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Information on EC 2.1.1.244 - protein N-terminal methyltransferase
for references in articles please use BRENDA:EC2.1.1.244
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EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.1 Methyltransferases
2.1.1.244 protein N-terminal methyltransferase
IUBMB Comments
This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys after the initiator L-methionine is cleaved. When the terminal amino acid is L-proline, the enzyme catalyses two successive methylations of its α-amino group. When the first amino acid is either L-alanine or L-serine, the enzyme catalyses three successive methylations. The Pro-Lys in positions 2-3 cannot be exchanged for other amino acids [1,2].
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 2.1.1.244
- methyltransferases
-
rna-dependent
- mtase
-
trimethylation
- dengue
- flavivirus
-
bisubstrate
-
methyltransferase-like
- drug development
- pharmacology
Reaction Schemes
show3
+
=
3
+
3
+
N-terminal-(A,S)PK-[protein]
=
3
+
N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]
2
+
=
2
+
2
+
N-terminal-PPK-[protein]
=
2
+
N-terminal-N,N-dimethyl-N-PPK-[protein]
Synonyms
nrmt1, ntmt1, mettl13, n-terminal methyltransferase, protein n-terminal methyltransferase 1, n-terminal rcc1 methyltransferase, mettl11a, ylr285w, ybr261c/tae1, n6amt2, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-N-terminal methyltransferase 1
FEAT
methyltransferase-like protein 13
METTL11A
N-terminal methyltransferase
N-terminal Xaa-Pro-Lys N-methyltransferase 1
NMT1
-
-
-
-
NRMT1
NTMT1
protein N-terminal methyltransferase 1
Rkm2
FEAT
Faintly Expressed in healthy tissues, Aberrantly overexpressed in Tumors
METTL11A
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 S-adenosyl-L-methionine + N-terminal-PPK-[protein] = 2 S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein]
(2)
-
-
-
3 S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = 3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]
(1)
-
-
-
S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,S)PK-[protein]
(1a)
-
-
-
S-adenosyl-L-methionine + N-terminal-N,N-dimethyl-N-(A,S)PK-serine-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]
(1c)
-
-
-
S-adenosyl-L-methionine + N-terminal-N-methyl-N-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-(A,S)PK-[protein]
(1b)
-
-
-
S-adenosyl-L-methionine + N-terminal-N-methyl-N-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein]
(2b)
-
-
-
S-adenosyl-L-methionine + N-terminal-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-PPK-[protein]
(2a)
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:N-terminal-(A,P,S)PK-[protein] methyltransferase
This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys after the initiator L-methionine is cleaved. When the terminal amino acid is L-proline, the enzyme catalyses two successive methylations of its alpha-amino group. When the first amino acid is either L-alanine or L-serine, the enzyme catalyses three successive methylations.
The Pro-Lys in positions 2-3 cannot be exchanged for other amino acids [1,2].
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CAS REGISTRY NUMBER
COMMENTARY
9068-28-4
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 S-adenosyl-L-methionine + CPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: mono- and dimethylation by NTMT1
Products: -
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?
2 S-adenosyl-L-methionine + FPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation and low level trimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + HPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + IPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: mono- and dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + KPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation and low level trimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + LPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation and low level trimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + MPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation and low level trimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + N-terminal-histone 2B
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation of fruit fly histone 2B by NTMT1 over an N-terminal sequence of 1PPKTSGKAA9
Products: -
Products: -
?
2 S-adenosyl-L-methionine + N-terminal-methyl-SPKRIAKRRS
2 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRRS
-
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + N-terminal-PPKRIA
2 S-adenosyl-L-homocysteine + N-terminal-dimethyl-PPKRIA
2 S-adenosyl-L-methionine + NPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + PPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + QPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + RPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation and low level trimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + TPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: mono- and dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + VPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: mono- and dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + WPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: mono- and dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + YPKRIA
2 S-adenosyl-L-homocysteine + ?
Substrates: dimethylation by NTMT1
Products: -
Products: -
?
2 S-adenosyl-L-methionine + [eEF1A]-L-lysine55
2 S-adenosyl-L-homocysteine + [eEF1A]-N6,N6-dimethyl-L-lysine55
2 S-adenosyl-L-methionine + [eEFIA1]-L-lysine55
2 S-adenosyl-L-homocysteine + [eEFIA1]-N6,N6-dimethyl-L-lysine55
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + [eEFIA2]-L-lysine55
2 S-adenosyl-L-homocysteine + [eEFIA2]-N6,N6-dimethyl-L-lysine55
Substrates: -
Products: -
Products: -
?
3 (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine + N-terminal-OLA1
?
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + APKRIA
3 S-adenosyl-L-homocysteine + ?
Substrates: trimethylation by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + APKRQSPLPP
3 S-adenosyl-L-homocysteine + N-terminal methyl-APKRQSPLPP
Substrates: -
Products: -
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?
3 S-adenosyl-L-methionine + APKRVVQLSL
3 S-adenosyl-L-homocysteine + N-terminal trimethyl-APKRVVQLSL
Substrates: i.e. residues 1-10 of PAD1
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?
3 S-adenosyl-L-methionine + GPKRIA
3 S-adenosyl-L-homocysteine + N-terminal methyl-GPKRIA
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-APK-[SET10 peptide]
3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-APK-[SET10 peptide]
Substrates: SET-10 peptide sequence is APKRQSPLPP
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-CENP-A
3 S-adenosyl-L-homocysteine + ?
Substrates: human CENP-A histone, molecular details for CENP-A recognition by NRMT1. State-specific trimethylation of CENP-A by NRMT1
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-LPKRIA
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-LPKRIA
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-peptide-[BAP1 protein]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-peptide-[BAP1 protein]
-
Substrates: i.e. BRCA1 associated protein 1, a DNA repair protein
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-peptide-[DDB2 protein]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-peptide-[DDB2 protein]
-
Substrates: DDB2 is a DNA repair protein
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-peptide-[PAD1 protein]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-peptide-[PAD1 protein]
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-peptide-[PARP3 protein]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-peptide-[PARP3 protein]
-
Substrates: i.e. poly-ADP-ribosylase 3, a DNA repair protein
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-RPKRIA
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-RPKRIA
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-SPK-[RCC1 peptide]
3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-SPK-[RCC1 peptide]
Substrates: RCC1 peptide sequence is SPKRIAKRRS(CONH2)
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-SPKRIA-[RCC1]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIA-[RCC1]
3 S-adenosyl-L-methionine + N-terminal-SPKRIAKRR
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRR
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-SPKRIAKRRS
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRRS
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-SPKRIAKRRSPP
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRRSPP
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-WPKRIA
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-WPKRIA
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-YPKRIA
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-YPKRIA
-
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + SPKRIA
3 S-adenosyl-L-homocysteine + ?
Substrates: trimethylation by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + SPKRIA
3 S-adenosyl-L-homocysteine + N-terminal methyl-SPKRIA
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + SPKRIAKRRS-[RCC1]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRRS-[RCC1]
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + [eEF1A]-N-terminal glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-homocysteine + [eEF1A]-N-terminal N,N,N-trimethyl-glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-methionine + [eEFIA1]-N-terminal glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-homocysteine + [eEFIA1]-N-terminal N,N,N-trimethyl-glycine-L-lysine-L-glutamine-L-lysine
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + [eEFIA2]-N-terminal glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-homocysteine + [eEFIA2]-N-terminal N,N,N-trimethyl-glycine-L-lysine-L-glutamine-L-lysine
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + DPKRIA
S-adenosyl-L-homocysteine + ?
