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 approximately 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.
Langin
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Department of Medical and Physiological Chemistry 4, Lund University, Sweden.
Laurell
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Holst
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LS
Belfrage
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P
Holm
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D000273:Adipose Tissue / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D000864:Antarctic Regions; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D015723:Gene Library; D005798:Genes, Bacterial; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009016:Moraxella / Q000201:enzymology* / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D051381:Rats; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D002787:Sterol Esterase / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides; D004247:DNA; D002787:Sterol Esterase; D008049:Lipase