P13864

EV
Gene name
Dnmt1 (Dnmt, Met1, Uim)
Protein name
DNA (cytosine-5)-methyltransferase 1
Names
Dnmt1, Met-1, DNA methyltransferase MmuI, DNA MTase MmuI, M.MmuI, MCMT
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:13433
EC number
2.1.1.37: Methyltransferases
Protein Class
CYTOSINE-SPECIFIC METHYLTRANSFERASE (PTHR10629)

Descriptions

The mouse DNA methyltransferase-1 (DNMT1), composed of a replication foci-targeting domain (RFD), a DBA-binding CXXC domain, a pair of bromo-adjacent homology (BAH) domains, and a C-terminal catalytic domain bound to DNA-containing unmethylated CpG sites, mediates maintenance of genomic methylation patterns. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. Therefore, unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

Autoinhibitory domains (AIDs)

699-733 (CXXC-BAH1 linker) EV

Target domain

1140-1602 (Methyltransferase domain)

Relief mechanism

Others

Assay

Structural analysis, Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

12 structures for P13864

Entry ID Method Resolution Chain Position Source
3AV4 X-ray 275 A A 291-1620 PDB
3AV5 X-ray 325 A A 291-1620 PDB
3AV6 X-ray 309 A A 291-1620 PDB
3PT6 X-ray 300 A A/B 650-1602 PDB
3PT9 X-ray 250 A A 731-1602 PDB
4DA4 X-ray 260 A A/B 731-1602 PDB
5GUT X-ray 210 A A 731-1602 PDB
5GUV X-ray 308 A A 731-1602 PDB
5WY1 X-ray 327 A A 291-1620 PDB
6W8V X-ray 312 A A/B 731-1602 PDB
6W8W X-ray 300 A A/B 731-1602 PDB
AF-P13864-F1 Predicted AlphaFoldDB

9 variants for P13864

Variant ID(s) Position Change Description Diseaes Association Provenance
rs50974030 43 R>K No Ensembl
rs220029105 151 P>S No Ensembl
rs226863610 204 V>A No Ensembl
rs263555040 206 T>R No Ensembl
rs49516186 211 A>G No Ensembl
rs212515970 274 G>E No Ensembl
rs247707457 332 H>L No Ensembl
rs52009138 334 V>G No Ensembl
rs214129518 759 M>V No Ensembl

No associated diseases with P13864

7 regional properties for P13864

Type Name Position InterPro Accession
domain Bromo adjacent homology (BAH) domain 758 - 884 IPR001025-1
domain Bromo adjacent homology (BAH) domain 935 - 1103 IPR001025-2
domain Zinc finger, CXXC-type 649 - 695 IPR002857
domain DMAP1-binding domain 16 - 109 IPR010506
active_site DNA methylase, C-5 cytosine-specific, active site 1221 - 1233 IPR018117
domain DNA (cytosine-5)-methyltransferase 1, replication foci domain 406 - 539 IPR022702
conserved_site DNA methylase, C-5 cytosine-specific, conserved site 1576 - 1594 IPR031303

Functions

Description
EC Number 2.1.1.37 Methyltransferases
Subcellular Localization
  • Nucleus
  • Cytoplasm
  • It is nucleoplasmic through most of the cell cycle and associates with replication foci during S-phase
  • 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
  • In females, the protein is not detected in non-growing oocytes, in contrast to the growing oocytes
  • During the growing, the protein is no longer detectable in nuclei but accumulates to very high levels first throughout the cytoplasm
  • At the time of ovulation, all the protein is cytoplasmic and is actively associated with the oocyte cortex
  • After fecondation, in the preimplantation embryo, the protein remains cytoplasmic and after implantation, it is exclusively nuclear in all tissue types
  • 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
PANTHER Family PTHR10629 CYTOSINE-SPECIFIC METHYLTRANSFERASE
PANTHER Subfamily PTHR10629:SF52 DNA (CYTOSINE-5)-METHYLTRANSFERASE 1
PANTHER Protein Class DNA methyltransferase
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
heterochromatin A compact and highly condensed form of chromatin that is refractory to transcription.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
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.
pericentric heterochromatin Heterochromatin that is located adjacent to the CENP-A rich centromere 'central core' and characterized by methylated H3 histone at lysine 9 (H3K9me2/H3K9me3).
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
replication fork The Y-shaped region of a replicating DNA molecule, resulting from the separation of the DNA strands and in which the synthesis of new strands takes place. Also includes associated protein complexes.

