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      ELM—the eukaryotic linear motif resource in 2020

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          Abstract

          The eukaryotic linear motif (ELM) resource is a repository of manually curated experimentally validated short linear motifs (SLiMs). Since the initial release almost 20 years ago, ELM has become an indispensable resource for the molecular biology community for investigating functional regions in many proteins. In this update, we have added 21 novel motif classes, made major revisions to 12 motif classes and added >400 new instances mostly focused on DNA damage, the cytoskeleton, SH2-binding phosphotyrosine motifs and motif mimicry by pathogenic bacterial effector proteins. The current release of the ELM database contains 289 motif classes and 3523 individual protein motif instances manually curated from 3467 scientific publications. ELM is available at: http://elm.eu.org.

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          Most cited references64

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          PCNA, the maestro of the replication fork.

          Inheritance requires genome duplication, reproduction of chromatin and its epigenetic information, mechanisms to ensure genome integrity, and faithful transmission of the information to progeny. Proliferating cell nuclear antigen (PCNA)-a cofactor of DNA polymerases that encircles DNA-orchestrates several of these functions by recruiting crucial players to the replication fork. Remarkably, many factors that are involved in replication-linked processes interact with a particular face of PCNA and through the same interaction domain, indicating that these interactions do not occur simultaneously during replication. Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO.
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            Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation.

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              Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.

              The crystal structure of the human DNA polymerase delta processivity factor PCNA (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint protein p21(WAF1/CIP1) has been determined at 2.6 angstrom resolution. p21 binds to PCNA in a 1:1 stoichiometry with an extensive array of interactions that include the formation of a beta sheet with the interdomain connector loop of PCNA. An intact trimeric ring is maintained in the structure of the p21-PCNA complex, with a central hole available for DNA interaction. The ability of p21 to inhibit the action of PCNA is therefore likely to be due to its masking of elements on PCNA that are required for the binding of other components of the polymerase assembly.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2020
                04 November 2019
                04 November 2019
                : 48
                : D1
                : D296-D306
                Affiliations
                [1 ] Structural and Computational Biology Unit, European Molecular Biology Laboratory , Heidelberg 69117, Germany
                [2 ] Collaboration for Joint PhD Degree between EMBL and Heidelberg University, Faculty of Biosciences
                [3 ] Institute of Enzymology, Research Centre for Natural Sciences , Budapest 1117, Hungary
                [4 ] Instituto de Investigaciones Biotecnológicas (IIBio) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad Nacional de San Martín. Av. 25 de Mayo y Francia, CP1650, Buenos Aires, Argentina
                [5 ] Nazarbayev University , Nur-Sultan 010000, Kazakhstan
                [6 ] Department of Science and Technology, Universidad Nacional de Quilmes - CONICET , Bernal B1876BXD, Buenos Aires, Argentina
                [7 ] The Institute of Cancer Research, Chester Beatty Laboratories , 237 Fulham Rd, Chelsea, London SW3 6JB, UK
                Author notes
                To whom correspondence should be addressed. Tel: +49 6221 387 8530; Email: manjeet.kumar@ 123456embl.de
                Correspondence may also be addressed to Lucía B. Chemes. Tel: +54 11 40061500 x 2133; Email: lchemes@ 123456iib.unsam.edu.ar
                Correspondence may also be addressed to Toby J. Gibson. Tel: +49 6221 387 8398; Email: toby.gibson@ 123456embl.de

                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/0000-0002-7146-289X
                http://orcid.org/0000-0001-9248-8450
                http://orcid.org/0000-0001-8801-3196
                http://orcid.org/0000-0003-4744-4787
                http://orcid.org/0000-0003-0849-9312
                http://orcid.org/0000-0001-6336-1290
                http://orcid.org/0000-0002-5536-363X
                http://orcid.org/0000-0003-0752-1151
                http://orcid.org/0000-0003-0348-2677
                http://orcid.org/0000-0003-1047-4157
                http://orcid.org/0000-0001-7925-6436
                http://orcid.org/0000-0001-6988-4850
                http://orcid.org/0000-0003-0192-9906
                http://orcid.org/0000-0003-0657-5166
                Article
                gkz1030
                10.1093/nar/gkz1030
                7145657
                31680160
                87525a53-e996-40c9-89e3-68050bb4cf50
                © The Author(s) 2019. 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 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.

                History
                : 23 October 2019
                : 18 October 2019
                : 25 September 2019
                Page count
                Pages: 11
                Funding
                Funded by: European Molecular Biology Laboratory 10.13039/100013060
                Funded by: Argentine Ministry of Science and Technology
                Funded by: German Academic Exchange
                Award ID: CyCmotif DA/16/05
                Funded by: Agencia Nacional de Promoción Científica y Tecnológica 10.13039/501100003074
                Award ID: PICT 2017/1924
                Award ID: PICT 2015/3367
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas 10.13039/501100002923
                Funded by: Hungarian National Research
                Award ID: FK-128133
                Funded by: Hungarian Academy of Sciences 10.13039/501100003825
                Award ID: PREMIUM-2017–48
                Funded by: Cancer Research UK 10.13039/501100000289
                Award ID: C68484/A28159
                Funded by: Horizon 2020 10.13039/100010661
                Award ID: 778247
                Award ID: 675341
                Categories
                Database Issue

                Genetics
                Genetics

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