Phosphodiesterase I/nucleotide pyrophosphatase is a widely expressed membrane-bound enzyme that cleaves diester bonds of a variety of substrates. We have cloned brain-type cDNA for this enzyme from rat brain and designated it PD-I alpha (M. Narita, J. Goji, H. Nakamura, and K. Sano, 1994, J. Biol. Chem. 269: 28235-28242). In this study we have isolated cDNA and genomic DNA encoding human PD-I alpha. Human PD-I alpha cDNA, designated PDNP2 in HGMW nomenclature, has a 2589-nucleotide open reading frame encoding a polypeptide of 863 amino acids with a calculated M(r) of 99,034. Northern blot analysis revealed that human PD-I alpha transcript was present in brain, lung, placenta, and kidney. The database analysis showed that human PD-I alpha was identical with human autotaxin (ATX), a novel tumor motility-stimulating factor, except that human PD-I alpha lacks 156 nucleotides and 52 amino acids of human ATX. Human PD-I alpha and human ATX are likely to be alternative splicing products from the same gene. The 5' region of the human PDNP2 gene contains four putative binding sites of transcription factor Sp1 without typical TATA or CAAT boxes, and there is a potential octamer binding motif in intron 2. From the results of fluorescence in situ hybridization, the human PDNP2 gene is located at chromosome 8q24.1.