Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8

Dipeptidyl peptidase (DPP) IV has roles in T-cell costimulation, chemokine biology, type-II diabetes and tumor biology. Fibroblast activation protein (FAP) has been implicated in tumor growth and cirrhosis. Here we describe D PP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP. Northern-blot hybridization showed that the tissue expre ssion of DPP8 mRNA is ubiquitous, similar to that of DPPIV. The DPP8 gene w as localized to chromosome 15q22, distinct from a closely related gene at 1 9p13.3 which we named DPP9. The full-length DPP8 cDNA codes for an 882-amin o-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation. Western blots and confocal microscopy of transfected COS-7 cells showed DP P8 to be a 100-kDa monomeric protein expressed in the cytoplasm. Purified r ecombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pr o. Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase act ivity with DPPIV and FAP. DPP8 enzyme activity had a neutral pH optimum con sistent with it being nonlysosomal. The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.