Reviewed, UniProtKB/Swiss-Prot Q9Y6K1 (DNM3A_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	912 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for genome wide de novo methylation and is essential for development. DNA methylation is coordinated with methylation of histones. Ref.10
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Subunit structure	Binds the ZNF238 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD-type zinc-finger By similarity. Interacts with DNMT1 and DNMT3B. Interacts with the PRC2/EED-EZH2 complex.
Subcellular location	Nucleus. Cytoplasm. 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
Sequence similarities	Belongs to the C5-methyltransferase family. Contains 1 ADD-type zinc finger. Contains 1 PWWP domain.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.

Ontologies

Keywords
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	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA methylation Ref.2 Ref.7 Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Ref.2 Inferred from sequence or structural similarity. Source: UniProtKB euchromatin Ref.2 Inferred from sequence or structural similarity. Source: UniProtKB nuclear matrix Ref.2 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	DNA (cytosine-5-)-methyltransferase activity Ref.2 Ref.7 Inferred from sequence or structural similarity. Source: UniProtKB DNA binding Ref.1 Traceable author statement. Source: ProtInc protein binding Ref.9 Ref.10 Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EED	O75530	1	EBI-923653,EBI-923794
EZH2	Q15910	3	EBI-923653,EBI-530054
SETDB1	Q15047	2	EBI-923653,EBI-79691

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [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:
     1-223: Missing.

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

Zinc finger

494 – 586

93

ADD-type

Region

199 – 403

205

Interaction with DNMT1 and DNMT3B

Region

494 – 586

93

Interaction with the PRC2/EED-EZH2 complex By similarity

Sites

Active site

710

1

By similarity

Amino acid modifications

Modified residue

105

1

Phosphoserine Ref.8 Ref.13

Natural variations

Alternative sequence

1 – 223

223

Missing in isoform 2.

VSP_029985

Secondary structure

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912

Helix Strand Turn

Details...

Beta strand

631 – 636

6

Turn

639 – 641

3

Helix

642 – 649

8

Beta strand

654 – 660

7

Helix

664 – 673

10

Turn

674 – 676

3

Beta strand

678 – 681

4

Helix

684 – 686

3

Helix

689 – 694

6

Beta strand

699 – 703

5

Helix

708 – 710

3

Turn

719 – 721

3

Turn

723 – 726

4

Helix

727 – 738

12

Beta strand

749 – 758

10

Helix

760 – 770

11

Helix

779 – 781

3

Beta strand

783 – 785

3

Beta strand

788 – 793

6

Beta strand

798 – 800

3

Helix

812 – 814

3

Beta strand

821 – 827

7

Beta strand

847 – 849

3

Beta strand

852 – 854

3

Helix

858 – 865

8

Turn

869 – 872

4

Helix

879 – 887

9

Helix

892 – 899

8

Helix

900 – 905

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. Checksum: A4117B9679A83508	FASTA	689	77,817
	10 20 30 40 50 60 MNAVEENQGP GESQKVEEAS PPAVQQPTDP ASPTVATTPE PVGSDAGDKN ATKAGDDEPE 70 80 90 100 110 120 YEDGRGFGIG ELVWGKLRGF SWWPGRIVSW WMTGRSRAAE GTRWVMWFGD GKFSVVCVEK 130 140 150 160 170 180 LMPLSSFCSA FHQATYNKQP MYRKAIYEVL QVASSRAGKL FPVCHDSDES DTAKAVEVQN 190 200 210 220 230 240 KPMIEWALGG FQPSGPKGLE PPEEEKNPYK EVYTDMWVEP EAAAYAPPPP AKKPRKSTAE 250 260 270 280 290 300 KPKVKEIIDE RTRERLVYEV RQKCRNIEDI CISCGSLNVT LEHPLFVGGM 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, 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: 10433969] [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: 12138111] [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: 12145218] [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: 15815621] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: 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: 10325416] [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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, MASS SPECTROMETRY. Tissue: Epithelium.
[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: 16682412] [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: 16357870] [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: 17200670] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

IPI

IPI00329216.
IPI00893229.

RefSeq

NP_072046.2.
NP_715640.2.
NP_783328.1.

UniGene

Hs.515840

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QRV	X-ray	2.89	A/D/E/H	627-909	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y6K1. 3 interactions.

Protein family/group databases

REBASE

4119. M.HsaDnmt3A.

PTM databases

PhosphoSite

Q9Y6K1.

Proteomic databases

PRIDE

Q9Y6K1.

Genome annotation databases

Ensembl

ENSG00000119772. Homo sapiens. [Contig view]

GeneID

1788.

KEGG

hsa:1788.

Organism-specific databases

GeneCards

GC02M025367.

HGNC

HGNC:2978. DNMT3A.

HPA

CAB009469.

MIM

602769. gene.

PharmGKB

PA27445.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9Y6K1.

OMA

Q9Y6K1. TNIESMK.

Enzyme and pathway databases

BRENDA

2.1.1.37. 247.

Gene expression databases

ArrayExpress

Q9Y6K1.

Bgee

Q9Y6K1.

CleanEx

HS_DNMT3A.

GermOnline

ENSG00000119772. Homo sapiens.

Family and domain databases

InterPro

IPR001525. C5_DNA_meth.
IPR018117. C5_DNA_meth_AS.
IPR000313. PWWP.
[Graphical view]

Pfam

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

SMART

SM00293. PWWP. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

7279.

SOURCE

Search...

Entry information

Entry name

DNM3A_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	January 15, 2008
Last modified:	June 16, 2009
This is version 76 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)