SUPFAM - a database of potential protein superfamily relationships derived by comparing sequence-based and structure-based families: implications for structural genomics and function annotation in genomes

Members of a superfamily of proteins could result from divergent evolution of homologues with insignificant similarity in the amino acid sequences. A superfamily relationship is detected commonly after the three-dimensional structures of the proteins are determined using X-ray analysis or NMR. The SUPFAM database described here relates two homologous protein families in a multiple sequence alignment database of either known or unknown structure. The present release (1.1), which is the first version of the SUPFAM database, has been derived by analysing Pfam, which is one of the commonly used databases of multiple sequence alignments of homologous proteins. The first step in establishing SUPFAM is to relate Pfam families with the families in PALI, which is an alignment database of homologous proteins of known structure that is derived largely from SCOP. The second step involves relating Pfam families which could not be associated reliably with a protein superfamily of known structure. The profile matching procedure, IMPALA, has been used in these steps. The first step resulted in identification of 1280 Pfam families (out of 2697, i.e. 47%) which are related, either by close homologous connection to a SCOP family or by distant relationship to a SCOP family, potentially forming new superfamily connections. Using the profiles of 1417 Pfam families with apparently no structural information, an all-against-all comparison involving a sequence-profile match using IMPALA resulted in clustering of 67 homologous protein families of Pfam into 28 potential new superfamilies. Expansion of groups of related proteins of yet unknown structural information, as proposed in SUPFAM, should help in identifying 'priority proteins' for structure determination in structural genomics initiatives to expand the coverage of structural information in the protein sequence space. For example, we could assign 858 distinct Pfam domains in 2203 of the gene products in the genome of Mycobacterium tubercolosis. Fifty-one of these Pfam families of unknown structure could be clustered into 17 potentially new superfamilies forming good targets for structural genomics. SUPFAM database can be accessed at http://pauling.mbu.iisc.ernet.in/~supfam.

[1]  N Srinivasan,et al.  Use of a database of structural alignments and phylogenetic trees in investigating the relationship between sequence and structural variability among homologous proteins. , 2001, Protein engineering.

[2]  E. Lindahl,et al.  Identification of related proteins on family, superfamily and fold level. , 2000, Journal of molecular biology.

[3]  Frances M. G. Pearl,et al.  The CATH Dictionary of Homologous Superfamilies (DHS): a consensus approach for identifying distant structural homologues. , 2000, Protein engineering.

[4]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[5]  A. Sali,et al.  Protein structure modeling for structural genomics , 2000, Nature Structural Biology.

[6]  Chris Sander,et al.  Completeness in structural genomics , 2001, Nature Structural Biology.

[7]  Steven E. Brenner,et al.  The PRESAGE database for structural genomics , 1999, Nucleic Acids Res..

[8]  Sean R. Eddy,et al.  Pfam: multiple sequence alignments and HMM-profiles of protein domains , 1998, Nucleic Acids Res..

[9]  S. Balaji,et al.  PALI - a database of Phylogeny and ALIgnment of homologous protein structures , 2001, Nucleic Acids Res..

[10]  B. Barrell,et al.  Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence , 1998, Nature.

[11]  Alejandro A. Schäffer,et al.  IMPALA: matching a protein sequence against a collection of PSI-BLAST-constructed position-specific score matrices , 1999, Bioinform..

[12]  Annabel E. Todd,et al.  From structure to function: Approaches and limitations , 2000, Nature Structural Biology.

[13]  Jiye Shi,et al.  HOMSTRAD: adding sequence information to structure-based alignments of homologous protein families , 2001, Bioinform..

[14]  C Sander,et al.  Mapping the Protein Universe , 1996, Science.

[15]  S. Brenner,et al.  Expectations from structural genomics , 2008, Protein science : a publication of the Protein Society.

[16]  David C. Jones,et al.  GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences. , 1999, Journal of molecular biology.

[17]  Robert D. Finn,et al.  The Pfam protein families database , 2004, Nucleic Acids Res..

[18]  Arne Elofsson,et al.  A comparison of sequence and structure protein domain families as a basis for structural genomics , 1999, Bioinform..