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

Eur J Biochem. 2000 Oct;267(20):6140-50. doi: 10.1046/j.1432-1327.2000.01617.x.

Abstract

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 DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP. Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV. The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9. The full-length DPP8 cDNA codes for an 882-amino-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 DPP8 to be a 100-kDa monomeric protein expressed in the cytoplasm. Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro. Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP. DPP8 enzyme activity had a neutral pH optimum consistent 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm*
  • Biomarkers, Tumor*
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15*
  • Chromosomes, Human, Pair 19
  • Cloning, Molecular
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / genetics*
  • Endopeptidases
  • Gelatinases
  • Growth Substances / chemistry
  • Humans
  • Lymphocytes / enzymology
  • Membrane Proteins
  • Molecular Sequence Data
  • Monocytes / enzymology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / chemistry

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Growth Substances
  • Membrane Proteins
  • Recombinant Proteins
  • Endopeptidases
  • Dipeptidyl Peptidase 4
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases

Associated data

  • GENBANK/AF221634
  • GENBANK/AF221635
  • GENBANK/AF221636
  • GENBANK/AF221637