Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

Version 1 : Received: 12 July 2021 / Approved: 13 July 2021 / Online: 13 July 2021 (08:58:31 CEST)

A peer-reviewed article of this Preprint also exists.

Reed, C.J.; Hutinet, G.; de Crécy-Lagard, V. Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase. Biomolecules 2021, 11, 1282. Reed, C.J.; Hutinet, G.; de Crécy-Lagard, V. Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase. Biomolecules 2021, 11, 1282.

Abstract

Members of the DUF34 (domain of unknown function 34) family, also known as the NIF3 protein superfamily, are ubiquitous across superkingdoms. Proteins of this family have been widely annotated as “GTP cyclohydrolase I type 2” through electronic propagation based on one study. Here, the annotation status of this protein family was examined through comprehensive literature review and integrative bioinformatic analyses that revealed varied pleiotropic associations and phenotypes. This analysis combined with functional complementation studies strongly challenges the current annotation and suggests that DUF34 family members may serve as metal ion insertases, chaperones, or metallocofactor maturases. This general molecular function could explain how DUF34 subgroups participate in highly diversified pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox and universal stress responses.

Keywords

comparative genomics; metabolic reconstruction; bioinformatics; conserved unknowns; function prediction; functional annotation; orthology

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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