UPF0586 Protein C9orf41 Homolog Is Anserine-producing Methyltransferase

Drożak, Jakub; Piecuch, Maria; Poleszak, Olga; Kozłowski, Piotr; Chrobok, Łukasz; Baelde, Hans J.; Heer, Emile de

doi:10.1074/jbc.m115.640037

Cited by 45 publications

(42 citation statements)

References 47 publications

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“…GRWD1 is found in pre-ribosomal complexes (80), suggesting that the human complex may have a similar function in ribosome biogenesis as the yeast enzyme. A mammalian enzyme that catalyzes the methylation of the π-nitrogen of the histidine residue in the dipeptide carnosine (β-L-Ala-L-His) to form anserine has been recently described (81). It is unclear whether this enzyme may also be responsible for the methylation of actin and other non-ribosomal methylated proteins.…”

Section: Protein Histidine Methyltransferasesmentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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Cellular physiology depends on the alteration of protein structures by covalent modification reactions. Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for posttranslationally methylated amino acid residues and for the enzymes that catalyze these modifications. These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation. Two of these enzymes may modify their substrates during ribosomal assembly because the final methylated histidine and arginine residues are buried deep within the ribosome with contacts only with RNA. Two of these modifications occur broadly in eukaryotes, including humans, while the others demonstrate a more limited phylogenetic range. Analysis of strains where the methyltransferase genes are deleted has given insight into the physiological roles of these modifications. These reactions described here add diversity to the modifications that generate the typical methylated lysine and arginine residues previously described in histones and other proteins. Regulation of biological function by protein methylation reactionsIt is more and more apparent just how much of biological function is dependent upon posttranslational modifications (1). The human genome encodes some 900 enzymes catalyzing just protein phosphorylation or ubiquitination (2,3). However, it is now clear that methyl groups can stand beside phosphate groups and ubiquitin as major players in controlling the physiological functions of proteins. We are beginning to understand how the much greater diversity of protein methylation reactions can give rise to a greater diversity of function (1,4-8). We are also learning the importance of crosstalk between protein and DNA methylation reactions (9) and among protein methylation, phosphorylation, acetylation, and ubiquitination reactions (10-12). Finally, we are discovering how alterations in protein methylation pathways can lead to human pathology, particularly in cancer (13-15).The collection of over sixty human protein arginine and lysine methyltransferases that leave histone "marks" recognized by reader proteins to guide gene expression are perhaps the poster children for the importance of protein methyltransferases (16-17). However, recent work has emphasized the importance of methylating non-histone substrates at these residues, particularly ribosomal proteins, translation factors, and transcription factors in a wide variety of organisms (7,8,15,18,19). Furthermore, the methylation of lysine and arginine residues represents just the tip of the iceberg in protein methylation -modifications have also been established at histidine, modified histidine (diphthamide), glutamate, glutamine, asparagine, Lisoaspartate, D-aspartate, cysteine, isoprenylcysteine, me...

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Section: Protein Histidine Methyltransferasesmentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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“…4 Since then, carnosine and other IDPs, such as anserine (␤-alanyl-3-methyl-L-histidine) and homocarnosine (␥-aminobutyryl-L-histidine), have been observed at high concentrations in the skeletal muscles and central nervous systems of many vertebrates (1). The levels of the IDPs are regulated by metabolic enzymes, including carnosine synthase (CARNS) (2), methyltransferase (3), and dipeptidase (4,5), indicating that IDPs play physiological roles in the muscle and brain. It has been postulated that carnosine contributes significantly to physicochemical buffering in skeletal muscles by neutralizing the lactic acid produced during anaerobic glycolysis (6).…”

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2-Oxo-histidine–containing dipeptides are functional oxidation products

Ihara

Kakihana

Yamakage

et al. 2019

Journal of Biological Chemistry

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Figure 2. Quantitative identification of IDPs and oxidized IDPs in mouse tissues. A, LC-ESI-MS/MS analysis of endogenous carnosine in the mouse skeletal muscle. Representative LC-ESI-MS/MS chromatograms of spiked isotope-labeled carnosine (upper trace), and endogenous carnosine (lower trace) are shown. B, LC-ESI-MS/MS analysis of endogenous 2-oxo-carnosine in the mouse skeletal muscle. Representative LC-ESI-MS/MS chromatograms of spiked isotopelabeled 2-oxo-carnosine (upper trace), and endogenous 2-oxo-carnosine (lower trace) are shown. C, quantitative identification of IDPs (upper graph) and oxidized IDPs (lower graph) in the mouse tissues. The IDPs and oxidized IDPs in mouse tissues were quantified using LC-ESI-MS/MS coupled with a stable isotope dilution method. The data are means Ϯ S.D. (n ϭ 3). 2-Oxo-IDPs are functional oxidation products

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“… 49 Anserine (β-alanyl- N -π-methyl- l -histidine) is naturally occurring derivative of carnosine (β-alanyl- l -histidine) that has been reported to be present in the central nervous system and skeletal muscle of many vertebrates 50 ; besides that, its physiological function remains unknown. 51 (c) SG_1634 participates in the sulfur relay system and thiamine metabolism pathways with the cysteine desulfurase enzyme (EC 2.8.1.7) that catalyzes the chemical reaction l -cysteine + [enzyme]-cysteine <=> l -alanine + [enzyme]- S -sulfanylcysteine. In T. brucei , this enzyme is involved in the biosynthesis of iron-sulfur clusters, thio-nucleosides in transfer RNA, biotin, lipoate, thiamine, and pyranopterin (molybdopterin).…”

Section: Discussionmentioning

confidence: 99%

Homology Inference Based on a Reconciliation Approach for the Comparative Genomics of Protozoa

Campos

Pereira

Jardim

et al. 2018

Evol Bioinform Online

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Protozoa parasites are responsible for several diseases in tropical countries, such as malaria, sleeping sickness, Chagas disease, leishmaniasis, amebiasis, and giardiasis, which together threaten millions of people around the world. In addition, most of the classic parasitic diseases due to protozoa are zoonotic. Understanding the biology of these organisms plays a relevant role in combating these diseases. Using homology inference and comparative genomics, this study targeted 3 protozoan species from different Phyla: Cryptosporidium muris (Apicomplexa), Entamoeba invadens (Amoebozoa), and Trypanosoma grayi (Euglenozoa). In this study, we propose a new approach for the identification of homologs, based on the reconciliation of the results of 2 different homology inference software programs. Our results showed that 46.1% (59/128) of the groups inferred by our reconciliation approach could be validated using this methodology. These validated groups are here called homologous Supergroups and were compared with SUPERFAMILY and Pfam Clans.

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UPF0586 Protein C9orf41 Homolog Is Anserine-producing Methyltransferase

Cited by 45 publications

References 47 publications

The ribosome: A hot spot for the identification of new types of protein methyltransferases

The ribosome: A hot spot for the identification of new types of protein methyltransferases

2-Oxo-histidine–containing dipeptides are functional oxidation products

Homology Inference Based on a Reconciliation Approach for the Comparative Genomics of Protozoa

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