Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
2.7
3.2
Journals
Life
Special Issues
Structure, Activity, and Function of Protein Methyltransferases
share announcement

Structure, Activity, and Function of Protein Methyltransferases

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Proteins and Proteomics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 68605

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Albert Jeltsch

E-Mail Website
Guest Editor
Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Stuttgart, Germany
Interests: DNA methyltransferases; DNA methylation; protein methyltransferases; protein methylation; reading domains; molecular epigenetics; synthetic biology; molecular enzymology
Special Issues, Collections and Topics in MDPI journals
Dr. Arunkumar Dhayalan

E-Mail Website
Guest Editor
Department of Biotechnology, Pondicherry University, Puducherry 605014, India
Interests: protein arginine methyltransferases; histone arginine methylation; reader proteins; DEAD box family of RNA helicases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Life Special Issue entitled "Structure, Activity, and Function of Protein Methyltransferases” will collect reviews about individual Protein methyltransferases supplemented by some topical reviews all written by leading experts in the field. The scope covers Protein lysine methyltransferases, Protein arginine methyltransferases, but also the less abundant Protein glutamine methyltransferases, Protein histidine methyltransferases and Protein N-terminal end methyltransferases. This concept will make the special issue a very useful resource for researchers from the entire Protein methylation and Protein methyltransferase field.

The scope of the special issue includes histone methyltransferases involved chromatin regulation but also methylation of non-histone proteins. Topics to be considered in the individual enzyme reviews include structural features (domain architecture, homologs and paralogs, structure), biochemical features (mechanism, sequence specificity, product specificity, regulation, substrates), cellular features (subcellular localization, expression patterns, cellular roles and function, biological effects of substrate protein methylation, connection to cell signaling pathways, connection to chromatin regulation) as well as connection to diseases. Reviews should be closed with an outlook, open questions, and directions for future research.

We invite suggestions for manuscripts to be included in this special issue. Please contact the editors before preparing the manuscript for a pre-arrangement of the topic.

Prof. Dr. Albert Jeltsch
Dr. Arunkumar Dhayalan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • protein methyltransferase
  • protein lysine methyltransferase
  • protein arginine methyltransferase
  • protein glutamine methyltransferase
  • protein histidine methyltransferase
  • protein methylation
  • histone methylation
  • chromatin regulation
  • non-histone protein methylation

Published Papers (17 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Review

4 pages, 1892 KiB  
Editorial
Special Issue “Structure, Activity, and Function of Protein Methyltransferases”
by Arunkumar Dhayalan and Albert Jeltsch
Life 2022, 12(3), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/life12030405 - 10 Mar 2022
Cited by 1 | Viewed by 1656
Abstract
Post-translational modifications (PTMs) largely expand the functional diversity of the proteome [...] Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial

13 pages, 1070 KiB  
Review
The Role of Lysine Methyltransferase SET7/9 in Proliferation and Cell Stress Response
by Alexandra Daks, Elena Vasileva, Olga Fedorova, Oleg Shuvalov and Nickolai A. Barlev
Life 2022, 12(3), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/life12030362 - 02 Mar 2022
Cited by 9 | Viewed by 3025
Abstract
Lysine-specific methyltransferase 7 (KMT7) SET7/9, aka Set7, Set9, or SetD7, or KMT5 was discovered 20 years ago, yet its biological role remains rather enigmatic. In this review, we analyze the particularities of SET7/9 enzymatic activity and substrate specificity with respect to its biological [...] Read more.
Lysine-specific methyltransferase 7 (KMT7) SET7/9, aka Set7, Set9, or SetD7, or KMT5 was discovered 20 years ago, yet its biological role remains rather enigmatic. In this review, we analyze the particularities of SET7/9 enzymatic activity and substrate specificity with respect to its biological importance, mostly focusing on its two well-characterized biological functions: cellular proliferation and stress response. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

