Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | isozyme NRMT2 expression activates isozyme NRMT1 activity, not through priming, but by increasing its stability and substrate affinity. NRMT1 has increased N-terminal trimethylation activity when co-expressed with NRMT2. Catalytic activity of NRMT2 is not necessary for increased trimethylation by NRMT1 | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
gene NTMT1, recombinant expression of His-tagged NRMT1 in Escherichia coli and of FLAG-tagged wild-type and mutant NRMT1s in HEK-293 cells, recombinant expression of GFP-tagged enzyme in HCT-116 cells | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
analysis of crystal structures of NRMT1 and NRMT2 (PDB IDs 2EX4 and 5UBB, determined to 1.75 and 2.0 A, respectively), homology modeling | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | NRMT1 co-expression with NRMT2 increases the trimethylation rate of NRMT1. Generation of truncation constructs of NRMT1. Full-length FLAG-tagged NRMT1 only weakly interacts with the first 112 aa of NRMT2, though strongly interacts with a GFP-tagged NRMT2 fragment (amino acids 77-223) that is missing the 59 aa tail that is also lacking from the crystal structure and subsequent model. Full-length FLAG-tagged NRMT2 strongly interacts with the first 59 aa of NRMT1, as well as, amino acids 52-172. There is a decreased interaction of FLAG-tagged NRMT2-FLAG with the C-terminal fragment of NRMT1 (amino acids 178-223). Generation of NRMT1 knockout mutant, NRMT2 overexpression cannot rescue NRMT1 knockout phenotypes | Homo sapiens |
General Stability | Organism |
---|---|
the experimentally calculated half-life for endogenous NRMT1 is approximately 8.8 h. NRMT2 expression stabilizes NRMT1 in HCT-116 cells | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0009 | - |
SPKRIAKRRSPPADA | recombinant NRMT1, in presence of NRMT2, pH and temperature not specified in the publication | Homo sapiens | |
0.0011 | - |
SPKRIAKRRSPPADA | recombinant NRMT1, pH and temperature not specified in the publication | Homo sapiens | |
0.0044 | - |
SSKRAKAKTTKKRP | recombinant NRMT1, in presence of NRMT2 catalytically inactive V224L mutant, pH and temperature not specified in the publication | Homo sapiens | |
0.0066 | - |
SSKRAKAKTTKKRP | recombinant NRMT1, in presence of NRMT2, pH and temperature not specified in the publication | Homo sapiens | |
0.0156 | - |
SSKRAKAKTTKKRP | recombinant NRMT1, pH and temperature not specified in the publication | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
nucleus | - |
Homo sapiens | 5634 | - |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
33000 | - |
monomeric recombinant enzyme, analytical ultracentrifugation | Homo sapiens |
52000 | - |
dimeric recombinant enzyme, analytical ultracentrifugation | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + N-terminal-(A,P,S)PK-[protein] | Homo sapiens | - |
S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,P,S)PK-[protein] | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9BV86 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged NRMT1 from Escherichia coli | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
colorectal cancer cell | - |
Homo sapiens | - |
HCT-116 cell | - |
Homo sapiens | - |
additional information | NRMT1 is a ubiquitously expressed distributive trimethylase | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | NRMT1 exhibits distributive trimethylase activity in vitro. Isozymes NRMT1 and NRMT2 can interact both in vitro and in vivo, modeling of NRMT1 and NRMT2 interactions. The Ser-Pro-Lys consensus sequence of the RCC1 peptide is a preferred substrate for NRMT1 | Homo sapiens | ? | - |
- |
|
S-adenosyl-L-methionine + N-terminal-(A,P,S)PK-[protein] | - |
Homo sapiens | S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,P,S)PK-[protein] | - |
? | |
S-adenosyl-L-methionine + SPKRIAKRRSPPADA | substrate peptide consisting of the first 15 amino acids of RCC1. NRMT2 V224L is able to significantly decrease the NRMT1 Km with the RCC1 peptide | Homo sapiens | ? | - |
? | |
S-adenosyl-L-methionine + SSKRAKAKTTKKRP | substrate peptide consisting of the first 14 amino acids of MYL9 | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | 2 * 33000, recombinant isozyme NRMT1, SDS-PAGE and analytical ultracentrifugation | Homo sapiens |
More | isozyme NRMT1 primarily exists as a dimer. Isozymes NRMT1 and NRMT2, when co-expressed, form a heterotrimer, interaction analysis, overview. When NRMT2 monomer is present the NRMT1 dimer will bind it and the pool of NRMT1 dimer is completely depleted | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
METTL11A | - |
Homo sapiens |
N-terminal RCC1 methyltransferase 1 | - |
Homo sapiens |
N-terminal Xaa-Pro-Lys N-methyltransferase 1 | UniProt | Homo sapiens |
NRMT1 | - |
Homo sapiens |
NTMT1 | gene name, UniProt | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme belongs to the methyltransferase like (METTL) family of class I methyltransferases containing seven-beta-strand methyltransferase motifs and Rossman folds for binding SAM. The N-terminal methyltransferase homologs NRMT1 (N-terminal RCC1 methyltransferase 1) and NRMT2 (N-terminal RCC1 methyltransferase 2), which following cleavage of the initiating methionine, methylate the alpha-amine of the first N-terminal residue of their substrates. NRMT1 and NRMT2 are 50% identical and 75% similar and share an N-terminal X-P-K consensus sequence. Although structurally similar, they differ in their catalytic activities | Homo sapiens |
malfunction | in vivo, complete knockout of NRMT1 via homologous recombination or CRISPR/Cas9 abolishes N-terminal trimethylation | Homo sapiens |
additional information | analysis of crystal structures of NRMT1 and NRMT2 (PDB IDs 2EX4 and 5UBB, determined to 1.75 and 2.0 A, respectively), homology modeling. Modeling of NRMT1 and NRMT2 heterotrimer, interaction analysis, overview | Homo sapiens |
physiological function | NRMT1 is a ubiquitously expressed distributive trimethylase | Homo sapiens |