N-Terminal Xaa-Pro-Lys N-Methyltransferase 1 (NTMT1), also known as METTL11A, is a protein-coding gene that encodes an enzyme responsible for the methylation of the N-terminus of target proteins. This enzyme plays a crucial role in various cellular processes, including DNA damage response and mitosis. The human recombinant form of NTMT1 is produced through recombinant DNA technology, allowing for its use in research and therapeutic applications.
The NTMT1 gene is located on chromosome 9 and is also referred to by several aliases, including C9orf32 and HOMT1A . The protein encoded by this gene is a distributive alpha-N-methyltransferase that specifically methylates the N-terminus of proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator methionine is cleaved . This enzyme can catalyze 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 .
NTMT1 is responsible for the N-terminal methylation of several key proteins, including KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A, and SET . This methylation is essential for normal cellular functions, such as the formation of the bipolar spindle and chromosome segregation during mitosis . NTMT1 also plays a role in the DNA damage response pathway, contributing to the maintenance of genomic stability .
The enzyme’s activity is characterized by its ability to catalyze the trimethylation of the N-terminal glycine in CENPA after the removal of the initiator methionine . Some substrates may be primed by NTMT2-mediated monomethylation, which further highlights the interplay between different methyltransferases in regulating protein function .
The methylation of N-terminal residues by NTMT1 is a critical post-translational modification that influences protein stability, localization, and interaction with other cellular components. This modification can affect various biological processes, including cell cycle regulation, signal transduction, and gene expression . Dysregulation of NTMT1 activity has been implicated in several diseases, including cancer, where abnormal methylation patterns can lead to altered cellular behavior and tumor progression .
The human recombinant form of NTMT1 is widely used in research to study its enzymatic activity, substrate specificity, and role in cellular processes. Recombinant NTMT1 is produced using recombinant DNA technology, which involves the insertion of the NTMT1 gene into an expression vector, followed by the expression and purification of the protein in a suitable host system . This allows researchers to obtain large quantities of the enzyme for biochemical and structural studies.
In addition to its research applications, NTMT1 has potential therapeutic implications. Targeting NTMT1 and its associated pathways could provide new strategies for the treatment of diseases characterized by aberrant methylation patterns, such as cancer . The development of specific inhibitors or modulators of NTMT1 activity could offer novel therapeutic approaches for these conditions.