RGD Reference Report - Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity. - Rat Genome Database

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Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity.

Authors: Shiina, Yohei  Muto, Tomohiro  Zhang, Zhili  Baihaqie, Ahmad  Yoshizawa, Takamasa  Lee, Hye-In J  Park, Eulsoon  Tsukiji, Shinya  Takimoto, Koichi 
Citation: Shiina Y, etal., Sci Rep. 2016 May 20;6:26290. doi: 10.1038/srep26290.
RGD ID: 13441205
Pubmed: PMID:27198182   (View Abstract at PubMed)
PMCID: PMC4873792   (View Article at PubMed Central)
DOI: DOI:10.1038/srep26290   (Journal Full-text)

Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation. It also results in faster inactivation and recovery from inactivation. 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. Heterologously expressed Flag-tagged fly DPP10 and human DPP4 show similar Km values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative kcat value normalized with anti-Flag immunoreactivity than human DPP4. These results demonstrate that fly DPP10 is a dual functional protein, controlling Kv4 channel gating and removing bioactive peptides.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
potassium ion import across plasma membrane involved_inIDA 13441205PMID:27198182CAFA 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
voltage-gated potassium channel complex part_ofIPIUniProtKB:Q6289713441205PMID:27198182CAFA 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Kcnd3  (potassium voltage-gated channel subfamily D member 3)


Additional Information