13 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: S-adenosyl-L-methionine + DNA containing cytosine = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Catalysis of the reaction: S-adenosyl-L-methionine + CpG (in DNA) = S-adenosyl-L-homocysteine + 5-MeCpG (in DNA).
DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
DNA-methyltransferase activity Catalysis of the transfer of a methyl group to a DNA molecule.
estrogen receptor binding Binding to a nuclear estrogen receptor.
histone deacetylase binding Binding to histone deacetylase.
methyl-CpG binding Binding to a methylated cytosine/guanine dinucleotide.
methyltransferase activity Catalysis of the transfer of a methyl group to an acceptor molecule.
promoter-specific chromatin binding Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
protein domain specific binding Binding to a specific domain of a protein.
RNA binding Binding to an RNA molecule or a portion thereof.
zinc ion binding Binding to a zinc ion (Zn).

25 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.
cellular response to bisphenol A 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 a bisphenol A stimulus.
cellular response to transforming growth factor beta 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 a transforming growth factor beta stimulus.
DNA hypermethylation An increase in the epigenetic methylation of cytosine and adenosine residues in DNA.
DNA methylation The covalent transfer of a methyl group to either N-6 of adenine or C-5 or N-4 of cytosine.
DNA methylation involved in embryo development The covalent transfer of a methyl group to C-5 of cytosine that contributes to the epigenetic regulation of embryonic gene expression.
DNA methylation on cytosine The covalent transfer of a methyl group to C-5 or N-4 of cytosine in a DNA molecule.
DNA methylation on cytosine within a CG sequence The covalent transfer of a methyl group to C-5 or N-4 of a cytosine located within a CG sequence in a DNA molecule.
DNA methylation-dependent heterochromatin assembly Repression of transcription by methylation of DNA, leading to the formation of heterochromatin.
maintenance of DNA methylation Any process involved in maintaining the methylation state of a nucleotide sequence.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of histone H3-K9 methylation Any process that stops, prevents, or reduces the frequency, rate or extent of the covalent addition of a methyl group to the lysine at position 9 of histone H3.
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.
negative regulation of transcription, DNA-templated Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
negative regulation of vascular associated smooth muscle cell apoptotic process Any process that stops, prevents or reduces the frequency, rate or extent of vascular associated smooth muscle cell apoptotic process.
negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching Any process that stops, prevents or reduces the frequency, rate or extent of vascular smooth muscle cell differentiation involved in phenotypic switching.
positive regulation of DNA methylation-dependent heterochromatin assembly Any process that increases the rate, frequency, or extent of DNA methylation-dependent heterochromatin formation.
positive regulation of gene expression Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of histone H3-K4 methylation Any process that activates or increases the frequency, rate or extent of the covalent addition of a methyl group to the lysine at position 4 of histone H3.
