{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O88509","secondaryAccessions":["O88510","O88511"],"uniProtkbId":"DNM3B_MOUSE","entryAudit":{"firstPublicDate":"2001-09-26","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2000-05-01","entryVersion":207,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"DNA (cytosine-5)-methyltransferase 3B"},"shortNames":[{"value":"Dnmt3b"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27768276"}],"value":"2.1.1.37"}]},"alternativeNames":[{"fullName":{"value":"DNA methyltransferase MmuIIIB"},"shortNames":[{"value":"DNA MTase MmuIIIB"},{"value":"M.MmuIIIB"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12567489"},{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:1261819"}],"value":"Dnmt3b"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UBC3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10555141"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11836534"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11919202"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16567415"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17616512"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18567530"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27768276"}],"value":"DNA (cytosine-5)-methyltransferase that mediates genome-wide de novo methylation and which is essential for the establishment of DNA methylation patterns during development (PubMed:10555141, PubMed:11836534, PubMed:11919202, PubMed:12897133, PubMed:16567415, PubMed:17616512, PubMed:18056424, PubMed:27768276). Modifies DNA at CpG sites with selectivity for residues flanking the target CpG site at positions -1 and +1, and strong preference for a guanine (G) immediately following the CpG sites (By similarity). Methylates DNA in a non-cooperative processive manner, allowing the enzyme to diffuse along DNA and methylate multiple sites before dissociation (PubMed:27768276). DNA methylation is coordinated with methylation of histones (PubMed:10555141, PubMed:11836534, PubMed:11919202, PubMed:16567415, PubMed:18056424, PubMed:27768276). Plays a role in genomic imprinting (PubMed:12897133, PubMed:17616512). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9 (By similarity). Acts as a transcriptional corepressor by associating with CBX4 and independently of DNA methylation (PubMed:18567530). Functions as a transcriptional corepressor by associating with ZHX1 (By similarity). Required for DUX4 silencing in somatic cells (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"}],"value":"Shows DNA (cytosine-5)-methyltransferase activity"}],"commentType":"FUNCTION","molecule":"Isoform Dnmt3b1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33004415"}],"value":"Shows DNA (cytosine-5)-methyltransferase activity"}],"commentType":"FUNCTION","molecule":"Isoform Dnmt3b2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UBC3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33004415"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41525843"}],"value":"Inactive isoform that lacks (cytosine-5)-methyltransferase activity and acts as an accessory factor for de novo DNA methylation (PubMed:11522819, PubMed:12897133, PubMed:33004415, PubMed:41525843). Forms a heterotetramer complex with catalytic isoforms from DNMT3A or DNMT3B, and acts as a scaffold to bridge the heterotetramer complex to nucleosomes and orient the catalytic subunit toward the accessible linker DNA (PubMed:33004415, PubMed:41525843). The heterotetramer complex specifically methylates long DNA linker regions between two nucleosomes (By similarity). In contrast, short DNA linker regions, which are enriched at promoter regions, promote di-nucleosome bridging, blocking access to linker DNA, preventing methylation (By similarity). Stimulates the activity of DNMT3A (isoforms DNMT3A1 or DNMT3A2) and DNMT3B (isoforms DNMT3B1 or DNMT3B2), with a preference for DNMT3B-mediated DNA methylation (PubMed:33004415)"}],"commentType":"FUNCTION","molecule":"Isoform Dnmt3b3"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:13681"},{"database":"Rhea","id":"RHEA-COMP:11369"},{"database":"Rhea","id":"RHEA-COMP:11370"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:85452"},{"database":"ChEBI","id":"CHEBI:85454"}],"ecNumber":"2.1.1.37","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27768276"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:13682"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27768276"}]}]},{"commentType":"CATALYTIC ACTIVITY","molecule":"Isoform Dnmt3b1","reaction":{"name":"a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:13681"},{"database":"Rhea","id":"RHEA-COMP:11369"},{"database":"Rhea","id":"RHEA-COMP:11370"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:85452"},{"database":"ChEBI","id":"CHEBI:85454"}],"ecNumber":"2.1.1.37","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12897133"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:13682"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"}]}]},{"commentType":"CATALYTIC ACTIVITY","molecule":"Isoform Dnmt3b2","reaction":{"name":"a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:13681"},{"database":"Rhea","id":"RHEA-COMP:11369"},{"database":"Rhea","id":"RHEA-COMP:11370"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:85452"},{"database":"ChEBI","id":"CHEBI:85454"}],"ecNumber":"2.1.1.37","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33004415"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:13682"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11522819"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33004415"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15671018"}],"value":"Activated