DNMT3A: Proteins and Enzymes

DNMT3A (DNA [cytosine-5]-methyltransferase 3A) is a 130 kDa member of the C5-methlytransferase family of molecules. DNMT3A is expressed both during development and in virtually all adult tissues except for small intestine. DNMT3A is a nuclear protein that is found associated with heterochromatin. DNMT3A possesses DNA methyltransferase activity, and acts in a complex with DNMT3L in embryonic stem cells, forming a (3A)2:(3L)2 heterotetramer. DNMT3A also interacts with SETDB1 to form a transcriptional repressor. Human DNMT3A is 912 amino acids (aa) in length. It contains one ProTrpTrpPro domain (aa 292-350) and one ADD-type zinc finger region (aa 494-586). There is one 100 kDa splice variant termed DNMT3a2 that contains an alternative start site at Met224, and preferentially interacts with euchromatin. Other potential splice variants show a 16 aa substitution for aa 151-912, and a 24 aa substitution for aa 1-213. Over aa 353-486, human DNMT3A shares 96% aa identity with mouse DNMT3A.