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MGP000855

UniProt Annotations

Entry Information
Gene NameDNA (cytosine-5-)-methyltransferase 3 alpha
Protein EntryDNM3A_HUMAN
UniProt IDQ9Y6K1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative promoter usage, Alternative splicing; Named isoforms=3; Name=1; IsoId=Q9Y6K1-1; Sequence=Displayed; Name=2; IsoId=Q9Y6K1-2; Sequence=VSP_046254; Note=It is uncertain whether Met-1 or Met-35 is the initiator.; Name=3; IsoId=Q9Y6K1-3; Sequence=VSP_040998, VSP_040999; Note=Produced by alternative splicing.;
Catalytic ActivityS-adenosyl-L-methionine + DNA = S-adenosyl-L- homocysteine + DNA containing 5-methylcytosine. {ECO:0000255|PROSITE-ProRule:PRU10018}.
CautionIt is uncertain whether Met-1 or Met-4 is the initiator. {ECO:0000305}.
DiseaseTatton-Brown-Rahman syndrome (TBRS) [MIM:615879]: An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis. {ECO:0000269|PubMed:24614070}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (By similarity). {ECO:0000250}.
Enzyme RegulationActivated by binding to the regulatory factor DNMT3L. {ECO:0000250}.
FunctionRequired for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity. {ECO:0000269|PubMed:16357870}.
InteractionSelf; NbExp=4; IntAct=EBI-923653, EBI-923653; O75530:EED; NbExp=2; IntAct=EBI-923653, EBI-923794; Q15910:EZH2; NbExp=6; IntAct=EBI-923653, EBI-530054; P84243:H3F3B; NbExp=7; IntAct=EBI-923653, EBI-120658; Q15047:SETDB1; NbExp=7; IntAct=EBI-923653, EBI-79691; Q96T88:UHRF1; NbExp=7; IntAct=EBI-923653, EBI-1548946;
PtmSumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription. {ECO:0000250}.
Sequence CautionSequence=AAL57039.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAN40037.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU01016}.
SimilarityContains 1 ADD domain. {ECO:0000255|PROSITE- ProRule:PRU00865}.
SimilarityContains 1 GATA-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00865}.
SimilarityContains 1 PHD-type zinc finger. {ECO:0000255|PROSITE- ProRule:PRU00865}.
SimilarityContains 1 PWWP domain. {ECO:0000255|PROSITE- ProRule:PRU00162}.
SimilarityContains 1 SAM-dependent MTase C5-type domain. {ECO:0000255|PROSITE-ProRule:PRU01016}.
Subcellular LocationNucleus {ECO:0000269|PubMed:12145218}. Cytoplasm {ECO:0000269|PubMed:12145218}. Note=Accumulates in the major satellite repeats at pericentric heterochromatin. {ECO:0000250}.
SubunitHeterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with UBC9, PIAS1 and PIAS2 (By similarity). Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with UHRF1 (By similarity). Interacts with DNMT1 and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). {ECO:0000250, ECO:0000269|PubMed:12145218, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16682412, ECO:0000269|PubMed:17713477, ECO:0000269|PubMed:19834512, ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:22086334}.
Tissue SpecificityHighly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung. {ECO:0000269|PubMed:10325416}.
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