This entry represents the DNA-binding domain of classical SF1 and SF2 helicases. It does not recognise bacterial DinG and eukaryotic Rad3 which differ from other SF1-SF2 helicases by the presence of a large insert after the Walker A (see IPR014013 ).

Helicases have been classified in 5 superfamilies … expand

This entry represents the DNA-binding domain of classical SF1 and SF2 helicases. It does not recognise bacterial DinG and eukaryotic Rad3 which differ from other SF1-SF2 helicases by the presence of a large insert after the Walker A (see IPR014013 ).

Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) and Walker B (Mg2+-binding aspartic acid) motifs. For the two largest groups, commonly referred to as SF1 and SF2, a total of seven characteristic motifs has been identified [ PUBMED:2546125 ]. These two superfamilies encompass a large number of DNA and RNA helicases from archaea, eubacteria, eukaryotes and viruses that seem to be active as monomers or dimers. RNA and DNA helicases are considered to be enzymes that catalyse the separation of double-stranded nucleic acids in an energy-dependent manner [ PUBMED:11839499 ].

The various structures of SF1 and SF2 helicases present a common core with two α-β RecA-like domains [ PUBMED:11839499 PUBMED:11087862 ]. The structural homology with the RecA recombination protein covers the five contiguous parallel β-strands and the tandem α-helices. ATP binds to the amino proximal α-β domain, where the Walker A (motif I) and Walker B (motif II) are found. The N-terminal domain also contains motif III (S-A-T) which was proposed to participate in linking ATPase and helicase activities. The carboxy-terminal α-β domain is structurally very similar to the proximal one even though it is bereft of an ATP-binding site, suggesting that it may have originally arisen through gene duplication of the first one.

Some members of helicase superfamilies 1 and 2 are listed below:

• DEAD-box RNA helicases. The prototype of DEAD-box proteins is the translation initiation factor eIF4A. The eIF4A protein is an RNA-dependent ATPase which functions together with eIF4B as an RNA helicase [ PUBMED:11545728 ].
• DEAH-box RNA helicases. Mainly pre-mRNA-splicing factor ATP-dependent RNA helicases [ PUBMED:11545728 ].
• Eukaryotic DNA repair helicase RAD3/ERCC-2, an ATP-dependent 5'-3' DNA helicase involved in nucleotide excision repair of UV-damaged DNA.
• Eukaryotic TFIIH basal transcription factor complex helicase XPB subunit. An ATP-dependent 3'-5' DNA helicase which is a component of the core-TFIIH basal transcription factor, involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. It acts by opening DNA either around the RNA transcription start site or the DNA.
• Eukaryotic ATP-dependent DNA helicase Q. A DNA helicase that may play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens.
• Bacterial and eukaryotic antiviral SKI2-like helicase. SKI2 has a role in the 3'-mRNA degradation pathway, repressing dsRNA virus propagation by specifically blocking translation of viral mRNAs, perhaps recognizing the absence of CAP or poly(A).
• Bacterial DNA-damage-inducible protein G (DinG). A probable helicase involved in DNA repair and perhaps also replication [ PUBMED:8385320 ].
• Bacterial primosomal protein N' (PriA). PriA protein is one of seven proteins that make up the restart primosome, an apparatus that promotes assembly of replisomes at recombination intermediates and stalled replication forks.
• Bacterial ATP-dependent DNA helicase RecG. It has a critical role in recombination and DNA repair, helping process Holliday junction intermediates to mature products by catalysing branch migration. It has a DNA unwinding activity characteristic of helicases with a 3' to 5' polarity.
• A variety of DNA and RNA virus helicases and transcription factors