Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA (cytosine-5)-methyltransferase 3-like

Gene

DNMT3L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (By similarity). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:17687327). Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases (PubMed:17687327). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role in embryonic stem cells and germ cells (By similarity). In germ cells, required for the methylation of imprinted loci together with DNMT3A (By similarity). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (By similarity). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (By similarity). While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes (By similarity). Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes (By similarity). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (By similarity).By similarity1 Publication

Miscellaneous

Interaction with histone H3 is strongly inhibited by methylation at lysine 4 (H3K4me).

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri52 – 82GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri93 – 149PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

  • enzyme activator activity Source: MGI
  • enzyme binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB

GO - Biological processi

Keywordsi

Biological processDifferentiation, Spermatogenesis
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5334118 DNA methylation

Protein family/group databases

REBASEi4636 M.HsaDnmt3L

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3-like
Gene namesi
Name:DNMT3L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000142182.8
HGNCiHGNC:2980 DNMT3L
MIMi606588 gene
neXtProtiNX_Q9UJW3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi261F → A: Loss of binding to DNMT3A. 1 Publication1

Organism-specific databases

DisGeNETi29947
OpenTargetsiENSG00000142182
PharmGKBiPA27447

Chemistry databases

ChEMBLiCHEMBL3137291

Polymorphism and mutation databases

BioMutaiDNMT3L
DMDMi334302913

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880471 – 386DNA (cytosine-5)-methyltransferase 3-likeAdd BLAST386

Proteomic databases

PaxDbiQ9UJW3
PRIDEiQ9UJW3
ProteomicsDBi84672
84673 [Q9UJW3-2]

PTM databases

iPTMnetiQ9UJW3
PhosphoSitePlusiQ9UJW3

Expressioni

Tissue specificityi

Expressed at low levels in several tissues including testis, ovary, and thymus.1 Publication

Gene expression databases

BgeeiENSG00000142182
CleanExiHS_DNMT3L
ExpressionAtlasiQ9UJW3 baseline and differential
GenevisibleiQ9UJW3 HS

Organism-specific databases

HPAiHPA055234
HPA066780

Interactioni

Subunit structurei

Homodimer (PubMed:17687327, PubMed:17713477). Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (PubMed:17713477). Interacts with histone H3 (via N-terminus); interaction is strongly inhibited by methylation at lysine 4 (H3K4me) (PubMed:17687327). Interacts with EZH2; the interaction is direct (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118984, 81 interactors
CORUMiQ9UJW3
DIPiDIP-35238N
IntActiQ9UJW3, 9 interactors
MINTiQ9UJW3
STRINGi9606.ENSP00000270172

Chemistry databases

BindingDBiQ9UJW3

Structurei

Secondary structure

1386
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 43Combined sources9
Helixi49 – 51Combined sources3
Turni54 – 56Combined sources3
Beta strandi66 – 71Combined sources6
Helixi74 – 81Combined sources8
Turni82 – 85Combined sources4
Beta strandi89 – 93Combined sources5
Turni97 – 99Combined sources3
Helixi119 – 125Combined sources7
Helixi130 – 136Combined sources7
Turni143 – 145Combined sources3
Beta strandi154 – 156Combined sources3
Helixi160 – 171Combined sources12
Helixi184 – 186Combined sources3
Beta strandi192 – 197Combined sources6
Helixi200 – 206Combined sources7
Beta strandi218 – 222Combined sources5
Helixi224 – 226Combined sources3
Helixi229 – 234Combined sources6
Beta strandi239 – 244Combined sources6
Turni248 – 250Combined sources3
Helixi256 – 269Combined sources14
Beta strandi281 – 286Combined sources6
Helixi292 – 301Combined sources10
Beta strandi307 – 311Combined sources5
Beta strandi314 – 316Combined sources3
Beta strandi319 – 326Combined sources8
Helixi328 – 332Combined sources5
Helixi340 – 352Combined sources13
Helixi363 – 365Combined sources3
Helixi369 – 371Combined sources3
Turni372 – 374Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PV0X-ray3.30A/B/C1-386[»]
2PVCX-ray3.69A/B/C1-386[»]
2QRVX-ray2.89B/C/F/G160-386[»]
4U7PX-ray3.82B178-379[»]
4U7TX-ray2.90B/D178-379[»]
5YX2X-ray2.65B/C178-385[»]
6BRRX-ray2.97B/C178-386[»]
6F57X-ray3.10B/C178-386[»]
ProteinModelPortaliQ9UJW3
SMRiQ9UJW3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UJW3

