Home LiteratureArticle Details
PMID: 16859499 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like beta-grasp domains.

Genome biology ·Vol. 7 ·No. 7 ·2006-00-00 ·Pages R60

Iyer LM, Burroughs AM, Aravind L

Abstract

Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. We systematically analyzed prokaryotic Ub-related beta-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes.

MeSH Terms
Bacteria/metabolism Bacteriophages/metabolism Evolution, Molecular Signal Transduction Ubiquitin/chemistry,metabolism
Chemicals
Ubiquitin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Iyer Lakshminarayan M
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Burroughs A Maxwell
Aravind L
References (90)
90 references, click to expand
  1. The FSSP database: fold classification based on structure-structure alignment of proteins.
    Nucleic Acids Res. 1996 Jan 1;24(1):206-9 PMID: 8594580
  2. Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell.
    Genome Res. 1999 Jul;9(7):608-28 PMID: 10413400
  3. A workbench for multiple alignment construction and analysis.
    Proteins. 1991;9(3):180-90 PMID: 2006136
  4. Ubiquitin-mediated proteolysis: biological regulation via destruction.
    Bioessays. 2000 May;22(5):442-51 PMID: 10797484
  5. Genome alignment, evolution of prokaryotic genome organization, and prediction of gene function using genomic context.
    Genome Res. 2001 Mar;11(3):356-72 PMID: 11230160
  6. Attachment of the ubiquitin-related protein Urm1p to the antioxidant protein Ahp1p.
    Eukaryot Cell. 2003 Oct;2(5):930-6 PMID: 14555475
  7. Identification of molybdopterin as the organic component of the tungsten cofactor in four enzymes from hyperthermophilic Archaea.
    J Biol Chem. 1993 Mar 5;268(7):4848-52 PMID: 8444863
  8. Homologues of 26S proteasome subunits are regulators of transcription and translation.
    Protein Sci. 1998 May;7(5):1250-4 PMID: 9605331
  9. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events.
    Genome Res. 1999 Aug;9(8):689-710 PMID: 10447505
  10. T-Coffee: A novel method for fast and accurate multiple sequence alignment.
    J Mol Biol. 2000 Sep 8;302(1):205-17 PMID: 10964570
  11. Solution structure of the RWD domain of the mouse GCN2 protein.
    Protein Sci. 2004 Aug;13(8):2089-100 PMID: 15273307
  12. The ubiquitin system.
    Annu Rev Biochem. 1998;67:425-79 PMID: 9759494
  13. Biosynthesis and processing of the molybdenum cofactors.
    Biochem Soc Trans. 1997 Aug;25(3):757-61 PMID: 9388540
  14. The use of gene clusters to infer functional coupling.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2896-901 PMID: 10077608
  15. MUSCLE: a multiple sequence alignment method with reduced time and space complexity.
    BMC Bioinformatics. 2004 Aug 19;5:113 PMID: 15318951
  16. A natural classification of ribonucleases.
    Methods Enzymol. 2001;341:3-28 PMID: 11582786
  17. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling.
    Nature. 2004 Aug 5;430(7000):694-9 PMID: 15258597
  18. The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.
    Trends Biochem Sci. 1996 May;21(5):172-3 PMID: 8871400
  19. Characterization of Escherichia coli MoeB and its involvement in the activation of molybdopterin synthase for the biosynthesis of the molybdenum cofactor.
    J Biol Chem. 2001 Sep 14;276(37):34695-701 PMID: 11463785
  20. A superfamily of protein tags: ubiquitin, SUMO and related modifiers.
    Trends Biochem Sci. 2003 Jun;28(6):321-8 PMID: 12826404
  21. Structural analysis of Escherichia coli ThiF.
    J Mol Biol. 2005 Jun 17;349(4):774-86 PMID: 15896804
  22. Gibbs motif sampling: detection of bacterial outer membrane protein repeats.
    Protein Sci. 1995 Aug;4(8):1618-32 PMID: 8520488
  23. The NYN domains: novel predicted RNAses with a PIN domain-like fold.
    RNA Biol. 2006 Jan-Mar;3(1):18-27 PMID: 17114934
  24. Molybdenum cofactor biosynthesis and deficiency.
    Cell Mol Life Sci. 2005 Dec;62(23):2792-810 PMID: 16261263
  25. The Pseudomonas siderophore quinolobactin is synthesized from xanthurenic acid, an intermediate of the kynurenine pathway.
    Mol Microbiol. 2004 Apr;52(2):371-84 PMID: 15066027
  26. Systematic identification of novel protein domain families associated with nuclear functions.
    Genome Res. 2002 Jan;12(1):47-56 PMID: 11779830
  27. Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains.
    J Mol Biol. 2001 Apr 13;307(5):1271-92 PMID: 11292341
  28. Predicting protein function by genomic context: quantitative evaluation and qualitative inferences.
    Genome Res. 2000 Aug;10(8):1204-10 PMID: 10958638
