Since proteins evolve by divergent evolution, proteins with distant homology to each other may or may not bear similar functions. Improved computational approaches are required to recognize distant homologues that are functionally similar. One of the methods of assigning function to sequences is to use profiles derived from sequences of known structure. We describe an update of the Genomic Distribution of protein structural domain Superfamilies (GenDiS) database, namely GenDiS+, which provides a projection of SCOP superfamily members on the sequence space (NR database, NCBI). The sequences are validated using structure-based sequence alignment profiles and domain and full-length sequence alignments. GenDiS+ is a `tour de force' for detecting homologues within around 160 000 taxonomic identifiers, starting from nearly 11 000 domains of known structure. Features, like full-sequence alignment and phylogeny, domain sequence alignment and phylogeny, list of associated structural and sequence domains with strength of interactions, links to databases like Pfam, UniProt and ModBase and list of sequences with a PDB structure, are provided.