O88509
SS
Gene name |
Dnmt3b |
Protein name |
DNA |
Names |
cytosine-5-methyltransferase 3B , Dnmt3b , EC 2.1.1.37 , DNA methyltransferase MmuIIIB , DNA MTase MmuIIIB , M.MmuIIIB |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:13436 |
EC number |
2.1.1.37: Methyltransferases |
Protein Class |
|
Descriptions
DNMT3A is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. The ADD domain of DNMT3A inhibits the enzymatic activity of its catalytic domain (CD) by blocking DNA-binding. Both the ADD domain (476-609) and the ADD-linker (476-626) show comparable binding affinity to the CD domain, but only the ADD-linker (476-626) retains its inhibitory function. Therefore, both the ADD domain and linker are important for the autoinhibition of DNMT3A.
Autoinhibitory domains (AIDs)
Target domain |
574-859 (Catalytic domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Guo X et al. (2015) "Structural insight into autoinhibition and histone H3-induced activation of DNMT3A", Nature, 517, 640-4
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Uehara R et al. (2023) "The DNMT3A ADD domain is required for efficient de novo DNA methylation and maternal imprinting in mouse oocytes", PLoS genetics, 19, e1010855
Autoinhibited structure
Activated structure
2 structures for O88509
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1KHC | X-ray | 180 A | A | 219-362 | PDB |
| AF-O88509-F1 | Predicted | AlphaFoldDB |
42 variants for O88509
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs236121010 | 24 | N>S | No | EVA | |
| rs263288182 | 27 | F>C | No | EVA | |
| rs225110864 | 37 | A>V | No | EVA | |
| rs3388602211 | 54 | P>R | No | EVA | |
| rs27400092 | 86 | R>G | No | EVA | |
| rs3388592108 | 119 | V>A | No | EVA | |
| rs220011319 | 121 | T>A | No | EVA | |
| rs3388593647 | 122 | R>P | No | EVA | |
| rs33122388 | 133 | Q>R | No | EVA | |
| rs3388593568 | 135 | A>T | No | EVA | |
| rs3388603550 | 136 | S>F | No | EVA | |
| rs3388592110 | 176 | S>T | No | EVA | |
| rs3388604336 | 181 | D>E | No | EVA | |
| rs3388597504 | 204 | Q>E | No | EVA | |
| rs3388602427 | 229 | E>G | No | EVA | |
| rs3388592026 | 233 | G>D | No | EVA | |
| rs864269117 | 235 | L>I | No | EVA | |
| rs3388599226 | 236 | V>L | No | EVA | |
| rs3388592083 | 268 | V>I | No | EVA | |
| rs3388603587 | 363 | V>A | No | EVA | |
| rs245832034 | 364 | V>A | No | EVA | |
| rs3388604291 | 365 | N>I | No | EVA | |
| rs3392245852 | 366 | K>N | No | EVA | |
| rs3540816401 | 389 | R>H | No | EVA | |
| rs3540829132 | 403 | K>R | No | EVA | |
| rs3388604301 | 450 | S>P | No | EVA | |
| rs1133620620 | 521 | A>V | No | EVA | |
| rs3540828952 | 542 | R>Q | No | EVA | |
| rs3388602432 | 583 | V>D | No | EVA | |
| rs3388593269 | 639 | K>T | No | EVA | |
| rs864306089 | 640 | K>R | No | EVA | |
| rs3388600198 | 653 | G>S | No | EVA | |
| rs3388605131 | 660 | L>I | No | EVA | |
| rs3388592100 | 677 | L>V | No | EVA | |
| rs3388593320 | 706 | V>E | No | EVA | |
| rs3388603589 | 706 | V>M | No | EVA | |
| rs3388597453 | 710 | V>L | No | EVA | |
| rs3388601773 | 722 | C>F | No | EVA | |
| rs3388593338 | 774 | L>S | No | EVA | |
| rs3388593611 | 804 | D>E | No | EVA | |
| rs3388604340 | 807 | W>* | No | EVA | |
| rs3388602419 | 847 | H>Y | No | EVA |
No associated diseases with O88509
6 regional properties for O88509
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | PWWP domain | 230 - 311 | IPR000313 |
| active_site | DNA methylase, C-5 cytosine-specific, active site | 649 - 661 | IPR018117 |
| domain | ADD domain | 428 - 560 | IPR025766 |
| domain | DNA (cytosine-5)-methyltransferase 3B, ADD domain | 436 - 555 | IPR030488 |
| domain | DNMT3, cysteine rich ADD domain, GATA1-like zinc finger | 421 - 476 | IPR040552 |
| domain | DNMT3, ADD domain, PHD zinc finger | 483 - 532 | IPR049554 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.1.1.37 | Methyltransferases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| chromosome, centromeric region | The region of a chromosome that includes the centromeric DNA and associated proteins. In monocentric chromosomes, this region corresponds to a single area of the chromosome, whereas in holocentric chromosomes, it is evenly distributed along the chromosome. |
| heterochromatin | A compact and highly condensed form of chromatin that is refractory to transcription. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| chromatin binding | Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. |
