Review. Comparative structures and evolution of mammalian lipase I (LIPI) genes and proteins: A close relative of vertebrate phospholipase LIPH

Abstract

Lipase I (enzyme name LIPI or LPDL) (gene name LIPI [human] or Lipi[mouse]) is a phospholipase which generates 2-acyl lysophosphatidic acid (LPA),a lipid mediator required for maintaining homeostasis of diverse biological functionsand in activating cell surface recaptors. Bioinformatic methods were used to predictthe amino acid sequences, secondary and tertiary structures and gene locationsfor LIPI genes and encoded proteins using data from several mammalian genomeprojects. LIPI is located on human chromosome 21 and is distinct from otherphospholipase A1-like genes (LIPH and PS-PLA1). Mammalian LIPI genes contained10 (human) or 11 (mouse) coding exons transcribed predominantly on the negativeDNA strand. Mammalian LIPI protein subunits shared 61% - 99% sequenceidentities and exhibited sequence alignments and identities for key LIPI aminoacid residues as well as extensive conservation of predicted secondary andtertiary structures with those previously reported for pancreatic lipase (PL),with “N-signal peptide”, “lipase” and “plat” structural domains. Comparativestudies of mammalian LIPI sequences with LIPH, PS-PLA1 and pancreatic lipase(PL) confirmed predictions for LIPI N-terminal signal peptides (residues 1 - 15);predominantly conserved mammalian LIPI N-glycosylation sites (63NNSL and396NISS for human LIPI); active site “triad” residues (Ser159; Asp183; His253);disulfide bond residues (238 - 251; 275 - 286; 289 - 297; 436 - 455); and a 12 residue “active site lid”, which is shorter thanfor other lipases examined. Phylogenetic analyses supported a hypothesisthat LIPI arose from a vertebrate LIPH gene duplication event within amammalian common ancestral genome. In addition, LIPI, LIPH and PL-PLA1 geneswere distinct from the vascular lipase (LIPG, LIPC and LPL) and pancreatic lipase(PL) gene families.