InterPro domain: IPR034680

The KEOPS/EKC complex is a tRNA modification complex involved in the biosynthesis of N6-threonylcarbamoyladenosine (t6A), a universally conserved tRNA modification found on ANN-codon recognizing tRNAs [ 1 ]. In archaea and eukaryotes, KEOPS is composed of Kae1, a highly conserved protein present in bacteria, archaea and eukaryotes, kinase PRPK/Bud32, and three additional polypeptides (Pcc1, Cgi121, and Gon7) [ 2 , 3 ].

This family represents Kae1 and its homologues from archaea and eukaryotes.

The first characterised member of the Kae1/TsaD family was annotated as Gcp for O-sialoglycoprotein endopeptidase [ 4 ], but this activity could not be confirmed [ 5 ]. Later, its homologue, Kae1 from Pyrococcus abyssi, has been shown to have DNA-binding properties and apurinic-endonuclease activity [ 6 ]. Members of this family have since been studied in yeast, archaea and bacteria resulting in sometimes conflicting data, several proposed functions and annotations but no definitive characterisation. For instance, some members have been linked to DNA maintenance in bacteria and mitochondria [ 6 ] and transcription regulation and telomere homeostasis in eukaryotes [ 7 , 8 ], but their function remained unclear. Recent research indicates that this family is involved in the biosynthesis of N6-threonylcarbamoyl adenosine, a universal modification found at position 37 of tRNAs that read codons beginning with adenine [ 9 ].

1. Diversity of the biosynthesis pathway for threonylcarbamoyladenosine (t(6)A), a universal modification of tRNA. RNA Biol 11, 1529-39
2. The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J. 30, 873-81
3. Proteomic analysis of the human KEOPS complex identifies C14ORF142 as a core subunit homologous to yeast Gon7. Nucleic Acids Res. 45, 805-817
4. Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene. J. Bacteriol. 173, 5597-603
5. An archaeal orthologue of the universal protein Kae1 is an iron metalloprotein which exhibits atypical DNA-binding properties and apurinic-endonuclease activity in vitro. Nucleic Acids Res. 35, 6042-51
6. Qri7/OSGEPL, the mitochondrial version of the universal Kae1/YgjD protein, is essential for mitochondrial genome maintenance. Nucleic Acids Res. 37, 5343-52
7. Yeast homolog of a cancer-testis antigen defines a new transcription complex. EMBO J. 25, 3576-85
8. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell 124, 1155-68
9. A role for the universal Kae1/Qri7/YgjD (COG0533) family in tRNA modification. EMBO J. 30, 882-93