positive regulation of vascular associated smooth muscle cell proliferation Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation.
Ras protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
regulation of cell population proliferation Any process that modulates the frequency, rate or extent of cell proliferation.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
response to xenobiotic stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
S-adenosylmethionine metabolic process The chemical reactions and pathways involving S-adenosylmethionine, S-(5'-adenosyl)-L-methionine, an important intermediate in one-carbon metabolism.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q24K09 DNMT1 DNA (cytosine-5)-methyltransferase 1 Bos taurus (Bovine) SS
Q92072 DNMT1 DNA Gallus gallus (Chicken) SS
P26358 DNMT1 DNA (cytosine-5)-methyltransferase 1 Homo sapiens (Human) EV
Q9Z330 Dnmt1 DNA (cytosine-5)-methyltransferase 1 Rattus norvegicus (Rat) SS
O49139 CMT1 Putative DNA (cytosine-5)-methyltransferase CMT1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MPARTAPARV PALASPAGSL PDHVRRRLKD LERDGLTEKE CVREKLNLLH EFLQTEIKSQ
70 80 90 100 110 120
LCDLETKLHK EELSEEGYLA KVKSLLNKDL SLENGTHTLT QKANGCPANG SRPTWRAEMA
130 140 150 160 170 180
DSNRSPRSRP KPRGPRRSKS DSDTLSVETS PSSVATRRTT RQTTITAHFT KGPTKRKPKE
190 200 210 220 230 240
ESEEGNSAES AAEERDQDKK RRVVDTESGA AAAVEKLEEV TAGTQLGPEE PCEQEDDNRS
250 260 270 280 290 300
LRRHTRELSL RRKSKEDPDR EARPETHLDE DEDGKKDKRS SRPRSQPRDP AAKRRPKEAE
310 320 330 340 350 360
PEQVAPETPE DRDEDEREEK RRKTTRKKLE SHTVPVQSRS ERKAAQSKSV IPKINSPKCP
370 380 390 400 410 420
ECGQHLDDPN LKYQQHPEDA VDEPQMLTSE KLSIYDSTST WFDTYEDSPM HRFTSFSVYC
430 440 450 460 470 480
SRGHLCPVDT GLIEKNVELY FSGCAKAIHD ENPSMEGGIN GKNLGPINQW WLSGFDGGEK
490 500 510 520 530 540
VLIGFSTAFA EYILMEPSKE YEPIFGLMQE KIYISKIVVE FLQNNPDAVY EDLINKIETT
550 560 570 580 590 600
VPPSTINVNR FTEDSLLRHA QFVVSQVESY DEAKDDDETP IFLSPCMRAL IHLAGVSLGQ
610 620 630 640 650 660
RRATRRVMGA TKEKDKAPTK ATTTKLVYQI FDTFFSEQIE KYDKEDKENA MKRRRCGVCE
670 680 690 700 710 720
VCQQPECGKC KACKDMVKFG GTGRSKQACL KRRCPNLAVK EADDDEEADD DVSEMPSPKK
730 740 750 760 770 780
LHQGKKKKQN KDRISWLGQP MKIEENRTYY QKVSIDEEML EVGDCVSVIP DDSSKPLYLA
790 800 810 820 830 840
RVTALWEDKN GQMMFHAHWF CAGTDTVLGA TSDPLELFLV GECENMQLSY IHSKVKVIYK
850 860 870 880 890 900
APSENWAMEG GTDPETTLPG AEDGKTYFFQ LWYNQEYARF ESPPKTQPTE DNKHKFCLSC
910 920 930 940 950 960
IRLAELRQKE MPKVLEQIEE VDGRVYCSSI TKNGVVYRLG DSVYLPPEAF TFNIKVASPV
970 980 990 1000 1010 1020
KRPKKDPVNE TLYPEHYRKY SDYIKGSNLD APEPYRIGRI KEIHCGKKKG KVNEADIKLR
1030 1040 1050 1060 1070 1080
LYKFYRPENT HRSYNGSYHT DINMLYWSDE EAVVNFSDVQ GRCTVEYGED LLESIQDYSQ
1090 1100 1110 1120 1130 1140
GGPDRFYFLE AYNSKTKNFE DPPNHARSPG NKGKGKGKGK GKGKHQVSEP KEPEAAIKLP
1150 1160 1170 1180 1190 1200
KLRTLDVFSG CGGLSEGFHQ AGISETLWAI EMWDPAAQAF RLNNPGTTVF TEDCNVLLKL
1210 1220 1230 1240 1250 1260
VMAGEVTNSL GQRLPQKGDV EMLCGGPPCQ GFSGMNRFNS RTYSKFKNSL VVSFLSYCDY
1270 1280 1290 1300 1310 1320
YRPRFFLLEN VRNFVSYRRS MVLKLTLRCL VRMGYQCTFG VLQAGQYGVA QTRRRAIILA
1330 1340 1350 1360 1370 1380
AAPGEKLPLF PEPLHVFAPR ACQLSVVVDD KKFVSNITRL SSGPFRTITV RDTMSDLPEI
1390 1400 1410 1420 1430 1440
QNGASNSEIP YNGEPLSWFQ RQLRGSHYQP ILRDHICKDM SPLVAARMRH IPLFPGSDWR
1450 1460 1470 1480 1490 1500
DLPNIQVRLG DGVIAHKLQY TFHDVKNGYS STGALRGVCS CAEGKACDPE SRQFSTLIPW
1510 1520 1530 1540 1550 1560
CLPHTGNRHN HWAGLYGRLE WDGFFSTTVT NPEPMGKQGR VLHPEQHRVV SVRECARSQG
1570 1580 1590 1600 1610
FPDSYRFFGN ILDRHRQVGN AVPPPLAKAI GLEIKLCLLS SARESASAAV KAKEEAATKD