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      MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations

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          Abstract

          The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning with the MitoCarta2.0 inventory, we performed manual review to remove 100 genes and introduce 78 additional genes, arriving at an updated inventory of 1136 human genes. We now include manually curated annotations of sub-mitochondrial localization (matrix, inner membrane, intermembrane space, outer membrane) as well as assignment to 149 hierarchical ‘MitoPathways’ spanning seven broad functional categories relevant to mitochondria. MitoCarta3.0, including sub-mitochondrial localization and MitoPathway annotations, is freely available at http://www.broadinstitute.org/mitocarta and should serve as a continued community resource for mitochondrial biology and medicine.

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          KEGG: kyoto encyclopedia of genes and genomes.

          M Kanehisa (2000)
          KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).
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            UniProt: a worldwide hub of protein knowledge

            (2018)
            Abstract The UniProt Knowledgebase is a collection of sequences and annotations for over 120 million proteins across all branches of life. Detailed annotations extracted from the literature by expert curators have been collected for over half a million of these proteins. These annotations are supplemented by annotations provided by rule based automated systems, and those imported from other resources. In this article we describe significant updates that we have made over the last 2 years to the resource. We have greatly expanded the number of Reference Proteomes that we provide and in particular we have focussed on improving the number of viral Reference Proteomes. The UniProt website has been augmented with new data visualizations for the subcellular localization of proteins as well as their structure and interactions. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.
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              Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.

              We describe and validate a new membrane protein topology prediction method, TMHMM, based on a hidden Markov model. We present a detailed analysis of TMHMM's performance, and show that it correctly predicts 97-98 % of the transmembrane helices. Additionally, TMHMM can discriminate between soluble and membrane proteins with both specificity and sensitivity better than 99 %, although the accuracy drops when signal peptides are present. This high degree of accuracy allowed us to predict reliably integral membrane proteins in a large collection of genomes. Based on these predictions, we estimate that 20-30 % of all genes in most genomes encode membrane proteins, which is in agreement with previous estimates. We further discovered that proteins with N(in)-C(in) topologies are strongly preferred in all examined organisms, except Caenorhabditis elegans, where the large number of 7TM receptors increases the counts for N(out)-C(in) topologies. We discuss the possible relevance of this finding for our understanding of membrane protein assembly mechanisms. A TMHMM prediction service is available at http://www.cbs.dtu.dk/services/TMHMM/. Copyright 2001 Academic Press.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2021
                11 November 2020
                11 November 2020
                : 49
                : D1
                : D1541-D1547
                Affiliations
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Broad Institute of MIT and Harvard, Cambridge , MA 02142, USA
                Howard Hughes Medical Institute and Departments of Molecular Biology and Medicine, Massachusetts General Hospital, Boston , MA 02114, USA
                Department of Systems Biology, Harvard Medical School , Boston, MA 02115, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 617 643 3059; Email: vamsi@ 123456hms.harvard.edu
                Correspondence may also be addressed to Sarah E. Calvo. Email: scalvo@ 123456broadinstitute.org

                The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.

                Author information
                http://orcid.org/0000-0001-8839-1285
                http://orcid.org/0000-0002-1847-682X
                http://orcid.org/0000-0001-8263-2455
                http://orcid.org/0000-0001-5321-6938
                http://orcid.org/0000-0003-4983-1414
                http://orcid.org/0000-0002-0817-553X
                http://orcid.org/0000-0001-6449-6058
                http://orcid.org/0000-0001-9924-642X
                Article
                gkaa1011
                10.1093/nar/gkaa1011
                7778944
                33174596
                387d8df3-02fb-45d6-878c-a336cb877bd0
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 14 October 2020
                : 12 October 2020
                : 18 September 2020
                Page count
                Pages: 7
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: K00CA212468
                Award ID: T32AG000222
                Award ID: K08DK115881
                Award ID: R01AR071942
                Award ID: T32AG000222
                Award ID: F32GM128259
                Award ID: F32GM133047
                Award ID: T32DK007028
                Award ID: R35GM122455
                Funded by: Jane Coffin Childs;
                Funded by: Deutsche Forschungsgemeinschaft, DOI 10.13039/501100001659;
                Award ID: 431313887
                Funded by: Massachusetts General Hospital Department of Neurology;
                Funded by: Dollis Huntington Endowment Fund for Cancer Research;
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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