Substrates: monomethylation by NTMT1
Products: -
Products: -
?
S-adenosyl-L-methionine + EPKRIA
S-adenosyl-L-homocysteine + ?
Substrates: monomethylation by NTMT1
Products: -
Products: -
?
S-adenosyl-L-methionine + human histone H3
S-adenosyl-L-homocysteine + ?
-
Substrates: lower activity with histone H3 compared to histone H4
Products: -
Products: -
?
S-adenosyl-L-methionine + human histone H4
S-adenosyl-L-homocysteine + ?
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + N-terminal peptide sequence of a protein
S-adenosyl-L-homocysteine + methylated N-terminal peptide sequence of a protein
-
Substrates: all known substrates of NTMT1 contain the N-terminal consensus sequence XPK (X = S/P/A/G), although NTMT1 can also methylate peptides with X being F, Y, C, M, K, R, N, Q, or H in vitro, substrate specificity of NTMT1, overview. Structural basis for the specific N-terminal methylation of a consensus motif, XPK, by NTMT1, overview. Hexapeptides composed of the first six residues of RCC1, i.e. regulator of chromosome condensation 1, are recognized by the enzyme. The first residue within the consensus sequence of the NTMT1 substrates is anchored through a hydrogen bond with the conserved Asn168 of NTMT1 in a spacious binding pocket, which exposes the substrate's reactive alpha-amino group to S-adenosyl-L-methionine in the complex structures, and this very N-terminal residue can tolerate most residue substitutions except the negatively charged residues D and E. Asp180 and His140 can act as bases to facilitate deprotonation of the target alpha-N-terminal amino group. Catalytic reaction proceeds probably involving a SN1 mechanism, overview
Products: S-adenosyl-L-homocysteine is bound to NTMT1 in an extended conformation. The carboxylate moiety of SAH forms a salt bridge interaction with the highly conserved Arg74, and the ribosyl group stacks with the indole ring of Trp20. In addition, the adenine moiety of SAH is flanked by the hydrophobic side chains of Ile92 and Val137 and interacts with the main chain amide group of Leu119 and the side chain of Gln120 through hydrogen bonding
Products: S-adenosyl-L-homocysteine is bound to NTMT1 in an extended conformation. The carboxylate moiety of SAH forms a salt bridge interaction with the highly conserved Arg74, and the ribosyl group stacks with the indole ring of Trp20. In addition, the adenine moiety of SAH is flanked by the hydrophobic side chains of Ile92 and Val137 and interacts with the main chain amide group of Leu119 and the side chain of Gln120 through hydrogen bonding
?
S-adenosyl-L-methionine + N-terminal-(A,P,S)PK-[protein]
S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,P,S)PK-[protein]
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + N-terminal-CENP-A
S-adenosyl-L-homocysteine + ?
Substrates: human CENP-A histone
Products: -
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?
S-adenosyl-L-methionine + N-terminal-dimethyl-SPKRIAKRRS
S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIAKRRS
-
Substrates: -
Products: -
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?
S-adenosyl-L-methionine + N-terminal-histone 2B
S-adenosyl-L-homocysteine + ?
Substrates: fruit fly histone 2B
Products: -
Products: -
?
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1
S-adenosyl-L-homocysteine + ?
S-adenosyl-L-methionine + retinoblastoma protein
S-adenosyl-L-homocysteine + ?
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
?
-
Substrates: methylation of Rpl12ab at the N-terminal proline residue
Products: -
Products: -
?
S-adenosyl-L-methionine + SET/TAF-I/PHAPII
S-adenosyl-L-homocysteine + ?
-
Substrates: only the SETalpha splicing variant is a substrate for NRMT, since it begins with the NRMT consensus in contrast to the beta splicing variant
Products: -
Products: -
?
S-adenosyl-L-methionine + SPKRIAKRRSPPADA
?
Substrates: 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
Products: -
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?
S-adenosyl-L-methionine + SSKRAKAKTTKKRP
?
Substrates: substrate peptide consisting of the first 14 amino acids of MYL9
Products: -
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?
2 S-adenosyl-L-methionine + N-terminal-PPKRIA
2 S-adenosyl-L-homocysteine + N-terminal-dimethyl-PPKRIA
-
Substrates: best substrate
Products: -
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?
2 S-adenosyl-L-methionine + N-terminal-PPKRIA
2 S-adenosyl-L-homocysteine + N-terminal-dimethyl-PPKRIA
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + [eEF1A]-L-lysine55
2 S-adenosyl-L-homocysteine + [eEF1A]-N6,N6-dimethyl-L-lysine55
Substrates: -
Products: -
Products: -
?
2 S-adenosyl-L-methionine + [eEF1A]-L-lysine55
2 S-adenosyl-L-homocysteine + [eEF1A]-N6,N6-dimethyl-L-lysine55
Substrates: the enzyme trimethylates the N-terminus and dimethylates Lys55 in the eukaryotic translation elongation factor 1 alpha
Products: -
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?
3 S-adenosyl-L-methionine + GPKRIA
3 S-adenosyl-L-homocysteine + ?
Substrates: trimethylation by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + GPKRIA
3 S-adenosyl-L-homocysteine + ?
-
Substrates: trimethylation by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-OLA1
3 S-adenosyl-L-homocysteine + ?
Substrates: i.e. Obg-like ATPase 1 (OLA1) protein, target validation using normal and NTMT1 knockout HEK-293FT cells demonstrates that OLA1, a protein involved in many critical cellular functions, is methylated in vivo by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-OLA1
3 S-adenosyl-L-homocysteine + ?
Substrates: i.e. Obg-like ATPase 1 (OLA1) protein
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-SPKRIA-[RCC1]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIA-[RCC1]
-
Substrates: high activity
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-SPKRIA-[RCC1]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIA-[RCC1]
-
Substrates: -
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-SPKRIA-[RCC1]
3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIA-[RCC1]
-
Substrates: i.e. regulator of chromosome condensation 1
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-[RCC1]
3 S-adenosyl-L-homocysteine + ?
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-[RCC1]
3 S-adenosyl-L-homocysteine + ?
-
Substrates: -
Products: -
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?
3 S-adenosyl-L-methionine + N-terminal-[RCC1]
3 S-adenosyl-L-homocysteine + ?
Substrates: RCC1p and methionine-removed RCC1
Products: -
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?
