Hexa-Longin domain scaffolds for inter-Rab signalling

Luis Sanchez-Pulido; Chris P Ponting

doi:10.1093/bioinformatics/btz739

Hexa-Longin domain scaffolds for inter-Rab signalling

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Abstract

SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17, and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Original language	English
Journal	Bioinformatics
Early online date	28 Sept 2019
DOIs	https://doi.org/10.1093/bioinformatics/btz739
Publication status	Published - 15 Feb 2020

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10.1093/bioinformatics/btz739

Ponting C Hexa-longin domain...
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Accepted author manuscript, 820 KBLicence: Creative Commons: Attribution (CC-BY)

Computational and Disease Genomics
Ponting, C. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

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title = "Hexa-Longin domain scaffolds for inter-Rab signalling",

abstract = "SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17, and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",

author = "Luis Sanchez-Pulido and Ponting, {Chris P}",

note = "{\textcopyright} The Author(s) 2019. Published by Oxford University Press.",

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doi = "10.1093/bioinformatics/btz739",

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T1 - Hexa-Longin domain scaffolds for inter-Rab signalling

AU - Sanchez-Pulido, Luis

AU - Ponting, Chris P

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N2 - SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17, and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AB - SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17, and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

U2 - 10.1093/bioinformatics/btz739

DO - 10.1093/bioinformatics/btz739

M3 - Article

C2 - 31562761

SN - 1367-4803

JO - Bioinformatics

JF - Bioinformatics

ER -

Hexa-Longin domain scaffolds for inter-Rab signalling

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Computational and Disease Genomics

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