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更新于：2025-05-07

NTMT2

更新于：2025-05-07

基本信息

别名

Alpha N-terminal protein methyltransferase 1B、C1orf184、HOMT1B

+ [7]

简介

Alpha N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif (PubMed:24090352, PubMed:30417120). Predominantly functions as a mono-methyltransferase but is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide (in vitro) (PubMed:30417120). May activate NTMT1 by priming its substrates for trimethylation (PubMed:24090352).

关联

项与 NTMT2 相关的药物

BM30

靶点

NTMT1 x NTMT2

作用机制

NTMT1 inhibitors [+1]

在研机构

Virginia Commonwealth University

原研机构

Virginia Commonwealth University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

DC432

靶点

NTMT1 x NTMT2

作用机制

NTMT1 inhibitors [+1]

在研机构-

原研机构

Virginia Commonwealth University

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 NTMT2 相关的临床结果

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100 项与 NTMT2 相关的转化医学

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0 项与 NTMT2 相关的专利（医药）

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项与 NTMT2 相关的文献（医药）

2023-04-01·Journal of Biological Chemistry

Opposing regulation of the Nα-trimethylase METTL11A by its family members METTL11B and METTL13

Article

作者: Schaner Tooley, Christine E ; Parker, Haley V

N-terminal protein methylation (Nα-methylation) is a posttranslational modification that influences numerous biological processes by regulating protein stability, protein-DNA interactions, and protein-protein interactions. Although significant progress has been made in understanding the biological roles of Nα-methylation, we still do not completely understand how the modifying methyltransferases are regulated. A common mode of methyltransferase regulation is through complex formation with close family members, and we have previously shown that the Nα-trimethylase METTL11A (NRMT1/NTMT1) is activated through binding of its close homolog METTL11B (NRMT2/NTMT2). Other recent reports indicate that METTL11A co-fractionates with a third METTL family member METTL13, which methylates both the N-terminus and lysine 55 (K55) of eukaryotic elongation factor 1 alpha. Here, using co-immunoprecipitations, mass spectrometry, and in vitro methylation assays, we confirm a regulatory interaction between METTL11A and METTL13 and show that while METTL11B is an activator of METTL11A, METTL13 inhibits METTL11A activity. This is the first example of a methyltransferase being opposingly regulated by different family members. Similarly, we find that METTL11A promotes the K55 methylation activity of METTL13 but inhibits its Nα-methylation activity. We also find that catalytic activity is not needed for these regulatory effects, demonstrating new, noncatalytic functions for METTL11A and METTL13. Finally, we show METTL11A, METTL11B, and METTL13 can complex together, and when all three are present, the regulatory effects of METTL13 take precedence over those of METTL11B. These findings provide a better understanding of Nα-methylation regulation and suggest a model where these methyltransferases can serve in both catalytic and noncatalytic roles.

2023-01-15·Journal of Cell Science

Three's a crowd – why did three N-terminal methyltransferases evolve for one job?

Article

作者: Conner, Meghan M. ; Schaner Tooley, Christine E.

ABSTRACTN-terminal methylation of the α-amine group (Nα-methylation) is a post-translational modification (PTM) that was discovered over 40 years ago. Although it is not the most abundant of the Nα-PTMs, there are more than 300 predicted substrates of the three known mammalian Nα-methyltransferases, METTL11A and METTL11B (also known as NTMT1 and NTMT2, respectively) and METTL13. Of these ∼300 targets, the bulk are acted upon by METTL11A. Only one substrate is known to be Nα-methylated by METTL13, and METTL11B has no proven in vivo targets or predicted targets that are not also methylated by METTL11A. Given that METTL11A could clearly handle the entire substrate burden of Nα-methylation, it is unclear why three distinct Nα-methyltransferases have evolved. However, recent evidence suggests that many methyltransferases perform important biological functions outside of their catalytic activity, and the Nα-methyltransferases might be part of this emerging group. Here, we describe the distinct expression, localization and physiological roles of each Nα-methyltransferase, and compare these characteristics to other methyltransferases with non-catalytic functions, as well as to methyltransferases with both catalytic and non-catalytic functions, to give a better understanding of the global roles of these proteins. Based on these comparisons, we hypothesize that these three enzymes do not just have one common function but are actually performing three unique jobs in the cell.

2023-01-01·Methods in enzymology

Optimizing purification and activity assays of N-terminal methyltransferase complexes.

Article

作者: Parker, Haley V ; Schaner Tooley, Christine E ; Tooley, John G

In vitro methyltransferase assays have traditionally been carried out with tritiated S-adenosyl-methionine (SAM) as the methyl donor, as site-specific methylation antibodies are not always available for Western or dot blots and structural requirements of many methyltransferases prohibit the use of peptide substrates in luminescent or colorimetric assays. The discovery of the first N-terminal methyltransferase, METTL11A, has allowed for a second look at non-radioactive in vitro methyltransferase assays, as N-terminal methylation is amenable to antibody production and the limited structural requirements of METTL11A allow for its methylation of peptide substrates. We have used a combination of Western blots and luminescent assays to verify substrates of METTL11A and the two other known N-terminal methyltransferases, METTL11B and METTL13. We have also developed these assays for use beyond substrate identification, showing that METTL11A activity is opposingly regulated by METTL11B and METTL13. Here we provide two methods for non-radioactive characterization of N-terminal methylation, Western blots with full-length recombinant protein substrates and luminescent assays with peptide substrates, and describe how each can be additionally adapted to look at regulatory complexes. We will review the advantages and disadvantages of each method in context with the other types of in vitro methyltransferase assays and discuss why these types of assays could be of general use to the N-terminal modification field.