DNMT1_MOUSE
ID DNMT1_MOUSE Reviewed; 1620 AA.
AC P13864; P97413; Q80ZU3; Q9CSC6; Q9QXX6;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2002, sequence version 5.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=DNA (cytosine-5)-methyltransferase 1;
DE Short=Dnmt1;
DE Short=Met-1;
DE EC=2.1.1.37;
DE AltName: Full=DNA methyltransferase MmuI;
DE Short=DNA MTase MmuI;
DE Short=M.MmuI;
DE AltName: Full=MCMT;
GN Name=Dnmt1; Synonyms=Dnmt, Met1, Uim;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3210246; DOI=10.1016/0022-2836(88)90122-2;
RA Bestor T.H., Laudano A., Mattaliano R., Ingram V.;
RT "Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse
RT cells. The carboxyl-terminal domain of the mammalian enzymes is related to
RT bacterial restriction methyltransferases.";
RL J. Mol. Biol. 203:971-983(1988).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS.
RC TISSUE=Embryo;
RX PubMed=8940105; DOI=10.1074/jbc.271.49.31092;
RA Yoder J.A., Yen R.-W.C., Vertino P.M., Bestor T.H., Baylin S.B.;
RT "New 5' regions of the murine and human genes for DNA (cytosine-5)-
RT methyltransferase.";
RL J. Biol. Chem. 271:31092-31097(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RX PubMed=11063128;
RA Aguirre-Arteta A.M., Grunewald I., Cardoso M.C., Leonhardt H.;
RT "Expression of an alternative Dnmt1 isoform during muscle
RT differentiation.";
RL Cell Growth Differ. 11:551-559(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RX PubMed=10715201; DOI=10.1006/jmbi.2000.3588;
RA Margot J.B., Aguirre-Arteta A.M., Di Giacco B.V., Pradhan S., Roberts R.J.,
RA Cardoso M.C., Leonhardt H.;
RT "Structure and function of the mouse DNA methyltransferase gene: Dnmt1
RT shows a tripartite structure.";
RL J. Mol. Biol. 297:293-300(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-27 AND 119-1619 (ISOFORMS 1
RP AND 2).
RX PubMed=9449671; DOI=10.1242/dev.125.5.889;
RA Mertineit C., Yoder J.A., Taketo T., Laird D.W., Trasler J.M., Bestor T.H.;
RT "Sex-specific exons control DNA methyltransferase in mammalian germ
RT cells.";
RL Development 125:889-897(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 1-144 (ISOFORMS 1 AND 2), AND PROTEIN SEQUENCE OF
RP 3-6.
RC STRAIN=129/Sv, and BALB/cJ; TISSUE=Embryonic stem cell;
RX PubMed=9830015; DOI=10.1074/jbc.273.49.32725;
RA Gaudet F., Talbot D., Leonhardt H., Jaenisch R.;
RT "A short DNA methyltransferase isoform restores methylation in vivo.";
RL J. Biol. Chem. 273:32725-32729(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-119 (ISOFORM 1).
RC STRAIN=129/Sv; TISSUE=Embryonic stem cell, and Kidney;
RX PubMed=8917520; DOI=10.1073/pnas.93.23.12920;
RA Tucker K.L., Talbot D., Lee M.A., Leonhardt H., Jaenisch R.;
RT "Complementation of methylation deficiency in embryonic stem cells by a DNA
RT methyltransferase minigene.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12920-12925(1996).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-272 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [10]
RP PROTEIN SEQUENCE OF 1108-1154, AND ACTIVITY REGULATION.
RX PubMed=1628623; DOI=10.1002/j.1460-2075.1992.tb05326.x;
RA Bestor T.H.;
RT "Activation of mammalian DNA methyltransferase by cleavage of a Zn binding
RT regulatory domain.";
RL EMBO J. 11:2611-2617(1992).
RN [11]
RP PHOSPHORYLATION AT SER-515, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Erythroleukemia;
RX PubMed=9211941; DOI=10.1074/jbc.272.28.17851;
RA Glickman J.F., Pavlovich J.G., Reich N.O.;
RT "Peptide mapping of the murine DNA methyltransferase reveals a major
RT phosphorylation site and the start of translation.";
RL J. Biol. Chem. 272:17851-17857(1997).
RN [12]
RP INTERACTION WITH HDAC1.
RX PubMed=10615135; DOI=10.1038/71750;
RA Fuks F., Burgers W.A., Brehm A., Hughes-Davies L., Kouzarides T.;
RT "DNA methyltransferase Dnmt1 associates with histone deacetylase
RT activity.";
RL Nat. Genet. 24:88-91(2000).
RN [13]
RP INTERACTION WITH HDAC2 AND DMAP1.