3 S-adenosyl-L-methionine + [eEF1A]-N-terminal glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-homocysteine + [eEF1A]-N-terminal N,N,N-trimethyl-glycine-L-lysine-L-glutamine-L-lysine
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + [eEF1A]-N-terminal glycine-L-lysine-L-glutamine-L-lysine
3 S-adenosyl-L-homocysteine + [eEF1A]-N-terminal N,N,N-trimethyl-glycine-L-lysine-L-glutamine-L-lysine
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + APKQQLSKY
?
Substrates: synthetic peptide, modified yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + APKQQLSKY
?
-
Substrates: synthetic peptide, modified yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + APKQQLSKY
?
-
Substrates: synthetic peptide, modified Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + PPKQQLSKY
?
Substrates: synthetic peptide, yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + PPKQQLSKY
?
-
Substrates: synthetic peptide, yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + PPKQQLSKY
?
-
Substrates: synthetic peptide, Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1
S-adenosyl-L-homocysteine + ?
-
Substrates: NRMT is the predominant alpha-N-methyltransferase for RCC1
Products: -
Products: -
?
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1
S-adenosyl-L-homocysteine + ?
-
Substrates: substrate docking and mutational analysis of RCC1 defining the NRMT recognition sequence, the first 3 residues Ser-Pro-Lys interact with NRMT, overview
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66. Utilization of top down mass spectrometry to determine the sites of methylation of Rpl12ab
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66. Utilization of top down mass spectrometry to determine the sites of methylation of Rpl12ab
Products: -
Products: -
?
S-adenosyl-L-methionine + Rps25a
?
-
Substrates: Rps25a and Rps25b differ only at position 104, a threonine residue is present in the former and an alanine residue in the latter
Products: -
Products: -
?
S-adenosyl-L-methionine + Rps25b
?
-
Substrates: Rps25a and Rps25b differ only at position 104, a threonine residue is present in the former and an alanine residue in the latter
Products: -
Products: -
?
S-adenosyl-L-methionine + SPKQQLSKY
?
Substrates: synthetic peptide, modified yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + SPKQQLSKY
?
-
Substrates: synthetic peptide, modified yeast protein Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
S-adenosyl-L-methionine + SPKQQLSKY
?
-
Substrates: synthetic peptide, modified Rps25a/Rps25b-derived peptide
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme methylates the eukaryotic elongation factor 1 alpha on the N-terminal amino group (3fold) and lysine 55 (2fold)
Products: -
Products: -
-
additional information
?
-
Substrates: the methyltransferases specifically recognizes the N-terminal X-Pro-Lys sequence motif. Localization of methylation sites by top down mass spectrometry using collisionally activated dissociation or electron capture dissociation. The enzyme can also recognize species with N-terminal alanine and serine residues in addition to those with proline residues, but the proline residue in position 1 is a preferred substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: the methyltransferases specifically recognizes the N-terminal X-Pro-Lys sequence motif. Localization of methylation sites by top down mass spectrometry using collisionally activated dissociation or electron capture dissociation. The enzyme can also recognize species with N-terminal alanine and serine residues in addition to those with proline residues, but the proline residue in position 1 is a preferred substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows a ternary complex mechanism of catalysis, involving formation of a SAM-enzyme-acceptor complex and direct transfer of the methyl group from SAM to the acceptor protein
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: the protein N-terminal methyltransferase 1 (NTMT1) methylates the alpha-N-terminal amines of proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme NTMT1 catalyzes the transfer of the methyl group from the S-adenosyl-L-methionine to the protein alpha-amine, resulting in formation of S-adenosyl-L-homocysteine and alpha-N-methylated proteins. Inhibition pattern and methylation progress analyses are performed to determine the kinetic mechanism and processivity of NTMT1, the enzyme NTMT1 utilizes a random sequential bi bi mechanism and proceeds in a distributive manner. Residues of RCC1, i.e. regulator of chromosome condensation 1, are recognized by the enzyme. Methylation status of products is analyzed by MALDI-mass spectrometry
Products: -
Products: -
?
additional information
?
-
Substrates: protein N-terminal methyltransferase 1 (NTMT1/NRMT1) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to protein alpha-N-terminal amines. It recognizes a specific motif X-P-K/R (X represents any amino acid other than D/E)
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: NTMT1 is a tri-methyltransferase
Products: -
Products: -
?
additional information
?
-
-
Substrates: NTMT1 is a tri-methyltransferase
Products: -
Products: -
?
additional information
?
-
Substrates: histone peptide profiling reveals that human NRMT1is highly selective to human CENP-A and fruit fly H2B, which share a common Xaa-Pro-Lys/Arg motif
Products: -
Products: -
?
additional information
?
-
-
Substrates: histone peptide profiling reveals that human NRMT1is highly selective to human CENP-A and fruit fly H2B, which share a common Xaa-Pro-Lys/Arg motif
Products: -
Products: -
?
additional information
?
-
Substrates: motif sequence and signal peptide analyses, and activity-based substrate profiling of NTMT1 utilizing (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine (Hey-SAM) reveals 72 potential targets, overview
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme catalyzes SAM-dependent methylation of both isoforms of the eukaryotic elongation factor, eEFIA1 and eEFIA2, at two sites: lysine 55 and the N-terminal glycine. The N-terminal domain (MT13-N), which encompasses residues 46 through 160, catalyzes the dimethylation of lysine 55, and the C-terminal domain (MT13-C), encompassing residues 499 through 673, catalyzes the trimethylation of the N-terminal glycine
Products: -
Products: -
-
additional information
?
-
Substrates: the enzyme's recognition motif is XPK/R
Products: -
Products: -
-
additional information
?
-
-
Substrates: the N-terminal protein methyltransferase catalyzes the modification of two ribosomal protein substrates, Rpl12ab and Rps25a/Rps25b. The yeast RPS25A and RPS25B genes and differ only at a single amino acid residue
Products: -
Products: -
?
additional information
?
-
-
Substrates: the methyltransferases specifically recognizes the N-terminal X-Pro-Lys sequence motif. Localization of methylation sites by top down mass spectrometry using collisionally activated dissociation or electron capture dissociation. The yeast enzyme can also recognize species with N-terminal alanine and serine residues in addition to those with proline residues, although to a lesser extent, the proline residue in position 1 is a preferred substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme alpha-N-methylates the small subunit of ribulose-1,5-bisphohate carboxylase/oxygenase
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 S-adenosyl-L-methionine + N-terminal-PPKRIA
2 S-adenosyl-L-homocysteine + N-terminal-dimethyl-PPKRIA
Substrates: -
Products: -
Products: -
?
3 S-adenosyl-L-methionine + GPKRIA
3 S-adenosyl-L-homocysteine + ?
Substrates: trimethylation by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-OLA1
3 S-adenosyl-L-homocysteine + ?
Substrates: i.e. Obg-like ATPase 1 (OLA1) protein, target validation using normal and NTMT1 knockout HEK-293FT cells demonstrates that OLA1, a protein involved in many critical cellular functions, is methylated in vivo by NTMT1
Products: -
Products: -
?
