N-terminal Xaa-Pro-Lys N-methyltransferase 1 (NTMT1)
The protein contains 223 amino acids for an estimated molecular weight of 25387 Da.
Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by METTL11B-mediated monomethylation (PubMed:24090352). Catalyzes the trimethylation of the N-terminal Gly in CENPA (after removal of Met-1). Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Chromosome segregation
Histone methylation
N-terminal peptidyl-alanine methylation
N-terminal peptidyl-alanine trimethylation
N-terminal peptidyl-glycine methylation
N-terminal peptidyl-proline dimethylation
N-terminal peptidyl-proline methylation
N-terminal peptidyl-serine dimethylation
N-terminal peptidyl-serine methylation
N-terminal peptidyl-serine trimethylation
N-terminal protein amino acid methylation
Spindle organization
The reference OMIM entry for this protein is 613560
N-terminal x-pro-lys n-methyltransferase 1; ntmt1
Methyltransferase-like 11a; mettl11a
N-terminal rcc1 methyltransferase; nrmt
Rcc1 methyltransferase, n-terminal
C9orf32
DESCRIPTION
The METTL11A gene encodes an N-terminal methyltransferase for the RAN (601179) guanine nucleotide exchange factor regulator of chromosome condensation 1 (RCC1; 179710). METTL11A enzyme alpha-N-methylates other protein targets such as SET (600960) and RB1 (614041).CLONING
Schaner Tooley et al. (2010) purified the RCC1 N-terminal methyltransferase (NRMT, also known as METTL11A) using immunoassays and mass spectrometry. NRMT encodes a 25-kD protein in the methyltransferase-11 family, most members of which methylate metabolites or other small molecules. NRMT lacks a SET domain but possesses a Rossman-like alpha/beta fold. It has been conserved throughout eukaryotic evolution. Schaner Tooley et al. (2010) noted that according to genomewide expression databases, it is ubiquitously expressed in normal tissue and robustly overexpressed in gastrointestinal cancers.GENE FUNCTION
Schaner Tooley et al. (2010) confirmed that NRMT is the authentic RCC1 alpha-N-methyltransferase using in vivo methylation assays. Knockdown of NRMT recapitulated the multispindle phenotype seen with methylation-defective RCC1 mutants, demonstrating the importance of alpha-N-methylation for normal bipolar spindle formation and chromosome segregation. At the time of the report of Schaner Tooley et al. (2010), the RAN guanine nucleotide exchange factor RCC1 (179710) was the only protein for which any biologic function of alpha-N-methylation had been identified. Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, met-(ala/pro/ser)-pro-lys, indicating that they may be targets of the same enzyme. The initiating met is cleaved, and the exposed alpha-amino group is mono-, di-, or trimethylated. Using met-(ala/ser/pro)-pro-lys, Schaner Tooley et al. (2010) searched GenBank for candidate substrates of NRMT. More than 35 annotated genes contain this N-terminal motif. Schaner Tooley et al. (2010) confirmed 6 target genes of NRMT including RCC1, SET (600960), ribosomal protein L23A (602326), myosin light chain polypeptide-3 (160790), myosin light chain polypeptide-2 (160781), and kelch-like protein-31 (610749).BIOCHEMICAL FEATURES
Schaner Tooley et al. (2010) noted that the crystal structure of NRMT in complex with S-adenosylhomocysteine (SAH) to 1.75-angstrom resolution was solved by the Structural Genomics Consortium. A large cavity opposite the SAH binding site could accommodate N-terminal peptides and contains an arrangement of aromatic residues similar to those in chromodomains. Using a computer-generated model of an RCC1 N-terminal peptide in the putative active site, Schaner Tooley et al. (2010) found that only the first 3 residues (ser-pro-lys) interact with NRMT. The optimum conformation positions the substrate alpha-NH2 close to the SAH, in the correct orientation for methyl transfer, within 3.6 angstroms of the sulfur atom. The peptide lys4 side chain forms hydrogen bonds and electrostatic interactions with acidic residues at the lip of the active site.MAPPING
Gross (2014) mapped the NTMT1 gene to chromosome 9q34.11 based on an alignment of the NTMT1 sequence (GenBank GENBANK BC033234) with the genomic sequence (GRCh37). ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 613560 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).