by binding to the regulatory factor DNMT3L"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UBC3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12867029"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15671018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16085498"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16357870"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18567530"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19798101"}],"value":"Heterotetramer composed of two catalytic DNMT3B subunits and regulatory subunit homodimer (either DNMT3L or isoform DNMT3B3 of DNMT3B) (PubMed:15671018). Interacts with BAZ2A/TIP5, UHRF1, SUV39H1 and CBX4 (PubMed:12867029, PubMed:16085498, PubMed:18567530, PubMed:19798101). Interacts with DNMT1 and DNMT3A, SETDB1, UBL1, UBE2I9 and ZHX1 (By similarity). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33004415"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41525843"}],"value":"Heterotetramer composed of two regulatory DNMT3B3 subunits and a catalytic homodimer (either isoforms DNMT3A1 or DNMT3A2 of DNMT3A or isoforms DNMT3B1 or DNMT3B2 of DNMT3B)"}],"commentType":"SUBUNIT","molecule":"Isoform Dnmt3b3"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"O88509","intActId":"EBI-7987547"},"interactantTwo":{"uniProtKBAccession":"P25916","geneName":"Bmi1","intActId":"EBI-927401"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O88509","intActId":"EBI-7987547"},"interactantTwo":{"uniProtKBAccession":"Q9CWR8","geneName":"Dnmt3l","intActId":"EBI-3043871"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O88509","intActId":"EBI-7987547"},"interactantTwo":{"uniProtKBAccession":"Q9Z148-2","geneName":"Ehmt2","intActId":"EBI-15737169"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O88509","intActId":"EBI-7987547"},"interactantTwo":{"uniProtKBAccession":"Q60848","geneName":"Hells","intActId":"EBI-3043887"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15456878"}],"value":"Accumulates in the major satellite repeats at pericentric heterochromatin"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15456878"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15456878"}],"value":"Chromosome","id":"SL-0468"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"Dnmt3b1"},"synonyms":[{"value":"5"}],"isoformIds":["O88509-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"Dnmt3b2"},"synonyms":[{"value":"6"}],"isoformIds":["O88509-2"],"sequenceIds":["VSP_005642"],"isoformSequenceStatus":"Described"},{"name":{"value":"Dnmt3b3"},"synonyms":[{"value":"8"}],"isoformIds":["O88509-3"],"sequenceIds":["VSP_005642","VSP_005643"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"synonyms":[{"value":"7"}],"isoformIds":["O88509-4"],"sequenceIds":["VSP_005643"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10555141"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18814855"}],"value":"Expressed in almost all blastocysts at 3.0 dpc. Preferentially expressed in the trophectoderm (TE) in 3.5 dpc and polar TE in 4.0 dpc blastocysts. In 4.5 dpc embryos, expressed in the polar TE and some inner cell mass (ICM) embryonic lineage cells. In post-implantation embryo at 5.5 dpc, expressed in the epiblast (embryonic lineage) derived from the ICM. Highly expressed, at 7.5 dpc, in the embryonic ectoderm, neural ectoderm, and chorionic ectoderm; a weak expression is also detected in mesodermal and endodermal cells. At later stages, the expression is detected predominantly in the forebrain and eyes but weakly throughout the embryo"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UBC3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15456878"}],"value":"The PWWP domain specifically recognizes and binds histone H3 dimethylated at 'Lys-36' (H3K36me2) (By similarity). H3K36me2 recognition is however blocked when the heterotrameric complex bridges di-nucleosomes with short linkers (By similarity). The PWWP domain is essential for targeting to pericentric heterochromatin (PubMed:15456878)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UBC3"}],"value":"Sumoylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24463520"}],"value":"Citrullinated by PADI4"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01016"}],"value":"Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":859,"modifier":"EXACT"}},"description":"DNA (cytosine-5)-methyltransferase 3B","featureId":"PRO_0000088046"},{"type":"Domain","location":{"start":{"value":232,"modifier":"EXACT"},"end":{"value":290,"modifier":"EXACT"}},"description":"PWWP","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00162"}]},{"type":"Domain","location":{"start":{"value":428,"modifier":"EXACT"},"end":{"value":560,"modifier":"EXACT"}},"description":"ADD","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00865"}]},{"type":"Domain","location":{"start":{"value":581,"modifier":"EXACT"},"end":{"value":859,"modifier":"EXACT"}},"description":"SAM-dependent MTase C5-type","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01016"}]},{"type":"Zinc 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