17 pages, 1862 KiB  
Review
Structure, Activity, and Function of SETMAR Protein Lysine Methyltransferase
by Michael Tellier
Life 2021, 11(12), 1342; https://0-doi-org.brum.beds.ac.uk/10.3390/life11121342 - 04 Dec 2021
Cited by 6 | Viewed by 2984
Abstract
SETMAR is a protein lysine methyltransferase that is involved in several DNA processes, including DNA repair via the non-homologous end joining (NHEJ) pathway, regulation of gene expression, illegitimate DNA integration, and DNA decatenation. However, SETMAR is an atypical protein lysine methyltransferase since in [...] Read more.
SETMAR is a protein lysine methyltransferase that is involved in several DNA processes, including DNA repair via the non-homologous end joining (NHEJ) pathway, regulation of gene expression, illegitimate DNA integration, and DNA decatenation. However, SETMAR is an atypical protein lysine methyltransferase since in anthropoid primates, the SET domain is fused to an inactive DNA transposase. The presence of the DNA transposase domain confers to SETMAR a DNA binding activity towards the remnants of its transposable element, which has resulted in the emergence of a gene regulatory function. Both the SET and the DNA transposase domains are involved in the different cellular roles of SETMAR, indicating the presence of novel and specific functions in anthropoid primates. In addition, SETMAR is dysregulated in different types of cancer, indicating a potential pathological role. While some light has been shed on SETMAR functions, more research and new tools are needed to better understand the cellular activities of SETMAR and to investigate the therapeutic potential of SETMAR. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

13 pages, 2526 KiB  
Review
Structure, Activity and Function of the PRMT2 Protein Arginine Methyltransferase
by Vincent Cura and Jean Cavarelli
Life 2021, 11(11), 1263; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111263 - 19 Nov 2021
Cited by 28 | Viewed by 2914
Abstract
PRMT2 belongs to the protein arginine methyltransferase (PRMT) family, which catalyzes the arginine methylation of target proteins. As a type I enzyme, PRMT2 produces asymmetric dimethyl arginine and has been shown to have weak methyltransferase activity on histone substrates in vitro, suggesting that [...] Read more.
PRMT2 belongs to the protein arginine methyltransferase (PRMT) family, which catalyzes the arginine methylation of target proteins. As a type I enzyme, PRMT2 produces asymmetric dimethyl arginine and has been shown to have weak methyltransferase activity on histone substrates in vitro, suggesting that its authentic substrates have not yet been found. PRMT2 contains the canonical PRMT methylation core and a unique Src homology 3 domain. Studies have demonstrated its clear implication in many different cellular processes. PRMT2 acts as a coactivator of several nuclear hormone receptors and is known to interact with a multitude of splicing-related proteins. Furthermore, PRMT2 is aberrantly expressed in several cancer types, including breast cancer and glioblastoma. These reports highlight the crucial role played by PRMT2 and the need for a better characterization of its activity and cellular functions. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

23 pages, 802 KiB  
Review
Structure, Activity, and Function of PRMT1
by Charlène Thiebaut, Louisane Eve, Coralie Poulard and Muriel Le Romancer
Life 2021, 11(11), 1147; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111147 - 27 Oct 2021
Cited by 37 | Viewed by 4581
Abstract
PRMT1, the major protein arginine methyltransferase in mammals, catalyzes monomethylation and asymmetric dimethylation of arginine side chains in proteins. Initially described as a regulator of chromatin dynamics through the methylation of histone H4 at arginine 3 (H4R3), numerous non-histone substrates have since been [...] Read more.
PRMT1, the major protein arginine methyltransferase in mammals, catalyzes monomethylation and asymmetric dimethylation of arginine side chains in proteins. Initially described as a regulator of chromatin dynamics through the methylation of histone H4 at arginine 3 (H4R3), numerous non-histone substrates have since been identified. The variety of these substrates underlines the essential role played by PRMT1 in a large number of biological processes such as transcriptional regulation, signal transduction or DNA repair. This review will provide an overview of the structural, biochemical and cellular features of PRMT1. After a description of the genomic organization and protein structure of PRMT1, special consideration was given to the regulation of PRMT1 enzymatic activity. Finally, we discuss the involvement of PRMT1 in embryonic development, DNA damage repair, as well as its participation in the initiation and progression of several types of cancers. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

