This entry represents DNA (cytosine-5)-methyltransferase 1 (Dnmt1; ), which methylates CpG residues, with a preference for hemimethylated DNA. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Dnmt1 mediates transcriptional repression (silencing) by establishing a repressive transcription complex where the N terminus of Dnmt1 binds to HDAC2 (histone deacetylase-2) as well as to DMAP1 (Dnmt1-associated protein) []. LSH, which is related to the SNF2 chromatin-remodelling ATPases, is also required for efficient DNA methylation [].
This entry represents a domain found in DNA methyltransferase 1-associated protein 1 (DMAP1). DNA methylation can contribute to transcriptional silencing through several transcriptionally repressive complexes, which include methyl-CpG binding domain proteins (MBDs) and histone deacetylases (HDACs). The chief enzyme that maintains mammalian DNA methylation, DNMT1, can also establish a repressive transcription complex. The non-catalytic N terminus of DNMT1 binds to HDAC2 and DMAP1, and can mediate transcriptional repression. DMAP1 has intrinsic transcription repressive activity, and binds to the transcriptional co-repressor TSG101. DMAP1 is targeted to replication foci through interaction with the far N terminus of DNMT1 throughout S phase, whereas HDAC2 joins DNMT1 and DMAP1 only during late S phase, providing a platform for how histones may become deacetylated in heterochromatin following replication [].
This entry includes PHF20 and PHF20L1 proteins.PHD finger protein 20 (PHF20) binds dimethyl lysine residues via its Tudor domain []. It is a component of the MLL1, MOF histone acetyltransferase []and NSL protein complexes [].PHF20L1 binds to monomethylated lysine 142 on DNA (cytosine-5) methyltransferase 1 (DNMT1). It has been shown to antagonize DNMT1 proteasomal degradation [].
This domain is part of a cytosine specific DNA methyltransferase enzyme (DNMT). It functions non-catalytically to target the protein towards replication foci. This allows the DNMT1 protein to methylate the correct residues. This domain targets DMAP1 and HDAC2 to the replication foci during the S phase of mitosis. They are thought to have some importance in conversion of critical histone lysine moieties [].A structure exists for the human cytosine specific DNA methyltransferase replication foci domain [].
PHD finger protein 20 (PHF20) is a Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. It consists of tandem Tudor domains at the N-terminal, an AT hook, a C2H2-type zinc finger, and a plant homeodomain (PHD) finger [, , ]. PHF20L1 binds to monomethylated lysine 142 on DNA (cytosine-5) methyltransferase 1 (DNMT1). It has been shown to antagonize DNMT1 proteasomal degradation [].This is the AT-hook domain found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like (PHF20L) [, , ].
This entry represents the RGS domain of RGS6 (regulator of G-protein signaling 6). RGS6 is a member of the R7 RGS protein subfamily. Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control []. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains []. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation []. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes [].
This is a ~120-amino acid protein-protein interaction module that binds DMAP1 (DNA methyltransferase-associated protein 1), a transcriptional co-repressor. It is found at the N terminus of DNMT1 (DNA methyltransferase 1) []and animal disco-interacting protein 2 (DIP-2), a protein that maintains morphology of mature neurons [, ]. This domain is also found in N-acetylglucosamine-1-phosphotransferase subunits alpha/beta (GNPTA) and gamma (GNPTG) from animals, which are members of a complex that catalyses 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 [, ].The DMAP1-binding domain is predicted to adopt a long helix-turn-helix structure that is rich in leucine residues [].
