We thank Professor L.N. Johnson for encouragement and support. We are indebted to Dr D.T. Jones (University of Warwick) for giving advice on the THREADER program and its database, Dr B. Rost (EMBL, Heidelberg) for providing the PHD program, Drs P. Bork (EMBL, Heidelberg) and S.J. Perkins (Royal Free Hospital, London) for providing prediction data for the PID and vWF domains, Dr S.K. Burley (Rockefeller University, New York) for providing the coordinates of the HNF-3 structure and Mr A. S. Siddiqui (LMB, Oxford) for providing a database of protein structural domains. RBR thanks Dr C. P. Ponting (Fibrinolysis Research Unit, Oxford) for helpful discussions. RBR and GJB thank the Royal Commission for the Exhibition of 1851 and the Royal Society for support. RRC is funded by an MRC studentship. This research was funded in part by a grant from the BBSRC (UK).