Alternative titles; symbols
HGNC Approved Gene Symbol: DPP10
Cytogenetic location: 2q14.1 Genomic coordinates (GRCh38) : 2:114,442,641-115,845,780 (from NCBI)
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned DPP10, which they designated KIAA1492. The deduced 711-amino acid protein shares 52% identity with DPP6 (126141). RT-PCR ELISA detected low expression in whole adult brain and all individual brain regions examined except cerebellum, which did not express DPP10. Little to no expression was detected in all other tissues examined, including fetal brain.
By searching an EST database for sequences similar to DPP4 (102720), followed by 5-prime and 3-prime RACE and PCR of a hypothalamus cDNA library, Qi et al. (2003) cloned DPP10. The deduced 796-amino acid protein contains a transmembrane domain, 10 N-glycosylation sites, and several conserved amino acids found in the 6 domains characteristic of members of the peptidase, lipase, esterase, epoxide hydrolase, or serine hydrolase (PLEES) superfamily. However, DPP10 lacks the active-site serine, which is substituted with a glycine residue. Database analysis suggested the presence of a second DPP10 transcript. DPP10 shares 48% and 51% amino acid identity with the short and long DPP6 isoforms, respectively. Northern blot analysis of several human tissues detected a major 3.5-kb DPP10 transcript expressed only in brain and pancreas. Transcripts of 5.0 and 7.5 kb were also detected in brain. ESTs representing DPP10 mRNA were abundant in tissues derived from multiple sclerosis (126200) lesions, retinoblastoma (180200), hypothalamus, hippocampus, and whole brain, with few transcripts found in uterus, colon, and various tumors. Analysis of mouse ESTs indicated that mouse Dpp10 was expressed in several brain regions and retina. DPP10 was recovered in the membrane fraction of transfected cells.
Qi et al. (2003) confirmed that DPP10 does not possess dipeptidyl peptidase activity due to the lack of a critical active-site serine.
Qi et al. (2003) determined that the DPP10 gene contains at least 23 exons.
By genomic sequence analysis, Qi et al. (2003) mapped the DPP10 gene to chromosome 2q12.3-q14.2.
Allen et al. (2003) pointed out that 4 separate reports had linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32, and that 2 mouse genome screens linked bronchial hyperresponsiveness to the region homologous to 2q14. They found and replicated association between asthma and the D2S308 microsatellite marker, 800 kb distal to the IL1 (IL1A; 147760) cluster on 2q14. Sequencing the surrounding region, they constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium map. They found SNP association limited to the initial exons of the DPP10 gene. DPP10 encodes a homolog of dipeptidylpeptidases that cleave terminal dipeptides from cytokines and chemokines, and presents a potential new target for asthma therapy.
Allen, M., Heinzmann, A., Noguchi, E., Abecasis, G., Broxholme, J., Ponting, C. P., Bhattacharyya, S., Tinsley, J., Zhang, Y., Holt, R., Jones, E. Y., Lench, N., and 18 others. Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nature Genet. 35: 258-263, 2003. [PubMed: 14566338] [Full Text: https://doi.org/10.1038/ng1256]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331] [Full Text: https://doi.org/10.1093/dnares/7.2.143]
Qi, S. Y., Riviere, P. J., Trojnar, J., Junien, J.-L., Akinsanya, K. O. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem. J. 373: 179-189, 2003. [PubMed: 12662155] [Full Text: https://doi.org/10.1042/BJ20021914]