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.
Qian Y. van Meel E. Flanagan-Steet H. Yox A. Steet R. Kornfeld S.
Title
Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition.
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