title: The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse.
abstract: ADP-ribosyltransferases including toxins secreted by Vibrio cholera, Pseudomonas aerurginosa, and other pathogenic bacteria inactivate the function of human target proteins by attaching ADP-ribose onto a critical amino acid residue. Cross-species polymerase chain reaction (PCR) and database mining identified the orthologs of these ADP-ribosylating toxins in humans and the mouse. The human genome contains four functional toxin-related ADP-ribosyltransferase genes (ARTs) and two related intron-containing pseudogenes; the mouse has six functional orthologs. The human and mouse ART genes map to chromosomal regions with conserved linkage synteny. The individual ART genes reveal highly restricted expression patterns, which are largely conserved in humans and the mouse. We confirmed the predicted extracellular location of the ART proteins by expressing recombinant ARTs in insect cells. Two human and four mouse ARTs contain the active site motif (R-S-EXE) typical of arginine-specific ADP-ribosyltransferases and exhibit the predicted enzyme activities. Two other human ARTs and their murine orthologues deviate in the active site motif and lack detectable enzyme activity. Conceivably, these ARTs may have acquired a new specificity or function. The position-sensitive iterative database search program PSI-BLAST connected the mammalian ARTs with most known bacterial ADP-ribosylating toxins. In contrast, no related open reading frames occur in the four completed genomes of lower eucaryotes (yeast, worm, fly, and mustard weed). Interestingly, these organisms also lack genes for ADP-ribosylhydrolases, the enzymes that reverse protein ADP-ribosylation. This suggests that the two enzyme families that catalyze reversible mono-ADP-ribosylation either were lost from the genomes of these nonchordata eucaryotes or were subject to horizontal gene transfer between kingdoms.
authors.affiliation: Institute of Immunology, University Hospital, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Glowacki
authors.forename: Rickmer
authors.initials: R
authors.lastname: Braren
authors.forename: Kathrin
authors.initials: K
authors.lastname: Firner
authors.forename: Marion
authors.initials: M
authors.lastname: Nissen
authors.forename: Maren
authors.initials: M
authors.lastname: Kühl
authors.forename: Pedro
authors.initials: P
authors.lastname: Reche
authors.forename: Fernando
authors.initials: F
authors.lastname: Bazan
authors.forename: Marina
authors.initials: M
authors.lastname: Cetkovic-Cvrlje
authors.forename: Edward
authors.initials: E
authors.lastname: Leiter
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D022761:Gene Transfer, Horizontal; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D036002:ADP Ribose Transferases