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

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-...

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Veröffentlicht in:Marine drugs 2015-05, Vol.13 (5), p.2955-2966
Hauptverfasser: Li, Yuanyuan, Wang, Weidong, Cheng, Dandan, Wang, Tao, Lu, Conger, Chen, Jian, Nie, Zuoming, Zhang, Wenping, Lv, Zhengbing, Wu, Wutong, Shu, Jianhong
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container_end_page 2966
container_issue 5
container_start_page 2955
container_title Marine drugs
container_volume 13
creator Li, Yuanyuan
Wang, Weidong
Cheng, Dandan
Wang, Tao
Lu, Conger
Chen, Jian
Nie, Zuoming
Zhang, Wenping
Lv, Zhengbing
Wu, Wutong
Shu, Jianhong
description 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.
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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.</description><identifier>ISSN: 1660-3397</identifier><identifier>EISSN: 1660-3397</identifier><identifier>DOI: 10.3390/md13052955</identifier><identifier>PMID: 25984991</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Amino Acid Sequence ; Animals ; Chiloscyllium ; Chiloscyllium plagiosum ; Diabetes Mellitus, Type 2 - metabolism ; Gene Library ; GTPase-Activating Proteins - metabolism ; Liver - metabolism ; Molecular Sequence Data ; Protein Structure, Tertiary ; rab GTP-Binding Proteins - metabolism ; Sequence Alignment ; Sharks - metabolism ; Signal Transduction - physiology</subject><ispartof>Marine drugs, 2015-05, Vol.13 (5), p.2955-2966</ispartof><rights>Copyright MDPI AG 2015</rights><rights>2015 by the authors; licensee MDPI, Basel, Switzerland. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-7feea4f8fab238720f80ceeb9a24a35b6c6eb35561210737871e664d6b0fb3f33</citedby><cites>FETCH-LOGICAL-c439t-7feea4f8fab238720f80ceeb9a24a35b6c6eb35561210737871e664d6b0fb3f33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446614/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446614/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25984991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yuanyuan</creatorcontrib><creatorcontrib>Wang, Weidong</creatorcontrib><creatorcontrib>Cheng, Dandan</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Lu, Conger</creatorcontrib><creatorcontrib>Chen, Jian</creatorcontrib><creatorcontrib>Nie, Zuoming</creatorcontrib><creatorcontrib>Zhang, Wenping</creatorcontrib><creatorcontrib>Lv, Zhengbing</creatorcontrib><creatorcontrib>Wu, Wutong</creatorcontrib><creatorcontrib>Shu, Jianhong</creatorcontrib><title>A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate</title><title>Marine drugs</title><addtitle>Mar Drugs</addtitle><description>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. 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>25984991</pmid><doi>10.3390/md13052955</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
Animals
Chiloscyllium
Chiloscyllium plagiosum
Diabetes Mellitus, Type 2 - metabolism
Gene Library
GTPase-Activating Proteins - metabolism
Liver - metabolism
Molecular Sequence Data
Protein Structure, Tertiary
rab GTP-Binding Proteins - metabolism
Sequence Alignment
Sharks - metabolism
Signal Transduction - physiology
title A New Member of the TBC1D15 Family from Chiloscyllium plagiosum: Rab GTPase-Activating Protein Based on Rab7 as a Substrate
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