| DNA (cytosine-5-)-methyltransferase activity | Catalysis of the reaction |
| DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates | Catalysis of the reaction |
| DNA (cytosine-5-)-methyltransferase activity, acting on CpN substrates | Catalysis of the reaction |
| DNA binding | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). |
| histone deacetylase binding | Binding to histone deacetylase. |
| lncRNA binding | Binding to a long noncoding RNA (lncRNA). |
| metal ion binding | Binding to a metal ion. |
| methyltransferase activity | Catalysis of the transfer of a methyl group to an acceptor molecule. |
10 GO annotations of biological process
| Name | Definition |
|---|---|
| cellular response to amino acid stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups. |
| DNA methylation-dependent heterochromatin formation | Repression of transcription by methylation of DNA, leading to the formation of heterochromatin. |
| heterochromatin formation | An epigenetic gene silencing mechanism in which chromatin is compacted into heterochromatin, resulting in a chromatin conformation refractory to transcription. This process starts with heterochromatin nucleation, its spreading, and ends with heterochromatin boundary formation. |
| methylation | The process in which a methyl group is covalently attached to a molecule. |
| negative regulation of DNA-templated transcription | Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription. |
| negative regulation of gene expression, epigenetic | An epigenetic process that silences gene expression at specific genomic regions through chromatin remodelling either by modifying higher order chromatin fiber structure, nucleosomal histones, or the DNA. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| positive regulation of neuron differentiation | Any process that activates or increases the frequency, rate or extent of neuron differentiation. |
| post-fertilization epigenetic regulation of gene expression | The covalent transfer of a methyl group to C-5 of cytosine that contributes to the epigenetic regulation of embryonic gene expression. |
| protein-containing complex localization | A localization process that acts on a protein complex; the complex is transported to, or maintained in, a specific location. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q4W5Z4 | DNMT3A | DNA | Gallus gallus (Chicken) | SS |
| Q9Y6K1 | DNMT3A | DNA (cytosine-5)-methyltransferase 3A | Homo sapiens (Human) | EV |
| Q9UBC3 | DNMT3B | DNA | Homo sapiens (Human) | EV |
| O88508 | Dnmt3a | DNA | Mus musculus (Mouse) | EV |
| Q1LZ53 | Dnmt3a | DNA | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MKGDSRHLNE | EEGASGYEEC | IIVNGNFSDQ | SSDTKDAPSP | PVLEAICTEP | VCTPETRGRR |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SSSRLSKREV | SSLLNYTQDM | TGDGDRDDEV | DDGNGSDILM | PKLTRETKDT | RTRSESPAVR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TRHSNGTSSL | ERQRASPRIT | RGRQGRHHVQ | EYPVEFPATR | SRRRRASSSA | STPWSSPASV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DFMEEVTPKS | VSTPSVDLSQ | DGDQEGMDTT | QVDAESRDGD | STEYQDDKEF | GIGDLVWGKI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| KGFSWWPAMV | VSWKATSKRQ | AMPGMRWVQW | FGDGKFSEIS | ADKLVALGLF | SQHFNLATFN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KLVSYRKAMY | HTLEKARVRA | GKTFSSSPGE | SLEDQLKPML | EWAHGGFKPT | GIEGLKPNKK |
| 370 | 380 | 390 | 400 | 410 | 420 |
| QPVVNKSKVR | RSDSRNLEPR | RRENKSRRRT | TNDSAASESP | PPKRLKTNSY | GGKDRGEDEE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| SRERMASEVT | NNKGNLEDRC | LSCGKKNPVS | FHPLFEGGLC | QSCRDRFLEL | FYMYDEDGYQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SYCTVCCEGR | ELLLCSNTSC | CRCFCVECLE | VLVGAGTAED | AKLQEPWSCY | MCLPQRCHGV |
| 550 | 560 | 570 | 580 | 590 | 600 |
| LRRRKDWNMR | LQDFFTTDPD | LEEFEPPKLY | PAIPAAKRRP | IRVLSLFDGI | ATGYLVLKEL |
| 610 | 620 | 630 | 640 | 650 | 660 |
| GIKVEKYIAS | EVCAESIAVG | TVKHEGQIKY | VNDVRKITKK | NIEEWGPFDL | VIGGSPCNDL |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SNVNPARKGL | YEGTGRLFFE | FYHLLNYTRP | KEGDNRPFFW | MFENVVAMKV | NDKKDISRFL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| ACNPVMIDAI | KVSAAHRARY | FWGNLPGMNR | PVMASKNDKL | ELQDCLEFSR | TAKLKKVQTI |
| 790 | 800 | 810 | 820 | 830 | 840 |
| TTKSNSIRQG | KNQLFPVVMN | GKDDVLWCTE | LERIFGFPAH | YTDVSNMGRG | ARQKLLGRSW |
| 850 | |||||
| SVPVIRHLFA | PLKDYFACE |