Functional Classification of cNMP-binding Proteins and Nucleotide Cyclases with Implications for Novel Regulatory Pathways in Mycobacterium tuberculosis

Table 1.

Nucleotide Cyclases and cNMP-Binding Proteins Identified in This study—Cellular Localization and Function

Species/group Mammals Other eukaryotes Eukaryotic microbes Eubacteria Archaea
HS MM other DM CE plant other P DD SC fungi EC TP S C MT ML other A
Complete genome sequence available? N N N N Y N N N N Y N Y Y Y N Y N Y/N Y/N
Class I cyclase 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 8 0
Class III adenylyl cyclase
 cytoplasmic 0 0 0 0 0 0 0 0 0 1 6 0 0 2 5 9 1 6 0
 receptor-type 0 0 0 0 0 0 0 6 1 0 0 0 1 1 3 1 0 0 0
 integral membrane 3 5 14 2 3 0 2 0 1 0 0 0 0 0 0 5 1 2 0
Class III guanylyl cyclase
 cytoplasmic 5 1 6 3 11 0 6 0 0 0 0 N.D. N.D. N.D. N.D. N.D. N.D. N.D. 0
 receptor-type 6 2 14 2 20 0 9 0 0 0 0 N.D. N.D. N.D. N.D. N.D. N.D. N.D. 0
 integral membrane 0 0 0 0 0 0 0 0 0 0 0 N.D. N.D. N.D. N.D. N.D. N.D. N.D. 0
cNMP-binding proteins
 kinase 8 3 11 7 4 0 4 1 1 1 8 0 0 0 0 0 0 0 0
 channel 6 9 23 4 7 14 4 0 0 0 0 0 0 0 0 0 0 0 0
 cAMP-GEF 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
 DNA binding 0 0 0 0 0 0 0 0 0 0 0 2 1 4 5 2 0 43 0
 ABC-transporter 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 2 0 0 0
 translocase 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0
 esterase 1 0 0 0 2 0 0 0 0 1 0 0 0 0 0 3 0 0 0
 cNMP-binding only 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 0 3 0
 others 0 0 0 0 0 1 0 0 0 0 1 1 3 6 0 3 0 4 0

  • ↵(HS) Homo sapiens; (MM)Mus musculus; (other) Rattus norvegicus, Bos taurus, Canis familiaris, Oryctolagus cuniculus, Sus scrofa, andCavia porcellus.

  • ↵(DM) Drosophila melanogaster; (CE)Caenorhabditis elegans; (plant) Arabidopsis thaliana, Hordeum vulgare, Nicotiana tabacum, Solanum tuberosum, Vicia faba,and Zea mays; (other) Anguilla japonica, Aplysia californica, Ciona intestinalis, Fugu rubripes, Gallus gallus, Hemicentrotus pulcherrimus, Hydra oligactis, Ictalurus punctatus, Manduca sexta, Oryzias latipes, Strongylocentrotus purpuratus, andXenopus laevis.

  • ↵(P) Protozoans are Leishmania donovani, Paramecium tetraurelia, Trypanosoma brucei brucei, andTrypanosoma cruzi; (DD) Dictyostelium discoideum; (SC) Saccharomyces cerevisiae; (other fungi)Blastocladiella emersonii, Colletotrichum trifolii, Emericella nidulans, Magnaporthe grisea, Neurospora crassa, Podospora anserina, Saccharomyces kluyveri, Schizosaccharomyces pombe, andUstilago maydis.

  • ↵(EC) Escherichia coli; (TP)Treponema pallidum; (S) Synechocystis PCC6803; (C) other cyanobacteria are Anabaena cylindrica, AnabaenaPCC7120, Anabaena variabilis, Cyanothece ATCC51142,Spirulina platensis, Synechococcus PCC7942, andSynechococcus WH7803; (MT) Mycobacterium tuberculosis; (ML) Mycobasterium leprae; (other)Actinobacillus pleuropneumoniae, Aeromonas hydrophila, Alcaligenes eutrophus, Aquifex aeolicus, Azorhizobium caulinodans, Azotobacter vinelandii, Bacillus licheniformis, Bacillus subtilis, Bradyrhizobium japonicum, Chlamydia trachomatis, Corynebacterium liquefaciens, Erwinia chrysanthemi, Haemophilus influenzae, Haemophilus somnus, Myxococcus xanthus, Paracoccus denitrificans, Pasteurella haemolytica, Pasteurella multocida, Proteus mirabilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas G-179,Pseudomonas putida, Pseudomonas stutzeri, Rhizobium etli, Rhizobium IC3342, Rhizobium leguminosarum, Rhizobium meliloti, Rhodobacter capsulatus, Rhodobacter sphaeroides, Rhodopseudomonas palustris, Salmonella typhimurium, Shewanella putrefaciens, Stigmatella aurantiaca, Streptomyces coelicolor, Streptomyces griseus, Thiobacillus ferrooxidans, Vibrio cholerae, Xanthomonas campestris, Yersinia intermedia, and Yersinia pestis.

  • ↵The complete C. elegans genome sequence became available after the original recruitment and analysis of the superfamilies; this information added two cNMP-dependent kinases, one integral membrane adenylyl cyclase, one cytoplasmic guanylyl cyclase, and one receptor-type guanylyl cyclase to these superfamilies.

  • ↵Class I adenylyl cyclases have been identified in Aeromonas hydrophila, Erwinia chrysanthemi, Escherichia coli, Haemophilus influenzae, Pasteurella multocida, Proteus mirabilis, Salmonella typhimurium, Yersinia intermedia, and Yersinia pestis.

  • ↵Includes both α and β subunits of eukaryotic soluble guanylyl cyclases.

  • ↵Functions of cNMP-binding proteins were based on experimental evidence, BLAST homology to proteins of known function, or homology to a Pfam domain.

  • ↵All CRP and FNR homologs were included.

  • ↵Proteins with <30 amino acids on either side of the cNMP-binding region.

  • ↵Proteins with no known or predicted function.

  • ↵One of the C. elegans kinases (CE03979) had only one cNMP-binding site and a kinase domain. During our classification, this protein classified in class 7.

  • ↵The two M. tuberculosis proteins (Rv3239c and Rv3728) that have homology to several antibiotic efflux proteins also have an esterase domain, so are included in both categories.

  • (N.D.) Not determined. The determinants of substrate specificity of the eubacterial cyclases are not known; therefore, all eubacterial cyclases are listed in the adenylyl cyclase row.

This Article

  1. Genome Res. 10: 204-219

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