Q9Y6K1 (DNM3A_HUMAN) 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 HsaIIIA
Short name=DNA MTase HsaIIIA
Short name=M.HsaIIIA

Gene names

Name:

DNMT3A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	912 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 By similarity. Ref.10
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 By similarity.
Subunit structure	Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with UBC9, PIAS1 and PIAS2 By similarity. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with UHRF1 By similarity. Interacts with DNMT1 and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Ref.3 Ref.9 Ref.10 Ref.14 Ref.17 Ref.18 Ref.19
Subcellular location	Nucleus. Cytoplasm. Note: Accumulates in the major satellite repeats at pericentric heterochromatin By similarity. Ref.3
Tissue specificity	Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung. Ref.7
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 By similarity.
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.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.
Sequence caution	The sequence AAL57039.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAN40037.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
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 electronic annotation. Source: Compara DNA methylation involved in gamete generation Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara hypermethylation of CpG island Inferred from electronic annotation. Source: Compara methylation-dependent chromatin silencing Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of gene expression by genetic imprinting Traceable author statement Ref.2. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	chromosome, centromeric region Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB euchromatin Inferred from direct assay Ref.2. Source: UniProtKB nuclear heterochromatin Inferred from electronic annotation. Source: Compara nuclear matrix Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	DNA (cytosine-5-)-methyltransferase activity Inferred from direct assay Ref.2. Source: UniProtKB DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Inferred from electronic annotation. Source: Compara DNA binding Inferred from direct assay Ref.2. Source: UniProtKB chromatin binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW unmethylated CpG binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EED	O75530	2	EBI-923653,EBI-923794
EZH2	Q15910	4	EBI-923653,EBI-530054
SETDB1	Q15047	7	EBI-923653,EBI-79691

Alternative products

This entry describes 3 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6K1-1)

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: Q9Y6K1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-213: MPAMPSSGPG...DEWLARWKRE → MGILERVVRRNGRVDRSLKDECDT

Note: It is uncertain whether Met-1 or Met-35 is the initiator.

Isoform 3 (identifier: Q9Y6K1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     151-166: KEQKETNIESMKMEGS → ESSAPGAASSGPTSIP
     167-912: Missing.

Note: Produced by alternative splicing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 912

912

DNA (cytosine-5)-methyltransferase 3A

PRO_0000088043

Regions

Domain

292 – 350

59

PWWP

Domain

482 – 614

133

ADD

Zinc finger

493 – 523

31

GATA-type; atypical

Zinc finger

534 – 590

57

PHD-type; atypical

Region

199 – 403

205

Interaction with DNMT1 and DNMT3B

Region

494 – 586

93

Interaction with the PRC2/EED-EZH2 complex By similarity

Region

641 – 645

5

S-adenosyl-L-methionine binding Probable

Region

686 – 688

3

S-adenosyl-L-methionine binding Probable

Region

891 – 893

3

S-adenosyl-L-methionine binding Probable

Sites

Active site

710

1

By similarity

Binding site

664

1

S-adenosyl-L-methionine Probable

Amino acid modifications

Modified residue

105

1

Phosphoserine Ref.8 Ref.13 Ref.16

Modified residue

243

1

Phosphoserine Ref.15 Ref.16

Modified residue

255

1

Phosphoserine Ref.16

Modified residue

261

1

Phosphothreonine Ref.16

Modified residue

267

1

Phosphoserine Ref.16

Natural variations

Alternative sequence

1 – 213

213

MPAMP…RWKRE → MGILERVVRRNGRVDRSLKD ECDT in isoform 2.

VSP_046254

Alternative sequence

151 – 166

16

KEQKE…KMEGS → ESSAPGAASSGPTSIP in isoform 3.

VSP_040998

Alternative sequence

167 – 912

746

Missing in isoform 3.

VSP_040999

Natural variant

699

1

G → D in a patient with chronic myelomonocytic leukemia. Ref.21

VAR_067234

Natural variant

731

1

Missing in a patient with chronic myelomonocytic leukemia. Ref.21

VAR_067235

Natural variant

882

1

R → C in a patient with chronic myelomonocytic leukemia; somatic mutation. Ref.21

VAR_067236

Natural variant

882

1

R → H in a patient with chronic myelomonocytic leukemia; somatic mutation. Ref.21

VAR_067237

Natural variant

882

1

R → P in a patient with chronic myelomonocytic leukemia; somatic mutation. Ref.21

VAR_067238

Experimental info

Mutagenesis

732

1

F → A: Loss of activity du to the incapacity to bind the regulatory subunit DNMT3L. Ref.17

Secondary structure

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912

Helix Strand Turn

Details...