12 pages, 850 KiB  
Review
Activity and Function of the PRMT8 Protein Arginine Methyltransferase in Neurons
by Rui Dong, Xuejun Li and Kwok-On Lai
Life 2021, 11(11), 1132; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111132 - 24 Oct 2021
Cited by 13 | Viewed by 2906
Abstract
Among the nine mammalian protein arginine methyltransferases (PRMTs), PRMT8 is unusual because it has restricted expression in the nervous system and is the only membrane-bound PRMT. Emerging studies have demonstrated that this enzyme plays multifaceted roles in diverse processes in neurons. Here we [...] Read more.
Among the nine mammalian protein arginine methyltransferases (PRMTs), PRMT8 is unusual because it has restricted expression in the nervous system and is the only membrane-bound PRMT. Emerging studies have demonstrated that this enzyme plays multifaceted roles in diverse processes in neurons. Here we will summarize the unique structural features of PRMT8 and describe how it participates in various neuronal functions such as dendritic growth, synapse maturation, and synaptic plasticity. Recent evidence suggesting the potential role of PRMT8 function in neurological diseases will also be discussed. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

12 pages, 1672 KiB  
Review
Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13
by Magnus E. Jakobsson
Life 2021, 11(11), 1121; https://0-doi-org.brum.beds.ac.uk/10.3390/life11111121 - 21 Oct 2021
Cited by 5 | Viewed by 2145
Abstract
METTL13 (also known as eEF1A-KNMT and FEAT) is a dual methyltransferase reported to target the N-terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13-mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of [...] Read more.
METTL13 (also known as eEF1A-KNMT and FEAT) is a dual methyltransferase reported to target the N-terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13-mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of global protein synthesis and translation of specific codons. Aberrant regulation of METTL13 has been linked to several types of cancer but the precise mechanisms are not yet fully understood. In this article, the current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context. The links between METTL13 and diseases, mainly different types of cancer, are also summarized. Finally, key challenges and opportunities for METTL13 research are pinpointed in a prospective outlook. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

25 pages, 3749 KiB  
Review
Structure, Activity, and Function of the Protein Lysine Methyltransferase G9a
by Coralie Poulard, Lara M. Noureddine, Ludivine Pruvost and Muriel Le Romancer
Life 2021, 11(10), 1082; https://0-doi-org.brum.beds.ac.uk/10.3390/life11101082 - 14 Oct 2021
Cited by 22 | Viewed by 4561
Abstract
G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several [...] Read more.
G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several transcription factors. This review will provide an overview of the structural features of G9a and its paralog called G9a-like protein (GLP), explore the biochemical features of G9a, and describe its post-translational modifications and the specific inhibitors available to target its catalytic activity. Aside from its role on histone substrates, the review will highlight some non-histone targets of G9a, in order gain insight into their role in specific cellular mechanisms. Indeed, G9a was largely described to be involved in embryonic development, hypoxia, and DNA repair. Finally, the involvement of G9a in cancer biology will be presented. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

16 pages, 1173 KiB  
Review
The Structure and Functions of PRMT5 in Human Diseases
by Aishat Motolani, Matthew Martin, Mengyao Sun and Tao Lu
Life 2021, 11(10), 1074; https://0-doi-org.brum.beds.ac.uk/10.3390/life11101074 - 12 Oct 2021
Cited by 25 | Viewed by 4734
Abstract
Since the discovery of protein arginine methyltransferase 5 (PRMT5) and the resolution of its structure, an increasing number of papers have investigated and delineated the structural and functional role of PRMT5 in diseased conditions. PRMT5 is a type II arginine methyltransferase that catalyzes [...] Read more.
Since the discovery of protein arginine methyltransferase 5 (PRMT5) and the resolution of its structure, an increasing number of papers have investigated and delineated the structural and functional role of PRMT5 in diseased conditions. PRMT5 is a type II arginine methyltransferase that catalyzes symmetric dimethylation marks on histones and non-histone proteins. From gene regulation to human development, PRMT5 is involved in many vital biological functions in humans. The role of PRMT5 in various cancers is particularly well-documented, and investigations into the development of better PRMT5 inhibitors to promote tumor regression are ongoing. Notably, emerging studies have demonstrated the pathological contribution of PRMT5 in the progression of inflammatory diseases, such as diabetes, cardiovascular diseases, and neurodegenerative disorders. However, more research in this direction is needed. Herein, we critically review the position of PRMT5 in current literature, including its structure, mechanism of action, regulation, physiological and pathological relevance, and therapeutic strategies. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