RX PubMed=10888872; DOI=10.1038/77023;
RA Rountree M.R., Bachman K.E., Baylin S.B.;
RT "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at
RT replication foci.";
RL Nat. Genet. 25:269-277(2000).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11290321; DOI=10.1016/s0092-8674(01)00280-x;
RA Howell C.Y., Bestor T.H., Ding F., Latham K.E., Mertineit C., Trasler J.M.,
RA Chaillet J.R.;
RT "Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1
RT gene.";
RL Cell 104:829-838(2001).
RN [15]
RP ALLOSTERIC REGULATION.
RX PubMed=11399088; DOI=10.1006/jmbi.2001.4709;
RA Fatemi M., Hermann A., Pradhan S., Jeltsch A.;
RT "The activity of the murine DNA methyltransferase Dnmt1 is controlled by
RT interaction of the catalytic domain with the N-terminal part of the enzyme
RT leading to an allosteric activation of the enzyme after binding to
RT methylated DNA.";
RL J. Mol. Biol. 309:1189-1199(2001).
RN [16]
RP FUNCTION.
RX PubMed=15550930; DOI=10.1038/sj.embor.7400295;
RA Easwaran H.P., Schermelleh L., Leonhardt H., Cardoso M.C.;
RT "Replication-independent chromatin loading of Dnmt1 during G2 and M
RT phases.";
RL EMBO Rep. 5:1181-1186(2004).
RN [17]
RP INTERACTION WITH BAZ2A.
RX PubMed=16085498; DOI=10.1016/j.cub.2005.06.057;
RA Zhou Y., Grummt I.;
RT "The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16
RT and is sufficient for rDNA silencing.";
RL Curr. Biol. 15:1434-1438(2005).
RN [18]
RP INTERACTION WITH THE PRC2 COMPLEX.
RX PubMed=16357870; DOI=10.1038/nature04431;
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RT "The Polycomb group protein EZH2 directly controls DNA methylation.";
RL Nature 439:871-874(2006).
RN [19]
RP ERRATUM OF PUBMED:16357870.
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RL Nature 446:824-824(2006).
RN [20]
RP PHOSPHORYLATION AT SER-515, AND MUTAGENESIS OF SER-515.
RX PubMed=17965600; DOI=10.4161/epi.2.3.4768;
RA Goyal R., Rathert P., Laser H., Gowher H., Jeltsch A.;
RT "Phosphorylation of serine-515 activates the mammalian maintenance
RT methyltransferase Dnmt1.";
RL Epigenetics 2:155-160(2007).
RN [21]
RP FUNCTION, MUTAGENESIS OF GLN-162; PHE-169 AND CYS-1229, AND ACTIVE SITE.
RX PubMed=17576694; DOI=10.1093/nar/gkm432;
RA Schermelleh L., Haemmer A., Spada F., Roesing N., Meilinger D.,
RA Rothbauer U., Cardoso M.C., Leonhardt H.;
RT "Dynamics of Dnmt1 interaction with the replication machinery and its role
RT in postreplicative maintenance of DNA methylation.";
RL Nucleic Acids Res. 35:4301-4312(2007).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152 AND SER-717, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-717, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-138; SER-140;
RP SER-146; SER-150; SER-152; SER-240; SER-713 AND SER-717, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [25]
RP UBIQUITINATION, DEUBIQUITINATION BY USP7, AND INTERACTION WITH USP7 AND
RP UHRF1.
RX PubMed=21268065; DOI=10.1002/jcb.22998;
RA Qin W., Leonhardt H., Spada F.;
RT "Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA
RT methyltransferase Dnmt1.";
RL J. Cell. Biochem. 112:439-444(2011).
RN [26]
RP PHOSPHORYLATION AT SER-146 BY CSNK1D/CK1, AND INTERACTION WITH CSNK1D.
RX PubMed=20192920; DOI=10.1042/bj20091856;
RA Sugiyama Y., Hatano N., Sueyoshi N., Suetake I., Tajima S., Kinoshita E.,
RA Kinoshita-Kikuta E., Koike T., Kameshita I.;
RT "The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by
RT phosphorylation with casein kinase 1delta/epsilon.";
RL Biochem. J. 427:489-497(2010).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1122 AND LYS-1124, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [28]
RP INTERACTION WITH SIRT7.
RX PubMed=28842251; DOI=10.1016/j.bbrc.2017.08.081;
RA Ianni A., Hoelper S., Krueger M., Braun T., Bober E.;
RT "Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and
RT Sirt1.";
RL Biochem. Biophys. Res. Commun. 492:434-440(2017).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 731-1602 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND DNA, AND AUTOINHIBITORY LINKER.
