Human “PKNOX” gene is a homeobox gene (1), belongs to the homeobox gene family, involved in the regulation of development of animals. It is also known as “PREP”. They play important roles in different steps of body pattern formation during early embryogenesis of animals. Homeobox genes are generally highly conserved and control similar phenotypic characters among distantly related organisms (2). However, they are also responsible for controlling different phenotypic characters among relatively closely related species (3). The formation of similar phenotypic characters can be explained by the conservation of shared homeobox genes.
Fig1: Evolutionary tree of homeobox gene including PKNOX
PKNOX is the member of the three-amino-acid loop extension (TALE) homeodomain proteins family and are highly conserved transcription regulators. TALE homeodomain proteins include the PBC and the MEINOX sub-families. MEINOX proteins form heterodimer complexes with PBC proteins. Heterodimerization is crucial to DNA binding and for nuclear localization. The PKNOX/ PREP has two members in mice and humans, known as PKNOX1/ PREP1 and PKNOX2/ PREP2. Sequence comparisons indicate that PREP1 and PREP2 define a novel sub-family of MEINOX proteins. PKNOX1 is composed of 435 amino acids and mapped on human chromosome 21 (21q22.3). In complexes with PBX (another TALE family member), PREP1 regulates the transcription of HOX-dependent (Hoxb2) and HOX-independent (urokinase plasminogen activator, glucagon) target genes. PKNOX2 is composed of 460 amino acids and contains HR1, HR2, and homeodomain, which are highly similar to PKNOX1, suggesting that PKNOX2 may also interact with PBX proteins as well as the same DNA sequence as PKNOX1. Genomic organization of PKNOX2 also showed high similarity to PKNOX1, though PKNOX2 lies on a different chromosomal region, 11q24. Unlike PKNOX1, which