Q9UJW3 (DNM3L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA (cytosine-5)-methyltransferase 3-like

Gene names

Name:

DNMT3L

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	386 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytically inactive regulatory factor of DNA methyltransferases. It is essential for the function of DNMT3A and DNMT3B. Activates DNMT3A and DNMT3B by binding to their catalytic domain. Accelerates the binding of DNA and AdoMet to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases. Recognizes unmethylated histone H3 lysine 4 (H3K4) and induces de novo DNA methylation by recruitment or activation of DNMT3. Ref.5
Subunit structure	Homodimer. Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with histone H3 (via N-terminus). Ref.5 Ref.6
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed at low levels in several tissues including testis, ovary, and thymus.
Miscellaneous	Interaction with histone H3 is strongly inhibited by methylation at lysine 4 (H3K4me).
Sequence similarities	Belongs to the C5-methyltransferase family. Contains 1 ADD domain. Contains 1 GATA-type zinc finger. Contains 1 PHD-type zinc finger.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation Non-traceable author statement PubMed 12202768. Source: UniProtKB chorionic trophoblast cell differentiation Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 12202768. Source: UniProtKB placenta development Inferred from electronic annotation. Source: Compara regulation of gene expression by genetic imprinting Non-traceable author statement PubMed 12202768. Source: UniProtKB spermatogenesis Non-traceable author statement PubMed 11934864. Source: UniProtKB
Cellular_component	condensed nuclear chromosome Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay PubMed 16780588. Source: UniProtKB nuclear heterochromatin Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 16780588. Source: UniProtKB
Molecular_function	enzyme activator activity Inferred from direct assay PubMed 16543361. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HDAC1	Q13547	3	EBI-740967,EBI-301834

Alternative products

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

Note: Other splice isoforms seem to exist.

Isoform 1 (identifier: Q9UJW3-1)

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: Q9UJW3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     332-332: S → SS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 386

386

DNA (cytosine-5)-methyltransferase 3-like

PRO_0000088047

Regions

Domain

41 – 173

133

ADD

Zinc finger

52 – 82

31

GATA-type; atypical

Zinc finger

93 – 149

57

PHD-type; atypical

Natural variations

Alternative sequence

332

1

S → SS in isoform 2.

VSP_041295

Natural variant

278

1

R → G. Ref.4
Corresponds to variant rs7354779 [ dbSNP | Ensembl ].

VAR_051962

Experimental info

Mutagenesis

261

1

F → A: Loss of binding to DNMT3A. Ref.6

Sequence conflict

246

1

P → A in AAF05812. Ref.1

Sequence conflict

266

1

L → F in AAF05812. Ref.1

Secondary structure

1

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386

Helix Strand Turn

Details...

