p62 is a novel immediate early response gene encoding a ubiquitin chain binding protein. To investigate the mechanism of p62 gene expression, we isolated and characterized the 20 kb long human p62 gene. The p62 gene contains seven introns and eight exons. The splice sites conformed to the GT/AG rule, except introns 6 and 7 which used the unusual GC dinucleotides. The p62 promoter is TATA-less, and 357 nucleotides of the 5'-flanking region contain basic machineries for transcription. A reporter gene linked to 1800 nucleotides of the 5'-flanking region was rapidly activated by various extracellular signals. The presence of a CpG island as well as multiple binding sites for SP-1, AP-1, NF-kappaB, and Ets-1 family in the promoter region supports the regulated activation of the p62 gene.