DPP10 explained

Inactive dipeptidyl peptidase 10 is a protein that in humans is encoded by the DPP10 gene.^{[1] [2] [3]} Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Function

This gene encodes a single-pass type II membrane protein that is a member of the S9B family in clan SC of the serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties.

Clinical significance

Mutations in this gene have been associated with asthma and autism spectrum disorders.^[4]

Further reading

• Yamada R, Ymamoto K . Recent findings on genes associated with inflammatory disease . Mutat. Res. . 573 . 1–2 . 136–51 . 2005 . 15829243 . 10.1016/j.mrfmmm.2004.06.061 .
• Book: Chen T, Ajami K, McCaughan GW, Gorrell MD, Abbott CA . Dipeptidyl peptidase IV gene family. The DPIV family . Dipeptidyl Peptidase IV Gene Family . Adv. Exp. Med. Biol. . 524 . 79–86 . 2003 . Springer . 12675227 . 10.1007/0-306-47920-6_10 . 9780306479205 .
• Allen M, Heinzmann A, Noguchi E, Abecasis G, Broxholme J, Ponting CP, Bhattacharyya S, Tinsley J, Zhang Y, Holt R, Jones EY, Lench N, Carey A, Jones H, Dickens NJ, Dimon C, Nicholls R, Baker C, Xue L, Townsend E, Kabesch M, Weiland SK, Carr D, von Mutius E, Adcock IM, Barnes PJ, Lathrop GM, Edwards M, Moffatt MF, Cookson WO . Positional cloning of a novel gene influencing asthma from chromosome 2q14 . Nat. Genet. . 35 . 3 . 258–63 . November 2003 . 14566338 . 10.1038/ng1256 . 40595323 .
• Jerng HH, Qian Y, Pfaffinger PJ . Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10) . Biophys. J. . 87 . 4 . 2380–96 . 2005 . 15454437 . 10.1529/biophysj.104.042358 . 1304660 .
• Zagha E, Ozaita A, Chang SY, Nadal MS, Lin U, Saganich MJ, McCormack T, Akinsanya KO, Qi SY, Rudy B . DPP10 modulates Kv4-mediated A-type potassium channels . J. Biol. Chem. . 280 . 19 . 18853–61 . May 2005 . 15671030 . 10.1074/jbc.M410613200 . free .
• Ren X, Hayashi Y, Yoshimura N, Takimoto K . Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels . Mol. Cell. Neurosci. . 29 . 2 . 320–32 . 2005 . 15911355 . 10.1016/j.mcn.2005.02.003 . 34065803 .
• Chen T, Ajami K, McCaughan GW, Gai WP, Gorrell MD, Abbott CA . Molecular characterization of a novel dipeptidyl peptidase like 2-short form (DPL2-s) that is highly expressed in the brain and lacks dipeptidyl peptidase activity . Biochim. Biophys. Acta . 1764 . 1 . 33–43 . January 2006 . 16290253 . 10.1016/j.bbapap.2005.09.013 .
• Takimoto K, Hayashi Y, Ren X, Yoshimura N . Species and tissue differences in the expression of DPPY splicing variants . Biochem. Biophys. Res. Commun. . 348 . 3 . 1094–100 . 2006 . 16899223 . 10.1016/j.bbrc.2006.07.157 .
• Jerng HH, Lauver AD, Pfaffinger PJ . DPP10 splice variants are localized in distinct neuronal populations and act to differentially regulate the inactivation properties of Kv4-based ion channels . Mol. Cell. Neurosci. . 35 . 4 . 604–24 . 2007 . 17475505 . 10.1016/j.mcn.2007.03.008 . 3674967 .
• Hersh CP, Raby BA, Soto-Quirós ME, Murphy AJ, Avila L, Lasky-Su J, Sylvia JS, Klanderman BJ, Lange C, Weiss ST, Celedón JC . Comprehensive testing of positionally cloned asthma genes in two populations . Am. J. Respir. Crit. Care Med. . 176 . 9 . 849–57 . November 2007 . 17702965 . 2048676 . 10.1164/rccm.200704-592OC .

Notes and References

1. 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 . 2 . 143–50 . Sep 2000 . 10819331 . 10.1093/dnares/7.2.143 . free .
2. Qi SY, Riviere PJ, Trojnar J, Junien JL, Akinsanya KO . Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases . Biochem J . 373 . Pt 1 . 179–89 . Jun 2003 . 12662155 . 1223468 . 10.1042/BJ20021914 .
3. Web site: Entrez Gene: DPP10 dipeptidyl-peptidase 10.
4. Girirajan S, Dennis MY, Baker C, Malig M, Coe BP, Campbell CD, Mark K, Vu TH, Alkan C, Cheng Z, Biesecker LG, Bernier R, Eichler EE . Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder . Am. J. Hum. Genet. . 92 . 2 . 221–37 . February 2013 . 23375656 . 3567267 . 10.1016/j.ajhg.2012.12.016 .