21 pages, 4786 KiB  
Review
The Structure, Activity, and Function of the SETD3 Protein Histidine Methyltransferase
by Apolonia Witecka, Sebastian Kwiatkowski, Takao Ishikawa and Jakub Drozak
Life 2021, 11(10), 1040; https://0-doi-org.brum.beds.ac.uk/10.3390/life11101040 - 02 Oct 2021
Cited by 6 | Viewed by 3203
Abstract
SETD3 has been recently identified as a long sought, actin specific histidine methyltransferase that catalyzes the Nτ-methylation reaction of histidine 73 (H73) residue in human actin or its equivalent in other metazoans. Its homologs are widespread among multicellular eukaryotes and expressed in [...] Read more.
SETD3 has been recently identified as a long sought, actin specific histidine methyltransferase that catalyzes the Nτ-methylation reaction of histidine 73 (H73) residue in human actin or its equivalent in other metazoans. Its homologs are widespread among multicellular eukaryotes and expressed in most mammalian tissues. SETD3 consists of a catalytic SET domain responsible for transferring the methyl group from S-adenosyl-L-methionine (AdoMet) to a protein substrate and a RuBisCO LSMT domain that recognizes and binds the methyl-accepting protein(s). The enzyme was initially identified as a methyltransferase that catalyzes the modification of histone H3 at K4 and K36 residues, but later studies revealed that the only bona fide substrate of SETD3 is H73, in the actin protein. The methylation of actin at H73 contributes to maintaining cytoskeleton integrity, which remains the only well characterized biological effect of SETD3. However, the discovery of numerous novel methyltransferase interactors suggests that SETD3 may regulate various biological processes, including cell cycle and apoptosis, carcinogenesis, response to hypoxic conditions, and enterovirus pathogenesis. This review summarizes the current advances in research on the SETD3 protein, its biological importance, and role in various diseases. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

22 pages, 2454 KiB  
Review
Structure, Activity and Function of the Protein Arginine Methyltransferase 6
by Somlee Gupta, Rajashekar Varma Kadumuri, Anjali Kumari Singh, Sreenivas Chavali and Arunkumar Dhayalan
Life 2021, 11(9), 951; https://0-doi-org.brum.beds.ac.uk/10.3390/life11090951 - 11 Sep 2021
Cited by 11 | Viewed by 3589
Abstract
Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. [...] Read more.
Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

16 pages, 1082 KiB  
Review
NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
by Samantha Tauchmann and Juerg Schwaller
Life 2021, 11(9), 877; https://0-doi-org.brum.beds.ac.uk/10.3390/life11090877 - 25 Aug 2021
Cited by 13 | Viewed by 5468
Abstract
Recurrent epigenomic alterations associated with multiple human pathologies have increased the interest in the nuclear receptor binding SET domain protein 1 (NSD1) lysine methyltransferase. Here, we review the current knowledge about the biochemistry, cellular function and role of NSD1 in human diseases. Several [...] Read more.
Recurrent epigenomic alterations associated with multiple human pathologies have increased the interest in the nuclear receptor binding SET domain protein 1 (NSD1) lysine methyltransferase. Here, we review the current knowledge about the biochemistry, cellular function and role of NSD1 in human diseases. Several studies have shown that NSD1 controls gene expression by methylation of lysine 36 of histone 3 (H3K36me1/2) in a complex crosstalk with de novo DNA methylation. Inactivation in flies and mice revealed that NSD1 is essential for normal development and that it regulates multiple cell type-specific functions by interfering with transcriptional master regulators. In humans, putative loss of function NSD1 mutations characterize developmental syndromes, such as SOTOS, as well as cancer from different organs. In pediatric hematological malignancies, a recurrent chromosomal translocation forms a NUP98-NSD1 fusion with SET-dependent leukemogenic activity, which seems targetable by small molecule inhibitors. To treat or prevent diseases driven by aberrant NSD1 activity, future research will need to pinpoint the mechanistic correlation between the NSD1 gene dosage and/or mutational status with development, homeostasis, and malignant transformation. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

