PROSITE documentation PDOC52020
CRESS-DNA virus replication initiator protein (Rep) endonuclease domain profile


Circular Rep-encoding single-stranded DNA (CRESS-DNA) viruses, such as circoviruses, nanoviruses, and geminiviruses, are eukaryotic viruses with small circular single-stranded DNA (ssDNA) genomes encoding a replication initiator protein (Rep) with a distinctive two functional domain organization, containing an endonuclease domain toward the N-terminus and a superfamily 3 (SF3) helicase domain at the C-terminus. The Rep endonuclease domain is responsible for initiating, progressing, and completing rolling circle replication (RCR) of the genome. The Rep endonuclease domain is characterized by RCR motifs I through III, which are important for RCR initiation and termination. Motif I, UUTU (U denotes hydrophobic residues), is thought to be involved in the recognition of the origin of replication. Motif II, HU(H/Q), is involved in the coordination of divalent metal ions, Mg(2+) or Mn(2+), which are essential for endonuclease activity at the origin of replication. Motif III (YxxK, where x is any amino acid) is involved in dsDNA cleavage and subsequent covalent attachment of the Rep through the catalytic tyrosine residue to the 5' end of the cleaved product [1,2,3,4,5].

The CRESS-DNA Rep endonuclease domain consists of a central 5-stranded antiparallel β-sheet covered on one side by an α-helix and irregular loops and on the other, more open side of the domain, by an α-helix containing the catalytic tyrosine residue (the catalytic helix) (see <PDB:2HWO>) [5].

The profile we developed covers the entire CRESS-DNA Rep endonuclease domain.

Last update:

March 2023 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CRESS_DNA_REP, PS52020; CRESS-DNA virus replication initiator protein (Rep) endonuclease domain profile  (MATRIX)


1AuthorsCastrignano S.B. Nagasse-Sugahara T.K. Garrafa P. Monezi T.A. Barrella K.M. Mehnert D.U.
TitleIdentification of circo-like virus-Brazil genomic sequences in raw sewage from the metropolitan area of Sao Paulo: evidence of circulation two and three years after the first detection.
SourceMem. Inst. Oswaldo. Cruz. 112:175-181(2017).
PubMed ID28146157

2AuthorsZhao L. Rosario K. Breitbart M. Duffy S.
TitleEukaryotic Circular Rep-Encoding Single-Stranded DNA (CRESS DNA) Viruses: Ubiquitous Viruses With Small Genomes and a Diverse Host Range.
SourceAdv. Virus. Res. 103:71-133(2019).
PubMed ID30635078

3AuthorsTarasova E. Dhindwal S. Popp M. Hussain S. Khayat R.
TitleMechanism of DNA Interaction and Translocation by the Replicase of a Circular Rep-Encoding Single-Stranded DNA Virus.
SourcemBio 12:E0076321-E0076321(2021).
PubMed ID34311576

4AuthorsKazlauskas D. Varsani A. Koonin E.V. Krupovic M.
TitleMultiple origins of prokaryotic and eukaryotic single-stranded DNA viruses from bacterial and archaeal plasmids.
SourceNat. Commun. 10:3425-3425(2019).
PubMed ID31366885

5AuthorsVega-Rocha S. Byeon I.-J.L. Gronenborn B. Gronenborn A.M. Campos-Olivas R.
TitleSolution structure, divalent metal and DNA binding of the endonuclease domain from the replication initiation protein from porcine circovirus 2.
SourceJ. Mol. Biol. 367:473-487(2007).
PubMed ID17275023

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)