Background:
METTL11A, also named N terminal RCC1 methyltransferase (NRMT), is an alpha N methyltransferase that methylates the N terminal amino group of target proteins containing the N terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved (1). It is responsible for N terminal methylation of RCC1, KLHL31, MYL2, MYL3, RB1, RPL23A and SET. NRMT lacks a SET domain but possesses a Rossman like a/b fold. The residues Asn169, Asp178, Asp181, and Ser183 of NRMT are important for substrate binding (2). RCC1 (Ran guanine nucleotide exchange factor) is the first protein for which any biological function of alpha N methylation by NRMT has been identified (3, 4). The multi spindle phenotype associated with either NRMT knockdown or methylation defective RCC1 mutants demonstrated the importance of alpha N methylation of RCC1 for normal bipolar spindle formation and chromosome aggregation (2). NRMT is robustly overexpressed in gastrointestinal cancers.