Helix

35 – 43

9

Helix

49 – 51

3

Turn

54 – 56

3

Beta strand

66 – 71

6

Helix

74 – 81

8

Turn

82 – 85

4

Beta strand

89 – 93

5

Turn

97 – 99

3

Helix

119 – 125

7

Helix

130 – 136

7

Turn

143 – 145

3

Beta strand

154 – 156

3

Helix

160 – 171

12

Helix

184 – 186

3

Beta strand

192 – 197

6

Turn

200 – 207

8

Beta strand

218 – 222

5

Helix

229 – 234

6

Beta strand

239 – 244

6

Turn

248 – 250

3

Helix

257 – 270

14

Beta strand

281 – 286

6

Helix

292 – 302

11

Beta strand

308 – 310

3

Beta strand

314 – 316

3

Beta strand

322 – 325

4

Beta strand

327 – 331

5

Helix

340 – 351

12

Helix

362 – 365

4

Helix

369 – 373

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 31, 2011. Version 3. Checksum: 65EC2AB7492D53B3	FASTA	386	43,583
	10 20 30 40 50 60 MAAIPALDPE AEPSMDVILV GSSELSSSVS PGTGRDLIAY EVKANQRNIE DICICCGSLQ 70 80 90 100 110 120 VHTQHPLFEG GICAPCKDKF LDALFLYDDD GYQSYCSICC SGETLLICGN PDCTRCYCFE 130 140 150 160 170 180 CVDSLVGPGT SGKVHAMSNW VCYLCLPSSR SGLLQRRRKW RSQLKAFYDR ESENPLEMFE 190 200 210 220 230 240 TVPVWRRQPV RVLSLFEDIK KELTSLGFLE SGSDPGQLKH VVDVTDTVRK DVEEWGPFDL 250 260 270 280 290 300 VYGATPPLGH TCDRPPSWYL FQFHRLLQYA RPKPGSPRPF FWMFVDNLVL NKEDLDVASR 310 320 330 340 350 360 FLEMEPVTIP DVHGGSLQNA VRVWSNIPAI RSRHWALVSE EELSLLAQNK QSSKLAAKWP 370 380 TKLVKNCFLP LREYFKYFST ELTSSL
	Isoform 2 [UniParc]. Checksum: 699AAC1929D473A9	FASTA	387	43,670
	10 20 30 40 50 60 MAAIPALDPE AEPSMDVILV GSSELSSSVS PGTGRDLIAY EVKANQRNIE DICICCGSLQ 70 80 90 100 110 120 VHTQHPLFEG GICAPCKDKF LDALFLYDDD GYQSYCSICC SGETLLICGN PDCTRCYCFE 130 140 150 160 170 180 CVDSLVGPGT SGKVHAMSNW VCYLCLPSSR SGLLQRRRKW RSQLKAFYDR ESENPLEMFE 190 200 210 220 230 240 TVPVWRRQPV RVLSLFEDIK KELTSLGFLE SGSDPGQLKH VVDVTDTVRK DVEEWGPFDL 250 260 270 280 290 300 VYGATPPLGH TCDRPPSWYL FQFHRLLQYA RPKPGSPRPF FWMFVDNLVL NKEDLDVASR 310 320 330 340 350 360 FLEMEPVTIP DVHGGSLQNA VRVWSNIPAI RSSRHWALVS EEELSLLAQN KQSSKLAAKW 370 380 PTKLVKNCFL PLREYFKYFS TELTSSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family." Aapola U., Shibuya K., Scott H.S., Ollila J., Vihinen M., Heino M., Shintani A., Kawasaki K., Minoshima S., Krohn K., Antonarakis S.E., Shimizu N., Kudoh J., Peterson P. Genomics 65:293-298(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[2]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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), VARIANT GLY-278. Tissue: Placenta.
[5]	"DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA." Ooi S.K., Qiu C., Bernstein E., Li K., Jia D., Yang Z., Erdjument-Bromage H., Tempst P., Lin S.-P., Allis C.D., Cheng X., Bestor T.H. Nature 448:714-717(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS), FUNCTION, HOMODIMERIZATION.
[6]	"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 160-387, SUBUNIT, MUTAGENESIS OF PHE-261.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF194032 mRNA. Translation: AAF05812.1.
AP001753 Genomic DNA. Translation: BAA95556.1.
AP001059 Genomic DNA. No translation available.
AP001060 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09445.1.
BC002560 mRNA. Translation: AAH02560.1.

IPI

IPI00002935.
IPI00375360.

RefSeq

NP_037501.2. NM_013369.3.
NP_787063.1. NM_175867.2.

UniGene

Hs.592165.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2PV0	X-ray	3.30	A/B/C	1-386	[»]
2PVC	X-ray	3.69	A/B/C	1-386	[»]
2QRV	X-ray	2.89	B/C/F/G	160-386	[»]

ProteinModelPortal

Q9UJW3.

SMR

Q9UJW3. Positions 34-380.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UJW3. 3 interactions.

MINT

MINT-1448248.

STRING

9606.ENSP00000270172.

Protein family/group databases

REBASE

4636. M.HsaDnmt3L.

PTM databases

PhosphoSite

Q9UJW3.

Polymorphism databases

DMDM

20141446.

Proteomic databases

PaxDb

Q9UJW3.

PRIDE

Q9UJW3.

Protocols and materials databases

DNASU

29947.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000270172; ENSP00000270172; ENSG00000142182.
ENST00000418993; ENSP00000412862; ENSG00000142182.

GeneID

29947.

KEGG

hsa:29947.

UCSC

uc002zeg.1. human.
uc002zeh.1. human.

Organism-specific databases

CTD

29947.

GeneCards

GC21M045666.

HGNC

HGNC:2980. DNMT3L.

MIM

606588. gene.

neXtProt

NX_Q9UJW3.

PharmGKB

PA27447.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG69419.

HOGENOM

HOG000246422.

HOVERGEN

HBG051382.

InParanoid

Q9UJW3.

KO

K00558.

OMA

CICCGSL.

OrthoDB

EOG4T1HMN.

Gene expression databases

ArrayExpress

Q9UJW3.

Bgee

Q9UJW3.

CleanEx

HS_DNMT3L.

Genevestigator

Q9UJW3.

GermOnline

ENSG00000142182. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR025766. ADD.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS51533. ADD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UJW3.

GenomeRNAi

29947.

NextBio

52621.

SOURCE

Search...

Entry information

Entry name

DNM3L_HUMAN

Accession

Primary (citable) accession number: Q9UJW3
Secondary accession number(s): E9PB42, Q9BUJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 31, 2011
Last modified:	April 3, 2013
This is version 107 of the entry and version 3 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.