3 S-adenosyl-L-methionine + N-terminal-SPK-[RCC1 peptide]
3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-SPK-[RCC1 peptide]
Substrates: RCC1 peptide sequence is SPKRIAKRRS(CONH2)
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?
3 S-adenosyl-L-methionine + N-terminal-[RCC1]
3 S-adenosyl-L-homocysteine + ?
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + N-terminal-(A,P,S)PK-[protein]
S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,P,S)PK-[protein]
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + N-terminal-CENP-A
S-adenosyl-L-homocysteine + ?
Substrates: human CENP-A histone
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?
S-adenosyl-L-methionine + N-terminal-histone 2B
S-adenosyl-L-homocysteine + ?
Substrates: fruit fly histone 2B
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?
S-adenosyl-L-methionine + Ran guanine nucleotide-exchange factor RCC1
S-adenosyl-L-homocysteine + ?
-
Substrates: NRMT is the predominant alpha-N-methyltransferase for RCC1
Products: -
Products: -
?
S-adenosyl-L-methionine + retinoblastoma protein
S-adenosyl-L-homocysteine + ?
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
?
-
Substrates: methylation of Rpl12ab at the N-terminal proline residue
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66
Products: -
Products: -
?
S-adenosyl-L-methionine + Rpl12ab
S-adenosyl-L-homocysteine + ?
-
Substrates: the yeast Rpl12ab protein is dimethylated at the N-terminal proline residue, trimethylated at Lys-3 by Rkm2, and monomethylated at Arg66
Products: -
Products: -
?
additional information
?
-
-
Substrates: the protein N-terminal methyltransferase 1 (NTMT1) methylates the alpha-N-terminal amines of proteins
Products: -
Products: -
?
additional information
?
-
Substrates: protein N-terminal methyltransferase 1 (NTMT1/NRMT1) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to protein alpha-N-terminal amines. It recognizes a specific motif X-P-K/R (X represents any amino acid other than D/E)
Products: -
Products: -
?
additional information
?
-
-
Substrates: the N-terminal protein methyltransferase catalyzes the modification of two ribosomal protein substrates, Rpl12ab and Rps25a/Rps25b. The yeast RPS25A and RPS25B genes and differ only at a single amino acid residue
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[(naphthalen-1-yl)acetyl]-L-prolyl-L-lysyl-L-argininamide
compound significantly inhibits metrimethylation of RCC1 at 100 microM and shows an IC50 value of about 30 microM on the trimethyl-RCC1 level in HT-29 cells, inhibitor displays more than 300fold selectivity against methyltransferases tested
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-L-lysyl-N5-methyl-L-ornithinamide
-
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-phenylethyl)-L-lysinamide
inhibits cellular N-terminal methylation levels of the regulator of chromosome condensation 1 and the oncoprotein SET with an IC50 value of about 50 microM in HCT-116 cells, and exhibits over 100fold selectivity for NTMT1 against several other methyltransferases
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(3-carbamoylphenyl)-L-lysinamide
-
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-(2-[[2-(2-[2-[([(4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethoxy)ethyl]carbamoyl]phenyl)-L-lysina
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-[2-[(2-[2-[([(4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethyl)carbamoyl]phenyl]-L-lysinamide
the compound reduces enzyme protein levels effectively and selectively in time- and dose-dependent manners in colorectal carcinoma cell lines HCT116 and HT29. Degrader 1 displays DC50 of 0.00753 mM and Dmax higher than 90% in HCT-116 cells. The compound i
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-[2-[(2-[2-[([(4S)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethyl)carbamoyl]phenyl]-L-lysinamide
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-[2-[(2-[2-[2-(2-[2-[([(4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethoxy)ethoxy]ethoxy]ethyl)carbam
-
2-[[(2R)-2-aminopiperidin-1-yl]methyl]-N-(3-chlorophenyl)-9-ethyl-9H-purin-6-amine
-
-
5'-([3-[(2S)-2-acetylpyrrolidin-1-yl]propyl][(3S)-3-amino-3-carboxypropyl]amino)-5'-deoxyadenosine
-
METTL11A
METTL11A binding to the enzyme inhibits the trimethylation of the eukaryotic elongation factor N-terminal, with no significant effect on Km and a decrease in Vmax, suggesting that the interaction may be that of a standard non-competitive inhibitor. In contrast, METTL11A complexation with METTL13 promotes the dimethylation of eukaryotic elongation factor K55
-
N-terminal-acetyl-SPKRIAKRRS-[RCC1]
-
noncompetitive versus S-adenosyl-L-methionine and protein substrate
-
N-terminal-trimethyl-SPKRIA-[RCC1]
-
product inhibition, competitive inhibitor versus protein substrate, noncompetitive versus S-adenosyl-L-methionine
-
NAH-C4-GPKRIA
bisubstrate inhibitor containing a 4-C atom linker, shows picomolar inhibition for NTMT1 and more than 100000fold selectivity over other methyltransferases
-
NAM-C3-PKRIA-NH2
discovery of the potent NTMT1 bisubstrate inhibitor NAM-C3-PKRIA-NH2 that exhibits greater than 100fold selectivity against a panel of methyltransferases. Crystal structure analysis of NTMT1 in complex with the inhibitor reveals that NAM-C3-PKRIA-NH2 occupies substrate and cofactor binding sites of NTMT1
sinefungin
-
noncompetitive versus S-adenosyl-L-methionine and protein substrate
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-carbamoylphenyl)-L-lysinamide
-
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-carbamoylphenyl)-L-lysinamide
DC541, peptidomimetic inhibitor
NAM-TZ-SPKRIA
-
the inhibitor is enzyme-specific with a competitive inhibition pattern for both substrates, selective versus protein lysine methyltransferase G9a and arginine methyltransferase 1. The inhibitor substantially suppresses the methylation progression. The sulfur is replaced with a less reactive nitrogen to yield N-adenosyl-L-methionine as a stable analogue of S-adenosyl-L-methionine. Hexapeptide SPKRIA is derived from the N-terminus of regulator of chromosome condensation 1, RCC1. Binding structure modeling using the crystal structure of NTMT1 with S-adenosyl-L-homocysteine, PDB ID 2EX4. The two parts are connected via the triazole linker. NAM-TZ-SPKRIA acts as a competitive inhibitor when the concentration of S-adenosyl-L-methionine is varied from 0.003-0.010 mM and RCC1-10 substrate peptide is at a fixed concentration at 0.003 mM
S-adenosyl-L-homocysteine
-
product inhibition, competitive inhibitor versus S-adenosyl-L-methionine, noncompetitive versus protein substrate
additional information
-
the inhibition patterns indicate a rapid equilibrium random kinetic mechanism
-
additional information
-
feasibility of using a triazole group to link an S-adenosyl-L-methionine analogue with a peptide substrate to construct bisubstrate analogues as NTMT1 potent and selective inhibitors, a general strategy for the development of selective protein methyltransferase inhibitors
-
additional information
synthesis of NTMT1 degraders based on proteolysis-targeting chimera (PROTAC) strategy, i.e. a heterobifunctional molecule (called degrader) recruits both the protein of interest and E3 ubiquitin ligase to form a ternary complex. A cell permeable degrader involving a von Hippel-Lindau E3 ligase ligand and inhibitor (S)-N-((S)-6-amino-1-((2-carbamoylphenyl)amino)-1-oxohexan-2-yl)-1-(2-(naphthalen-1-yl)acetyl)pyrrolidine-2-carboxamide reduces NTMT1 protein levels effectively and selectively in time- and dose-dependent manners in cell lines HCT-116 and HT-29
-
additional information
analysis of bisubstrate analogues. A 2-C to 4-C atom linker enables its respective bisubstrate analogue to occupy both substrate- and cofactor-binding sites of NTMT1. Increasing the carbon linker length to a 5-C atom results in a substrate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Breast Neoplasms
Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.
