title: A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate.
abstract: 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.
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. liyy_08@163.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. liyy_08@163.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. wangweidong0106@163.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. wangweidong0106@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. ddCzstu1990@126.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. ddCzstu1990@126.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Cheng
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. wangtao900121@163.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. wangtao900121@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. luconger0302@163.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. luconger0302@163.com.
authors.forename: Conger
authors.initials: C
authors.lastname: Lu
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. chj1999@126.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. chj1999@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. wuxinzm@zstu.edu.cn.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. wuxinzm@zstu.edu.cn.
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Nie
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. zwpcc@126.com.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. zwpcc@126.com.
authors.forename: Wenping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. zhengbingl@zstu.edu.cn.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. zhengbingl@zstu.edu.cn.
authors.forename: Zhengbing
authors.initials: Z
authors.lastname: Lv
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. wangweidong0106@163.com.
authors.forename: Wutong
authors.initials: W
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. shujianhong@zstu.edu.cn.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China. shujianhong@zstu.edu.cn.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Shu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015723:Gene Library; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012754:Sharks / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D020690:GTPase-Activating Proteins; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins
keywords: APSL; Rab-GAP activity; TBC1D15 protein; type 2 diabetes