14 pages, 790 KiB  
Review
Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase
by Alexia Klonou, Sarantis Chlamydas and Christina Piperi
Life 2021, 11(8), 823; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080823 - 12 Aug 2021
Cited by 9 | Viewed by 4765
Abstract
The Mixed Lineage Leukemia 2 (MLL2) protein, also known as KMT2B, belongs to the family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein of 2715 amino acids, widely expressed in adult human tissues and a paralog of the [...] Read more.
The Mixed Lineage Leukemia 2 (MLL2) protein, also known as KMT2B, belongs to the family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein of 2715 amino acids, widely expressed in adult human tissues and a paralog of the MLL1 protein. MLL2 contains a characteristic C-terminal SET domain responsible for methyltransferase activity and forms a protein complex with WRAD (WDR5, RbBP5, ASH2L and DPY30), host cell factors 1/2 (HCF 1/2) and Menin. The MLL2 complex is responsible for H3K4 trimethylation (H3K4me3) on specific gene promoters and nearby cis-regulatory sites, regulating bivalent developmental genes as well as stem cell and germinal cell differentiation gene sets. Moreover, MLL2 plays a critical role in development and germ line deletions of Mll2 have been associated with early growth retardation, neural tube defects and apoptosis that leads to embryonic death. It has also been involved in the control of voluntary movement and the pathogenesis of early stage childhood dystonia. Additionally, tumor-promoting functions of MLL2 have been detected in several cancer types, including colorectal, hepatocellular, follicular cancer and gliomas. In this review, we discuss the main structural and functional aspects of the MLL2 methyltransferase with particular emphasis on transcriptional mechanisms, gene regulation and association with diseases. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

23 pages, 1478 KiB  
Review
Structure, Activity and Function of the SETDB1 Protein Methyltransferase
by Mariam Markouli, Dimitrios Strepkos and Christina Piperi
Life 2021, 11(8), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080817 - 11 Aug 2021
Cited by 23 | Viewed by 6255
Abstract
The SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) is a prominent member of the Suppressor of Variegation 3–9 (SUV39)-related protein lysine methyltransferases (PKMTs), comprising three isoforms that differ in length and domain composition. SETDB1 is widely expressed in human tissues, methylating Histone [...] Read more.
The SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) is a prominent member of the Suppressor of Variegation 3–9 (SUV39)-related protein lysine methyltransferases (PKMTs), comprising three isoforms that differ in length and domain composition. SETDB1 is widely expressed in human tissues, methylating Histone 3 lysine 9 (H3K9) residues, promoting chromatin compaction and exerting negative regulation on gene expression. SETDB1 has a central role in normal physiology and nervous system development, having been implicated in the regulation of cell cycle progression, inactivation of the X chromosome, immune cells function, expression of retroelements and formation of promyelocytic leukemia (PML) nuclear bodies (NB). SETDB1 has been frequently deregulated in carcinogenesis, being implicated in the pathogenesis of gliomas, melanomas, as well as in lung, breast, gastrointestinal and ovarian tumors, where it mainly exerts an oncogenic role. Aberrant activity of SETDB1 has also been implicated in several neuropsychiatric, cardiovascular and gastrointestinal diseases, including schizophrenia, Huntington’s disease, congenital heart defects and inflammatory bowel disease. Herein, we provide an update on the unique structural and biochemical features of SETDB1 that contribute to its regulation, as well as its molecular and cellular impact in normal physiology and disease with potential therapeutic options. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

