Cloning and sequence analysis of cDNA for a human homolog of eubacterial ATP-dependent Lon proteases

Overlapping cDNA clones containing mRNA for a putative Lon protease (LonHS) were isolated from cDNA libraries prepared from human brain poly(A)⁺ RNA. The determined nucleotide sequence contains a 2814-bp open reading frame with two potential initiation codons (positions 62-64 and 338-340). The 5'-terminal 337-nucleotide fragment of LonHS mRNA is highly enriched with G and C nucleotides and could direct synthesis of the LonHS N-terminal domain. More likely this region promotes initiation of protein synthesis from the second AUG codon in a cap-independent manner. The amino acid sequence initiated at the second AUG codon includes 845 residues, over 30% of which are identical to those of eubacterial Lon proteases. Residues of the 'A' and 'B' motifs of NTP-binding pattern and a plausible catalytic serine residue are conserved in LonHS. Northern blot analysis revealed LonHS mRNA in lung, duodenum, liver and heart, but not in thymus cells.