Breast Neoplasms
Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation.
Breast Neoplasms
Structural basis for substrate recognition by the human N-terminal methyltransferase 1.
Carcinogenesis
KRAS-Driven Cancers Are Dependent on METTL13-Mediated eEF1A Methylation.
Carcinogenesis
Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.
Carcinogenesis
METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.
Carcinogenesis
Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation.
Carcinoma
Methyltransferase-like protein 11A promotes migration of cervical cancer cells via up-regulating ELK3.
Carcinoma
METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1? pathway and c-Myc expression.
Carcinoma
METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion.
Carcinoma, Renal Cell
METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1? pathway and c-Myc expression.
Colorectal Neoplasms
Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.
Dengue
A crystal structure of the Dengue virus NS5 polymerase delineates inter-domain amino acids residues that enhance its thermostability and de novo initiation activities.
Dengue
Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach.
Dengue
Stabilization of dengue virus polymerase in de novo initiation assay provides advantages for compound screening.
Lung Neoplasms
METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.
Neoplasm Metastasis
METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1? pathway and c-Myc expression.
Neoplasm Metastasis
METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion.
Neoplasms
Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors.
Neoplasms
Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.
Neoplasms
Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma.
Neoplasms
METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion.
Neoplasms
METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.
Neoplasms
Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer.
Neoplasms
Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation.
Neoplasms
Structural basis for substrate recognition by the human N-terminal methyltransferase 1.
Neoplasms
Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.
Neoplasms
Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism.
Retinoblastoma
NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein.
Squamous Cell Carcinoma of Head and Neck
Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma.
Starvation
CREB-mediated transcriptional activation of NRMT1 drives muscle differentiation.
Urinary Bladder Neoplasms
METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion.
Uterine Cervical Neoplasms
Methyltransferase-like protein 11A promotes migration of cervical cancer cells via up-regulating ELK3.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0014
(E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
0.0043
N-terminal-dimethyl-SPKRIAKRRS
-
recombinant detagged enzyme, pH 7.5, 37°C
0.00038
S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
0.00196
N-terminal-[RCC1]
with S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
0.00209
N-terminal-[RCC1]
with (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
0.0009
SPKRIAKRRSPPADA
recombinant NRMT1, in presence of NRMT2, pH and temperature not specified in the publication
0.0011
SPKRIAKRRSPPADA
recombinant NRMT1, pH and temperature not specified in the publication
0.0044
SSKRAKAKTTKKRP
recombinant NRMT1, in presence of NRMT2 catalytically inactive V224L mutant, pH and temperature not specified in the publication
0.0066
SSKRAKAKTTKKRP
recombinant NRMT1, in presence of NRMT2, pH and temperature not specified in the publication
0.0156
SSKRAKAKTTKKRP
recombinant NRMT1, pH and temperature not specified in the publication
additional information
additional information
-
Michaelis-Menten model, steady-state kinetic analysis and mechanism
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0067
(E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
0.0098
N-terminal-dimethyl-SPKRIAKRRS
-
recombinant detagged enzyme, pH 7.5, 37°C
0.0075
S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
0.0087
N-terminal-[RCC1]
with (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
0.0097
N-terminal-[RCC1]
with S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.79
(E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
19.74
S-adenosyl-L-methionine
with RCC1, pH and temperature not specified in the publication
4.16
N-terminal-[RCC1]
with (E)-hex-2-en-5-ynyl-S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
4.95
N-terminal-[RCC1]
with S-adenosyl-L-methionine, pH and temperature not specified in the publication
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state inhibition of NTMT1 by NAM-TZ-SPKRIA, kinetic analysis
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
1-[(naphthalen-1-yl)acetyl]-L-prolyl-L-lysyl-L-argininamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00047
1-[(naphthalen-1-yl)acetyl]-L-prolyl-L-lysyl-N5-methyl-L-ornithinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00918
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-carboxyphenyl)-L-lysinamide
Homo sapiens
at pH 7.5 and 37°C
0.00093
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-phenylethyl)-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00017
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(3-bromophenyl)-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00013
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(3-carbamoylphenyl)-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00065
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(3-phenylpropyl)-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0009 - 4
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-benzyl-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00177
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-[2-[(2-[2-[([(4R)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethyl)carbamoyl]phenyl]-L-lysinamide
Homo sapiens
at pH 7.5 and 37°C
0.00242
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N6-(tert-butoxycarbonyl)-N-[2-[(2-[2-[([(4S)-4-hydroxy-1-[(2S)-3-methyl-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]-L-prolyl]amino)methyl]-5-(3-methylthiophen-2-yl)phenoxy]ethyl)carbamoyl]phenyl]-L-lysinamide
Homo sapiens
at pH 7.5 and 37°C
0.0153 - 0.0221
2-[[(2R)-2-aminopiperidin-1-yl]methyl]-N-(3-chlorophenyl)-9-ethyl-9H-purin-6-amine
-
0.00026
NAH-C2-GPKRIA
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00013
NAH-C3-GPKRIA
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000082
NAH-C4-GPKRIA
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00034
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-carbamoylphenyl)-L-lysinamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00438
1-[(naphthalen-1-yl)acetyl]-L-prolyl-N-(2-carbamoylphenyl)-L-lysinamide
Homo sapiens
at pH 7.5 and 37°C
0.0153
2-[[(2R)-2-aminopiperidin-1-yl]methyl]-N-(3-chlorophenyl)-9-ethyl-9H-purin-6-amine
Homo sapiens
fluorescence assay, pH 7.5, 37°C
-
0.0221
2-[[(2R)-2-aminopiperidin-1-yl]methyl]-N-(3-chlorophenyl)-9-ethyl-9H-purin-6-amine
Homo sapiens
MALDI-MS assay, pH 7.5, 37°C
-
0.0144
6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol
Homo sapiens
MALDI-MS assay, pH 7.5, 37°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strains BY4742 and BY4741 and the YBR261C/tae1 deletion strain in each background, gene YBR261C/TAE1
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
NRMT1 is a ubiquitously expressed distributive trimethylase
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the coding sequence of spinach SSMT includes a putative targeting presequence with sequence identity at a plastid processing site
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
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
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
evolution
structural comparison of isozymes NTMT1 and NTMT2 (EC 2.1.1.299), overview. NTMT1 and NTMT2 employ a similar substrate recognition mode
evolution
