Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member

Heparan sulfate proteoglycans are important constituents of the extracellul ar matrix and basement membrane. Cleavage of heparan sulfate by heparanase, an endoglycosidase, is implicated in the extravasation of leukocytes and m etastatic tumour cells, identifying this enzyme(s) as a target for anti-inf lammatory and anti-metastatic therapies. The cloning of a cDNA encoding hum an heparanase (Hpa1) was reported recently, together with evidence indicati ng that the hpa1 gene is unique and unlikely to belong to a family of relat ed genes. Here we report the cloning of a cDNA encoding a novel human prote in, HPA2, with significant homology to Hpa1. Alternative splicing of the hp a2 transcript yields three different mRNAs, encoding putative proteins of 4 80, 534, and 592 amino acids. Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes. Hpa2 also shows a mark edly different mRNA distribution to Hpa1 in both normal and cancer tissues. The difference in expression profiles and predicted cellular locations sug gests that Hpa2 and Hpa1 proteins have distinct biological functions. (C) 2 000 Academic Press.