SYSTERS Protein Family Database:Taxonomy Web Interface andTaxon-related Cluster FrequenciesThomas Meinel,Antje Krause,and Martin VingronMax Planck Institute for Molecular Geneticsputational Molecular BiologyIhnestrasse73,D-14195Berlin{Thomas.Meinel|Antje.Krause|Martin.Vingron}@molgen.mpg.dekeywords:SYSTERS,protein family,taxonomy,clustering,taxon-related,taxon-specific,cluster distribution IntroductionThe SYSTERS[5]protein family database provides an automatically generated clustering of all publicly available protein sequences into disjoint family and superfamily clusters.The underlying sequence set contains all sequences from the SWISS-PROT/TrEMBL[2]and from the PIR[10]databases as well as protein sequences of several com-pletely sequenced organisms.Alternatively spliced isoforms annotated in SWISS-PROT/TrEMBL are appended. Multiple alignments are generated for each cluster using ClustalW[8]and annotated with known domains from the Pfam database[1].Majority consensus sequences are derived from partial multiple alignments generated with MView[3];all consensus sequences together build a publicly searchable sequence database.To rely not only on preprocessed multiple sequence alignments of one SYSTERS protein family,we extended the functionality of our interface and allow the user interactively the selection of particular or species-related sequences in one or several SYSTERS clusters.This new set of sequences can be multiply aligned using the DIALIGN2program[6].We present the new SYSTERS taxonomy web interface as well as some taxonomic analyses and properties of the SYSTERS database.Taxonomy InterfaceEvery protein sequence in the underlying sequence set belongs to one organism,in terms of taxonomic classi-fication,this is a species,a subspecies or a strain.On the other hand,most SYSTERS protein families contain sequences from several different organisms.Thus,querying the SYSTERS database,one is often interested in •the taxonomic complexity of such a protein family,•all protein families a specific taxon is represented in,•protein families specific for one taxon,or•protein families shared by several different taxa.We assigned SYSTERS clusters to each taxon including the whole lineage of each organism,according to the NCBI taxonomy[9].SYSTERS clusters are taxon-related(t-r)or taxon-specific(t-s):at least one entry(t-r)or all entries(t-s)in a SYSTERS cluster belong to a taxon.For two or more taxa,the default selection result is the set of intersected clusters.SYSTERS Protein Families and Taxonomy-ResultsUsing the SYSTERS taxonomy web interface,the number of t-r and t-s protein families were obtained for eight taxonomic ranks(superkingdom,kingdom,phylum,class,order,family,genus,and species)of several completelyand uncompletely sequenced organisms.Numbers of non-redundant,taxon-correlated sequences will be shown.Taxon-correlated sequences in t-r clusters suggest an average taxon-based cluster size of3.4for46analysed taxa.However,log-log plots of cluster frequencies vs cluster sizes reveal long-tailed cluster distributions which are often observed for protein families[4],[7].Distributions are calculated for the whole sequence set as well as for selected taxa along the lineage of several orgamisms.Going from the sequence set of the cellular organisms to the species,we generally observe an increased negative slope of thefitted curves.Large protein families with>50non-redundant sequences,which evolved only in certain groups of organisms, are,e.g.,for mammals the major prion proteins and pregnancy-specific glycoproteins,or for arthropods larval serum proteins(arylphorin,hemocyanin,...)and pheromone-binding proteins.AccessIt is possible to enter the SYSTERS hierarchy of protein superfamilies,protein families(clusters),sequences, and protein domains at any layer,e.g.,by searching for a keyword,passing an external protein accession number, choosing a certain taxonomic composition as described above,or by selecting a known Pfam domain.A new protein sequence can be searched against the database of consensus sequences and subsequently multiply aligned together with a user defined selection of sequences from the SYSTERS data set.The SYSTERS protein family database is available at:http://systers.molgen.mpg.deAcknowledgementsWe would like to thank Christine Steinhoffand Thomas Manke for fruitful discussions about scale-free networks and some instructions in power-lawfitting.References[1] A.Bateman,E.Birney,L.Cerruti,R.Durbin,L.Etwiller,S.R.Eddy,S.Griffiths-Jones,K.L.Howe,M.Marshall,and E.L.Sonnhammer.The Pfam protein families database.Nucleic Acids Res,30(1):276–80,Jan2002.[2] B.Boeckmann,A.Bairoch,R.Apweiler,M.C.Blatter,A.Estreicher,E.Gasteiger,M.J.Martin,K.Michoud,C.O’Donovan,I.Phan,S.Pilbout,and M.Schneider.The SWISS-PROT protein knowledgebase and its 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