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 polypeptide (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 catalytic site (Ser423) and a possible lipid-binding region in the C-terminal part are encoded by exons 6 and 9, respectively. Exon 8 encodes the phosphorylation site (Ser551) that controls cAMP-mediated activity and a second site (Ser553) that is phosphorylated by 5'-AMP-activated protein kinase. Human HSL showed 83% identity with the rat enzyme and contained a 12-aa deletion immediately upstream of the phosphorylation sites with an unknown effect on the activity control. Besides the catalytic site motif (Gly-Xaa-Ser-Xaa-Gly) found in most lipases, HSL shows no homology with other known lipases or proteins, except for a recently reported unexpected homology between the region surrounding its catalytic site and that of the lipase 2 of Moraxella TA144, an antarctic psychrotrophic bacterium. The gene of lipase 2, which catalyses lipolysis below 4-degrees-C, was absent in the genomic DNA of five other Moraxella strains living at 37-degrees-C. The lipase 2-like sequence in HSL may reflect an evolutionarily conserved cold adaptability that might be of critical survival value when low-temperature-mobilized endogenous lipids are the primary energy source (e.g., in poikilotherms or hibernators). The finding that HSL at 10-degrees-C retained 3- to 5-fold more of its 37-degrees-C catalytic activity than lipoprotein lipase or carboxyl ester lipase is consistent with this hypothesis.