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Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins

Several proteins are secreted outside the cell, and in many cases, they may be identified by a characteristic signal peptide. However, more and more studies point to the evidence for an “unconventional” secretion, where proteins without a hitherto unknown signal are secreted, possibly in conditions...

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Autores principales: Biswal, Malay Ranjan, Padmanabhan, Sreedevi, Manjithaya, Ravi, Prakash, Meher K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136135/
https://www.ncbi.nlm.nih.gov/pubmed/35646924
http://dx.doi.org/10.3389/fcell.2022.863825
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author Biswal, Malay Ranjan
Padmanabhan, Sreedevi
Manjithaya, Ravi
Prakash, Meher K.
author_facet Biswal, Malay Ranjan
Padmanabhan, Sreedevi
Manjithaya, Ravi
Prakash, Meher K.
author_sort Biswal, Malay Ranjan
collection PubMed
description Several proteins are secreted outside the cell, and in many cases, they may be identified by a characteristic signal peptide. However, more and more studies point to the evidence for an “unconventional” secretion, where proteins without a hitherto unknown signal are secreted, possibly in conditions of starvation. In this work, we analyse a set of 202 RNA binding mammalian proteins, whose unconventional secretion has recently been established. Analysis of these proteins secreted by LC3 mediation, the largest unconventionally secreted dataset to our knowledge, identifies the role of KKX motif as well as triacidic amino acid motif in unconventional secretion, the latter being an extension of the recent implicated diacidic amino acid motif. Further data analysis evolves a hypothesis on the sequence or structural proximity of the triacidic or KKX motifs to the LC3 interacting region, and a phosphorylatable amino acid such as serine as a statistically significant feature among these unconventionally secreted proteins. This hypothesis, although needs to be validated in experiments that challenge the specific details of each of these aspects, appears to be one of the early steps in defining what may be a plausible signal for unconventional protein secretion.
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spelling pubmed-91361352022-05-28 Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins Biswal, Malay Ranjan Padmanabhan, Sreedevi Manjithaya, Ravi Prakash, Meher K. Front Cell Dev Biol Cell and Developmental Biology Several proteins are secreted outside the cell, and in many cases, they may be identified by a characteristic signal peptide. However, more and more studies point to the evidence for an “unconventional” secretion, where proteins without a hitherto unknown signal are secreted, possibly in conditions of starvation. In this work, we analyse a set of 202 RNA binding mammalian proteins, whose unconventional secretion has recently been established. Analysis of these proteins secreted by LC3 mediation, the largest unconventionally secreted dataset to our knowledge, identifies the role of KKX motif as well as triacidic amino acid motif in unconventional secretion, the latter being an extension of the recent implicated diacidic amino acid motif. Further data analysis evolves a hypothesis on the sequence or structural proximity of the triacidic or KKX motifs to the LC3 interacting region, and a phosphorylatable amino acid such as serine as a statistically significant feature among these unconventionally secreted proteins. This hypothesis, although needs to be validated in experiments that challenge the specific details of each of these aspects, appears to be one of the early steps in defining what may be a plausible signal for unconventional protein secretion. Frontiers Media S.A. 2022-05-13 /pmc/articles/PMC9136135/ /pubmed/35646924 http://dx.doi.org/10.3389/fcell.2022.863825 Text en Copyright © 2022 Biswal, Padmanabhan, Manjithaya and Prakash. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Biswal, Malay Ranjan
Padmanabhan, Sreedevi
Manjithaya, Ravi
Prakash, Meher K.
Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title_full Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title_fullStr Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title_full_unstemmed Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title_short Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins
title_sort early bioinformatic implication of triacidic amino acid motifs in autophagy-dependent unconventional secretion of mammalian proteins
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136135/
https://www.ncbi.nlm.nih.gov/pubmed/35646924
http://dx.doi.org/10.3389/fcell.2022.863825
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