RX PubMed=21163962; DOI=10.1126/science.1195380;
RA Song J., Rechkoblit O., Bestor T.H., Patel D.J.;
RT "Structure of DNMT1-DNA complex reveals a role for autoinhibition in
RT maintenance DNA methylation.";
RL Science 331:1036-1040(2011).
CC -!- FUNCTION: Methylates CpG residues. Preferentially methylates
CC hemimethylated DNA. Associates with DNA replication sites in S phase
CC maintaining the methylation pattern in the newly synthesized strand,
CC that is essential for epigenetic inheritance. Associates with chromatin
CC during G2 and M phases to maintain DNA methylation independently of
CC replication. It is responsible for maintaining methylation patterns
CC established in development. DNA methylation is coordinated with
CC methylation of histones. Mediates transcriptional repression by direct
CC binding to HDAC2. In association with DNMT3B and via the recruitment of
CC CTCFL/BORIS, involved in activation of BAG1 gene expression by
CC modulating dimethylation of promoter histone H3 at H3K4 and H3K9.
CC Probably forms a corepressor complex required for activated KRAS-
CC mediated promoter hypermethylation and transcriptional silencing of
CC tumor suppressor genes (TSGs) or other tumor-related genes in
CC colorectal cancer (CRC) cells (By similarity). Also required to
CC maintain a transcriptionally repressive state of genes in
CC undifferentiated embryonic stem cells (ESCs) (By similarity).
CC Associates at promoter regions of tumor suppressor genes (TSGs) leading
CC to their gene silencing (By similarity). Promotes tumor growth (By
CC similarity). {ECO:0000250|UniProtKB:P26358,
CC ECO:0000269|PubMed:11290321, ECO:0000269|PubMed:15550930,
CC ECO:0000269|PubMed:17576694}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-
CC methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10018};
CC -!- ACTIVITY REGULATION: Allosterically regulated. The binding of 5-
CC methylcytosine-containing DNA to the N-terminal parts of DNMT1 causes
CC an allosteric activation of the catalytic domain by a direct
CC interaction of its Zn-binding domain with the catalytic domain.
CC {ECO:0000269|PubMed:1628623}.
CC -!- SUBUNIT: Homodimer (By similarity). Forms a stable complex with E2F1,
CC BB1 and HDAC1 (By similarity). Forms a complex with DMAP1 and HDAC2,
CC with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-
CC EZH2 complex (PubMed:16357870). Probably part of a corepressor complex
CC containing ZNF304, TRIM28, SETDB1 and DNMT1 (By similarity). Interacts
CC with UHRF1; promoting its recruitment to hemimethylated DNA
CC (PubMed:21268065). Interacts with USP7, promoting its deubiquitination
CC (PubMed:21268065). Interacts with BAZ2A/TIP5 (PubMed:16085498).
CC Interacts with PCNA (By similarity). Interacts with MBD2 and MBD3 (By
CC similarity). Interacts with DNMT3A and DNMT3B (By similarity).
CC Interacts with UBC9 (By similarity). Interacts with HDAC1
CC (PubMed:10615135). Interacts with CSNK1D (PubMed:20192920). Interacts
CC with SIRT7 (PubMed:28842251). Interacts with ZNF263; recruited to the
CC SIX3 promoter along with other proteins involved in chromatin
CC modification and transcriptional corepression where it contributes to
CC transcriptional repression (By similarity).
CC {ECO:0000250|UniProtKB:P26358, ECO:0000269|PubMed:10615135,
CC ECO:0000269|PubMed:10888872, ECO:0000269|PubMed:16085498,
CC ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:20192920,
CC ECO:0000269|PubMed:21268065, ECO:0000269|PubMed:28842251}.
CC -!- INTERACTION:
CC P13864; O09106: Hdac1; NbExp=3; IntAct=EBI-301927, EBI-301912;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11290321}. Cytoplasm
CC {ECO:0000269|PubMed:11290321}. Note=It is nucleoplasmic through most of
CC the cell cycle and associates with replication foci during S-phase. In
CC germ cells, spermatogonia, preleptotene and leptotene spermatocytes all
CC express high levels of nuclear protein, while the protein is not
CC detected in pachytene spermatocytes, despite the fact they expressed
CC high levels of mRNA. In females, the protein is not detected in non-
CC growing oocytes, in contrast to the growing oocytes. During the
CC growing, the protein is no longer detectable in nuclei but accumulates
CC to very high levels first throughout the cytoplasm. At the time of
CC ovulation, all the protein is cytoplasmic and is actively associated
CC with the oocyte cortex. After fecondation, in the preimplantation
CC embryo, the protein remains cytoplasmic and after implantation, it is
CC exclusively nuclear in all tissue types. Isoform 2 is sequestered in
CC the cytoplasm of maturing oocytes and of preimplantation embryos,
CC except for the 8-cell stage, while isoform 1 is exclusively nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=P13864-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P13864-2; Sequence=VSP_005619;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in embryonic stem cells and
CC in somatic tissues. Isoform 2 is expressed in oocytes, preimplantation
CC embryos, testis and in skeletal muscle during myogenesis.
