Two SH3 domain-containing cytosolic components of the NADPH oxidase, p47(phox) and p40(phox), are shown by analyses of their sequences to contain single copies of a novel class of domain, the PX (phox) domain. Homologous domains are demonstrated to be present in the Cpk class of phosphatidylinositol 3-kinase, S. cerevisiae Bem1p, and S. pombe Scd2, and a large family of human sorting nexin 1 (SNX1) homologues. The majority of these domains contains a polyproline motif, typical of SH3 domain-binding proteins. Two further findings are reported. A third NADPH oxidase subunit, p67(phox), is shown to contain four tetratricopeptide repeats (TPRs) within its N-terminal RaC1(GTP)-binding region, and a 28 residue motif in p40(phox) is demonstrated to be present in protein kinase C isoforms iota/lambda and zeta, and in three ZZ domain-containing proteins.