PHOX2B contains an open reading frame of 314 amino acids spanning nucleotides 361 to 1,302. The polyadenylation signal AATAAA is located 17 bases upstream from the site of polyadenylation. The gene encodes a novel protein with a homeodomain that is significantly homologous with those in the various members of the paired-type homeobox genes. The amino acid sequences of the homeodomains of PHOX2B and PHOX2A each cover 60 amino acids and are a perfect match, but outside the homeodomain no significant sequence similarity was observed. A proline-rich domain lies between amino acids 192 and 284 of the PHOX2B protein, and a glycine-rich domain lies between amino acids 196 and 289. There are 2 alanine-rich repeats in the C terminus of the homeodomain.