InterPro domain: IPR004802

This family, found in archaea and eukaryotes, includes the only archaeal proteins markedly similar to bacterial TruB, the tRNA pseudouridine 55 synthase. However, among two related yeast proteins, the archaeal set matches yeast YLR175w far better than YNL292w. The first, termed centromere/microtubule binding protein 5 (CBF5), is an apparent rRNA pseudouridine synthase, while the second is the exclusive tRNA pseudouridine 55 synthase for both cytosolic and mitochondrial compartments. It is unclear whether archaeal proteins found by this entry modify tRNA, rRNA, or both.

Yeast CBF5 plays a central role in ribosomal RNA processing. It is a probable catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Its pseudouridine ('psi') residues may serve to stabilise the conformation of rRNAs. It may function as a pseudouridine synthase. It is also a centromeric DNA-CBF3-binding factor which is involved in mitotic chromosome segregation [ 1 , 2 , 3 , 4 ].

Human CBF5 homologue, DKC1 (also called Dyskerin), has been involved in a variety of disparate cellular functions. DKC1 isoform 1 is required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme [ 5 ]. In Hela cells, overexpression of DKC1 isoform 3 promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression [ 6 ]. Mutations in the human DKC1 gene cause the X-linked form of DC, a bone marrow failure syndrome characterised by mucosal leukoplakia, nail dystrophy, abnormal skin pigmentation, premature aging, stem cell dysfunction and increased susceptibility to cancer. DKC1 loss of function also causes the Hoyeraal-Hreidarsson syndrome, recognised as a severe X-DC allelic variant [ 7 , 8 , 9 , 10 , 11 , 12 ].

1. An essential yeast protein, CBF5p, binds in vitro to centromeres and microtubules. Mol. Cell. Biol. 13, 4884-93
2. The box H + ACA snoRNAs carry Cbf5p, the putative rRNA pseudouridine synthase. Genes Dev. 12, 527-37
3. Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA-binding protein, are present together with Gar1p in all H BOX/ACA-motif snoRNPs and constitute a common bipartite structure. RNA 4, 1549-68
4. Point mutations in yeast CBF5 can abolish in vivo pseudouridylation of rRNA. Mol. Cell. Biol. 19, 7461-72
5. hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, and telomerase. RNA 12, 832-40
6. A new human dyskerin isoform with cytoplasmic localization. Biochim. Biophys. Acta 1810, 1361-8
7. A novel DKC1 mutation, severe combined immunodeficiency (T+B-NK- SCID) and bone marrow transplantation in an infant with Hoyeraal-Hreidarsson syndrome. Br. J. Haematol. 119, 765-8
8. Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita. J. Invest. Dermatol. 123, 470-3
9. Identification of a novel mutation in DKC1 in dyskeratosis congenita. Pediatr Blood Cancer 52, 135-7
10. X-linked dyskeratosis congenita in Malaysia. Pediatr Blood Cancer 50, 432
11. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551-5
12. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am. J. Hum. Genet. 65, 50-8