SMEK Homolog 1, Suppressor Of Mek1 (SMEK1)

PP4R3-alpha interacted with PPP4C and PPP4R2 in a complex. Deletion of PP4R3 orthologs in yeast and Drosophila led to hypersensitivity to the chemotherapeutic agent cysplatin, and human PP4R3 reversed cysplatin sensitivity.Database analysis identified 2 human homologs SMEK1 and SMEK2. SMEK1 and SMEK2 contain several regions conserved in Dictyostelium, including a putative N-terminal Enabled/VASP homology-1 (EVH1) domain, a central domain of unknown function, and a C-terminal stretch of acidic residues followed by basic residues.The deduced 820-amino acid PP4R3-alpha shares 67% amino acid identity with PP4R3-beta (SMEK2). It contains an N-terminal domain that is similar to the RAN-binding domain of RANBP1 and to pleckstrin homology domains.