Focus on molecules: heparanase

Heparanase (NP_001092010) is a heparin-binding endo-bD-glucuronidase expressed by normal lacrimal gland (GEO Profiles: GDS1361), corneal epithelia (Berk et al., 2004), retinal pigment epithelium/choroid, lens (NEIBank) and some non-ocular tissues. Heparanase is over-expressed in essentially all human tumors examined. Western blotting suggests that heparanase is a constituent of normal tears (Ma, Laurie, unpublished). 119 37 pg/ml of active heparanase has been detected in normal saliva. Heparanase belongs to the glycoside hydrolase family 79. The heparanase gene ‘HPSE’ comprises fourteen exons over 39.8 kb of human chromosome 4, and forty-three orthologues have been documented (Ensembl release 57). HPSE is wellconserved from bony fish to human. Secreted heparanase in humans is 508 amino acids long, with a theoretical molecular weight and pI of 57.7 kDa and 9.2, respectively. Migration in SDS PAGE is approximately 65 kDa, in keeping with N-linked high mannose glycosylation at as many as six predicted sites (NetNGlyc 1.0). No O-glycosylation is predicted above threshold (NetOGlyc 3.1). Three splice variants have been recently reported (Barash et al., 2010) which vary in amino acid length, predicted molecular weight and charge as follows: 1) ‘T5’: 15.6 kDa and pI 6.9; 2)