nearly all aspects of rna metabolism involve rna helicases , enzymes that use atp to bind or remodel rna and rna  protein complexes ( 1 ) . as one of the largest class of enzymes in rna metabolism ,
rna helicases are encoded by organisms from all kingdoms of life and by many viruses ( 2 ) . in structure and sequence ,
however , rna helicases outnumber their dna bound cousins by a considerable margin and rna helicases often perform functions substantially different from those attributed to dna helicases ( 13 ) .
rna helicases are not only essential for most processes of rna metabolism including ribosome biogenesis , pre - mrna splicing and translation initiation ( 13 ) , but also for sensing viral rnas in the context of the innate immune system and for the biogenesis and function of mirnas ( 4,5 ) .
defects or misregulation of certain rna helicases have been linked to numerous health issues including cancer , neuro - degenerative disorders and infectious diseases ( 69 ) .
given their central biological roles , rna helicases are subject to intensive ongoing research in diverse fields . to date , more than 7000 articles and roughly 500 reviews have been published on subjects related to rna helicases . currently , about 500 publications appear per year , with an upward trajectory .
with increasing volume and diversity of the accumulating data on rna helicases the need arises to integrate the wealth of information in a timely and readily accessible format . to address this issue ,
this database is a completely restructured version of the dexh / d protein database from 1999 , which covered only a subset of rna helicases ( 10 ) .
we approached the design of the rna helicase database from the view of user who is interested in the fast retrieval of comprehensive information on one or more specific rna helicases , and in examining phylogenetic relations of rna helicases to each other .
therefore , the rna helicase database aims foremost to enable researchers to locate and retrieve comprehensive information about sequence , structure , biochemical and cellular function of rna helicases .
the database provides ready access to sequence , structure , biochemical and cellular function of all rna helicases from the most widely used model organisms escherichia coli , saccharomyces cerevisiae , caenorhabditis elegans , drosophila melanogaster , mouse and human .
also included are rna helicases from other organisms that are subject to specific investigation , e.g. ns3 from hepatitis c virus ( 11 ) , the p4 rna packaging motor from 12 ( 12 ) or rna helicase a from bovine ( 13 ) . focus on these rna helicases covers the vast majority of published data on rna helicases ( estimated to > 95% ) , while providing an enduring structure for the database .
notwithstanding , the database can be readily expanded to other organisms , if this need arises in the future .
in addition to enabling access to information on individual rna helicases , the database emphasizes phylogenetic relations between related rna helicases . as briefly outlined below and in more detail in several recent reviews , rna helicases are categorized in superfamilies and families , and many features are shared between rna helicases of a given family ( 3,14,15 ) .
functions and features of one rna helicase often provide clues for other , less well - characterized enzymes from the same family ( 3 )
. however , family relations are often not apparent to investigators outside the rna helicase field .
we therefore believe that emphasizing family relations is particularly useful for database users new to research on rna helicases .
the structure of the rna helicase database is based on the most recent helicase classification into helicase superfamilies ( sfs ) and families ( 3,14,15 ) . according to sequence and protein structures
sfs 1 and 2 contain non - ring - forming helicases , sfs 36 contain ring - forming enzymes .
all eukaryotic rna helicases identified to date belong to the non - ring - forming sfs 1 and 2 ( 3 ) .
although all sf1 and sf2 proteins share extensive structural similarities in the overall fold of their helicase core , the respective families have distinct structure and sequence characteristics that are reflected in specific functional features ( 3 ) . 

the cladogram was generated from an structure - aided sequence alignment of all sf1 and 2 proteins in yeast and human , described in ( 3 ) .
the alignment can also be found on the rna helicase primer page of the database .
branch lengths of the cladogram are not to scale . the oval marks uncertainty in the topology .
families containing rna helicases are marked with a circled r , the other families contain dna helicases .
( t1r , type 1 restriction enzymes ; rha , rna helicase a ) . 
 figure 2.structure of the rna helicase database .
the bold lines around the homepage , the sf2 : dead - box page and one individual dead - box protein page mark pages shown as screenshots in figure 3 .
the cladogram was generated from an structure - aided sequence alignment of all sf1 and 2 proteins in yeast and human , described in ( 3 ) .
the alignment can also be found on the rna helicase primer page of the database .
branch lengths of the cladogram are not to scale . the oval marks uncertainty in the topology .
families containing rna helicases are marked with a circled r , the other families contain dna helicases .
