PROSITE documentation PDOC51206
Superfamily 3 helicase domain profile


Helicases have been classified in 5 superfamilies (SF1-SF5) [1]. All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) (see <PDOC00017>) and Walker B (Mg2+-binding aspartic acid) motifs [1]. Superfamily 3 consists of helicases encoded mainly by small RNA and DNA viruses and some large nucleocytoplasmic DNA viruses [2,3]. Small viruses are very dependent on the host-cell machinery to replicate. SF3 helicase in small DNA viruses is associated with an origin-binding domain. By pairing a domain that recognizes the ori with a helicase, the virus can bypass the host-cell-based regulation pathway and initiate its own replication. The protein binds to the viral ori leading to origin unwinding. Cellular replication proteins are then recruited to the ori and the viral DNA is replicated.

In SF3 helicases the Walker A and Walker B motifs are separated by spacers of rather uniform, and relatively short, lenght. In addition to the A and B motifs this family is caracterized by a third motif (C) which resides between the B motif and the C-terminus of the conserved region. This motif consists of an Asn residue preceded by a run of hydrophobic residues [4].

Several structure of SF3 helicases have been solved (see <PDB:1N25>) [5]. They all possess the same core α/β fold, consisting of a five-stranded parallel β sheet flanked on both sides by several α helices. In contrast to SF1 and SF2 helicases, which have RecA-like core folds, the strand connectivity within the α/β core domain is that of AAA+ proteins [6]. The SF3 helicase proteins assemble into a hexameric ring.

Some proteins known to contain an SF3 helicase domain are listed below:

  • Polyomavirus large T antigen. It initiates DNA unwinding and replication via interactions with the viral origin of replication.
  • Papillomavirus E1 protein. An ATP-dependent DNA helicase required for initiation of viral DNA replication.
  • Parvovirus Rep/NS1 protein, which is also required for the initiation of viral replication.
  • Poxviridae and other large DNA viruses D5 protein.
  • Bacteriophage DNA primase/helicase protein.
  • Bacterial prophage DNA primase/helicase protein.
  • ssRNA positive strand viruses RNA1 polyprotein.

To recognize this domain we have developed two profiles. The first one is directed against DNA viruses SF3 helicase and the second one is specific for ssRNA positive-strand viruses SF3 helicase.

Last update:

June 2006 / Text revised; profile added.


Technical section

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

SF3_HELICASE_1, PS51206; Superfamily 3 helicase of DNA viruses domain profile  (MATRIX)

SF3_HELICASE_2, PS51218; Superfamily 3 helicase of positive ssRNA viruses domain profile  (MATRIX)


1AuthorsGorbalenya A.E. and Koonin E.V. .
TitleHelicases: amino acid sequence comparisons and structure-function relationships.
SourceCurr. Opin. Struct. Biol. 3:419-429(1993).

2AuthorsIyer L.M. Aravind L. Koonin E.V.
TitleCommon origin of four diverse families of large eukaryotic DNA viruses.
SourceJ. Virol. 75:11720-11734(2001).
PubMed ID11689653

3AuthorsIyer L.M. Leipe D.D. Koonin E.V. Aravind L.
TitleEvolutionary history and higher order classification of AAA+ ATPases.
SourceJ. Struct. Biol. 146:11-31(2004).
PubMed ID15037234

4AuthorsGorbalenya A.E. Koonin E.V. Wolf Y.I.
TitleA new superfamily of putative NTP-binding domains encoded by genomes of small DNA and RNA viruses.
SourceFEBS Lett. 262:145-148(1990).
PubMed ID2156730

5AuthorsLi D. Zhao R. Lilyestrom W. Gai D. Zhang R. DeCaprio J.A. Fanning E. Jochimiak A. Szakonyi G. Chen X.S.
TitleStructure of the replicative helicase of the oncoprotein SV40 large tumour antigen.
SourceNature 423:512-518(2003).
PubMed ID12774115

6AuthorsHickman A.B. Dyda F.
TitleBinding and unwinding: SF3 viral helicases.
SourceCurr. Opin. Struct. Biol. 15:77-85(2005).
PubMed ID15718137

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