The DNA methyltransferase 1 (DNMT1) is a multifunctional protein that is a critical DNA methyltransferase important for chromatin structure and gene silencing as well as methyltransferase-independent transcriptional repression. DNMT1 is composed of multiple functional domains. The N-terminal regulatory region contains conserved domains, including the DNA methyltransferase-associated protein 1 (DMAP1)-binding domain, the PCNA (proliferating cell nuclear antigen) binding domain (PBD) and the replication foci targeting sequence (RFTS) which control the subnuclear localization of DNMT1. In contrast, the C-terminal portion contains a catalytic domain (see <PDOC51555>). The DMAP1-binding domain is a ~120-amino acid protein-protein interaction module that binds notably DMAP1, a transcriptional co-repressor [1,2,3].

In addition to DNMT1, a DMAP1-binding domain is found in the following proteins:

• Animal disco-interacting protein 2 (DIP-2), that maintains morphology of mature neurons. DIP-2 consists of a DMAP1-binding domain and two adenylate- forming domains (AFDs) [4,5,6].
• Animal N-acetylglucosamine-1-phosphotransferase subunits α (GNPTA) and γ (GNPTG), members of a complex that catalyzes the initial step in the formation of the mannose 6-phopsphate targeting signal on newly synthesized lysosomal acid hydrolases. The DMAP1-binding domain mediates the selective binding GlcNAc-1-phosphotranferase to acid hydrolases [7,8].

The DMAP1-binding domain is predicted to adopt a long helix-turn-helix structure that is rich in leucine residues [1].

The profile we developed covers the entire DMAP1-binding domain.