  29. A novel integrative and conjugative element (ICE) of Escherichia coli: the putative progenitor of the Yersinia high-pathogenicity island.
    Mol Microbiol. 2004 Feb;51(3):837-48 PMID: 14731283
  30. Themes and variations on ubiquitylation.
    Nat Rev Mol Cell Biol. 2001 Mar;2(3):169-78 PMID: 11265246
  31. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action.
    Biol Direct. 2006 Mar 16;1:7 PMID: 16545108
  32. New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system.
    Genome Biol. 2003;4(12):R81 PMID: 14659018
  33. A superfamily of archaeal, bacterial, and eukaryotic proteins homologous to animal transglutaminases.
    Protein Sci. 1999 Aug;8(8):1714-9 PMID: 10452618
  34. The ESAT-6/WXG100 superfamily -- and a new Gram-positive secretion system?
    Trends Microbiol. 2002 May;10(5):209-12 PMID: 11973144
  35. JPred: a consensus secondary structure prediction server.
    Bioinformatics. 1998;14(10):892-3 PMID: 9927721
  36. ClpS is an essential component of the N-end rule pathway in Escherichia coli.
    Nature. 2006 Feb 9;439(7077):753-6 PMID: 16467841
  37. Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.
    Nucleic Acids Res. 2001 Jul 15;29(14):2994-3005 PMID: 11452024
  38. The PCI domain: a common theme in three multiprotein complexes.
    Trends Biochem Sci. 1998 Jun;23(6):204-5 PMID: 9644972
  39. Peptide-N-glycanases and DNA repair proteins, Xp-C/Rad4, are, respectively, active and inactivated enzymes sharing a common transglutaminase fold.
    Hum Mol Genet. 2001 Aug 1;10(16):1627-30 PMID: 11487565
  40. Comparative genomics of thiamin biosynthesis in procaryotes. New genes and regulatory mechanisms.
    J Biol Chem. 2002 Dec 13;277(50):48949-59 PMID: 12376536
  41. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis.
    Science. 1998 Oct 23;282(5389):754-9 PMID: 9784136
  42. Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation.
    Nat Struct Biol. 2001 Jan;8(1):42-6 PMID: 11135669
  43. Molybdenum cofactor biosynthesis and molybdenum enzymes.
    Annu Rev Plant Biol. 2006;57:623-47 PMID: 16669776
  44. Deubiquitinating enzymes--the importance of driving in reverse along the ubiquitin-proteasome pathway.
    Int J Biochem Cell Biol. 2003 May;35(5):590-605 PMID: 12672452
  45. Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1.
    Science. 2002 Oct 18;298(5593):608-11 PMID: 12183637
  46. Enhanced genome annotation using structural profiles in the program 3D-PSSM.
    J Mol Biol. 2000 Jun 2;299(2):499-520 PMID: 10860755
  47. Profile hidden Markov models.
    Bioinformatics. 1998;14(9):755-63 PMID: 9918945
  48. MOSC domains: ancient, predicted sulfur-carrier domains, present in diverse metal-sulfur cluster biosynthesis proteins including Molybdenum cofactor sulfurases.
    FEMS Microbiol Lett. 2002 Jan 22;207(1):55-61 PMID: 11886751
  49. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome.
    Science. 2002 Oct 18;298(5593):611-5 PMID: 12183636
  50. PUMA2--grid-based high-throughput analysis of genomes and metabolic pathways.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D369-72 PMID: 16381888
  51. Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.
    Genome Biol. 2003;4(2):R11 PMID: 12620121
  52. WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction.
    Nucleic Acids Res. 2000 Jan 1;28(1):123-5 PMID: 10592199
  53. PCMA: fast and accurate multiple sequence alignment based on profile consistency.
    Bioinformatics. 2003 Feb 12;19(3):427-8 PMID: 12584134
  54. Dali: a network tool for protein structure comparison.
    Trends Biochem Sci. 1995 Nov;20(11):478-80 PMID: 8578593
  55. REBASE--restriction enzymes and DNA methyltransferases.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D230-2 PMID: 15608184
  56. Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis.
    Biochemistry. 2006 Jan 10;45(1):11-9 PMID: 16388576
  57. Novel predicted peptidases with a potential role in the ubiquitin signaling pathway.
    Cell Cycle. 2004 Nov;3(11):1440-50 PMID: 15483401
  58. Bioinformatic analysis of ClpS, a protein module involved in prokaryotic and eukaryotic protein degradation.
    J Struct Biol. 2003 Jan;141(1):77-83 PMID: 12576022
  59. The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site.
    Cell. 1999 Apr 30;97(3):371-81 PMID: 10319817
  60. ESAT-6 proteins: protective antigens and virulence factors?
    Trends Microbiol. 2004 Nov;12(11):500-8 PMID: 15488391
  61. Crystal structure of the ubiquitin-like protein YukD from Bacillus subtilis.
    FEBS Lett. 2005 Jul 4;579(17):3837-41 PMID: 15978580