13 pages, 1173 KiB  
Review
Structure and Function of Protein Arginine Methyltransferase PRMT7
by Levon Halabelian and Dalia Barsyte-Lovejoy
Life 2021, 11(8), 768; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080768 - 30 Jul 2021
Cited by 14 | Viewed by 4142
Abstract
PRMT7 is a member of the protein arginine methyltransferase (PRMT) family, which methylates a diverse set of substrates. Arginine methylation as a posttranslational modification regulates protein–protein and protein–nucleic acid interactions, and as such, has been implicated in various biological functions. PRMT7 is a [...] Read more.
PRMT7 is a member of the protein arginine methyltransferase (PRMT) family, which methylates a diverse set of substrates. Arginine methylation as a posttranslational modification regulates protein–protein and protein–nucleic acid interactions, and as such, has been implicated in various biological functions. PRMT7 is a unique, evolutionarily conserved PRMT family member that catalyzes the mono-methylation of arginine. The structural features, functional aspects, and compounds that inhibit PRMT7 are discussed here. Several studies have identified physiological substrates of PRMT7 and investigated the substrate methylation outcomes which link PRMT7 activity to the stress response and RNA biology. PRMT7-driven substrate methylation further leads to the biological outcomes of gene expression regulation, cell stemness, stress response, and cancer-associated phenotypes such as cell migration. Furthermore, organismal level phenotypes of PRMT7 deficiency have uncovered roles in muscle cell physiology, B cell biology, immunity, and brain function. This rapidly growing information on PRMT7 function indicates the critical nature of context-dependent functions of PRMT7 and necessitates further investigation of the PRMT7 interaction partners and factors that control PRMT7 expression and levels. Thus, PRMT7 is an important cellular regulator of arginine methylation in health and disease. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

13 pages, 2243 KiB  
Review
Structure, Activity and Function of the NSD3 Protein Lysine Methyltransferase
by Philipp Rathert
Life 2021, 11(8), 726; https://0-doi-org.brum.beds.ac.uk/10.3390/life11080726 - 21 Jul 2021
Cited by 8 | Viewed by 3411
Abstract
NSD3 is one of six H3K36-specific lysine methyltransferases in metazoans, and the methylation of H3K36 is associated with active transcription. NSD3 is a member of the nuclear receptor-binding SET domain (NSD) family of histone methyltransferases together with NSD1 and NSD2, which generate mono- [...] Read more.
NSD3 is one of six H3K36-specific lysine methyltransferases in metazoans, and the methylation of H3K36 is associated with active transcription. NSD3 is a member of the nuclear receptor-binding SET domain (NSD) family of histone methyltransferases together with NSD1 and NSD2, which generate mono- and dimethylated lysine on histone H3. NSD3 is mutated and hyperactive in some human cancers, but the biochemical mechanisms underlying such dysregulation are barely understood. In this review, the current knowledge of NSD3 is systematically reviewed. Finally, the molecular and functional characteristics of NSD3 in different tumor types according to the current research are summarized. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

15 pages, 3968 KiB  
Review
Structure, Activity and Function of the Suv39h1 and Suv39h2 Protein Lysine Methyltransferases
by Sara Weirich, Mina S. Khella and Albert Jeltsch
Life 2021, 11(7), 703; https://0-doi-org.brum.beds.ac.uk/10.3390/life11070703 - 16 Jul 2021
Cited by 17 | Viewed by 5077
Abstract
SUV39H1 and SUV39H2 were the first protein lysine methyltransferases that were identified more than 20 years ago. Both enzymes introduce di- and trimethylation at histone H3 lysine 9 (H3K9) and have important roles in the maintenance of heterochromatin and gene repression. They consist [...] Read more.
SUV39H1 and SUV39H2 were the first protein lysine methyltransferases that were identified more than 20 years ago. Both enzymes introduce di- and trimethylation at histone H3 lysine 9 (H3K9) and have important roles in the maintenance of heterochromatin and gene repression. They consist of a catalytically active SET domain and a chromodomain, which binds H3K9me2/3 and has roles in enzyme targeting and regulation. The heterochromatic targeting of SUV39H enzymes is further enhanced by the interaction with HP1 proteins and repeat-associated RNA. SUV39H1 and SUV39H2 recognize an RKST motif with additional residues on both sides, mainly K4 in the case of SUV39H1 and G12 in the case of SUV39H2. Both SUV39H enzymes methylate different non-histone proteins including RAG2, DOT1L, SET8 and HupB in the case of SUV39H1 and LSD1 in the case of SUV39H2. Both enzymes are expressed in embryonic cells and have broad expression profiles in the adult body. SUV39H1 shows little tissue preference except thymus, while SUV39H2 is more highly expressed in the brain, testis and thymus. Both enzymes are connected to cancer, having oncogenic or tumor-suppressive roles depending on the tumor type. In addition, SUV39H2 has roles in the brain during early neurodevelopment. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-17
Back to TopTop