CC -!- DEVELOPMENTAL STAGE: In germ cells, it is present at high levels in
CC spermatogonia and spermatocytes until the pachytene stage, where it
CC falls to undetectable levels. The transient drop at the pachytene stage
CC coincides with the disappearance of the 5.2 kb mRNA and the
CC accumulation of a larger 6.0 kb mRNA. Oocytes accumulate very large
CC amounts of Dnmt1 protein during the growth phase.
CC -!- DOMAIN: The N-terminal part is required for homodimerization and acts
CC as a regulatory domain.
CC -!- DOMAIN: The CXXC-type zinc finger specifically binds to unmethylated
CC CpG dinucleotides, positioning the autoinhibitory linker between the
CC DNA and the active site, thus providing a mechanism to ensure that only
CC hemimethylated CpG dinucleotides undergo methylation.
CC {ECO:0000269|PubMed:21163962}.
CC -!- PTM: Sumoylated; sumoylation increases activity.
CC {ECO:0000250|UniProtKB:P26358}.
CC -!- PTM: Phosphorylation at Ser-146 by CK1 reduces DNA-binding activity.
CC {ECO:0000269|PubMed:17965600, ECO:0000269|PubMed:20192920,
CC ECO:0000269|PubMed:9211941}.
CC -!- PTM: Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates
CC cell cycle G(2)/M transition. Deacetylation of Lys-1352 and Lys-1418 by
CC SIRT1 increases methyltransferase activity.
CC {ECO:0000250|UniProtKB:P26358}.
CC -!- PTM: Phosphorylation of Ser-152 by CDKs is important for enzymatic
CC activity and protein stability. Phosphorylation of Ser-140 by AKT1
CC prevents methylation by SETD7 therebye increasing DNMT1 stability.
CC {ECO:0000250|UniProtKB:P26358}.
CC -!- PTM: Methylation at Lys-139 by SETD7 promotes DNMT1 proteasomal
CC degradation. {ECO:0000250|UniProtKB:P26358}.
CC -!- PTM: Ubiquitinated by UHRF1; interaction with USP7 counteracts
CC ubiquitination by UHRF1 by promoting deubiquitination and preventing
CC degradation by the proteasome. {ECO:0000269|PubMed:21268065}.
CC -!- MISCELLANEOUS: There are three 5' exons, one specific to the oocyte
CC (1c), one specific to the pachytene spermatocyte and also found in
CC skeletal muscle (1b) and one found in somatic cells (1a). Three
CC different mRNAs can be produced which give rise to two different
CC translation products: isoform 1 (mRNAs-1a) and isoform 2 (mRNA-1b or
CC -1c). Association of DNMT1 with the replication machinery is not
CC strictly required for maintaining global methylation but still enhances
CC methylation efficiency by 2-fold. Pre-existing cytosine methylation at
CC CpG and non-CpG sites enhances methylation activity.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01016}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52900.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X14805; CAA32910.1; -; mRNA.
DR EMBL; AF175432; AAF97695.1; -; mRNA.
DR EMBL; AF162282; AAF19352.1; -; mRNA.
DR EMBL; AF175431; AAF60965.1; -; Genomic_DNA.
DR EMBL; AF175412; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175413; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175414; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF244089; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF244090; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175416; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175417; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175418; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175419; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175420; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175421; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175422; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175423; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF234317; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175424; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175425; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175426; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF234318; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175427; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175428; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175429; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; AF175430; AAF60965.1; JOINED; Genomic_DNA.
DR EMBL; BC048148; AAH48148.2; -; mRNA.
DR EMBL; AF036007; AAC40061.1; -; mRNA.
DR EMBL; AF036008; AAC53551.1; -; Genomic_DNA.
DR EMBL; U70051; AAC52900.1; ALT_INIT; mRNA.
DR EMBL; AK013247; BAB28743.1; -; mRNA.
DR CCDS; CCDS57654.1; -. [P13864-2]
DR CCDS; CCDS57655.1; -. [P13864-1]
DR PIR; S01845; S01845.
DR RefSeq; NP_001186360.2; NM_001199431.1. [P13864-1]
DR RefSeq; NP_001186361.1; NM_001199432.1.
DR RefSeq; NP_001186362.1; NM_001199433.1. [P13864-2]
DR RefSeq; NP_001300940.1; NM_001314011.1.
DR RefSeq; NP_034196.5; NM_010066.4.
DR PDB; 3AV4; X-ray; 2.75 A; A=291-1620.
DR PDB; 3AV5; X-ray; 3.25 A; A=291-1620.
