Two novel human members of an emerging mammalian gene family related to mono-ADP-ribosylating bacterial toxins

Journal Article · Sat Feb 01 04:00:00 EST 1997 · Genomics

DOI:https://doi.org/10.1006/geno.1996.4520· OSTI ID:476888

Koch-Nolte, F; Haag, F; Braren, R ^[1]

---

1. Univ. Hospital, Hamburg (Germany); and others

Mono-ADP-ribosylation is one of the posttranslational protein modifications regulating cellular metabolism, e.g., nitrogen fixation, in prokaryotes. Several bacterial toxins mono-ADP-ribosylate and inactivate specific proteins in their animal hosts. Recently, two mammalian GPI-anchored cell surface enzymes with similar activities were cloned (designated ART1 and ART2). We have now identified six related expressed sequence tags (ESTs) in the public database and cloned the two novel human genes from which these are derived (designated ART3 and ART4). The deduced amino acid sequences of the predicted gene products show 28% sequence identity to one another and 32-41% identity vs the muscle and T cell enzymes. They contain signal peptide sequences characteristic of GPI anchorage. Southern Zoo blot analyses suggest the presence of related genes in other mammalian species. By PCR screening of somatic cell hybrids and by in situ hybridization, we have mapped the two genes to human chromosomes 4p14-p15.l and 12q13.2- q13.3. Northern blot analyses show that these genes are specifically expressed in testis and spleen, respectively. Comparison of genomic and cDNA sequences reveals a conserved exon/intron structure, with an unusually large exon encoding the predicted mature membrane proteins. Secondary structure prediction analyses indicate conserved motifs and amino acid residues consistent with a common ancestry of this emerging mammalian enzyme family and bacterial mono(ADP-ribosyl)transferases. It is possible that the four human gene family members identified so far represent the {open_quotes}tip of an iceberg,{close_quote} i.e., a larger family of enzymes that influences the function of target proteins via mono-ADP-ribosylation. 35 refs., 4 figs.

• OSTI ID: 476888
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 39; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ADP
AMINO ACID SEQUENCE
ANIMAL CELLS
BACTERIA
BACTERIAL DISEASES
BIOLOGICAL EVOLUTION
DNA SEQUENCING
DNA-CLONING
GENE REGULATION
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 12
HUMAN CHROMOSOMES
IN-SITU HYBRIDIZATION
MAMMALS
MEMBRANE PROTEINS
METABOLISM
PATHOGENESIS
POLYMERASE CHAIN REACTION
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
TISSUE DISTRIBUTION
TOXINS