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 173ADDPROSITE-ProRule annotationAdd BLAST133

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri52 – 82GATA-type; atypicalPROSITE-ProRule annotationAdd BLAST31
Zinc fingeri93 – 149PHD-type; atypicalPROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IIXK Eukaryota
ENOG4111C55 LUCA
GeneTreeiENSGT00390000008341
HOGENOMiHOG000246422
HOVERGENiHBG051382
InParanoidiQ9UJW3
KOiK17400
OMAiHTQHPLF
OrthoDBiEOG091G08YY
TreeFamiTF329039

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR025766 ADD
IPR030486 DNMT3L
IPR011011 Znf_FYVE_PHD
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR23068:SF13 PTHR23068:SF13, 1 hit
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS51533 ADD, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Other splice isoforms seem to exist.
Isoform 1 (identifier: Q9UJW3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAAIPALDPE AEPSMDVILV GSSELSSSVS PGTGRDLIAY EVKANQRNIE
60 70 80 90 100
DICICCGSLQ VHTQHPLFEG GICAPCKDKF LDALFLYDDD GYQSYCSICC
110 120 130 140 150
SGETLLICGN PDCTRCYCFE CVDSLVGPGT SGKVHAMSNW VCYLCLPSSR
160 170 180 190 200
SGLLQRRRKW RSQLKAFYDR ESENPLEMFE TVPVWRRQPV RVLSLFEDIK
210 220 230 240 250
KELTSLGFLE SGSDPGQLKH VVDVTDTVRK DVEEWGPFDL VYGATPPLGH
260 270 280 290 300
TCDRPPSWYL FQFHRLLQYA RPKPGSPRPF FWMFVDNLVL NKEDLDVASR
310 320 330 340 350
FLEMEPVTIP DVHGGSLQNA VRVWSNIPAI RSRHWALVSE EELSLLAQNK
360 370 380
QSSKLAAKWP TKLVKNCFLP LREYFKYFST ELTSSL
Length:386
Mass (Da):43,583
Last modified:May 31, 2011 - v3
Checksum:i65EC2AB7492D53B3
GO
Isoform 2 (identifier: Q9UJW3-2) [UniParc]FASTAAdd to basket

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

Show »
Length:387
Mass (Da):43,670
Checksum:i699AAC1929D473A9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246P → A in AAF05812 (PubMed:10857753).Curated1
Sequence conflicti266L → F in AAF05812 (PubMed:10857753).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051962278R → G1 PublicationCorresponds to variant dbSNP:rs7354779Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041295332S → SS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS13705.1 [Q9UJW3-2]
CCDS46650.1 [Q9UJW3-1]
RefSeqiNP_037501.2, NM_013369.3 [Q9UJW3-2]
NP_787063.1, NM_175867.2 [Q9UJW3-1]
UniGeneiHs.592165

Genome annotation databases

EnsembliENST00000270172; ENSP00000270172; ENSG00000142182 [Q9UJW3-2]
ENST00000628202; ENSP00000486001; ENSG00000142182 [Q9UJW3-1]
GeneIDi29947
KEGGihsa:29947
UCSCiuc002zeg.3 human [Q9UJW3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDNM3L_HUMAN
AccessioniPrimary (citable) accession number: Q9UJW3
Secondary accession number(s): E9PB42, Q9BUJ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 31, 2011
Last modified: June 20, 2018
This is version 153 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health