Recently, attention has focused on protein-kinase-C-like C1 and C2 domains, and pleckstrin homology (PH) domains, following the findings that they bind both to membrane-derived phospholipid second messengers and to plasma membranes1, 2. Identification of these lipidbinding domains in signalling proteins that have diverse architectures has provided insights into the molecular functions of these proteins, particularly in cases in which little more than the amino acid sequence was known. Functional predictions have been assisted by Webbased resources, such as SMART3, that can identify these and other signalling domains from sequence information.

PSI-BLAST4 searches designed to improve the prediction potential of SMART suggested that the C-terminal region of p122, a rat RHOA-specific GTPase-activating protein (RHOGAP) 5, is significantly similar both to homeodomain proteins of the plant Glabra2 (Gla2) family and to steroidogenic acute regulatory protein (StAR) orthologues. Further investigation demonstrated that these sequences are members of a homologous domain family that also includes bovine