C5-cytosine DNA methyltransferase-3A; DNA (cytosine-5)-methyltransferase 3A; Dnmt3a; DNA methyltransferase HsaIIIA; DNA MTase HsaIIIA; M.HsaIIIA (DNMT3A)

Function: - responsible for genome wide de novo methylation in mammals - catalyzes S-adenosylmethionine (SAM)-mediated methylation of cytosine to form 5-methylcytosine + S-adenosyl-l-homocysteine - essential for the establishment of DNA methylation patterns during development - DNA methylation is coordinated with methylation of histones - modifies DNA in a non-processive manner & also methylates non-CpG sites - may preferentially methylate DNA linker between 2 nucleosomal cores & is inhibited by histone H1 - role in paternal & maternal imprinting - required for methylation of most imprinted loci in germ cells - acts as a transcriptional corepressor for ZNF238 - can actively repress transcription through the recruitment of HDAC activity - activated by binding to the regulatory factor DNMT3L (putative) - sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 & HDAC2) & represses transcription - heterotetramer composed of 1 DNMT3A homodimer & 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) - interacts with UBC9, PIAS1 & PIAS2 (putative) - binds the ZNF238 transcriptional repressor - interacts with SETDB1 - associates with HDAC1 through its ADD-type Zn⁺²-finger (putative) - interacts with DNMT1 & DNMT3B - interacts with the PRC2/EED-EZH2 complex S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine Structure: - the PWWP domain is essential for targeting to pericentric heterochromatin - belongs to the C5-methyltransferase family - contains 1 ADD-type Zn⁺² finger - contains 1 PWWP domain Compartment: - nucleus, cytoplasm - accumulates in the major satellite repeats at pericentric heterochromatin Alternative promoter usage: named isoforms=2 Expression: - highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney - expressed at lower levels in placenta, brain, liver, colon, spleen, small intestine & lung Note: - uncertain whether Met-1 or Met-4 is the initiator

Properties

SIZE: entity length = 912 aa MW = 102 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S105} DNMT1 & DNMT3B interaction {199-403} MOTIF: PWWP domain {292-350} Zinc finger NAME: Zinc finger SITE: 494-586 EFFECTOR-BOUND: Zn+2 MOTIF: tPRC2/EED-EZH2 interaction {494-586} cysteine residue {C710}

Database Correlations

OMIM 602769 UniProt Q9Y6K1 PFAM correlations Entrez Gene 1788 Kegg hsa:1788 ENZYME 2.1.1.37

References

UniProt :accession Q9Y6K1