( t1r , type 1 restriction enzymes ; rha , rna helicase a ) . structure of the rna helicase database .
the bold lines around the homepage , the sf2 : dead - box page and one individual dead - box protein page mark pages shown as screenshots in figure 3 .
the user enters the database through the homepage ( figure 2 ) . from this page , via the main navigation ( figure 3a ) , pages for the helicase sfs 35 , as well as pages for the sf1 and 2 families can be accessed ( figures 2 and 3b ) . from these pages , one can directly reach  individual protein pages ( figure 2 ) .
these pages contain information on orthologs of a given rna helicase from s. cerevisiae , c. elegans , d. melanogaster , mouse and human ( figure 3c ) .
dead - box and deah / rha helicases from e. coli are listed on separate pages ( figure 2 ) , because there are considerably fewer enzymes than in eukaryotes and because the structure of the individual protein pages , which emphasizes orthologs of multiple organisms , appears not suitable for representing only one protein from e. coli . 

( a ) the main navigation is identical on all pages and provides immediate access to the sf35 and sf1 and 2 family pages , as well as to the search function .
cellular function marks the demonstrated involvement of one ortholog from either organism in the indicated process .
( c ) page for an individual protein ( prp28p ) . database links connect directly to the specific protein in the sequence databases indicated . cellular function is only marked if involvement in a specific process has been directly demonstrated for a given protein .
the ( prp28/ddx23 ) literature button provides a direct link to a customized pubmed search for all orthologs listed on the page .
( a ) the main navigation is identical on all pages and provides immediate access to the sf35 and sf1 and 2 family pages , as well as to the search function .
cellular function marks the demonstrated involvement of one ortholog from either organism in the indicated process .
cellular function is only marked if involvement in a specific process has been directly demonstrated for a given protein .
the ( prp28/ddx23 ) literature button provides a direct link to a customized pubmed search for all orthologs listed on the page .
individual protein pages provide links to various sequence databases with original information about a particular rna helicase .
links for each protein exist to genbank and uniprot , as well as to organism - specific databases sgd ( s. cerevisiae ) , wormbase ( c. elegans ) and flybase ( d. melanogaster ) ( figure 3c ) .
the user also has the option to perform a targeted pubmed literature search for the helicase orthologs ( figure 3c ) .
the cellular function of each protein is given only where explicitly tested , although it is generally believed that the cellular functions are largely conserved for orthologs .
this alignment enables the user to identify regions of conservation among orthologs that extend beyond the characteristic helicase motifs .
individual protein pages were designed based on our roughly decade - long experience with the dexh / d database .
guided by this experience , we chose to directly refer to the large sequence databases for detailed protein information , and not to copy this information into our database . directly linking to comprehensive , constantly updated sequence databases
further features of the rna helicase database include full - search ability by text - based queries that are commonplace from the ubiquitous google search engine ( figure 3a ) .
the search function can be accessed from any page and provides an alternative , yet important route to individual protein pages . a third route of access to individual protein pages is established by a list of proteins in the database ( figure 2 ) .
this list shows all rna helicases in our database , ordered by sf and family and by the organism of origin .
our rationale for incorporating the various routes of access to the individual protein pages is the heterogeneity in the database users , which ranges from researchers looking for updates on information on a helicase that they have long been working on , to those who retrieve the first comprehensive information on a protein they just came across in their research .
finally , the database also contains other information of interest for research on rna helicases , such as an rna helicase primer , the naming code for ddx / dhx rna helicases and a list of laboratories with specific interest in rna helicases .
funding for open access charge : national institutes of health ( gm067700 to e.j . ) .
 rna helicases are ubiquitous and essential enzymes that function in nearly all aspects of rna metabolism . 
 the rna helicase database ( www.rnahelicase.org ) integrates the wealth of accumulating information on rna helicases in a readily accessible format . 
 the database is a portal that allows straightforward retrieval of comprehensive information on sequence , structure and on biochemical and cellular functions of all rna helicases from the most widely used model organisms escherichia coli , saccharomyces cerevisiae , caenorhabditis elegans , drosophila melanogaster , mouse and human . 
 also included are rna helicases from other organisms that are subject to specific investigation . 
 the database is structured according to the most recent helicase classification into helicase superfamilies ( sfs ) and families , and thus emphasizes phyologenetic relations between rna helicases as well . 
 information on individual rna helicases can be accessed through various browsing routes or through text - based searches of the database . 