enzymatic functional conservation of NRMT1 across species, evolutionary conservation of histone alpha-N-modification. Coevolution of NRMT1 recognition motifs in RCC1, CENP-A, and CENP-B, in which sequences 1SPKRIA6 of RCC1, 1GPRRRS6 of CENP-A, and 1GPKRRQ6 of CENP-B co-occur in mammals but are all missing in lower organisms. In contrast, the NRMT1 recognition motif of histone H2B is conserved from ciliates to insects but is lost in mammals. Remarkably, yeast and chicken orthologues of the above proteins do not harbor an NRMT1 recognition motif, suggesting that NRMT1 may exert its cellular function in these organisms through other protein substrates
malfunction
-
loss of the Saccharomyces cerevisiae ORF YBR261c/TAE results in the loss of the N-terminal methylation of both Rpl12ab and Rps25a/Rps25b
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
malfunction
-
loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis. Enzyme NRMT1 knockdown significantly enhances the sensitivity of breast cancer cell lines to both etoposide treatment and gamma-irradiation, as well as, increases proliferation rate, invasive potential, anchorage-independent growth, xenograft tumor size, and tamoxifen sensitivity, e.g. in MCF-7 cells. NRMT1 knockdown promotes growth of excision repair positive breast cancer cell lines, but has no effect on the normally low NRMT1-expressing SKBR-3 and MDA-MB-231 cells. Phenotype, overview
malfunction
-
NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects
malfunction
in vivo, complete knockout of NRMT1 via homologous recombination or CRISPR/Cas9 abolishes N-terminal trimethylation
malfunction
knockdown of NTMT1 results in hypersensitivity of breast cancer cell lines to doublestranded DNA breaks (DSBs) and increased proliferation of estrogen receptor positive breast cancer cells MCF-7 and LCC9
malfunction
aberrant N-terminal methylation has been implicated in several cancers and developmental diseases
malfunction
enzyme knockout decreases the occupancy of all alanine codons, as well as [TGG] and [TAC] for tryptophan, [AAC] for aspartic acid, and [TCA] and [TCC] for serine
malfunction
in addition to the numerous links to different types of cancer, enzyme mutations are also associated with hearing loss
malfunction
enzyme depletion reduces the severity of germline tumors
physiological function
protein X-Pro-Lys N-terminal methylation reactions catalyzed by the enzyme may be widespread in nature
physiological function
-
the N-terminal protein methyltransferase catalyzes the modification of two ribosomal protein substrates, Rpl12ab and Rps25a/Rps25b, the YBR261C/TAE1 product is necessary for the formation of the dimethylproline residue in each of these ribosomal proteins. Protein X-Pro-Lys N-terminal methylation reactions catalyzed by the enzyme may be widespread in nature
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
physiological function
-
alpha-N-terminal methylation seems to regulate protein stability via N-end rule pathways or mediate proteinprotein interactions. The enzyme also mediates protein-DNA interactions between chromatin and regulator of chromatin condensation
physiological function
-
enzyme NRMT1 acts as a tumor suppressor protein involved in multiple DNA repair pathways, role of N-terminal methylation in DNA repair. N-terminal methylation of DDB2 by NRMT1 is necessary for its recruitment to UV-induced DNA damage and proper execution of nucleotide excision repai. Additional NRMT1 targets, BRCA1 associated protein 1 (BAP1) and poly-ADP-ribosylase 3 (PARP3), are involved in DNA double strand break repair. BAP1 is a deubiquitinating enzyme recruited to DNA and required for appropriate assembly of homologous recombination factors during DSB. PARP3 poly-ADP-ribosylates proteins at DSBs and promotes NHEJ
physiological function
NRMT1 is a ubiquitously expressed distributive trimethylase
physiological function
protein lysine/arginine methylation, the addition of a methyl group at the free alpha-N-termini of proteins represents a unique mode of post-translational modification. NTMT1 is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase. During the enzymatic reaction, NTMT1 transfers a methyl group from SAM to the alpha-amino group of the protein substrates, resulting in the production of S-adenosyl-L-homocysteine (SAH) and alpha-N-methylated proteins. NTMT1 recognizes proteins bearing an N-terminal X-P-K/R consensus sequence, including RCC1, RB1, DDB2, CENP-A/B, PARP3, etc.
physiological function
protein N-terminal methyltransferase 1 (NTMT1) plays an important role in regulating mitosis and DNA repair
physiological function
NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates
physiological function
N-terminal methylation is a regulator of protein-DNA and protein-protein interactions for a number of proteins, such as RCC1, CENPA/B, DDB2, PARP3, an MYL9, playing important roles in cell mitotic progression, DNA damage repair, and regulation of protein function. N-terminal methyltransferase 1 (NTMT1) catalyzes the N-terminal methylation of proteins with a specific N-terminal motif after methionine removal. Obg-like ATPase 1 (OLA1) protein, a protein involved in many critical cellular functions, is methylated in vivo by NTMT1, NTMT1 is responsible for OLA1 methylation in vivo
physiological function
the enzyme is involved in tumorigenesis and regulates the eukaryotic elongation factor function
physiological function
enzyme-dependent methylation of eukaryotic elongation factor 1 alpha (eEF-1A) promotes Caenorhabditis elegans tumorigenesis. The K55 methylation of eEF-1A increases the penetrance of germline tumors. The enzyme is non-essential for animal growth and development
additional information
-
both full-length and truncated forms of the enzyme catalyze methylation of the alpha-amine of the N-terminal methionine of the small subunit of Rubisco
additional information
-
the enzyme contains two characteristic structural elements, a beta hairpin and an N-terminal extension, that contribute to its substrate specificity. Identification of key elements involved in locking the consensus substrate motif XPK (X indicates any residue type other than D/E) into the catalytic pocket for alpha-N-terminal methylation, NTMT1 prefers an XPK sequence motif, catalytic mechanism for alpha-N-terminal methylation and overall structure of the NTMT1 ternary complexes, verview
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
additional information
substrate and ligand binding structures of NTMT1 and NTMT2 (EC 2.1.1.299), overview
additional information
-
substrate and ligand binding structures of NTMT1 and NTMT2 (EC 2.1.1.299), overview
additional information
ternary structures of human NRMT1 bound to alpha-N-methylated peptides of human histone CENP-A or fruit fly histone H2B in the presence of SAH, NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases, key substrate recognition and catalytic residues, NTMT1 structure-function analysis, overview. NRMT1 harbors a canonical SAM-dependent methyltransferase (SAM-MTase) core fold consisting of a seven-stranded beta-sheet (beta1-beta7) sandwiched by five flanking alpha-helices. Active site structure and catalytic mechanism analysis
additional information
-
ternary structures of human NRMT1 bound to alpha-N-methylated peptides of human histone CENP-A or fruit fly histone H2B in the presence of SAH, NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases, key substrate recognition and catalytic residues, NTMT1 structure-function analysis, overview. NRMT1 harbors a canonical SAM-dependent methyltransferase (SAM-MTase) core fold consisting of a seven-stranded beta-sheet (beta1-beta7) sandwiched by five flanking alpha-helices. Active site structure and catalytic mechanism analysis
Show AA Sequence and Transmembrane Helices (4229 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
2 * 33000, recombinant isozyme NRMT1, SDS-PAGE and analytical ultracentrifugation
additional information
additional information
-
NRMT lacks a SET domain but possesses a Rossman-like alpha/beta fold
additional information
-