Beta strand

295 – 298

4

Beta strand

306 – 311

6

Helix

313 – 315

3

Beta strand

325 – 330

6

Turn

331 – 333

3

Beta strand

336 – 340

5

Helix

341 – 343

3

Beta strand

344 – 346

3

Helix

347 – 349

3

Helix

350 – 353

4

Helix

356 – 361

6

Helix

363 – 380

18

Helix

399 – 411

13

Turn

415 – 417

3

Helix

419 – 422

4

Helix

476 – 484

9

Helix

490 – 492

3

Turn

495 – 497

3

Beta strand

507 – 513

7

Helix

515 – 524

10

Beta strand

532 – 536

5

Turn

538 – 540

3

Beta strand

544 – 548

5

Turn

552 – 554

3

Beta strand

557 – 559

3

Helix

560 – 566

7

Helix

571 – 576

6

Beta strand

578 – 580

3

Turn

584 – 586

3

Beta strand

595 – 597

3

Helix

601 – 609

9

Beta strand

634 – 639

6

Turn

642 – 644

3

Helix

645 – 652

8

Beta strand

657 – 663

7

Helix

667 – 676

10

Turn

677 – 679

3

Beta strand

681 – 684

4

Helix

687 – 689

3

Helix

692 – 697

6

Beta strand

702 – 706

5

Helix

711 – 713

3

Turn

722 – 724

3

Turn

726 – 729

4

Helix

730 – 741

12

Beta strand

752 – 761

10

Helix

763 – 773

11

Helix

782 – 784

3

Beta strand

786 – 788

3

Beta strand

791 – 796

6

Beta strand

801 – 803

3

Helix

815 – 817

3

Beta strand

824 – 830

7

Beta strand

850 – 852

3

Beta strand

855 – 857

3

Helix

861 – 868

8

Turn

872 – 875

4

Helix

882 – 890

9

Helix

895 – 902

8

Helix

903 – 908

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 4. Checksum: BD1FF7C5B4F54A33	FASTA	912	101,858
	10 20 30 40 50 60 MPAMPSSGPG DTSSSAAERE EDRKDGEEQE EPRGKEERQE PSTTARKVGR PGRKRKHPPV 70 80 90 100 110 120 ESGDTPKDPA VISKSPSMAQ DSGASELLPN GDLEKRSEPQ PEEGSPAGGQ KGGAPAEGEG 130 140 150 160 170 180 AAETLPEASR AVENGCCTPK EGRGAPAEAG KEQKETNIES MKMEGSRGRL RGGLGWESSL 190 200 210 220 230 240 RQRPMPRLTF QAGDPYYISK RKRDEWLARW KREAEKKAKV IAGMNAVEEN QGPGESQKVE 250 260 270 280 290 300 EASPPAVQQP TDPASPTVAT TPEPVGSDAG DKNATKAGDD EPEYEDGRGF GIGELVWGKL 310 320 330 340 350 360 RGFSWWPGRI VSWWMTGRSR AAEGTRWVMW FGDGKFSVVC VEKLMPLSSF CSAFHQATYN 370 380 390 400 410 420 KQPMYRKAIY EVLQVASSRA GKLFPVCHDS DESDTAKAVE VQNKPMIEWA LGGFQPSGPK 430 440 450 460 470 480 GLEPPEEEKN PYKEVYTDMW VEPEAAAYAP PPPAKKPRKS TAEKPKVKEI IDERTRERLV 490 500 510 520 530 540 YEVRQKCRNI EDICISCGSL NVTLEHPLFV GGMCQNCKNC FLECAYQYDD DGYQSYCTIC 550 560 570 580 590 600 CGGREVLMCG NNNCCRCFCV ECVDLLVGPG AAQAAIKEDP WNCYMCGHKG TYGLLRRRED 610 620 630 640 650 660 WPSRLQMFFA NNHDQEFDPP KVYPPVPAEK RKPIRVLSLF DGIATGLLVL KDLGIQVDRY 670 680 690 700 710 720 IASEVCEDSI TVGMVRHQGK IMYVGDVRSV TQKHIQEWGP FDLVIGGSPC NDLSIVNPAR 730 740 750 760 770 780 KGLYEGTGRL FFEFYRLLHD ARPKEGDDRP FFWLFENVVA MGVSDKRDIS RFLESNPVMI 790 800 810 820 830 840 DAKEVSAAHR ARYFWGNLPG MNRPLASTVN DKLELQECLE HGRIAKFSKV RTITTRSNSI 850 860 870 880 890 900 KQGKDQHFPV FMNEKEDILW CTEMERVFGF PVHYTDVSNM SRLARQRLLG RSWSVPVIRH 910 LFAPLKEYFA CV
	Isoform 2 [UniParc]. Checksum: 19341BDAE1B71C8B	FASTA	723	81,613
	10 20 30 40 50 60 MGILERVVRR NGRVDRSLKD ECDTAEKKAK VIAGMNAVEE NQGPGESQKV EEASPPAVQQ 70 80 90 100 110 120 PTDPASPTVA TTPEPVGSDA GDKNATKAGD DEPEYEDGRG FGIGELVWGK LRGFSWWPGR 130 140 150 160 170 180 IVSWWMTGRS RAAEGTRWVM WFGDGKFSVV CVEKLMPLSS FCSAFHQATY NKQPMYRKAI 190 200 210 220 230 240 YEVLQVASSR AGKLFPVCHD SDESDTAKAV EVQNKPMIEW ALGGFQPSGP KGLEPPEEEK 250 260 270 280 290 300 NPYKEVYTDM WVEPEAAAYA PPPPAKKPRK STAEKPKVKE IIDERTRERL VYEVRQKCRN 310 320 330 340 350 360 IEDICISCGS LNVTLEHPLF VGGMCQNCKN CFLECAYQYD DDGYQSYCTI CCGGREVLMC 370 380 390 400 410 420 GNNNCCRCFC VECVDLLVGP GAAQAAIKED PWNCYMCGHK GTYGLLRRRE DWPSRLQMFF 430 440 450 460 470 480 ANNHDQEFDP PKVYPPVPAE KRKPIRVLSL FDGIATGLLV LKDLGIQVDR YIASEVCEDS 490 500 510 520 530 540 ITVGMVRHQG KIMYVGDVRS VTQKHIQEWG PFDLVIGGSP CNDLSIVNPA RKGLYEGTGR 550 560 570 580 590 600 LFFEFYRLLH DARPKEGDDR PFFWLFENVV AMGVSDKRDI SRFLESNPVM IDAKEVSAAH 610 620 630 640 650 660 RARYFWGNLP GMNRPLASTV NDKLELQECL EHGRIAKFSK VRTITTRSNS IKQGKDQHFP 670 680 690 700 710 720 VFMNEKEDIL WCTEMERVFG FPVHYTDVSN MSRLARQRLL GRSWSVPVIR HLFAPLKEYF ACV
