Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV.
We used an in silico approach to identify new cDNAs with homology to dipeptidyl peptidase IV (DPP IV). DPP IV (EC 3.4.14.5) is a serine protease with a rare enzyme activity having an important role in the regulation of various processes, such as blood glucose control and immune responses. Here, we report the identification and characterization of a novel DPP IV-like molecule, termed dipeptidyl peptidase-like protein 9 (DPP9). The deduced amino acid sequence of DPP9 has a serine protease motif, GWSYG, identical to that found in DPP IV. The presence of this motif, together with a conserved order and spacing of the Ser, Asp, and His residues that form the catalytic triad in DPP IV, places DPP9 in the "DPP IV gene family". Northern blots showed that DPP9 is ubiquitously expressed, with the highest expression levels in skeletal muscle, heart, and liver, and the lowest in brain. In vitro translation of the cloned full-length DPP9 sequence resulted in a DPP9 protein product that migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis at a position similar to the predicted protein size of 98 kDa. Consistent with the lack of predicted transmembrane domains and a signal sequence, DPP9 was found in a soluble, putative cytosolic form. A DPP9 orthologue in mice was identified by expressed sequence tag database searches and verified by cDNA cloning.
Olsen
Christina
C
Department of Cloning Technology and Immunology, Novo Nordisk A/S, Novo Allé 6B2.98, DK-2880 Bagsvaerd, Denmark.
Wagtmann
Nicolai
N
D024506:5' Flanking Region / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D020014:K562 Cells; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D014176:Protein Biosynthesis; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; C585326:dipeptidyl peptidase 9, mouse