the structure of enzyme NTMT1 includes a typical methyltransferase Rossmann fold that consists of a seven-strand beta sheet and five alpha helixes, of which two alpha helixes (alpha6 and alpha7) pack on one side of the beta sheet, and the other three alpha helixes (alpha3, alpha4, and alpha5) pack on the other side of the beta sheet. In addition to the highly conserved Rossmann fold, enzyme NTMT1contains two unique structural elements distinct from other methyltransferases: a beta hairpin inserted between strand beta5 and helix alpha7 and an N-terminal extension consisting of two alpha helixes (alpha1 and alpha2) and one 310 helix. These two unique structural elements are extensively involved in substrate binding, suggesting their potential contributions to substrate specificity
additional information
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
additional information
-
the enzyme is a seven beta-strand methyltransferase
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of crystal structures of NRMT1 and NRMT2 (PDB IDs 2EX4 and 5UBB, determined to 1.75 and 2.0 A, respectively), homology modeling
purified recombinant His-tagged enzyme in complex with inhibitor NAM-C3-PKRIA-NH2 , hanging drop vapor diffusion method, mixing of 30 mg/ml protein and 2 mM ligand, with 1.5 M lithium sulfate and 0.1 M Na-HEPES, pH 7.5, 20°C, X-ray diffraction structure determination and analysis at 1.47 A resolution, molecular replacement using the structure PDB ID 6DTN as template, and modelling
purified recombinant NRMT1 bound to CENP-A peptide and to the fruit fly H2B peptide in presence of S-adenosyl-L-homocysteine, vapor diffusion method, X-ray diffraction structure determination and analysis at 1.3 A and 1.5 A resolution, respectively
recombinant purified full-length wild-type NTMT1 in complex with S-adenosyl-L-homocysteine and a peptide derived from either human (SPKRIA) or mouse (PPKRIA) RCC1, or crystals of NTMT1 in complex with S-adenosyl-L-homocysteine and either the RPK or YPK substrate peptide, sitting drop vapor diffusion method, mixing of 0.001 ml of 37 mg/ml protein and ligand in 20 mM Tris-HCl, pH 7.5, 150 mM NaCl, and 0.5 mM TECP, with 0.001 ml of reservoir solution containing 23-28% PET 3350 and 14-18% Tacsimate, pH 6.0, X-ray diffraction structure determination and analysis, molecular replacement
-
structure in complex with inhibitor N-2-[(2S)-1-[(naphthalen-1-yl)acetyl]-2,5-dihydro-1H-pyrrole-2-carbonyl]-L-lysyl-L-argininamide
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
D180N
site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type
D212N
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
E213A
site-directed mutagenesis, the mutant shows 15% reduced activity compared to wild-type
N168A
site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type
N168K
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S183K
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
W136L
site-directed mutagenesis, the mutant shows 92% reduced activity compared to wild-type
Y19A
site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type
Y19F
site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type
Y215A
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
Y215I
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
additional information
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
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
additional information
generation of NTMT1 knockout HEK-293FT cells by CRISPR-Cas9
additional information
-
the intact dimethylated Rpl12ab species isolated from the YBR261C/tae1 deletion strain is fragmented, and a b20 ion is detected with the addition of one methyl group, suggesting partial methylation of lysine 3. Neither of these species is dimethylated at the N-terminal residue. Rps25a/Rps25b isolated from the YBR261C/tae1 deletion strain is 28 Da less than the wild type, and the fragmentation data indicate no methylation is present
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
SAH-saturated NRMT1 displays a melting temperature (Tm) of 45°C, and the incubation with CENP-A (1-9) peptide further elevates the Tm by 3°C
additional information
additional information
all of the mutant peptides that lost methylation capacity display no or negligible stabilization effect of NRMT1, suggesting loss of peptide binding due to residue substitution. In contrast, G1A and G1P CENP-A mutants stabilize NRMT1 by 1.5°C and 5.5°C compared with that of the NRMT1-SAH binary complex, consistent with their retained methylation capacity
additional information
-
all of the mutant peptides that lost methylation capacity display no or negligible stabilization effect of NRMT1, suggesting loss of peptide binding due to residue substitution. In contrast, G1A and G1P CENP-A mutants stabilize NRMT1 by 1.5°C and 5.5°C compared with that of the NRMT1-SAH binary complex, consistent with their retained methylation capacity
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the experimentally calculated half-life for endogenous NRMT1 is approximately 8.8 h. NRMT2 expression stabilizes NRMT1 in HCT-116 cells
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21-CodonPlus(DE3)-RIL by nickel affinity chromatography
recombinant His-tagged METTL11A from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant N-terminally His6-tagged wild-type and mutant enzymes NTMT1 from Escherichia coli strain BL21(DE3) codon plus RIL by nickel affinity and anion exchange chromatography followed by gel filtration
-
recombinant N-terminally His6-tagged wild-type and mutant enzymes NTMT1 from Escherichia coli strain BL21(DE3) codon plus RIL by nickel affinity chromatography, tag cleavage through thrombin, another 3 steps of nickel affinity chromatography and dialysis
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
gene METTL11A, cloning of the His-tagged human enzyme using vector pET-100/DTOPO that carries a His6 tag in the linker region MRGSHHHHHHGMASMTGGQQMGRDLYDDDDKDHPFT, which is incorporated before the initiator methionine residue of the cloned protein, and expression in Escherichia coli strain BL21(DE3)
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
generbcMTS, DNA and amino acid sequence determination and analysis, expression of a N-terminal truncated form of spinach SSMT in Escherichia coli
-
N-terminally tagged FLAG-NRMT overexpression in HEK 293LT cell nuceli, that show 3fold increased RCC1 alpha-N-methyltransferase activity
-
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21-CodonPlus(DE3)-RIL
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli
recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes NTMT1 with a thrombin cleavage site at the N-terminus in Escherichia coli strain BL21(DE3) codon plus RIL
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a fluorescence-based methyltransferase assay miniaturized to 1536-well quantitative HTS format. The assay displays robust performance along with low reagent requirements and can potentially be employed for the discovery of inhibitors for any methyltransferase
drug development
medicine
drug development
-
design and synthesis of the inhibitors targeting NTMT1 as potential therapeutics in cancer treatment
medicine
the enzyme may be used as biomarker for disease prognosis, e.g. in diverse cancer diseases (lung adenocarcinoma, clear cell renal cell carcinoma, nasopharyngeal carcinoma, head and neck squamous cell carcinoma, gastric cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma) or non-cancer diseases like GAB1 associated profound deafness and ischemic heart failure
medicine
enzyme plasma levels are elevated in several cancer types, and specifically in ovarian cancer. High enzyme levels in clear cell renal cell carcinoma are linked to favorable prognosis and the enzyme inhibits growth and metastasis. In bladder cancer, the enzyme negatively regulates key cancer hallmarks including proliferation, migration and invasion
medicine
targeting the enzyme in cancer therapy can bypass the toxicity associated with targeting essential proteins
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ying, Z.; Mulligan, R.; Janney, N.; Royer, M.; Houtz, R.
