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A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate

by 1,2,†, 1,2,†, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1 and 1,2,*
1
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China
2
Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Peer Jacobson
Mar. Drugs 2015, 13(5), 2955-2966; https://doi.org/10.3390/md13052955
Received: 11 January 2015 / Revised: 28 April 2015 / Accepted: 5 May 2015 / Published: 13 May 2015
APSL (active peptide from shark liver) is a hepatic stimulator cytokine from the liver of Chiloscyllium. It can effectively protect islet cells and improve complications in mice with alloxan-induced diabetes. Here, we demonstrate that the APSL sequence is present in the N-terminus of novel TBC (Tre-2, Bub2 and Cdc16) domain family, member 15 (TBC1D15) from Chiloscyllium plagiosum. This shark TBC1D15 gene, which contains an ORF of 2088 bp, was identified from a cDNA library of regenerating shark liver. Bioinformatic analysis showed that the gene is highly homologous to TBC1D15 genes from other species. Moreover, the N-terminus of shark TBC1D15 contains a motif of unknown function (DUF3548), which encompasses the APSL fragment. Rab-GAP activity analysis showed that shark TBC1D15 is a new member of the TBC1D15 family. These results demonstrated that shark TBC1D15 possesses Rab-GAP activity using Rab7 as a substrate, which is a common property of the TBC1D15 family. The involvement of APSL at the N-terminus of TBC1D15 also demonstrates that this protein might be involved in insulin signaling and may be associated with the development of type 2 diabetes. The current findings pave the way for further functional and clinical studies of these proteins from marine sources. View Full-Text
Keywords: APSL; TBC1D15 protein; Rab-GAP activity; type 2 diabetes APSL; TBC1D15 protein; Rab-GAP activity; type 2 diabetes
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Li, Y.; Wang, W.; Cheng, D.; Wang, T.; Lu, C.; Chen, J.; Nie, Z.; Zhang, W.; Lv, Z.; Wu, W.; Shu, J. A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate. Mar. Drugs 2015, 13, 2955-2966.

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