A comparative study of human GS2, its paralogues, and its rat orthologue

Biochem Biophys Res Commun. 2007 Aug 24;360(2):501-6. doi: 10.1016/j.bbrc.2007.06.089. Epub 2007 Jun 26.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Humans
  • Hydrolysis
  • Kidney / metabolism*
  • Lipase
  • Lipolysis / physiology*
  • Molecular Sequence Data
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Rats
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Structure-Activity Relationship
  • Transaldolase / metabolism*

Substances

  • Proteins
  • Transaldolase
  • Lipase
  • PNPLA4 protein, human