GENE ORGANIZATION AND PRIMARY STRUCTURE OF HUMAN HORMONE-SENSITIVE LIPASE - POSSIBLE SIGNIFICANCE OF A SEQUENCE HOMOLOGY WITH A LIPASE OF MORAXELLA TA144, AN ANTARCTIC BACTERIUM

The human hormone-sensitive lipase (HSL) gene encodes a 786-aa polypep tide (85.5 kDa). It is composed of nine exons spanning almost-equal-to 11 kb, with exons 2-5 clustered in a 1.1-kb region. The putative cata lytic site (Ser423) and a possible lipid-binding region in the C-termi nal part are encoded by exons 6 and 9, respectively. Exon 8 encodes th e phosphorylation site (Ser551) that controls cAMP-mediated activity a nd a second site (Ser553) that is phosphorylated by 5'-AMP-activated p rotein kinase. Human HSL showed 83% identity with the rat enzyme and c ontained a 12-aa deletion immediately upstream of the phosphorylation sites with an unknown effect on the activity control. Besides the cata lytic site motif (Gly-Xaa-Ser-Xaa-Gly) found in most lipases, HSL show s no homology with other known lipases or proteins, except for a recen tly reported unexpected homology between the region surrounding its ca talytic site and that of the lipase 2 of Moraxella TA144, an antarctic psychrotrophic bacterium. The gene of lipase 2, which catalyses lipol ysis below 4-degrees-C, was absent in the genomic DNA of five other Mo raxella strains living at 37-degrees-C. The lipase 2-like sequence in HSL may reflect an evolutionarily conserved cold adaptability that mig ht be of critical survival value when low-temperature-mobilized endoge nous lipids are the primary energy source (e.g., in poikilotherms or h ibernators). The finding that HSL at 10-degrees-C retained 3- to 5-fol d more of its 37-degrees-C catalytic activity than lipoprotein lipase or carboxyl ester lipase is consistent with this hypothesis.