ID DNM3A_MOUSE Reviewed; 908 AA. AC O88508; Q3TZK8; Q3UH24; Q8CJ60; Q922J0; Q9CSE1; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 2. DT 03-APR-2013, entry version 133. DE RecName: Full=DNA (cytosine-5)-methyltransferase 3A; DE Short=Dnmt3a; DE EC=2.1.1.37; DE AltName: Full=DNA methyltransferase MmuIIIA; DE Short=DNA MTase MmuIIIA; DE Short=M.MmuIIIA; GN Name=Dnmt3a; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9662389; DOI=10.1038/890; RA Okano M., Xie S., Li E.; RT "Cloning and characterization of a family of novel mammalian DNA RT (cytosine-5) methyltransferases."; RL Nat. Genet. 19:219-220(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Mammary gland; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6, and C57BL/6J; TISSUE=Brain, Embryo, and Skin; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, RP ALTERNATIVE PROMOTER USAGE, AND TISSUE SPECIFICITY. RC STRAIN=129/SvJ; RX PubMed=12138111; DOI=10.1074/jbc.M205312200; RA Chen T., Ueda Y., Xie S., Li E.; RT "A novel Dnmt3a isoform produced from an alternative promoter RT localizes to euchromatin and its expression correlates with active de RT novo methylation."; RL J. Biol. Chem. 277:38746-38754(2002). RN [5] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=10555141; DOI=10.1016/S0092-8674(00)81656-6; RA Okano M., Bell D.W., Haber D.A., Li E.; RT "DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo RT methylation and mammalian development."; RL Cell 99:247-257(1999). RN [6] RP FUNCTION. RX PubMed=11399089; DOI=10.1006/jmbi.2001.4710; RA Gowher H., Jeltsch A.; RT "Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from RT mouse: the enzyme modifies DNA in a non-processive manner and also RT methylates non-CpG correction sites."; RL J. Mol. Biol. 309:1201-1208(2001). RN [7] RP ERRATUM. RA Gowher H., Jeltsch A.; RL J. Mol. Biol. 310:951-951(2001). RN [8] RP FUNCTION, AND INTERACTION WITH ZNF238 AND HDAC1. RX PubMed=11350943; DOI=10.1093/emboj/20.10.2536; RA Fuks F., Burgers W.A., Godin N., Kasai M., Kouzarides T.; RT "Dnmt3a binds deacetylases and is recruited by a sequence-specific RT repressor to silence transcription."; RL EMBO J. 20:2536-2544(2001). RN [9] RP FUNCTION. RX PubMed=11919202; DOI=10.1074/jbc.M202148200; RA Gowher H., Jeltsch A.; RT "Molecular enzymology of the catalytic domains of the Dnmt3a and RT Dnmt3b DNA methyltransferases."; RL J. Biol. Chem. 277:20409-20414(2002). RN [10] RP IDENTIFICATION IN A COMPLEX WITH HDAC1. RX PubMed=12616525; DOI=10.1002/jcb.10457; RA Datta J., Ghoshal K., Sharma S.M., Tajima S., Jacob S.T.; RT "Biochemical fractionation reveals association of DNA RT methyltransferase (Dnmt) 3b with Dnmt1 and that of Dnmt 3a with a RT histone H3 methyltransferase and Hdac1."; RL J. Cell. Biochem. 