Fig. 1 HERV-K (HML-2. HOM) ORFs, protease and endonuclease sequences a, Schematic illustration of the HERV-K (HML-2. HOM) provirus (GenBank accession number AF074086). A glucocorticoid responsive element (GRE), TATA-box (TATA) and poly (A) signal are present in the LTRs.‘CIDD’denotes a highly conserved motif of reverse transcriptases that is mutated in HERV-K (HML-2. HOM). Numbers indicate the positions of the LTRs and ORFs within the proviral sequence. RT, reverse transcriptase; EN, endonuclease. b, Alignment of retroviral proteases and HERV-K (HML-2. HOM) with the characteristic motifs ‘Active Site’,‘Flap’and ‘GRDLL’(ref. 13) indicated. c, Sequence comparison of the endonuclease and carboxy-terminal portion of the RNase H domains encoded by HERV-K10 (ref. 1) and HERV-K (HML-2. HOM). The HHCC-motif and the D, D (35) E-motif8, 14 are indicated by• and#, respectively. Sequence differences are located either in the RNase H domain or outside the catalytic motifs.