Figure 2

HMM-generated multiple sequence alignment of the EEP domain from a variety of Bacteria and Eucarya. The EEP domain at the C-terminus of REX2 and REX1 is the putative exonuclease component of the editosome. Residues that are conserved in >50% of the sequences are in black and numbers indicate the number of amino acids not shown explicitly. Six EEP domains of particular interest are in yellow. The Roman numerals above the alignment mark the six conserved sequence motifs that have been used to characterize EEP domain (see also Table 1). Columns in pink indicate the putative substrate specificity active-site hydrophobic pocket. The column in green marks the location of the essential Glu in DNaseI (DNaseI_Bt_1DNK, the last sequence highlighted in yellow). The proteins shown are REX1 (RNA editing exonuclease 1), REX2 (RNA editing exonuclease 2), I5PP (inositol polyphosphate 5'-phosphatase), APE1 (apurinic/apyrimidinic endonuclease 1), and APE2 (apurinic/apyrimidinic endonuclease 2); these sequences are from T. brucei (Tbrucei), T. gambiense (Tbgambiense), T. congolense (Tbcongolense), T. cruzi (Tcruzi), T. vivax (Tvivax), L. major (Lmajor), L. infantum (Linfantum), L. braziliensis (Lbraziliensis), Schizosaccharomyces pombe (Sp), Homo sapiens (Hs), Escherichia coli (Ec), and Bos taurus (Bt). EEP domains whose structures have been determined experimentally are I5PP_Sp_1I9Z (S. pombe phosphatidylinositol phosphate phosphatase, RCSB code1I9Z), APE1_Hs_1HD7 (H. sapiens AP endonuclease 1, 1HD7), ExoIII_Ec_1AKO, (E. coli exonuclease III, 1AKO); DNaseI_Bt_1DNK (B. taurus deoxyribonuclease I, 1DNK) and L1EN_Hs_1VYB: (H. sapiens L1 endonuclease, 1VYB). Cylinders and arrows denote the α-helices and β-strands given in the RCSB entries 1AKO and 1HD7. The protein sequences, EEP domain HMM and alignment are available as Supplementary material.