88:855-864(2003). RN [11] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 302-VAL-PRO-303 AND RP 705-PRO-CYS-706. RX PubMed=15456878; DOI=10.1128/MCB.24.20.9048-9058.2004; RA Chen T., Tsujimoto N., Li E.; RT "The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA RT methylation to the major satellite repeats at pericentric RT heterochromatin."; RL Mol. Cell. Biol. 24:9048-9058(2004). RN [12] RP FUNCTION. RX PubMed=15215868; DOI=10.1038/nature02633; RA Kaneda M., Okano M., Hata K., Sado T., Tsujimoto N., Li E., Sasaki H.; RT "Essential role for de novo DNA methyltransferase Dnmt3a in paternal RT and maternal imprinting."; RL Nature 429:900-903(2004). RN [13] RP SUMOYLATION, AND INTERACTION WITH UBC9; PIAS1 AND PIAS2. RX PubMed=14752048; DOI=10.1093/nar/gkh195; RA Ling Y., Sankpal U.T., Robertson A.K., McNally J.G., Karpova T., RA Robertson K.D.; RT "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 RT modulates its interaction with histone deacetylases (HDACs) and its RT capacity to repress transcription."; RL Nucleic Acids Res. 32:598-610(2004). RN [14] RP ENZYME REGULATION. RX PubMed=15671018; DOI=10.1074/jbc.M413412200; RA Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A.; RT "Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B RT DNA-(cytosine-C5)-methyltransferases by Dnmt3L."; RL J. Biol. Chem. 280:13341-13348(2005). RN [15] RP FUNCTION. RX PubMed=16567415; DOI=10.1093/jb/mvj044; RA Takeshima H., Suetake I., Shimahara H., Ura K., Tate S., Tajima S.; RT "Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked RT and nucleosomal DNA."; RL J. Biochem. 139:503-515(2006). RN [16] RP MUTAGENESIS OF PHE-636; GLU-660; ASP-682; CYS-706; ASN-707; SER-710; RP ARG-716; LYS-717; GLU-752; ASN-753; ARG-788; ARG-827; ARG-832; RP ARG-878; ARG-881 AND ARG-883. RX PubMed=16472822; DOI=10.1016/j.jmb.2006.01.035; RA Gowher H., Loutchanwoot P., Vorobjeva O., Handa V., Jurkowska R.Z., RA Jurkowski T.P., Jeltsch A.; RT "Mutational analysis of the catalytic domain of the murine Dnmt3a DNA- RT (cytosine C5)-methyltransferase."; RL J. Mol. Biol. 357:928-941(2006). RN [17] RP INTERACTION WITH THE PRC2/EED-EZH2 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 [18] RP ERRATUM. 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 [19] RP FUNCTION, ENZYME REGULATION, AND MUTAGENESIS OF PHE-728. RX PubMed=17713477; DOI=10.1038/nature06146; RA Jia D., Jurkowska R.Z., Zhang X., Jeltsch A., Cheng X.; RT "Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA RT methylation."; RL Nature 449:248-251(2007). RN [20] RP FUNCTION. RX PubMed=18823905; DOI=10.1016/j.jmb.2008.03.001; RA Takeshima H., Suetake I., Tajima S.; RT "Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by RT histone H1."; RL J. Mol. Biol. 383:810-821(2008). RN [21] RP INTERACTION WITH UHRF1. RX PubMed=19798101; DOI=10.1038/embor.2009.201; RA Meilinger D., Fellinger K., Bultmann S., Rothbauer U., Bonapace I.M., RA Klinkert W.E., Spada F., Leonhardt H.; RT "Np95 interacts with de novo DNA methyltransferases, Dnmt3a and RT Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in RT embryonic stem cells."; RL EMBO Rep. 10:1259-1264(2009). CC -!- FUNCTION: Required for genome-wide de novo methylation and is CC essential for the establishment of DNA methylation patterns during CC development. DNA methylation is coordinated with methylation of CC histones. It modifies DNA in a non-processive manner and also CC methylates non-CpG sites. May preferentially methylate DNA linker CC between 2 nucleosomal cores and is inhibited by histone H1. Plays CC a role in paternal and maternal imprinting. Required for CC methylation of most imprinted loci in germ cells. Acts as a CC transcriptional corepressor for ZNF238. Can actively repress CC transcription through the recruitment of HDAC activity. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + DNA = S-adenosyl-L- CC homocysteine + DNA containing 5-methylcytosine. CC -!- ENZYME REGULATION: Activated by binding to the regulatory factor CC DNMT3L. CC -!- SUBUNIT: Heterotetramer composed of 1 DNMT3A homodimer and 2 CC DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with CC DNMT1 and DNMT3B. Interacts with MPHOSPH8. Interacts with histone CC H3 that is not methylated at 'Lys-4' (H3K4) (By similarity). Binds CC the ZNF238 transcriptional repressor. Interacts with SETDB1. CC Associates with HDAC1 through its ADD domain. Interacts with the CC PRC2/EED-EZH2 complex. Interacts with UBC9, PIAS1 and PIAS2. CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity). CC Note=Accumulates in the major satellite repeats at pericentric CC heterochromatin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=1; CC IsoId=O88508-1; Sequence=Displayed; CC Name=2; CC IsoId=O88508-2; Sequence=VSP_009423; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed ubiquitously at low CC levels. Expression of isoform 2 is restricted to tissues CC containing cells which are undergoing active de novo methylation, CC including spleen, testis and thymus. CC -!- DEVELOPMENTAL STAGE: At E7.5, the protein is moderately expressed CC in embryonic ectoderm and weakly in mesodermal cells. At E8.5 and CC E9.5, the expression become ubiquitous with an increase in the CC somites and in the ventral part of the embryo. CC -!- DOMAIN: The PWWP domain is essential for targeting to pericentric CC heterochromatin. CC -!- PTM: Sumoylated; sumoylation disrupts the ability to interact with CC histone deacetylases (HDAC1 and HDAC2) and repress transcription. CC -!- SIMILARITY: Belongs to the C5-methyltransferase family. CC -!- SIMILARITY: Contains 1 ADD domain. CC -!- SIMILARITY: Contains 1 GATA-type zinc finger. CC -!- SIMILARITY: Contains 1 PHD-type zinc finger. CC -!- SIMILARITY: Contains 1 PWWP domain. CC -!- SEQUENCE CAUTION: CC Sequence=BAB28644.2; Type=Erroneous initiation; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF068625; AAC40177.2; -; mRNA. DR EMBL; AF480164; AAN40038.1; -; mRNA. DR EMBL; AK013096; BAB28644.2; ALT_INIT; mRNA. DR EMBL; AK090132; BAC41110.1; -; mRNA. DR EMBL; AK147263; BAE27806.1; -; mRNA. DR EMBL; AK147627; BAE28033.1; -; mRNA. DR EMBL; AK147642; BAE28043.1; -; mRNA. DR EMBL; AK147676; BAE28067.1; -; mRNA. DR EMBL; AK157792; BAE34200.1; -; mRNA. DR EMBL; BC007466; AAH07466.1; -; mRNA. DR IPI; IPI00131694; -. DR IPI; IPI00172129; -. DR RefSeq; NP_001258682.1; NM_001271753.1. DR RefSeq; NP_031898.1; NM_007872.4. DR RefSeq; NP_714965.1; NM_153743.4. DR UniGene; Mm.5001; -. DR PDB; 3SW9; X-ray; 3.05 A; P/Q=39-50. DR PDB; 3SWC; X-ray; 2.33 A; P/Q=39-50. DR PDBsum; 3SW9; -. DR PDBsum; 3SWC; -. DR ProteinModelPortal; O88508; -. DR SMR; O88508; 279-421, 469-908. DR DIP; DIP-38005N; -. DR IntAct; O88508; 3. DR MINT; MINT-2521021; -. DR REBASE; 3747; M.MmuDnmt3A. DR PhosphoSite; O88508; -. DR PaxDb; O88508; -. DR PRIDE; O88508; -. DR Ensembl; ENSMUST00000020991; ENSMUSP00000020991; ENSMUSG00000020661. DR Ensembl; ENSMUST00000111186; ENSMUSP00000106817; ENSMUSG00000020661. DR Ensembl; ENSMUST00000172689; ENSMUSP00000133543; ENSMUSG00000020661. DR Ensembl; ENSMUST00000174817; ENSMUSP00000134009; ENSMUSG00000020661. DR GeneID; 13435; -. DR KEGG; mmu:13435; -. DR UCSC; uc007mxb.1; mouse. DR UCSC; uc007mxd.1; mouse. DR CTD; 1788; -. DR MGI; MGI:1261827; Dnmt3a. DR eggNOG; NOG70699; -. DR GeneTree; ENSGT00390000008341; -. DR HOGENOM; HOG000230875; -. DR HOVERGEN; HBG051381; -. DR InParanoid; O88508; -. DR KO; K00558; -. DR OMA; FVGGMCQ; -. DR OrthoDB; EOG4T1HKX; -. DR BRENDA; 2.1.1.37; 3474. DR ChiTaRS; DNMT3A; mouse. DR NextBio; 283867; -. DR ArrayExpress; O88508; -. DR Bgee; O88508; -. DR CleanEx; MM_DNMT3A; -. DR Genevestigator; O88508; -. DR GermOnline; ENSMUSG00000020661; Mus musculus. DR GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB. DR GO; GO:0005720; C:nuclear heterochromatin; IDA:MGI. DR GO; GO:0016363; C:nuclear matrix; ISS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; ISS:UniProtKB. DR GO; GO:0051718; F:DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates; IEA:Compara. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0045322; F:unmethylated CpG binding; IEA:Compara. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI. DR GO; GO:0043045; P:DNA methylation involved in embryo development; IMP:UniProtKB. DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB. DR GO; GO:0010424; P:DNA methylation on cytosine within a CG sequence; IEA:Compara. DR GO; GO:0044027; P:hypermethylation of CpG island; IDA:BHF-UCL. DR GO; GO:0010216; P:maintenance of DNA methylation; TAS:BHF-UCL. DR GO; GO:0006346; P:methylation-dependent chromatin silencing; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0006349; P:regulation of gene expression by genetic imprinting; IDA:BHF-UCL. DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; IEA:Compara. DR GO; GO:0046499; P:S-adenosylmethioninamine metabolic process; IEA:Compara. DR GO; GO:0007283; P:spermatogenesis; IMP:MGI. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR InterPro; IPR025766; ADD. DR InterPro; IPR018117; C5_DNA_meth_AS. DR InterPro; IPR001525; C5_MeTfrase. DR InterPro; IPR025811; C5_MeTrfase_3. DR InterPro; IPR000313; PWWP. DR InterPro; IPR011011; Znf_FYVE_PHD. DR Pfam; PF00145; DNA_methylase; 1. DR Pfam; PF00855; PWWP; 1. DR SMART; SM00293; PWWP; 1. DR SUPFAM; SSF57903; FYVE_PHD_ZnF; 1. DR PROSITE; PS51533; ADD; 1. DR PROSITE; PS00094; C5_MTASE_1; 1. DR PROSITE; PS00095; C5_MTASE_2; FALSE_NEG. DR PROSITE; PS50812; PWWP; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Chromatin regulator; KW Complete proteome; Cytoplasm; DNA-binding; Metal-binding; KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 908 DNA (cytosine-5)-methyltransferase 3A. FT /FTId=PRO_0000088044. FT DOMAIN 288 346 PWWP. FT DOMAIN 478 610 ADD. FT ZN_FING 489 519 GATA-type; atypical. FT ZN_FING 530 586 PHD-type; atypical. FT REGION 195 399 Interaction with DNMT1 and DNMT3B (By FT similarity). FT REGION 490 582 Interaction with the PRC2/EED-EZH2 FT complex. FT REGION 637 641 S-adenosyl-L-methionine binding (By FT similarity). FT REGION 682 684 S-adenosyl-L-methionine binding (By FT similarity). FT REGION 887 889 S-adenosyl-L-methionine binding (By FT similarity). FT ACT_SITE 706 706 By similarity. FT BINDING 660 660 S-adenosyl-L-methionine (By similarity). FT MOD_RES 102 102 Phosphoserine (By similarity). FT MOD_RES 239 239 Phosphoserine (By similarity). FT MOD_RES 251 251 Phosphoserine (By similarity). FT MOD_RES 257 257 Phosphothreonine (By similarity). FT VAR_SEQ 1 219 Missing (in isoform 2). FT /FTId=VSP_009423. FT MUTAGEN 302 303 WP->ST: Prevents accumulation in FT pericentric heterochromatin. FT MUTAGEN 636 636 F->A: Reduces activity about 20-fold. FT Loss of substrate binding. FT MUTAGEN 660 660 E->A: Reduces activity about 15-fold. FT Loss of substrate binding. FT MUTAGEN 682 682 D->A: Strongly reduces substrate binding. FT No effect on activity. FT MUTAGEN 705 706 PC->VD: No effect on localization. FT MUTAGEN 706 706 C->A: Reduces activity about 5-fold. FT Reduces DNA-binding capacity. FT MUTAGEN 707 707 N->Q: Reduces activity about 3-fold. FT MUTAGEN 710 710 S->A: No effect on activity. FT MUTAGEN 716 716 R->A: Reduces activity about 30-fold. FT Reduces DNA-binding capacity. FT MUTAGEN 717 717 K->A: Reduces activity about 3-fold. FT MUTAGEN 728 728 F->A: Loss of activity du to the FT incapacity to bind the regulatory subunit FT DNMT3L. FT MUTAGEN 752 752 E->A: Reduces activity about 10-fold. FT MUTAGEN 753 753 N->A: Reduces activity about 10-fold. FT MUTAGEN 788 788 R->A: Reduces activity about 15-fold. FT MUTAGEN 827 827 R->A: Reduces activity about 2-fold. FT Reduces DNA-binding capacity. FT MUTAGEN 832 832 R->A: Reduces DNA-binding capacity. No FT effect on activity. FT MUTAGEN 878 878 R->A: Reduces activity about 6-fold. FT Reduces DNA-binding capacity. FT MUTAGEN 881 881 R->A: Loss of activity. Strongly reduces FT substrate binding. FT MUTAGEN 883 883 R->A: Reduces activity about 3-fold. FT Reduces DNA-binding capacity. FT CONFLICT 151 151 Q -> P (in Ref. 4; AAH07466). FT CONFLICT 775 775 M -> T (in Ref. 3; BAB28644). FT CONFLICT 781 781 V -> G (in Ref. 3; BAB28644). FT CONFLICT 791 791 W -> R (in Ref. 3; BAB28644). FT CONFLICT 809 809 L -> P (in Ref. 3; BAB28644). FT CONFLICT 904 904 Y -> I (in Ref. 3; BAB28644). SQ SEQUENCE 908 AA; 101672 MW; 5F98D5A8092C84A5 CRC64; MPSSGPGDTS SSSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR KRKHPPVESS DTPKDPAVTT KSQPMAQDSG PSDLLPNGDL EKRSEPQPEE GSPAAGQKGG APAEGEGTET PPEASRAVEN GCCVTKEGRG ASAGEGKEQK QTNIESMKME GSRGRLRGGL GWESSLRQRP MPRLTFQAGD PYYISKRKRD EWLARWKREA EKKAKVIAVM NAVEENQASG ESQKVEEASP PAVQQPTDPA SPTVATTPEP VGGDAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD SGKAVEVQNK QMIEWALGGF QPSGPKGLEP PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA KKPRKSTTEK PKVKEIIDER TRERLVYEVR QKCRNIEDIC ISCGSLNVTL EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR EVLMCGNNNC CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG IQVDRYIASE VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV IGGSPCNDLS IVNPARKGLY EGTGRLFFEF YRLLHDARPK EGDDRPFFWL FENVVAMGVS DKRDISRFLE SNPVMIDAKE VSAAHRARYF WGNLPGMNRP LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK DQHFPVFMNE KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP LKEYFACV //