Characterization of the human patatin-like phospholipase family.
Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Here, we report on the characterization and expression profiling of 10 human PNPLAs. A variety of bioinformatics approaches were used to identify and characterize all PNPLAs encoded by the human genome. The genes described represent a divergent family, most with a highly conserved ortholog in several mammalian species. In silico characterization predicts that two of the genes function as integral membrane proteins and are regulated by cAMP/cGMP. A structurally guided protein alignment of the patatin-like domain identifies a number of conserved residues in all family members. Quantitative PCR was used to determine the expression profile of each family member. Affymetrix-based profiling of a human preadipocyte cell line identified several members that are differentially regulated during cell differentiation. Cumulative data suggest that patatin-like genes normally expressed at very low levels are induced in response to environmental signals. Given the observed conservation of the patatin fold and lipase motif in all human PNPLAs, a single nomenclature to describe the PNPLA family is proposed.
Wilson
Paul A
PA
Bioinformatics Discovery and Analysis, GlaxoSmithKline Research and Development, Stevenage, England SG1 2NY, UK. paw84313@gsk.com
Gardner
Scott D
SD
Lambie
Natalie M
NM
Commans
Stephane A
SA
Crowther
Daniel J
DJ
D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010740:Phospholipases / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D017433:Protein Structure, Secondary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D007527:Isoenzymes; D010740:Phospholipases