DPP10 Membrane Protein Introduction

Introduction of DPP10

DPP10 is encoded by the DPP10 gene which is located on the long arm of chromosome 2 (2q12.3-2q14.2) and is identified as a candidate for susceptibility to asthma, a common disease of the airways. It belongs to the peptidase S9B serine proteases family. DPP10 is a single-pass type II membrane protein, of which N-terminus is on the cytoplasmic side of the membrane. The transmembrane domain is located close to the N-terminus and it functions as an anchor. DPP10 is expressed mainly in the brain and pancreas. The molecular mass of DPP10 is about 90 KDa.

Function of DPP10 Membrane Protein

DPP10 is identified based on its sequence conservation with DPP6. It belongs to the DPP classes of K⁺ channel ancillary subunit and is related to the dipeptidyl aminopeptidase DPP4. However, DPP10 is found to lack DPP activity because the active-site serine residue is replaced by a glycine residue. DPP10 can be found in serum, T-cells, and brain. It is expressed in brain, pancreas, spinal cord and adrenal glands. Besides, DPP10 may be a general modulator of voltage-gated K⁺ channel inactivation. DPP10 also participates in positive regulation of protein localization to plasma membrane, protein localization to plasma membrane and regulation of potassium ion transmembrane transport. It has been proved that DPP10 can increase surface expression of Kv4.2 (a member of Voltage-gated K⁺ channels) in heterologous expression systems through direct interaction with the α-subunit. It is also able to accelerate inactivation and recovery from inactivation kinetics. Moreover, DPP10 contributes to the molecular composition of A-type currents in the central nervous system.

Fig.1 Representation of Kv4.3-KChIP2b complex, DPP10, and mini-10. (Li, 2006)

Application of DPP10 Membrane Protein in Literature

1. Asl M., et al. Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10. Molecular Autism. 2017, 8(1):31. PubMed ID: 28670437
   
   

   This article reports that the DPP10 duplication may be a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings.

2. Shiina Y., et al. Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity. Scientific Reports. 2016, 6:26290. PubMed ID: 27198182
   
   

   This article reveals that fly DPP10 is similar to mammalian’ s, as the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. In addition to its channel regulatory role, fly DPP10 exhibits significant dipeptidyl peptidase activity with Gly-Pro-MCA (glycyl-L-proline 4-methylcoumaryl-7-amide) as a substrate.

3. Masahiro K., et al. Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit preferentially form a 4:2 (Kv4.2: DPP10) channel complex. Journal of Biological Chemistry. 2015, 290(37):22724-33. PubMed ID: 26209633
   
   

   Authors in this group find that the electrophysiological properties of Kv4.2 are affected by the expression level of DPP10. Moreover, about 70% of DPP10 on the membrane exists as dimers, and the rest exists as monomers. And the stoichiometry of Kv4.2-DPP10 is variable with a preference for the 4:2 configuration.

4. Wang W.C., et al. Immunohistochemical localization of DPP10 in rat brain supports the existence of a Kv4/KChIP/DPPL ternary complex in neurons. Journal of Comparative Neurology. 2015, 523(4):608-628. PubMed ID: 25355692
   
   

   This article is related to DPP10 protein localization. Authors generate a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. At last, they find that colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo.

5. Qi S R.P., et al. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochemical Journal. 2003, 373(1):179-89. PubMed ID: 12662155
   
   

   This article for the first time describes the cloning of DPP10, a member of an emerging subgroup of serine proteases. The article focuses on DPP10 expression, gene location, potential function, and some other basic features.

DPP10 Preparation Options

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Reference

1. Li H. L., et al. (2006). Dpp10 is an inactivation modulatory protein of kv4.3 and kv1.4. Ajp Cell Physiology. 291(291), C966-76.

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