	Isoform 3 [UniParc]. Checksum: 78756A71196D61B5	FASTA	166	16,866
	10 20 30 40 50 60 MPAMPSSGPG DTSSSAAERE EDRKDGEEQE EPRGKEERQE PSTTARKVGR PGRKRKHPPV 70 80 90 100 110 120 ESGDTPKDPA VISKSPSMAQ DSGASELLPN GDLEKRSEPQ PEEGSPAGGQ KGGAPAEGEG 130 140 150 160 AAETLPEASR AVENGCCTPK EGRGAPAEAG ESSAPGAASS GPTSIP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and chromosome locations of the human DNMT3 gene family." Xie S., Wang Z., Okano M., Nogami M., Li Y., He W.-W., Okumura K., Li E. Gene 236:87-95(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal testis.
[2]	"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).
[3]	"Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases." Kim G.-D., Ni J., Kelesoglu N., Roberts R.J., Pradhan S. EMBO J. 21:4183-4195(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DNMT1 AND DNMT3B, SUBCELLULAR LOCATION.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 3). Tissue: Lung, PNS and Skin.
[7]	"The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors." Robertson K.D., Uzvolgyi E., Liang G., Talmadge C., Sumegi J., Gonzales F.A., Jones P.A. Nucleic Acids Res. 27:2291-2298(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells." Li H., Rauch T., Chen Z.-X., Szabo P.E., Riggs A.D., Pfeifer G.P. J. Biol. Chem. 281:19489-19500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SETDB1.
[10]	"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: FUNCTION, INTERACTION WITH THE PRC2/EED-EZH2 COMPLEX.
[11]	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)
[12]	"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer." Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., Cedar H. Nat. Genet. 39:232-236(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DE NOVO DNA METHYLATION OF TARGET GENES.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion." Kokura K., Sun L., Bedford M.T., Fang J. EMBO J. 29:3673-3687(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MPHOSPH8.
[15]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105; SER-243; SER-255; THR-261 AND SER-267, MASS SPECTROMETRY.
[17]	"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: X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 627-909 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, MUTAGENESIS OF PHE-732.
[18]	"Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain." Otani J., Nankumo T., Arita K., Inamoto S., Ariyoshi M., Shirakawa M. EMBO Rep. 10:1235-1241(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 476-614 IN COMPLEXES WITH ZINC AND WITH HISTONE H3 PEPTIDE, SUBUNIT.
[19]	"MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a." Chang Y., Sun L., Kokura K., Horton J.R., Fukuda M., Espejo A., Izumi V., Koomen J.M., Bedford M.T., Zhang X., Shinkai Y., Fang J., Cheng X. Nat. Commun. 2:533-533(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 40-53 IN COMPLEX WITH MPHOSPH8, INTERACTION WITH MPHOSPH8.
[20]	"Structural and histone binding ability characterizations of human PWWP domains." Wu H., Zeng H., Lam R., Tempel W., Amaya M.F., Xu C., Dombrovski L., Qiu W., Wang Y., Min J. PLoS ONE 6:E18919-E18919(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 275-427.
[21]	"Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A." Jankowska A.M., Makishima H., Tiu R.V., Szpurka H., Huang Y., Traina F., Visconte V., Sugimoto Y., Prince C., O'Keefe C., Hsi E.D., List A., Sekeres M.A., Rao A., McDevitt M.A., Maciejewski J.P. Blood 118:3932-3941(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-699; PHE-731 DEL; CYS-882; HIS-882 AND PRO-882.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF067972 mRNA. Translation: AAD33084.2.
AF480163 mRNA. Translation: AAN40037.1. Different initiation.
AF331856 mRNA. Translation: AAL57039.1. Different initiation.
AC012074 Genomic DNA. Translation: AAY14761.1.
CH471053 Genomic DNA. Translation: EAX00727.1.
BC032392 mRNA. Translation: AAH32392.1.
BC043617 mRNA. Translation: AAH43617.1.
BC051864 mRNA. Translation: AAH51864.1.

