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Details on Person UniProt:P13864-2 Dnmt1
| Class:Id | ReferenceIsoform:146468 |
|---|---|
| _chainChangeLog | chain:1-1620 added on Fri February 6 2015 |
| _displayName | UniProt:P13864-2 Dnmt1 |
| _timestamp | 2026-02-20 22:20:47 |
| chain | chain:1-1620 |
| checksum | 4F9A98CEAF09F037 |
| comment | FUNCTION DNA methyltransferase that methylates CpG residues (PubMed:11290321, PubMed:11399088, PubMed:17576694, PubMed:17893328, PubMed:22323818). Preferentially methylates hemimethylated DNA (PubMed:11399088, PubMed:17576694, PubMed:17893328, PubMed:22323818). Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance (PubMed:11399088, PubMed:17576694, PubMed:22323818). Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication (PubMed:11399088, PubMed:15550930, PubMed:17576694). It is responsible for maintaining methylation patterns established in development (PubMed:11399088, PubMed:17576694). DNA methylation is coordinated with methylation of histones (By similarity). Mediates transcriptional repression by direct binding to HDAC2 (By similarity). In association with DNMT3B 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). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (By similarity). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity).CATALYTIC ACTIVITY a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)ACTIVITY REGULATION Allosterically regulated. The binding of 5-methylcytosine-containing DNA to the N-terminal parts of DNMT1 causes an allosteric activation of the catalytic domain by a direct interaction of its Zn-binding domain with the catalytic domain.SUBUNIT Homodimer (By similarity). Forms a stable complex with E2F1, BB1 and HDAC1 (By similarity). Forms a complex with DMAP1 and HDAC2, with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (By similarity). Interacts with UHRF1; promoting its recruitment to hemimethylated DNA (PubMed:21268065). Interacts with USP7, promoting its deubiquitination (PubMed:21268065). Interacts with BAZ2A/TIP5 (PubMed:16085498). Interacts with PCNA (By similarity). Interacts with MBD2 and MBD3 (By similarity). Interacts with DNMT3A and DNMT3B (By similarity). Interacts with UBC9 (By similarity). Interacts with HDAC1 (PubMed:10615135). Interacts with CSNK1D (PubMed:20192920). Interacts with SIRT7 (PubMed:28842251). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Interacts with L3MBTL3 and DCAF5; the interaction requires DNMT1 methylation at Lys-139 and is necessary to target DNMT1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex and proteasomal degradation (By similarity). Interacts with PHF20L1; the interaction requires DNMT1 methylation at Lys-139 and protects DNMT1 from ubiquitination and proteasomal degradation (By similarity).INTERACTION It is nucleoplasmic through most of the cell cycle and Associates with replication foci during S-phase: recruited to hemimethylated DNA sites via its RFTS domain, which specifically recognizes and binds histone H3 ubiquitinated at 'Lys-14', 'Lys-18' and 'Lys-23' (H3K14ub, H3K18ub and H3K23ub, respectively) (PubMed:11290321, PubMed:17893328, PubMed:26065575, PubMed:29053958). In germ cells, spermatogonia, preleptotene and leptotene spermatocytes all express high levels of nuclear protein, while the protein is not detected in pachytene spermatocytes, despite the fact they expressed high levels of mRNA (PubMed:9449671). In females, the protein is not detected in non-growing oocytes, in contrast to the growing oocytes (PubMed:9449671). During the growing, the protein is no longer detectable in nuclei but accumulates to very high levels first throughout the cytoplasm (PubMed:9449671). At the time of ovulation, all the protein is cytoplasmic and is actively associated with the oocyte cortex (PubMed:9449671). After fecondation, in the preimplantation embryo, the protein remains cytoplasmic and after implantation, it is exclusively nuclear in all tissue types (PubMed:9449671). Isoform 2 is sequestered in the cytoplasm of