Recombinant DNMT3B protein

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]

DNMT3B: a ubiquitous DNA methyltransferase required for genome wide de novo methylation and essential for development. DNA methylation is coordinated with methylation of histones. Numerous cancer cell lines and primary acute leukemias express aberrant DNMT3B transcripts, especially DNMT3B7. Transfection of DNMT3B7 into 293 cells alters the pattern of genes expressed in the transfected cells. Can interact with DNMT1, which might be a co-operative event during DNA methylation. Methylates CpG sites at a rate slower than DNMT3A and much slower than DNMT1. Interacts with SUV39H1, SETDB1, SUMO1 and UBE2I9. Interacts with DNMT1 and DNMT3A. Mutations in DNMT3B have been shown to cause immunodeficiency-centromeric instability-facial anomalies syndrome (ICF). Six alternatively spliced isoforms of the human protein have been reported. Isoform 1 is expressed in all tissues except brain, skeletal muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except brain, skeletal muscle, lung and prostate and 5 is detectable only in testis and at very low level in brain and prostate. Isoforms 4 and 5 are probably not enzymatically active due to the deletion of two conserved methyltransferase motifs.

Protein type: Methyltransferase; Methyltransferase, DNA; Cell development/differentiation; EC 2.1.1.37; Amino Acid Metabolism - cysteine and methionine

Chromosomal Location of Human Ortholog: 20q11.2

Cellular Component: nucleoplasm; intracellular membrane-bound organelle; cytoplasm; nuclear heterochromatin; nucleus

Molecular Function: DNA (cytosine-5-)-methyltransferase activity; protein binding; unmethylated CpG binding; DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates; metal ion binding; DNA-methyltransferase activity; transcription corepressor activity

Biological Process: response to drug; negative regulation of histone H3-K9 methylation; genetic imprinting; S-adenosylhomocysteine metabolic process; positive regulation of histone H3-K4 methylation; negative regulation of transcription from RNA polymerase II promoter; regulation of gene expression, epigenetic; cytosine methylation within a CG sequence; protein complex localization; methylation-dependent chromatin silencing; negative regulation of gene expression, epigenetic; DNA methylation; S-adenosylmethioninamine metabolic process; gene expression; response to ionizing radiation; positive regulation of neuron differentiation; DNA methylation on cytosine

Disease: Immunodeficiency-centromeric Instability-facial Anomalies Syndrome 1