Related alphaN- and epsilonN-methyltransferases methylate the large and small subunits of Rubisco
Acta Biol. Hung.
49
173-184
1998
Spinacia oleracea
brenda
Webb, K.J.; Lipson, R.S.; Al-Hadid, Q.; Whitelegge, J.P.; Clarke, S.G.
Identification of protein N-terminal methyltransferases in yeast and humans
Biochemistry
49
5225-5235
2010
Homo sapiens (Q9BV86), Homo sapiens, Mus musculus, Saccharomyces cerevisiae
brenda
Richon, V.M.; Johnston, D.; Sneeringer, C.J.; Jin, L.; Majer, C.R.; Elliston, K.; Jerva, L.F.; Scott, M.P.; Copeland, R.A.
Chemogenetic analysis of human protein methyltransferases
Chem. Biol. Drug Des.
78
199-210
2011
Homo sapiens
brenda
Webb, K.; Laganowsky, A.; Whitelegge, J.; Clarke, S.
Identification of two SET domain proteins required for methylation of lysine residues in yeast ribosomal protein Rpl42ab
J. Biol. Chem.
283
35561-35568
2008
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4742
brenda
Tooley, C.E.; Petkowski, J.J.; Muratore-Schroeder, T.L.; Balsbaugh, J.L.; Shabanowitz, J.; Sabat, M.; Minor, W.; Hunt, D.F.; Macara, I.G.
NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein
Nature
466
1125-1128
2010
Homo sapiens
brenda
Dong, C.; Mao, Y.; Tempel, W.; Qin, S.; Li, L.; Loppnau, P.; Huang, R.; Min, J.
Structural basis for substrate recognition by the human N-terminal methyltransferase 1
Genes Dev.
29
2343-2348
2015
Homo sapiens
brenda
Richardson, S.L.; Mao, Y.; Zhang, G.; Hanjra, P.; Peterson, D.L.; Huang, R.
Kinetic mechanism of protein N-terminal methyltransferase 1
J. Biol. Chem.
290
11601-11610
2015
Homo sapiens
brenda
Bonsignore, L.A.; Butler, J.S.; Klinge, C.M.; Schaner Tooley, C.E.
Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis
Oncotarget
6
12248-12263
2015
Homo sapiens
brenda
Zhang, G.; Richardson, S.L.; Mao, Y.; Huang, R.
Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors
Org. Biomol. Chem.
13
4149-4154
2015
Homo sapiens
brenda
Jia, K.; Huang, G.; Wu, W.; Shrestha, R.; Wu, B.; Xiong, Y.; Li, P.
In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1
Chem. Sci.
10
8094-8099
2019
Homo sapiens (Q9BV86)
brenda
Dong, C.; Dong, G.; Li, L.; Zhu, L.; Tempel, W.; Liu, Y.; Huang, R.; Min, J.
An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2
Commun. Biol.
1
183
2018
Homo sapiens (Q9BV86), Homo sapiens
brenda
Wu, R.; Yue, Y.; Zheng, X.; Li, H.
Molecular basis for histone N-terminal methylation by NRMT1
Genes Dev.
29
2337-2342
2015
Homo sapiens (Q9BV86), Homo sapiens
brenda
Chen, D.; Dong, G.; Noinaj, N.; Huang, R.
Discovery of bisubstrate inhibitors for protein N-terminal methyltransferase 1
J. Med. Chem.
62
3773-3779
2019
Homo sapiens (Q9BV86)
brenda
Faughn, J.D.; Dean, W.L.; Schaner Tooley, C.E.
The N-terminal methyltransferase homologs NRMT1 and NRMT2 exhibit novel regulation of activity through heterotrimer formation
Protein Sci.
27
1585-1599
2018
Homo sapiens (Q9BV86)
brenda
Dong, G.; Yasgar, A.; Peterson, D.L.; Zakharov, A.; Talley, D.; Cheng, K.C.; Jadhav, A.; Simeonov, A.; Huang, R.
Optimization of high-throughput methyltransferase assays for the discovery of small molecule inhibitors
ACS Comb. Sci.
22
422-432
2020
Homo sapiens (Q9BV86)
brenda
Chen, D.; Dong, G.; Deng, Y.; Noinaj, N.; Huang, R.
Structure-based discovery of cell-potent peptidomimetic inhibitors for protein N-terminal methyltransferase 1
ACS Med. Chem. Lett.
12
485-493
2021
Homo sapiens (Q9BV86)
brenda
Boulter, M.; Biggar, K.K.
Biological Relevance of dual lysine and N-terminal methyltransferase METTL13
Biomolecules
14
1112
2024
Homo sapiens (Q8N6R0)
brenda
Zhou, Q.; Wu, W.; Jia, K.; Qi, G.; Sun, X.; Li, P.
Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1
Eur. J. Med. Chem.
244
114830
2022
Homo sapiens (Q9BV86)
brenda
Chen, D.; Dong, C.; Dong, G.; Srinivasan, K.; Min, J.; Noinaj, N.; Huang, R.
Probing the plasticity in the active site of protein N-terminal methyltransferase 1 using bisubstrate analogues
J. Med. Chem.
63
8419-8431
2020
Homo sapiens (Q9BV86)
brenda
Meng, Y.; Li, Z.; He, M.; Zhang, Q.; Deng, Y.; Wang, Y.; Huang, R.
Characterizations of protein arginine deiminase 1 as a substrate of NTMT1 implications of Nalpha-methylation in protein stability and Iiteraction
J. Proteome Res.
23
4589-4600
2024
Homo sapiens (Q9BV86)
brenda
Jakobsson, M.E.
Structure, Activity and function of the dual protein lysine and protein N-terminal methyltransferase METTL13
Life (Basel)
11
1121
2021
Homo sapiens (Q8N6R0)
brenda
Meng, Y.; Huang, R.
Site-specific methylation on alpha-N-terminus of peptides through chemical and enzymatic methods
Methods Enzymol.
684
113-133
2023
Homo sapiens (Q9BV86)
brenda
Dong, G.; Iyamu, I.D.; Vilseck, J.Z.; Chen, D.; Huang, R.
Improved cell-potent and selective peptidomimetic inhibitors of protein N-terminal methyltransferase 1
Molecules
27
1381
2022
Homo sapiens (Q9BV86)
brenda
Engelfriet, M.L.; Malecki, J.M.; Forsberg, A.F.; Falnes, P.; Ciosk, R.
Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans
PLoS ONE
18
e0287558
2023
Caenorhabditis elegans (Q17539)
brenda
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