Cloned (Comment) | Organism |
---|---|
N-terminally tagged FLAG-NRMT overexpression in HEK 293LT cell nuceli, that show 3fold increased RCC1 alpha-N-methyltransferase activity | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
D168X | site-directed mutagenesis, the mutation has no effect on methylation | Homo sapiens |
D178A/D181A | site-directed mutagenesis, mutating the residues Asp178 and Asp181 at the lip of the active site to Ala decreases enzyme activity, which is further decreased by reverse-charge mutagenesis to Lys | Homo sapiens |
additional information | depleting NRMT in 293LT cells, using lentivirus, significantly decreases methylation of endogenous RCC1, while not affecting overall RCC1 level, depleting NRMT in HeLa cells using short interfering RNAs causing the same effects, RCC1 methylation is rescued by expression of murine NRMT-FLAG, which is not targeted by the human shRNA | Homo sapiens |
Q169K | site-directed mutagenesis, inactive mutant | Homo sapiens |
S183K | site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
nucleus | - |
Homo sapiens | 5634 | - |
soluble | - |
Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1 | Homo sapiens | NRMT is the predominant alpha-N-methyltransferase for RCC1 | S-adenosyl-L-homocysteine + ? | - |
? | |
S-adenosyl-L-methionine + retinoblastoma protein | Homo sapiens | - |
S-adenosyl-L-homocysteine + ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
gene METTL11a/C9orf32/Ad-003 | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HeLa cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | enzyme substrates have a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys. The initiating Met is cleaved, and the exposed alpha-amino group is mono-, di-, or trimethylated | Homo sapiens | ? | - |
? | |
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1 | NRMT is the predominant alpha-N-methyltransferase for RCC1 | Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? | |
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1 | substrate docking and mutational analysis of RCC1 defining the NRMT recognition sequence, the first 3 residues Ser-Pro-Lys interact with NRMT, overview | Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? | |
S-adenosyl-L-methionine + retinoblastoma protein | - |
Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? | |
S-adenosyl-L-methionine + SET/TAF-I/PHAPII | only the SETalpha splicing variant is a substrate for NRMT, since it begins with the NRMT consensus in contrast to the beta splicing variant | Homo sapiens | S-adenosyl-L-homocysteine + ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | NRMT lacks a SET domain but possesses a Rossman-like alpha/beta fold | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
alpha-N-methyltransferase | - |
Homo sapiens |
METTL11a/C9orf32/Ad-003 | - |
Homo sapiens |
N-terminal RCC1 methyltransferase | - |
Homo sapiens |
NRMT | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | METTL11a, i.e. NRMT, encodes a 25 kDa protein in the methyltransferase 11 family, most members of which methylate metabolites or other small molecules. alpha-N-methyltransferase is a conserved member of a superfamily of non-SET domain enzymes | Homo sapiens |
malfunction | methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects, and non-methylatable mutants of RCC1 are defective in chromatin association, and their expression in a wild-type background produces supernumerary spindle poles and missegregation of mitotic chromosomes, most likely due to the disruption of the Ran gradient | Homo sapiens |
physiological function | importance of alpha-N-methylation for normal bipolar spindle formation and chromosome segregation. Function of the alpha-N-methylation is not solely to stabilize chromatin associations, but may have a more general role in the regulation of electrostatic interactions | Homo sapiens |