  62. A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems.
    Trends Biochem Sci. 2001 Jun;26(6):347-50 PMID: 11406394
  63. Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex.
    Nature. 2001 Nov 15;414(6861):325-9 PMID: 11713534
  64. Mechanisms underlying ubiquitination.
    Annu Rev Biochem. 2001;70:503-33 PMID: 11395416
  65. A novel superfamily of predicted cysteine proteases from eukaryotes, viruses and Chlamydia pneumoniae.
    Trends Biochem Sci. 2000 Feb;25(2):50-2 PMID: 10664582
  66. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
    Electrophoresis. 1997 Dec;18(15):2714-23 PMID: 9504803
  67. Detection of common three-dimensional substructures in proteins.
    Proteins. 1991;11(1):52-8 PMID: 1660134
  68. Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods.
    Methods Enzymol. 1996;266:418-27 PMID: 8743697
  69. A protein conjugation system in yeast with homology to biosynthetic enzyme reaction of prokaryotes.
    J Biol Chem. 2000 Mar 17;275(11):7462-5 PMID: 10713047
  70. E3 ubiquitin ligases.
    Essays Biochem. 2005;41:15-30 PMID: 16250895
  71. DNA polymerase beta-like nucleotidyltransferase superfamily: identification of three new families, classification and evolutionary history.
    Nucleic Acids Res. 1999 Apr 1;27(7):1609-18 PMID: 10075991
  72. Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complex.
    Biochemistry. 2004 Sep 21;43(37):11647-57 PMID: 15362849
  73. Deubiquitinating enzymes are IN/(trinsic to proteasome function).
    Curr Protein Pept Sci. 2004 Jun;5(3):201-11 PMID: 15188770
  74. Crystal structure of the toluene/o-xylene monooxygenase hydroxylase from Pseudomonas stutzeri OX1. Insight into the substrate specificity, substrate channeling, and active site tuning of multicomponent monooxygenases.
    J Biol Chem. 2004 Jul 16;279(29):30600-10 PMID: 15096510
  75. The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue.
    Nat Struct Biol. 2000 Jun;7(6):449-55 PMID: 10881189
  76. The genome of the novel phage Rtp, with a rosette-like tail tip, is homologous to the genome of phage T1.
    J Bacteriol. 2006 Feb;188(4):1419-36 PMID: 16452425
  77. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.
    PLoS Comput Biol. 2005 Nov;1(6):e60 PMID: 16292354
  78. A genomic and functional inventory of deubiquitinating enzymes.
    Cell. 2005 Dec 2;123(5):773-86 PMID: 16325574
  79. SCOP database in 2004: refinements integrate structure and sequence family data.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D226-9 PMID: 14681400
  80. Deubiquitinating enzymes: their functions and substrate specificity.
    Curr Protein Pept Sci. 2004 Jun;5(3):191-200 PMID: 15180524
  81. Biochemistry. All in the ubiquitin family.
    Science. 2000 Jul 28;289(5479):563-4 PMID: 10939967
  82. Overexpression in Escherichia coli of the rnf genes from Rhodobacter capsulatus--characterization of two membrane-bound iron-sulfur proteins.
    Eur J Biochem. 1998 Jan 15;251(1-2):54-64 PMID: 9492268
  83. Diversity of siderophore-mediated iron uptake systems in fluorescent pseudomonads: not only pyoverdines.
    Environ Microbiol. 2002 Dec;4(12):787-98 PMID: 12534462
  84. SMART 5: domains in the context of genomes and networks.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D257-60 PMID: 16381859
  85. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  86. On the maximum likelihood method in molecular phylogenetics.
    J Mol Evol. 1991 May;32(5):443-5 PMID: 1904100
  87. Comparative genomics of the FtsK-HerA superfamily of pumping ATPases: implications for the origins of chromosome segregation, cell division and viral capsid packaging.
    Nucleic Acids Res. 2004;32(17):5260-79 PMID: 15466593
  88. The role of adenylyltransferase and uridylyltransferase in the regulation of glutamine synthetase in Escherichia coli.
    Curr Top Cell Regul. 1985;27:221-32 PMID: 2868842
  89. Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: identification of an acyldisulfide-linked protein--protein conjugate that is functionally analogous to the ubiquitin/E1 complex.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8513-8 PMID: 11438688
  90. Three-dimensional structure of the AAH26994.1 protein from Mus musculus, a putative eukaryotic Urm1.
    Protein Sci. 2005 Aug;14(8):2095-102 PMID: 16046629
Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2006-7-7-r60
Published
2006-00-00
Pages
R60
Language
English
Region
England
NLM ID
100960660
PMCID
PMC1779556
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1186/gb-2006-7-7-r60 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2