The SUPERFAMILY resource provides protein domain assignments at the structural classification of protein (SCOP) superfamily level for over 1400 completely sequenced genomes, over 120 meta- genomes and other gene collections such as UniProt. All models and assignments are available to browse and download at http://supfam.org. A new hidden Markov model library based on SCOP 1.75 has been created and a previously ignored class of SCOP, coiled coils, is now included. Our scoring component now uses HMMER3, which is in orders of magnitude faster and produces superior results. A cloud-based pipeline was implemented and is publicly available at Amazon web services elastic computer cloud. The SUPERFAMILY refer- ence tree of life has been improved allowing the user to highlight a chosen superfamily, family or domain architecture on the tree of life. The most sig- nificant advance in SUPERFAMILY is that now it contains a domain-based gene ontology (GO) at the superfamily and family levels. A new methodo- logy was developed to ensure a high quality GO annotation. The new methodology is general purpose and has been used to produce domain- based phenotypic ontologies in addition to GO.