IPI

IPI00220006.
IPI00328540.
IPI00329216.
IPI00893229.

RefSeq

NP_072046.2. NM_022552.4.
NP_715640.2. NM_153759.3.
NP_783328.1. NM_175629.2.
NP_783329.1. NM_175630.1.

UniGene

Hs.515840.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QRV	X-ray	2.89	A/D/E/H	627-909	[»]
3A1A	X-ray	2.30	A	476-614	[»]
3A1B	X-ray	2.29	A	476-614	[»]
3LLR	X-ray	2.30	A/B/C/D/E	275-427	[»]
3SVM	X-ray	2.31	P	40-53	[»]

ProteinModelPortal

Q9Y6K1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38004N.

IntAct

Q9Y6K1. 16 interactions.

STRING

9606.ENSP00000264709.

Protein family/group databases

REBASE

4119. M.HsaDnmt3A.

PTM databases

PhosphoSite

Q9Y6K1.

Polymorphism databases

DMDM

166215081.

Proteomic databases

PaxDb

Q9Y6K1.

PRIDE

Q9Y6K1.

Protocols and materials databases

DNASU

1788.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264709; ENSP00000264709; ENSG00000119772.
ENST00000321117; ENSP00000324375; ENSG00000119772.
ENST00000380746; ENSP00000370122; ENSG00000119772.
ENST00000402667; ENSP00000384237; ENSG00000119772.
ENST00000406659; ENSP00000384852; ENSG00000119772.

GeneID

1788.

KEGG

hsa:1788.

UCSC

uc002rgc.3. human.
uc002rgf.3. human.

Organism-specific databases

CTD

1788.

GeneCards

GC02M025455.

HGNC

HGNC:2978. DNMT3A.

HPA

CAB009469.
HPA026588.

MIM

602769. gene.

neXtProt

NX_Q9Y6K1.

PharmGKB

PA27445.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG70699.

HOGENOM

HOG000230875.

HOVERGEN

HBG051381.

InParanoid

Q9Y6K1.

KO

K00558.

OMA

FVGGMCQ.

OrthoDB

EOG4T1HKX.

Enzyme and pathway databases

BRENDA

2.1.1.37. 2681.

Gene expression databases

ArrayExpress

Q9Y6K1.

Bgee

Q9Y6K1.

CleanEx

HS_DNMT3A.

Genevestigator

Q9Y6K1.

GermOnline

ENSG00000119772. Homo sapiens.

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

Search...

Other

ChEMBL

CHEMBL1992.

EvolutionaryTrace

Q9Y6K1.

GenomeRNAi

1788.

NextBio

7279.

SOURCE

Search...

Entry information

Entry name

DNM3A_HUMAN

Accession

Primary (citable) accession number: Q9Y6K1
Secondary accession number(s): E9PEB8 , Q86TE8, Q86XF5, Q8IZV0, Q8WXU9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 116 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.