild-type cDNA. Splice 5 is expressed as a 55 kDa protein compared to the 65 and 50 kDa latent and active wild-type enzyme. Splice 5 was not detected in the incubation medium of tumor cells as opposed to the wild-type latent heparanase. Splice 5 escaped proteolytic cleavage, was devoid of HS degradation activity and exhibited diffused rather than granular cellular localization.
authors.affiliation: Institute of Evolution, International Graduate Center of Evolution, University of Haifa, Haifa 31905, Israel. aaron@research.haifa.ac.il
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Nasser
authors.forename: Aaron
authors.initials: A
authors.lastname: Avivi
authors.forename: Moran
authors.initials: M
authors.lastname: Shushy
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Eviatar
authors.initials: E
authors.lastname: Nevo
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D014644:Genetic Variation / Q000235:genetics; D005910:Glioma / Q000201:enzymology* / Q000235:genetics*; D005966:Glucuronidase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase