UniProtKB - O88509 (DNM3B_MOUSE)
DNA (cytosine-5)-methyltransferase 3B
Dnmt3b
Functioni
Required 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. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing. 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. Functions as a transcriptional corepressor by associating with ZHX1 (By similarity).
Required for DUX4 silencing in somatic cells (By similarity).
By similarity6 PublicationsCatalytic activityi
- a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + H+ + S-adenosyl-L-homocysteinePROSITE-ProRule annotationEC:2.1.1.37PROSITE-ProRule annotation
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 611 | S-adenosyl-L-methionineBy similarity | 1 | |
Active sitei | 657 | PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 439 – 469 | GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 480 – 536 | PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST | 57 |
GO - Molecular functioni
- chromatin binding Source: MGI
- DNA (cytosine-5-)-methyltransferase activity Source: MGI
- DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Source: MGI
- DNA (cytosine-5-)-methyltransferase activity, acting on CpN substrates Source: Reactome
- DNA binding Source: MGI
- histone deacetylase binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- methyltransferase activity Source: UniProtKB
- transcription corepressor activity Source: MGI
GO - Biological processi
- C-5 methylation of cytosine Source: MGI
- cellular response to amino acid stimulus Source: MGI
- DNA methylation Source: MGI
- DNA methylation-dependent heterochromatin assembly Source: MGI
- DNA methylation involved in embryo development Source: MGI
- negative regulation of gene expression, epigenetic Source: UniProtKB
- negative regulation of histone H3-K9 methylation Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of histone H3-K4 methylation Source: MGI
- positive regulation of neuron differentiation Source: MGI
- protein-containing complex localization Source: MGI
- regulation of gene expression by genetic imprinting Source: MGI
Keywordsi
Molecular function | Activator, DNA-binding, Methyltransferase, Repressor, Transferase |
Ligand | Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
BRENDAi | 2.1.1.37, 3474 |
Reactomei | R-MMU-212300, PRC2 methylates histones and DNA R-MMU-4655427, SUMOylation of DNA methylation proteins |
Protein family/group databases
REBASEi | 3748, M.MmuDnmt3B |
Names & Taxonomyi
Protein namesi | Recommended name: DNA (cytosine-5)-methyltransferase 3B (EC:2.1.1.37)Short name: Dnmt3b Alternative name(s): DNA methyltransferase MmuIIIB Short name: DNA MTase MmuIIIB Short name: M.MmuIIIB |
Gene namesi | Name:Dnmt3b |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1261819, Dnmt3b |
VEuPathDBi | HostDB:ENSMUSG00000027478 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Note: Accumulates in the major satellite repeats at pericentric heterochromatin.
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- chromosome, centromeric region Source: UniProtKB
- cytoplasm Source: MGI
- heterochromatin Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 236 – 237 | VW → RR: Prevents accumulation in pericentric heterochromatin. 1 Publication | 2 | |
Mutagenesisi | 277 | S → P: Prevents accumulation in pericentric heterochromatin. 1 Publication | 1 | |
Mutagenesisi | 609 | A → T: Significantly reduces activity. 1 Publication | 1 | |
Mutagenesisi | 656 – 657 | PC → GT: No effect on localization. 1 Publication | 2 | |
Mutagenesisi | 669 | G → S: Significantly reduces activity. 1 Publication | 1 | |
Mutagenesisi | 670 | L → T: Significantly reduces activity. 1 Publication | 1 | |
Mutagenesisi | 725 | V → G: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 823 | D → G: Significantly reduces activity. 1 Publication | 1 | |
Mutagenesisi | 824 | V → M: Significantly reduces activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL2189115 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000088046 | 1 – 859 | DNA (cytosine-5)-methyltransferase 3BAdd BLAST | 859 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 96 | PhosphoserineBy similarity | 1 | |
Cross-linki | 102 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 112 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 116 | PhosphoserineBy similarity | 1 | |
Modified residuei | 216 | PhosphoserineBy similarity | 1 | |
Modified residuei | 415 | Citrulline1 Publication | 1 | |
Cross-linki | 623 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity |
Post-translational modificationi
Keywords - PTMi
Citrullination, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | O88509 |
MaxQBi | O88509 |
PaxDbi | O88509 |
PeptideAtlasi | O88509 |
PRIDEi | O88509 |
ProteomicsDBi | 277365 [O88509-1] 277366 [O88509-2] 277367 [O88509-3] 277368 [O88509-4] |
PTM databases
iPTMneti | O88509 |
PhosphoSitePlusi | O88509 |
Expressioni
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000027478, Expressed in epiblast (generic) and 302 other tissues |
ExpressionAtlasi | O88509, baseline and differential |
Genevisiblei | O88509, MM |
Interactioni
Subunit structurei
Interacts with CBX4, DNMT1, DNMT3A, SETDB1, UBE2I9, UBL1 and ZHX1 (By similarity).
Interacts with SUV39H1 and BAZ2A/TIP5.
Interacts with the PRC2/EED-EZH2 complex.
Interacts with UHRF1.
By similarity6 PublicationsBinary interactionsi
O88509
With | #Exp. | IntAct |
---|---|---|
Bmi1 [P25916] | 2 | EBI-7987547,EBI-927401 |
Dnmt3l [Q9CWR8] | 6 | EBI-7987547,EBI-3043871 |
Ehmt2 - isoform 2 [Q9Z148-2] | 3 | EBI-7987547,EBI-15737169 |
Hells [Q60848] | 4 | EBI-7987547,EBI-3043887 |
GO - Molecular functioni
- histone deacetylase binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 199262, 11 interactors |
CORUMi | O88509 |
DIPi | DIP-43736N |
IntActi | O88509, 11 interactors |
MINTi | O88509 |
STRINGi | 10090.ENSMUSP00000105396 |
Chemistry databases
BindingDBi | O88509 |
Miscellaneous databases
RNActi | O88509, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O88509 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O88509 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 232 – 290 | PWWPPROSITE-ProRule annotationAdd BLAST | 59 | |
Domaini | 428 – 560 | ADDPROSITE-ProRule annotationAdd BLAST | 133 | |
Domaini | 581 – 859 | SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd BLAST | 279 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 305 | Interaction with DNMT1 and DNMT3ABy similarityAdd BLAST | 305 | |
Regioni | 25 – 226 | DisorderedSequence analysisAdd BLAST | 202 | |
Regioni | 348 – 429 | DisorderedSequence analysisAdd BLAST | 82 | |
Regioni | 440 – 532 | Interaction with the PRC2/EED-EZH2 complexAdd BLAST | 93 | |
Regioni | 588 – 592 | S-adenosyl-L-methionine bindingBy similarity | 5 | |
Regioni | 633 – 635 | S-adenosyl-L-methionine bindingBy similarity | 3 | |
Regioni | 838 – 840 | S-adenosyl-L-methionine bindingBy similarity | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 102 – 118 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 119 – 135 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 163 – 178 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 186 – 209 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 210 – 226 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 366 – 392 | Basic and acidic residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 408 – 427 | Basic and acidic residuesSequence analysisAdd BLAST | 20 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 439 – 469 | GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 480 – 536 | PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST | 57 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502QR6U, Eukaryota |
GeneTreei | ENSGT00940000156928 |
HOGENOMi | CLU_006958_9_1_1 |
InParanoidi | O88509 |
OMAi | IKPMLDW |
OrthoDBi | 1015783at2759 |
TreeFami | TF329039 |
Family and domain databases
CDDi | cd11728, ADDz_Dnmt3b, 1 hit |
IDEALi | IID50164 |
InterProi | View protein in InterPro IPR025766, ADD IPR018117, C5_DNA_meth_AS IPR001525, C5_MeTfrase IPR040552, DNMT3_ADD IPR030488, DNMT3B_ADD IPR000313, PWWP_dom IPR029063, SAM-dependent_MTases IPR011011, Znf_FYVE_PHD |
Pfami | View protein in Pfam PF17980, ADD_DNMT3, 1 hit PF00145, DNA_methylase, 1 hit PF00855, PWWP, 1 hit |
SMARTi | View protein in SMART SM00293, PWWP, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51533, ADD, 1 hit PS00094, C5_MTASE_1, 1 hit PS50812, PWWP, 1 hit PS51679, SAM_MT_C5, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKGDSRHLNE EEGASGYEEC IIVNGNFSDQ SSDTKDAPSP PVLEAICTEP
60 70 80 90 100
VCTPETRGRR SSSRLSKREV SSLLNYTQDM TGDGDRDDEV DDGNGSDILM
110 120 130 140 150
PKLTRETKDT RTRSESPAVR TRHSNGTSSL ERQRASPRIT RGRQGRHHVQ
160 170 180 190 200
EYPVEFPATR SRRRRASSSA STPWSSPASV DFMEEVTPKS VSTPSVDLSQ
210 220 230 240 250
DGDQEGMDTT QVDAESRDGD STEYQDDKEF GIGDLVWGKI KGFSWWPAMV
260 270 280 290 300
VSWKATSKRQ AMPGMRWVQW FGDGKFSEIS ADKLVALGLF SQHFNLATFN
310 320 330 340 350
KLVSYRKAMY HTLEKARVRA GKTFSSSPGE SLEDQLKPML EWAHGGFKPT
360 370 380 390 400
GIEGLKPNKK QPVVNKSKVR RSDSRNLEPR RRENKSRRRT TNDSAASESP
410 420 430 440 450
PPKRLKTNSY GGKDRGEDEE SRERMASEVT NNKGNLEDRC LSCGKKNPVS
460 470 480 490 500
FHPLFEGGLC QSCRDRFLEL FYMYDEDGYQ SYCTVCCEGR ELLLCSNTSC
510 520 530 540 550
CRCFCVECLE VLVGAGTAED AKLQEPWSCY MCLPQRCHGV LRRRKDWNMR
560 570 580 590 600
LQDFFTTDPD LEEFEPPKLY PAIPAAKRRP IRVLSLFDGI ATGYLVLKEL
610 620 630 640 650
GIKVEKYIAS EVCAESIAVG TVKHEGQIKY VNDVRKITKK NIEEWGPFDL
660 670 680 690 700
VIGGSPCNDL SNVNPARKGL YEGTGRLFFE FYHLLNYTRP KEGDNRPFFW
710 720 730 740 750
MFENVVAMKV NDKKDISRFL ACNPVMIDAI KVSAAHRARY FWGNLPGMNR
760 770 780 790 800
PVMASKNDKL ELQDCLEFSR TAKLKKVQTI TTKSNSIRQG KNQLFPVVMN
810 820 830 840 850
GKDDVLWCTE LERIFGFPAH YTDVSNMGRG ARQKLLGRSW SVPVIRHLFA
PLKDYFACE
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ3KR45 | Q3KR45_MOUSE | DNA (cytosine-5-)-methyltransferase | Dnmt3b | 860 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 217 – 218 | RD → IY in AAF74515 (PubMed:12567489).Curated | 2 | |
Sequence conflicti | 217 – 218 | RD → IY in AAF74516 (PubMed:12567489).Curated | 2 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005642 | 363 – 382 | Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST | 20 | |
Alternative sequenceiVSP_005643 | 750 – 812 | Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST | 63 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF068626 mRNA Translation: AAC40178.2 AF068627 mRNA Translation: AAC40179.2 AF068628 mRNA Translation: AAC40180.2 AF151969 mRNA Translation: AAF74515.1 AF151970 mRNA Translation: AAF74516.1 AF151971 mRNA Translation: AAF74517.1 AF151972 mRNA Translation: AAF74518.1 AF151973 mRNA Translation: AAF74519.1 AF151974 mRNA Translation: AAF74520.1 AF151975 mRNA Translation: AAF74521.1 AF151976 mRNA Translation: AAF74522.1 |
CCDSi | CCDS16913.1 [O88509-2] CCDS16914.1 [O88509-1] CCDS16915.1 [O88509-4] CCDS16916.1 [O88509-3] |
RefSeqi | NP_001003960.2, NM_001003960.4 [O88509-2] NP_001003961.2, NM_001003961.4 [O88509-1] NP_001258673.1, NM_001271744.1 [O88509-1] NP_001258674.1, NM_001271745.1 [O88509-2] NP_001258676.1, NM_001271747.1 [O88509-3] NP_034198.3, NM_010068.5 [O88509-3] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF068626 mRNA Translation: AAC40178.2 AF068627 mRNA Translation: AAC40179.2 AF068628 mRNA Translation: AAC40180.2 AF151969 mRNA Translation: AAF74515.1 AF151970 mRNA Translation: AAF74516.1 AF151971 mRNA Translation: AAF74517.1 AF151972 mRNA Translation: AAF74518.1 AF151973 mRNA Translation: AAF74519.1 AF151974 mRNA Translation: AAF74520.1 AF151975 mRNA Translation: AAF74521.1 AF151976 mRNA Translation: AAF74522.1 |
CCDSi | CCDS16913.1 [O88509-2] CCDS16914.1 [O88509-1] CCDS16915.1 [O88509-4] CCDS16916.1 [O88509-3] |
RefSeqi | NP_001003960.2, NM_001003960.4 [O88509-2] NP_001003961.2, NM_001003961.4 [O88509-1] NP_001258673.1, NM_001271744.1 [O88509-1] NP_001258674.1, NM_001271745.1 [O88509-2] NP_001258676.1, NM_001271747.1 [O88509-3] NP_034198.3, NM_010068.5 [O88509-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1KHC | X-ray | 1.80 | A | 219-362 | [»] | |
SMRi | O88509 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 199262, 11 interactors |
CORUMi | O88509 |
DIPi | DIP-43736N |
IntActi | O88509, 11 interactors |
MINTi | O88509 |
STRINGi | 10090.ENSMUSP00000105396 |
Chemistry databases
BindingDBi | O88509 |
ChEMBLi | CHEMBL2189115 |
Protein family/group databases
REBASEi | 3748, M.MmuDnmt3B |
PTM databases
iPTMneti | O88509 |
PhosphoSitePlusi | O88509 |
Proteomic databases
jPOSTi | O88509 |
MaxQBi | O88509 |
PaxDbi | O88509 |
PeptideAtlasi | O88509 |
PRIDEi | O88509 |
ProteomicsDBi | 277365 [O88509-1] 277366 [O88509-2] 277367 [O88509-3] 277368 [O88509-4] |
Protocols and materials databases
DNASUi | 13436 |
Genome annotation databases
Organism-specific databases
CTDi | 1789 |
MGIi | MGI:1261819, Dnmt3b |
VEuPathDBi | HostDB:ENSMUSG00000027478 |
Phylogenomic databases
eggNOGi | ENOG502QR6U, Eukaryota |
GeneTreei | ENSGT00940000156928 |
HOGENOMi | CLU_006958_9_1_1 |
InParanoidi | O88509 |
OMAi | IKPMLDW |
OrthoDBi | 1015783at2759 |
TreeFami | TF329039 |
Enzyme and pathway databases
BRENDAi | 2.1.1.37, 3474 |
Reactomei | R-MMU-212300, PRC2 methylates histones and DNA R-MMU-4655427, SUMOylation of DNA methylation proteins |
Miscellaneous databases
BioGRID-ORCSi | 13436, 2 hits in 65 CRISPR screens |
ChiTaRSi | Dnmt3b, mouse |
EvolutionaryTracei | O88509 |
PROi | PR:O88509 |
RNActi | O88509, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000027478, Expressed in epiblast (generic) and 302 other tissues |
ExpressionAtlasi | O88509, baseline and differential |
Genevisiblei | O88509, MM |
Family and domain databases
CDDi | cd11728, ADDz_Dnmt3b, 1 hit |
IDEALi | IID50164 |
InterProi | View protein in InterPro IPR025766, ADD IPR018117, C5_DNA_meth_AS IPR001525, C5_MeTfrase IPR040552, DNMT3_ADD IPR030488, DNMT3B_ADD IPR000313, PWWP_dom IPR029063, SAM-dependent_MTases IPR011011, Znf_FYVE_PHD |
Pfami | View protein in Pfam PF17980, ADD_DNMT3, 1 hit PF00145, DNA_methylase, 1 hit PF00855, PWWP, 1 hit |
SMARTi | View protein in SMART SM00293, PWWP, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51533, ADD, 1 hit PS00094, C5_MTASE_1, 1 hit PS50812, PWWP, 1 hit PS51679, SAM_MT_C5, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DNM3B_MOUSE | |
Accessioni | O88509Primary (citable) accession number: O88509 Secondary accession number(s): O88510, O88511 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2001 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 185 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families