Structure of the Xq22.3 HERV-W locus. (A) Organization of the HERV-W locus on human chromosome Xq22.3. Shown on the top is a screenshot from the UCSC Human Genome Browser  depicting the chromosome × region of interest and the flanking RBM41 gene. Note that the Xq22.3 HERV-W locus is located in antisense orientation on the chromosome. Start and stop codons within the env region are indicated by green and red vertical lines. The start (nt 1) and end of the 1629 nt long env ORF are marked by green and red arrows. The stop codon at position 39 and the start codon at codon 68 are marked by a red and a green arrowhead. Portions of the Xq22.3 HERV-W locus that were inserted into the phCMV expression vector for subsequent in vitro studies are depicted below. (B) Amino acid sequence alignment of Xq22.3 Env, MSRV Env (AAK18189.1), and Syncytin-1 (NP_055405.3). Signal peptides (SignalP 3.0, http://www.cbs.dtu.dk/services/SignalP) are shaded in gray. The stop codon at position 39 of Xq22.3 HERV-W Env is indicated by an asterisk (*) and the start codon at position 68 is highlighted in green. The consensus C-X-X-C motif is shown in boldface. The boundary between SU and TM regions is indicated by arrows. The proteolytic cleavage site between SU and TM is highlighted in red letters. The C-terminal region of MSRV Env, likely resulting from a recombination event with a HERV-W locus on chromosome 5p12 [see text and 24], is highlighted in yellow. The N-terminal fragment of Syncytin-1 and the C-terminal fragment of Xq22.3 Env used for generation of the anti-Syncytin-1 and anti-Xq22.3 Env polyclonal rabbit antisera are underlined.