maturing oocytes and of preimplantation embryos, except for the 8-cell stage, while isoform 1 is exclusively nuclear (PubMed:9449671).ALTERNATIVE PRODUCTS Expressed in embryonic stem cells and in somatic tissues.TISSUE SPECIFICITY Expressed in oocytes, preimplantation embryos, testis and in skeletal muscle during myogenesis.DEVELOPMENTAL STAGE In germ cells, it is present at high levels in spermatogonia and spermatocytes until the pachytene stage, where it falls to undetectable levels (PubMed:9449671). The transient drop at the pachytene stage coincides with the disappearance of the 5.2 kb mRNA and the accumulation of a larger 6.0 kb mRNA (PubMed:9449671). Oocytes accumulate very large amounts of Dnmt1 protein during the growth phase (PubMed:9449671).DOMAIN The RFTS domain specifically recognizes and binds histone H3 monoubiquitinated at two sites, either at 'Lys-14', 'Lys-18' and/or 'Lys-23' (H3K14ub, H3K18ub and H3K23ub, respectively) (PubMed:26065575, PubMed:29053958). These histone marks are present at hemimethylated DNA sites at replication forks and act as docking site for DNMT1 (PubMed:26065575, PubMed:29053958). In absence of H3K14ub, H3K18ub and H3K23ub chromatin marks, the RFTS domain inhibits the DNA methyltransferase activity by forming hydrogen bonds with the catalytic center (PubMed:21518897, PubMed:29053958). Binding to ubiquitinated histones relieves inhibition (PubMed:29053958).DOMAIN The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.PTM Sumoylated; sumoylation increases activity.PTM Phosphorylation at Ser-146 by CK1 reduces DNA-binding activity.PTM Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/M transition. Deacetylation of Lys-1352 and Lys-1418 by SIRT1 increases methyltransferase activity.PTM Phosphorylation of Ser-152 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-140 by AKT1 prevents methylation by SETD7 thereby increasing DNMT1 stability.PTM Methylation at Lys-139 by SETD7 is necessary for the regulation of DNMT1 proteasomal degradation.PTM Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.DISRUPTION PHENOTYPE Hypomethylation of genomic DNA, leading to postimplantation lethality.MISCELLANEOUS There are three 5' exons, one specific to the oocyte (1c), one specific to the pachytene spermatocyte and also found in skeletal muscle (1b) and one found in somatic cells (1a). Three different mRNAs can be produced which give rise to two different translation products: isoform 1 (mRNAs-1a) and isoform 2 (mRNA-1b or -1c). Association of DNMT1 with the replication machinery is not strictly required for maintaining global methylation but still enhances methylation efficiency by 2-fold. Pre-existing cytosine methylation at CpG and non-CpG sites enhances methylation activity.SIMILARITY Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: DNA (cytosine-5)-methyltransferase 1 shortName: Dnmt1 shortName: Met-1 ecNumber evidence="12 18 24"2.1.1.37 alternativeName: DNA methyltransferase MmuI shortName: DNA MTase MmuI shortName: M.MmuI alternativeName: MCMT |
| geneName | Dnmt1 Dnmt Met1 Uim |
| identifier | P13864 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Activator Allosteric enzyme Alternative splicing Chromatin regulator Chromosome Cytoplasm Direct protein sequencing DNA-binding Isopeptide bond Metal-binding Methylation Methyltransferase Nucleus Phosphoprotein Reference proteome Repeat Repressor S-adenosyl-L-methionine Transcription Transcription regulation Transferase Ubl conjugation Zinc Zinc-finger |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8869714] Weiser, JD [InstanceEdit:8964659] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9834092] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Dnmt1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | DNMT1_MOUSE P97413 Q80ZU3 Q9CSC6 Q9QXX6 |
| sequenceLength | 1620 |
| species | [Species:48892] Mus musculus |
| variantIdentifier | P13864-2 |
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No pathways have been reviewed or authored by UniProt:P13864-2 Dnmt1 (146468)