DR PDB; 3AV6; X-ray; 3.09 A; A=291-1620.
DR PDB; 3PT6; X-ray; 3.00 A; A/B=650-1602.
DR PDB; 3PT9; X-ray; 2.50 A; A=731-1602.
DR PDB; 4DA4; X-ray; 2.60 A; A/B=731-1602.
DR PDB; 5GUT; X-ray; 2.10 A; A=731-1602.
DR PDB; 5GUV; X-ray; 3.08 A; A=731-1602.
DR PDB; 5WY1; X-ray; 3.27 A; A=291-1620.
DR PDB; 6W8V; X-ray; 3.12 A; A/B=731-1602.
DR PDB; 6W8W; X-ray; 3.00 A; A/B=731-1602.
DR PDBsum; 3AV4; -.
DR PDBsum; 3AV5; -.
DR PDBsum; 3AV6; -.
DR PDBsum; 3PT6; -.
DR PDBsum; 3PT9; -.
DR PDBsum; 4DA4; -.
DR PDBsum; 5GUT; -.
DR PDBsum; 5GUV; -.
DR PDBsum; 5WY1; -.
DR PDBsum; 6W8V; -.
DR PDBsum; 6W8W; -.
DR AlphaFoldDB; P13864; -.
DR SMR; P13864; -.
DR BioGRID; 199259; 38.
DR CORUM; P13864; -.
DR IntAct; P13864; 12.
DR MINT; P13864; -.
DR STRING; 10090.ENSMUSP00000004202; -.
DR BindingDB; P13864; -.
DR ChEMBL; CHEMBL3351195; -.
DR REBASE; 2844; M.MmuDnmt1.
DR iPTMnet; P13864; -.
DR PhosphoSitePlus; P13864; -.
DR SwissPalm; P13864; -.
DR EPD; P13864; -.
DR jPOST; P13864; -.
DR MaxQB; P13864; -.
DR PaxDb; P13864; -.
DR PeptideAtlas; P13864; -.
DR PRIDE; P13864; -.
DR ProteomicsDB; 277482; -. [P13864-1]
DR ProteomicsDB; 277483; -. [P13864-2]
DR Antibodypedia; 1052; 1617 antibodies from 51 providers.
DR DNASU; 13433; -.
DR Ensembl; ENSMUST00000004202; ENSMUSP00000004202; ENSMUSG00000004099. [P13864-1]
DR Ensembl; ENSMUST00000216540; ENSMUSP00000150433; ENSMUSG00000004099. [P13864-2]
DR GeneID; 13433; -.
DR KEGG; mmu:13433; -.
DR UCSC; uc009ojo.2; mouse. [P13864-1]
DR CTD; 1786; -.
DR MGI; MGI:94912; Dnmt1.
DR VEuPathDB; HostDB:ENSMUSG00000004099; -.
DR eggNOG; ENOG502QPKK; Eukaryota.
DR GeneTree; ENSGT00390000005100; -.
DR InParanoid; P13864; -.
DR OMA; CPEPFRI; -.
DR OrthoDB; 898916at2759; -.
DR PhylomeDB; P13864; -.
DR TreeFam; TF328926; -.
DR BRENDA; 2.1.1.37; 3474.
DR Reactome; R-MMU-212300; PRC2 methylates histones and DNA.
DR Reactome; R-MMU-4655427; SUMOylation of DNA methylation proteins.
DR BioGRID-ORCS; 13433; 13 hits in 76 CRISPR screens.
DR ChiTaRS; Dnmt1; mouse.
DR EvolutionaryTrace; P13864; -.
DR PRO; PR:P13864; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P13864; protein.
DR Bgee; ENSMUSG00000004099; Expressed in floor plate of midbrain and 314 other tissues.
DR ExpressionAtlas; P13864; baseline and differential.
DR Genevisible; P13864; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0001674; C:female germ cell nucleus; IDA:MGI.
DR GO; GO:0043073; C:germ cell nucleus; IDA:MGI.
DR GO; GO:0000792; C:heterochromatin; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005657; C:replication fork; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IDA:MGI.
DR GO; GO:0051718; F:DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0009008; F:DNA-methyltransferase activity; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:MGI.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IDA:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI.
DR GO; GO:1903926; P:cellular response to bisphenol A; IDA:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0044026; P:DNA hypermethylation; ISO:MGI.
DR GO; GO:0006306; P:DNA methylation; IDA:MGI.
DR GO; GO:0043045; P:DNA methylation involved in embryo development; IMP:MGI.
DR GO; GO:0032776; P:DNA methylation on cytosine; IMP:MGI.
DR GO; GO:0010424; P:DNA methylation on cytosine within a CG sequence; ISO:MGI.
DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin assembly; IDA:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; ISO:MGI.
