title: A comparative study of human GS2, its paralogues, and its rat orthologue.
abstract: We have previously shown that human GS2 (hGS2) catalyzes keratinocyte retinylester and triglyceride hydrolysis. hGS2 and its rat orthologue, rGS2, are 80% homologous and share a proline insertion at residue 56 and a C-terminal truncation compared to the hGS2 paralogues. Both changes are required for hGS2 function. However, the catalytic capabilities of hGS2 are more similar to the paralogue, TTS-2.2, than to rGS2. Only hGS2 and hTTS-2.2 transfer fatty acid from triglyceride to retinol, hydrolyze retinylesters, and generate 1,3-diacylglycerol from triglycerides. Rat-human chimeras containing either the N- or C-terminus of rGS2 are without activity and single substitutions of rat for human residues cause activity loss. The differences between orthologues suggest that GS2 has a unique function in humans or has a function that is fulfilled by other enzymes in rodents. Since retinoid and triglyceride metabolites are transcription factor ligands, we expect that these enzymes will coordinately regulate epidermal homeostasis.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8702, USA.
authors.forename: Jay G
authors.initials: JG
authors.lastname: Gao
authors.forename: Marcia
authors.initials: M
authors.lastname: Simon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism*; D008049:Lipase; D008066:Lipolysis / Q000502:physiology*; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014153:Transaldolase / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D008049:Lipase; D011506:Proteins; D014153:Transaldolase; C091246:PNPLA4 protein, human; D000217:Acyltransferases