title: Distribution, classification, domain architectures and evolution of prolyl oligopeptidases in prokaryotic lineages.
abstract: BACKGROUND
  Prolyl oligopeptidases (POPs) are proteolytic enzymes, widely distributed in all the kingdoms of life. Bacterial POPs are pharmaceutically important enzymes, yet their functional and evolutionary details are not fully explored. Therefore, current analysis is aimed at understanding the distribution, domain architecture, probable biological functions and gene family expansion of POPs in bacterial and archaeal lineages.
  
  
  RESULTS
  Exhaustive sequence analysis of 1,202 bacterial and 91 archaeal genomes revealed ~3,000 POP homologs, with only 638 annotated POPs. We observed wide distribution of POPs in all the analysed bacterial lineages. Phylogenetic analysis and co-clustering of POPs of different phyla suggested their common functions in all the prokaryotic species. Further, on the basis of unique sequence motifs we could classify bacterial POPs into eight subtypes. Analysis of coexisting domains in POPs highlighted their involvement in protein-protein interactions and cellular signaling. We proposed significant extension of this gene family by characterizing 39 new POPs and 158 new α/β hydrolase members.
  
  
  CONCLUSIONS
  Our study reflects diversity and functional importance of POPs in bacterial species. Many genomes with multiple POPs were identified with high sequence variations and different cellular localizations. Such anomalous distribution of POP genes in different bacterial genomes shows differential expansion of POP gene family primarily by multiple horizontal gene transfer events.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore, 560065, India. Swati.Kaushik@ucsf.edu.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA. Swati.Kaushik@ucsf.edu.
authors.forename: Swati
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore, 560065, India. mini@ncbs.res.in.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Sowdhamini
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001105:Archaea / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D001419:Bacteria / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology; D016000:Cluster Analysis; D017124:Conserved Sequence; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial / Q000235:genetics; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D010802:Phylogeny; D000085822:Prolyl Oligopeptidases; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases