O88508 (DNM3A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA (cytosine-5)-methyltransferase 3A
Short name=Dnmt3a
EC=2.1.1.37

Alternative name(s):
DNA methyltransferase MmuIIIA
Short name=DNA MTase MmuIIIA
Short name=M.MmuIIIA

Gene names

Name:

Dnmt3a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity. Ref.5 Ref.6 Ref.8 Ref.9 Ref.12 Ref.15 Ref.19 Ref.20
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Enzyme regulation	Activated by binding to the regulatory factor DNMT3L. Ref.14 Ref.19
Subunit structure	Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with DNMT1 and DNMT3B. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4) By similarity. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with the PRC2/EED-EZH2 complex. Interacts with UBC9, PIAS1 and PIAS2. Ref.8 Ref.10 Ref.13 Ref.17 Ref.21
Subcellular location	Nucleus. Cytoplasm By similarity. Note: Accumulates in the major satellite repeats at pericentric heterochromatin. Ref.4 Ref.11
Tissue specificity	Isoform 1 is expressed ubiquitously at low levels. Expression of isoform 2 is restricted to tissues containing cells which are undergoing active de novo methylation, including spleen, testis and thymus. Ref.4
Developmental stage	At E7.5, the protein is moderately expressed in embryonic ectoderm and weakly in mesodermal cells. At E8.5 and E9.5, the expression become ubiquitous with an increase in the somites and in the ventral part of the embryo. Ref.5
Domain	The PWWP domain is essential for targeting to pericentric heterochromatin.
Post-translational modification	Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription. Ref.13
Sequence similarities	Belongs to the C5-methyltransferase family. Contains 1 ADD domain. Contains 1 GATA-type zinc finger. Contains 1 PHD-type zinc finger. Contains 1 PWWP domain.
Sequence caution	The sequence BAB28644.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative promoter usage
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation involved in embryo development Inferred from mutant phenotype Ref.12. Source: UniProtKB DNA methylation involved in gamete generation Inferred from mutant phenotype Ref.12. Source: UniProtKB DNA methylation on cytosine within a CG sequence Inferred from electronic annotation. Source: Compara S-adenosylhomocysteine metabolic process Inferred from electronic annotation. Source: Compara S-adenosylmethioninamine metabolic process Inferred from electronic annotation. Source: Compara cellular response to amino acid stimulus Inferred from direct assay PubMed 20548288. Source: MGI hypermethylation of CpG island Inferred from direct assay PubMed 21047779. Source: BHF-UCL maintenance of DNA methylation Traceable author statement PubMed 21047779. Source: BHF-UCL methylation-dependent chromatin silencing Inferred from direct assay PubMed 16322236. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16322236. Source: MGI regulation of gene expression by genetic imprinting Inferred from direct assay PubMed 21047779. Source: BHF-UCL spermatogenesis Inferred from mutant phenotype PubMed 11934864. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	chromosome, centromeric region Inferred from direct assay Ref.11. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB euchromatin Inferred from sequence or structural similarity. Source: UniProtKB nuclear heterochromatin Inferred from direct assay PubMed 11934864. Source: MGI nuclear matrix Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA (cytosine-5-)-methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Inferred from electronic annotation. Source: Compara DNA binding Inferred from sequence or structural similarity. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 16322236. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW unmethylated CpG binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform 1 (identifier: O88508-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O88508-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 908	908	DNA (cytosine-5)-methyltransferase 3A		PRO_0000088044
Regions
	Domain	288 – 346	59	PWWP
	Domain	478 – 610	133	ADD
	Zinc finger	489 – 519	31	GATA-type; atypical
	Zinc finger	530 – 586	57	PHD-type; atypical
	Region	195 – 399	205	Interaction with DNMT1 and DNMT3B By similarity
	Region	490 – 582	93	Interaction with the PRC2/EED-EZH2 complex
	Region	637 – 641	5	S-adenosyl-L-methionine binding By similarity
	Region	682 – 684	3	S-adenosyl-L-methionine binding By similarity
	Region	887 – 889	3	S-adenosyl-L-methionine binding By similarity
Sites
	Active site	706	1	By similarity
	Binding site	660	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	102	1	Phosphoserine By similarity
	Modified residue	239	1	Phosphoserine By similarity
	Modified residue	251	1	Phosphoserine By similarity
	Modified residue	257	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1 – 219	219	Missing in isoform 2.		VSP_009423
Experimental info
	Mutagenesis	302 – 303	2	WP → ST: Prevents accumulation in pericentric heterochromatin. Ref.11
	Mutagenesis	636	1	F → A: Reduces activity about 20-fold. Loss of substrate binding. Ref.11 Ref.16
	Mutagenesis	660	1	E → A: Reduces activity about 15-fold. Loss of substrate binding. Ref.11 Ref.16
	Mutagenesis	682	1	D → A: Strongly reduces substrate binding. No effect on activity. Ref.11 Ref.16
	Mutagenesis	705 – 706	2	PC → VD: No effect on localization. Ref.11 Ref.16
	Mutagenesis	706	1	C → A: Reduces activity about 5-fold. Reduces DNA-binding capacity. Ref.11 Ref.16
	Mutagenesis	707	1	N → Q: Reduces activity about 3-fold. Ref.11 Ref.16
	Mutagenesis	710	1	S → A: No effect on activity. Ref.11 Ref.16
	Mutagenesis	716	1	R → A: Reduces activity about 30-fold. Reduces DNA-binding capacity. Ref.11 Ref.16
	Mutagenesis	717	1	K → A: Reduces activity about 3-fold. Ref.11 Ref.16
	Mutagenesis	728	1	F → A: Loss of activity du to the incapacity to bind the regulatory subunit DNMT3L. Ref.11 Ref.19
	Mutagenesis	752	1	E → A: Reduces activity about 10-fold. Ref.11 Ref.16
	Mutagenesis	753	1	N → A: Reduces activity about 10-fold. Ref.11 Ref.16
	Mutagenesis	788	1	R → A: Reduces activity about 15-fold. Ref.11 Ref.16
	Mutagenesis	827	1	R → A: Reduces activity about 2-fold. Reduces DNA-binding capacity. Ref.11 Ref.16
	Mutagenesis	832	1	R → A: Reduces DNA-binding capacity. No effect on activity. Ref.11 Ref.16
	Mutagenesis	878	1	R → A: Reduces activity about 6-fold. Reduces DNA-binding capacity. Ref.11 Ref.16
	Mutagenesis	881	1	R → A: Loss of activity. Strongly reduces substrate binding. Ref.11 Ref.16
	Mutagenesis	883	1	R → A: Reduces activity about 3-fold. Reduces DNA-binding capacity. Ref.11 Ref.16
	Sequence conflict	151	1	Q → P in AAH07466. Ref.4
	Sequence conflict	775	1	M → T in BAB28644. Ref.3
	Sequence conflict	781	1	V → G in BAB28644. Ref.3
	Sequence conflict	791	1	W → R in BAB28644. Ref.3
	Sequence conflict	809	1	L → P in BAB28644. Ref.3
	Sequence conflict	904	1	Y → I in BAB28644. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 2. Checksum: 5F98D5A8092C84A5	FASTA	908	101,672
	10 20 30 40 50 60 MPSSGPGDTS SSSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR KRKHPPVESS 70 80 90 100 110 120 DTPKDPAVTT KSQPMAQDSG PSDLLPNGDL EKRSEPQPEE GSPAAGQKGG APAEGEGTET 130 140 150 160 170 180 PPEASRAVEN GCCVTKEGRG ASAGEGKEQK QTNIESMKME GSRGRLRGGL GWESSLRQRP 190 200 210 220 230 240 MPRLTFQAGD PYYISKRKRD EWLARWKREA EKKAKVIAVM NAVEENQASG ESQKVEEASP 250 260 270 280 290 300 PAVQQPTDPA SPTVATTPEP VGGDAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS 310 320 330 340 350 360 WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF HQATYNKQPM 370 380 390 400 410 420 YRKAIYEVLQ VASSRAGKLF PACHDSDESD SGKAVEVQNK QMIEWALGGF QPSGPKGLEP 430 440 450 460 470 480 PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA KKPRKSTTEK PKVKEIIDER TRERLVYEVR 490 500 510 520 530 540 QKCRNIEDIC ISCGSLNVTL EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR 550 560 570 580 590 600 EVLMCGNNNC CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR 610 620 630 640 650 660 LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG IQVDRYIASE 670 680 690 700 710 720 VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV IGGSPCNDLS IVNPARKGLY 730 740 750 760 770 780 EGTGRLFFEF YRLLHDARPK EGDDRPFFWL FENVVAMGVS DKRDISRFLE SNPVMIDAKE 790 800 810 820 830 840 VSAAHRARYF WGNLPGMNRP LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK 850 860 870 880 890 900 DQHFPVFMNE KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP LKEYFACV
	Isoform 2 [UniParc]. Checksum: 0C1093AF43717684	FASTA	689	77,824
	10 20 30 40 50 60 MNAVEENQAS GESQKVEEAS PPAVQQPTDP ASPTVATTPE PVGGDAGDKN ATKAADDEPE 70 80 90 100 110 120 YEDGRGFGIG ELVWGKLRGF SWWPGRIVSW WMTGRSRAAE GTRWVMWFGD GKFSVVCVEK 130 140 150 160 170 180 LMPLSSFCSA FHQATYNKQP MYRKAIYEVL QVASSRAGKL FPACHDSDES DSGKAVEVQN 190 200 210 220 230 240 KQMIEWALGG FQPSGPKGLE PPEEEKNPYK EVYTDMWVEP EAAAYAPPPP AKKPRKSTTE 250 260 270 280 290 300 KPKVKEIIDE RTRERLVYEV RQKCRNIEDI CISCGSLNVT LEHPLFIGGM CQNCKNCFLE 310 320 330 340 350 360 CAYQYDDDGY QSYCTICCGG REVLMCGNNN CCRCFCVECV DLLVGPGAAQ AAIKEDPWNC 370 380 390 400 410 420 YMCGHKGTYG LLRRREDWPS RLQMFFANNH DQEFDPPKVY PPVPAEKRKP IRVLSLFDGI 430 440 450 460 470 480 ATGLLVLKDL GIQVDRYIAS EVCEDSITVG MVRHQGKIMY VGDVRSVTQK HIQEWGPFDL 490 500 510 520 530 540 VIGGSPCNDL SIVNPARKGL YEGTGRLFFE FYRLLHDARP KEGDDRPFFW LFENVVAMGV 550 560 570 580 590 600 SDKRDISRFL ESNPVMIDAK EVSAAHRARY FWGNLPGMNR PLASTVNDKL ELQECLEHGR 610 620 630 640 650 660 IAKFSKVRTI TTRSNSIKQG KDQHFPVFMN EKEDILWCTE MERVFGFPVH YTDVSNMSRL 670 680 ARQRLLGRSW SVPVIRHLFA PLKEYFACV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases." Okano M., Xie S., Li E. Nat. Genet. 19:219-220(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6 and C57BL/6J. Tissue: Brain, Embryo and Skin.
[4]	"A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation." Chen T., Ueda Y., Xie S., Li E. J. Biol. Chem. 277:38746-38754(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY. Strain: 129/SvJ.
[5]	"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development." Okano M., Bell D.W., Haber D.A., Li E. Cell 99:247-257(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[6]	"Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpG correction sites." Gowher H., Jeltsch A. J. Mol. Biol. 309:1201-1208(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	Erratum Gowher H., Jeltsch A. J. Mol. Biol. 310:951-951(2001)
[8]	"Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription." Fuks F., Burgers W.A., Godin N., Kasai M., Kouzarides T. EMBO J. 20:2536-2544(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZBTB18 AND HDAC1.
[9]	"Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases." Gowher H., Jeltsch A. J. Biol. Chem. 277:20409-20414(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Biochemical fractionation reveals association of DNA methyltransferase (Dnmt) 3b with Dnmt1 and that of Dnmt 3a with a histone H3 methyltransferase and Hdac1." Datta J., Ghoshal K., Sharma S.M., Tajima S., Jacob S.T. J. Cell. Biochem. 88:855-864(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH HDAC1.
[11]	"The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin." Chen T., Tsujimoto N., Li E. Mol. Cell. Biol. 24:9048-9058(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 302-VAL-PRO-303 AND 705-PRO-CYS-706.
[12]	"Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting." Kaneda M., Okano M., Hata K., Sado T., Tsujimoto N., Li E., Sasaki H. Nature 429:900-903(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription." Ling Y., Sankpal U.T., Robertson A.K., McNally J.G., Karpova T., Robertson K.D. Nucleic Acids Res. 32:598-610(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION, INTERACTION WITH UBC9; PIAS1 AND PIAS2.
[14]	"Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L." Gowher H., Liebert K., Hermann A., Xu G., Jeltsch A. J. Biol. Chem. 280:13341-13348(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[15]	"Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA." Takeshima H., Suetake I., Shimahara H., Ura K., Tate S., Tajima S. J. Biochem. 139:503-515(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Mutational analysis of the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase." Gowher H., Loutchanwoot P., Vorobjeva O., Handa V., Jurkowska R.Z., Jurkowski T.P., Jeltsch A. J. Mol. Biol. 357:928-941(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PHE-636; GLU-660; ASP-682; CYS-706; ASN-707; SER-710; ARG-716; LYS-717; GLU-752; ASN-753; ARG-788; ARG-827; ARG-832; ARG-878; ARG-881 AND ARG-883.
[17]	"The Polycomb group protein EZH2 directly controls DNA methylation." Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 439:871-874(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THE PRC2/EED-EZH2 COMPLEX.
[18]	Erratum Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 446:824-824(2006)
[19]	"Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation." Jia D., Jurkowska R.Z., Zhang X., Jeltsch A., Cheng X. Nature 449:248-251(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF PHE-728.
[20]	"Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1." Takeshima H., Suetake I., Tajima S. J. Mol. Biol. 383:810-821(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells." Meilinger D., Fellinger K., Bultmann S., Rothbauer U., Bonapace I.M., Klinkert W.E., Spada F., Leonhardt H. EMBO Rep. 10:1259-1264(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UHRF1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF068625 mRNA. Translation: AAC40177.2.
AF480164 mRNA. Translation: AAN40038.1.
AK013096 mRNA. Translation: BAB28644.2. Different initiation.
AK090132 mRNA. Translation: BAC41110.1.
AK147263 mRNA. Translation: BAE27806.1.
AK147627 mRNA. Translation: BAE28033.1.
AK147642 mRNA. Translation: BAE28043.1.
AK147676 mRNA. Translation: BAE28067.1.
AK157792 mRNA. Translation: BAE34200.1.
BC007466 mRNA. Translation: AAH07466.1.

IPI

IPI00131694.
IPI00172129.

RefSeq

NP_001258682.1. NM_001271753.1.
NP_031898.1. NM_007872.4.
NP_714965.1. NM_153743.4.

UniGene

Mm.5001.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3SW9	X-ray	3.05	P/Q	39-50	[»]
3SWC	X-ray	2.33	P/Q	39-50	[»]

ProteinModelPortal

O88508.

SMR

O88508. Positions 279-421, 469-908.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38005N.

IntAct

O88508. 3 interactions.

MINT

MINT-2521021.

Protein family/group databases

REBASE

3747. M.MmuDnmt3A.

PTM databases

PhosphoSite

O88508.

Proteomic databases

PaxDb

O88508.

PRIDE

O88508.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000020991; ENSMUSP00000020991; ENSMUSG00000020661.
ENSMUST00000111186; ENSMUSP00000106817; ENSMUSG00000020661.
ENSMUST00000172689; ENSMUSP00000133543; ENSMUSG00000020661.
ENSMUST00000174817; ENSMUSP00000134009; ENSMUSG00000020661.

GeneID

13435.

KEGG

mmu:13435.

UCSC

uc007mxb.1. mouse.
uc007mxd.1. mouse.

Organism-specific databases

CTD

1788.

MGI

MGI:1261827. Dnmt3a.

Phylogenomic databases

eggNOG

NOG70699.

GeneTree

ENSGT00390000008341.

HOGENOM

HOG000230875.

HOVERGEN

HBG051381.

InParanoid

O88508.

KO

K00558.

OMA

FVGGMCQ.

OrthoDB

EOG4T1HKX.

Enzyme and pathway databases

BRENDA

2.1.1.37. 3474.

Gene expression databases

ArrayExpress

O88508.

Bgee

O88508.

CleanEx

MM_DNMT3A.

Genevestigator

O88508.

GermOnline

ENSMUSG00000020661. Mus musculus.

Family and domain databases

InterPro

IPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR025811. C5_MeTrfase_3.
IPR000313. PWWP.
IPR011011. Znf_FYVE_PHD.
[Graphical view]

Pfam

PF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]

SMART

SM00293. PWWP. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. False negative.
PS50812. PWWP. 1 hit.
[Graphical view]

ProtoNet

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Other

ChiTaRS

DNMT3A. mouse.

NextBio

283867.

SOURCE

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Entry information

Entry name

DNM3A_MOUSE

Accession

Primary (citable) accession number: O88508
Secondary accession number(s): Q3TZK8 , Q3UH24, Q8CJ60, Q922J0, Q9CSE1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program