We introduce BAR-PLUS (BAR(+)), a web server for functional and structural annotation of protein sequences. BAR(+) is based on a large-scale genome cross comparison and a non-hierarchical clustering procedure characterized by a metric that ensures a reliable transfer of features within clusters. In this version, the method takes advantage of a large-scale pairwise sequence comparison of 13,495,736 protein chains also including 988 complete proteomes. Available sequence annotation is derived from UniProtKB, GO, Pfam and PDB. When PDB templates are present within a cluster (with or without their SCOP classification), profile Hidden Markov Models (HMMs) are computed on the basis of sequence to structure alignment and are cluster-associated (Cl...