DR GO; GO:1905931; P:negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching; ISO:MGI.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; ISO:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:MGI.
DR Gene3D; 2.30.30.490; -; 2.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001025; BAH_dom.
DR InterPro; IPR043151; BAH_sf.
DR InterPro; IPR018117; C5_DNA_meth_AS.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR031303; C5_meth_CS.
DR InterPro; IPR022702; Cytosine_MeTrfase1_RFD.
DR InterPro; IPR010506; DMAP1-bd.
DR InterPro; IPR017198; DNMT1-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR002857; Znf_CXXC.
DR Pfam; PF01426; BAH; 2.
DR Pfam; PF06464; DMAP_binding; 1.
DR Pfam; PF00145; DNA_methylase; 1.
DR Pfam; PF12047; DNMT1-RFD; 1.
DR Pfam; PF02008; zf-CXXC; 1.
DR PIRSF; PIRSF037404; DNMT1; 1.
DR PRINTS; PR00105; C5METTRFRASE.
DR SMART; SM00439; BAH; 2.
DR SMART; SM01137; DMAP_binding; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51038; BAH; 2.
DR PROSITE; PS00094; C5_MTASE_1; 1.
DR PROSITE; PS00095; C5_MTASE_2; 1.
DR PROSITE; PS51912; DMAP1_BIND; 1.
DR PROSITE; PS51679; SAM_MT_C5; 1.
DR PROSITE; PS51058; ZF_CXXC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Allosteric enzyme;
KW Alternative splicing; Chromatin regulator; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Isopeptide bond; Metal-binding;
KW Methylation; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Zinc; Zinc-finger.
FT CHAIN 1..1620
FT /note="DNA (cytosine-5)-methyltransferase 1"
FT /id="PRO_0000088035"
FT DOMAIN 16..109
FT /note="DMAP1-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01260"
FT DOMAIN 758..884
FT /note="BAH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT DOMAIN 976..1103
FT /note="BAH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT REPEAT 1112..1113
FT /note="1"
FT REPEAT 1114..1115
FT /note="2"
FT REPEAT 1116..1117
FT /note="3"
FT REPEAT 1118..1119
FT /note="4"
FT REPEAT 1120..1121
FT /note="5"
FT REPEAT 1122..1123
FT /note="6"
FT REPEAT 1124..1125
FT /note="7; approximate"
FT DOMAIN 1142..1601
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ZN_FING 649..695
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 1..343
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT REGION 1..145
FT /note="Interaction with DNMT3A"
FT /evidence="ECO:0000250"
FT REGION 1..120
FT /note="Interaction with DMAP1"
FT /evidence="ECO:0000269|PubMed:10888872"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 96..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..217
FT /note="Interaction with DNMT3B"
FT /evidence="ECO:0000250"
FT REGION 161..172
FT /note="Interaction with PCNA"
FT REGION 305..609
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT REGION 328..556
FT /note="DNA replication foci-targeting sequence"
FT /evidence="ECO:0000250"
FT REGION 696..813
FT /note="Interaction with HDAC1"
FT /evidence="ECO:0000269|PubMed:10615135"
FT REGION 696..757
FT /note="Autoinhibitory linker"
FT REGION 702..732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1097..1136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1112..1125
FT /note="7 X 2 AA tandem repeats of K-G"
FT REGION 1124..1620
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT REGION 1142..1620
FT /note="Catalytic"
FT MOTIF 175..202
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 144..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 173..206
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..306
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..337
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1122..1136
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1229
FT /evidence="ECO:0000269|PubMed:17576694"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 656
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 662
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 670
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 673
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 689
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 694
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1149
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PT6, ECO:0007744|PDB:4DA4"
FT BINDING 1153..1154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PT6, ECO:0007744|PDB:3PT9,
FT ECO:0007744|PDB:4DA4"
FT BINDING 1171..1172
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PT6, ECO:0007744|PDB:3PT9,
FT ECO:0007744|PDB:4DA4"
FT BINDING 1193..1194
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PT6, ECO:0007744|PDB:3PT9"
FT BINDING 1582
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PT6, ECO:0007744|PDB:3PT9,
FT ECO:0007744|PDB:4DA4"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 70
FT /note="N6,N6-dimethyllysine; by EHMT2"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 139
FT /note="N6-methyllysine; by SETD7"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 146
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000269|PubMed:20192920,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 164
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 255
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 372
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965600,
FT ECO:0000269|PubMed:9211941"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 713
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 717
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 752
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 895
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 961
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 965
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 979
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1114
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1116
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1118
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1120
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1122
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 1124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 1352
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT MOD_RES 1418
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT CROSSLNK 1611
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P26358"
FT VAR_SEQ 1..118
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10715201,
FT ECO:0000303|PubMed:11063128, ECO:0000303|PubMed:9449671"
FT /id="VSP_005619"
FT MUTAGEN 162
FT /note="Q->E: Abolishes interaction with PCNA. No effect on
FT activity."
FT /evidence="ECO:0000269|PubMed:17576694"
FT MUTAGEN 169
FT /note="F->S: Abolishes interaction with PCNA. No effect on
FT activity."
FT /evidence="ECO:0000269|PubMed:17576694"
FT MUTAGEN 515
FT /note="S->A: Loss of activity. No effect on DNA-binding
FT capacity."
FT /evidence="ECO:0000269|PubMed:17965600"
FT MUTAGEN 515
FT /note="S->E: Slightly reduces activity."
FT /evidence="ECO:0000269|PubMed:17965600"
FT MUTAGEN 1229
FT /note="C->W: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17576694"
FT CONFLICT 146..147
FT /note="SV -> F (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 299..309
FT /note="AEPEQVAPETP -> VRARAGSSRDS (in Ref. 1; CAA32910 and
FT 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 936
FT /note="V -> C (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 947
FT /note="P -> R (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 969..976
FT /note="NETLYPEH -> KENPVPRDT (in Ref. 1; CAA32910 and 6;
FT AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 987
FT /note="S -> R (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 1046
FT /note="Y -> C (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 1068
FT /note="G -> R (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 1429
FT /note="R -> P (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT CONFLICT 1456
FT /note="H -> D (in Ref. 1; CAA32910 and 6; AAC40061)"
FT /evidence="ECO:0000305"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:5WY1"
FT HELIX 383..387
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:3AV5"
FT STRAND 410..419
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:3AV6"
FT TURN 432..436
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 454..458
FT /evidence="ECO:0007829|PDB:3AV6"
FT STRAND 459..465
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 469..473
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 475..479
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 482..486
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 491..494
FT /evidence="ECO:0007829|PDB:3AV4"
FT TURN 499..501
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 502..524
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 530..539
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 553..558
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 560..573
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 581..583
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 585..593
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 625..635
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 657..659
FT /evidence="ECO:0007829|PDB:3AV4"
FT TURN 660..663
FT /evidence="ECO:0007829|PDB:3AV4"
FT TURN 671..675
FT /evidence="ECO:0007829|PDB:3PT6"
FT TURN 677..680
FT /evidence="ECO:0007829|PDB:3PT6"
FT HELIX 690..692
FT /evidence="ECO:0007829|PDB:3PT6"
FT HELIX 695..704
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 734..739
FT /evidence="ECO:0007829|PDB:3PT9"
FT STRAND 741..743
FT /evidence="ECO:0007829|PDB:3PT9"
FT STRAND 745..751
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 753..755
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 758..760
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 765..768
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 774..776
FT /evidence="ECO:0007829|PDB:4DA4"
FT STRAND 778..788
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 793..802
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 803..805
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 806..808
FT /evidence="ECO:0007829|PDB:6W8W"
FT HELIX 809..811
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 816..827
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 828..830
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 831..835
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 837..839
FT /evidence="ECO:0007829|PDB:3PT9"
FT HELIX 846..848
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 868..874
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 875..878
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 879..881
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 890..895
FT /evidence="ECO:0007829|PDB:3PT9"
FT HELIX 898..910
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 913..920
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 922..924
FT /evidence="ECO:0007829|PDB:3AV5"
FT STRAND 925..932
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 935..938
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 942..945
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 947..949
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 970..972
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 976..979
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 996..1008
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1011..1023
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1027..1029
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1031..1036
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1037..1039
FT /evidence="ECO:0007829|PDB:3PT6"
FT STRAND 1044..1047
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1051..1055
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1056..1058
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1061..1067
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1068..1070
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1075..1081
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1085..1091
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1094..1096
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1098..1100
FT /evidence="ECO:0007829|PDB:4DA4"
FT HELIX 1104..1106
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1142..1147
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1153..1161
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1163..1170
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1174..1183
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1187..1190
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1194..1202
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1217..1219
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1221..1225
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1230..1232
FT /evidence="ECO:0007829|PDB:4DA4"
FT STRAND 1234..1236
FT /evidence="ECO:0007829|PDB:3AV4"
FT HELIX 1240..1247
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1250..1261
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1264..1271
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1272..1275
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1277..1293
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1296..1303
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1304..1307
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1314..1321
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1339..1341
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1346..1348
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1351..1353
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1370..1374
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1375..1377
FT /evidence="ECO:0007829|PDB:3PT6"
FT STRAND 1387..1390
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1398..1404
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1411..1413
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1422..1429
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1433..1436
FT /evidence="ECO:0007829|PDB:3AV5"
FT HELIX 1439..1441
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1450..1452
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1454..1456
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1465..1467
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1477..1479
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1480..1483
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1489..1491
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 1495..1498
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1501..1505
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1506..1512
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1513..1516
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1525..1527
FT /evidence="ECO:0007829|PDB:3AV4"
FT STRAND 1536..1538
FT /evidence="ECO:0007829|PDB:5GUT"
FT STRAND 1544..1549
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1552..1558
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1571..1580
FT /evidence="ECO:0007829|PDB:5GUT"
FT HELIX 1584..1596
FT /evidence="ECO:0007829|PDB:5GUT"
FT TURN 1607..1611
FT /evidence="ECO:0007829|PDB:5WY1"
SQ SEQUENCE 1620 AA; 183189 MW; 4F9A98CEAF09F037 CRC64;
MPARTAPARV PALASPAGSL PDHVRRRLKD LERDGLTEKE CVREKLNLLH EFLQTEIKSQ
LCDLETKLHK EELSEEGYLA KVKSLLNKDL SLENGTHTLT QKANGCPANG SRPTWRAEMA
DSNRSPRSRP KPRGPRRSKS DSDTLSVETS PSSVATRRTT RQTTITAHFT KGPTKRKPKE
ESEEGNSAES AAEERDQDKK RRVVDTESGA AAAVEKLEEV TAGTQLGPEE PCEQEDDNRS
LRRHTRELSL RRKSKEDPDR EARPETHLDE DEDGKKDKRS SRPRSQPRDP AAKRRPKEAE
PEQVAPETPE DRDEDEREEK RRKTTRKKLE SHTVPVQSRS ERKAAQSKSV IPKINSPKCP
ECGQHLDDPN LKYQQHPEDA VDEPQMLTSE KLSIYDSTST WFDTYEDSPM HRFTSFSVYC
SRGHLCPVDT GLIEKNVELY FSGCAKAIHD ENPSMEGGIN GKNLGPINQW WLSGFDGGEK
VLIGFSTAFA EYILMEPSKE YEPIFGLMQE KIYISKIVVE FLQNNPDAVY EDLINKIETT
VPPSTINVNR FTEDSLLRHA QFVVSQVESY DEAKDDDETP IFLSPCMRAL IHLAGVSLGQ
RRATRRVMGA TKEKDKAPTK ATTTKLVYQI FDTFFSEQIE KYDKEDKENA MKRRRCGVCE
VCQQPECGKC KACKDMVKFG GTGRSKQACL KRRCPNLAVK EADDDEEADD DVSEMPSPKK
LHQGKKKKQN KDRISWLGQP MKIEENRTYY QKVSIDEEML EVGDCVSVIP DDSSKPLYLA
RVTALWEDKN GQMMFHAHWF CAGTDTVLGA TSDPLELFLV GECENMQLSY IHSKVKVIYK
APSENWAMEG GTDPETTLPG AEDGKTYFFQ LWYNQEYARF ESPPKTQPTE DNKHKFCLSC
IRLAELRQKE MPKVLEQIEE VDGRVYCSSI TKNGVVYRLG DSVYLPPEAF TFNIKVASPV
KRPKKDPVNE TLYPEHYRKY SDYIKGSNLD APEPYRIGRI KEIHCGKKKG KVNEADIKLR
LYKFYRPENT HRSYNGSYHT DINMLYWSDE EAVVNFSDVQ GRCTVEYGED LLESIQDYSQ
GGPDRFYFLE AYNSKTKNFE DPPNHARSPG NKGKGKGKGK GKGKHQVSEP KEPEAAIKLP
KLRTLDVFSG CGGLSEGFHQ AGISETLWAI EMWDPAAQAF RLNNPGTTVF TEDCNVLLKL
VMAGEVTNSL GQRLPQKGDV EMLCGGPPCQ GFSGMNRFNS RTYSKFKNSL VVSFLSYCDY
YRPRFFLLEN VRNFVSYRRS MVLKLTLRCL VRMGYQCTFG VLQAGQYGVA QTRRRAIILA
AAPGEKLPLF PEPLHVFAPR ACQLSVVVDD KKFVSNITRL SSGPFRTITV RDTMSDLPEI
QNGASNSEIP YNGEPLSWFQ RQLRGSHYQP ILRDHICKDM SPLVAARMRH IPLFPGSDWR
DLPNIQVRLG DGVIAHKLQY TFHDVKNGYS STGALRGVCS CAEGKACDPE SRQFSTLIPW
CLPHTGNRHN HWAGLYGRLE WDGFFSTTVT NPEPMGKQGR VLHPEQHRVV SVRECARSQG
FPDSYRFFGN ILDRHRQVGN AVPPPLAKAI GLEIKLCLLS SARESASAAV KAKEEAATKD
