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Protein

DNA (cytosine-5)-methyltransferase 3-like

Gene

DNMT3L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 DNMT3.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri52 – 8231GATA-type; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 14957PHD-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • enzyme activator activity Source: MGI
  • enzyme binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • DNA methylation Source: UniProtKB
  • DNA methylation on cytosine Source: Reactome
  • gene expression Source: Reactome
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of catalytic activity Source: GOC
  • regulation of gene expression, epigenetic Source: Reactome
  • regulation of gene expression by genetic imprinting Source: UniProtKB
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_268237. 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
ProteomesiUP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:2980. DNMT3L.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi261 – 2611F → A: Loss of binding to DNMT3A. 1 Publication

Organism-specific databases

PharmGKBiPA27447.

Polymorphism and mutation databases

BioMutaiDNMT3L.
DMDMi334302913.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 386386DNA (cytosine-5)-methyltransferase 3-likePRO_0000088047Add
BLAST

Proteomic databases

PaxDbiQ9UJW3.
PRIDEiQ9UJW3.

PTM databases

PhosphoSiteiQ9UJW3.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9UJW3.
CleanExiHS_DNMT3L.
ExpressionAtlasiQ9UJW3. baseline.
GenevisibleiQ9UJW3. HS.

Organism-specific databases

HPAiHPA066780.

Interactioni

Subunit structurei

Homodimer. Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with histone H3 (via N-terminus).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC1Q135473EBI-740967,EBI-301834
RSL24D1Q9UHA34EBI-740967,EBI-749321

Protein-protein interaction databases

BioGridi118984. 12 interactions.
DIPiDIP-35238N.
IntActiQ9UJW3. 7 interactions.
MINTiMINT-1448248.
STRINGi9606.ENSP00000270172.

Structurei

Secondary structure

1
386
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi35 – 439Combined sources
Helixi49 – 513Combined sources
Turni54 – 563Combined sources
Beta strandi66 – 716Combined sources
Helixi74 – 818Combined sources
Turni82 – 854Combined sources
Beta strandi89 – 935Combined sources
Turni97 – 993Combined sources
Helixi119 – 1257Combined sources
Helixi130 – 1367Combined sources
Turni143 – 1453Combined sources
Beta strandi154 – 1563Combined sources
Helixi160 – 17112Combined sources
Helixi184 – 1863Combined sources
Beta strandi192 – 1976Combined sources
Turni200 – 2078Combined sources
Beta strandi218 – 2225Combined sources
Helixi224 – 2263Combined sources
Helixi229 – 2346Combined sources
Beta strandi239 – 2446Combined sources
Turni248 – 2503Combined sources
Helixi257 – 27014Combined sources
Beta strandi281 – 2866Combined sources
Helixi292 – 30211Combined sources
Beta strandi308 – 3103Combined sources
Beta strandi314 – 3163Combined sources
Beta strandi322 – 3254Combined sources
Beta strandi327 – 3315Combined sources
Helixi340 – 35112Combined sources
Helixi362 – 3654Combined sources
Helixi369 – 3735Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ9UJW3.
SMRiQ9UJW3. Positions 34-380.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UJW3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 173133ADDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 ADD domain.PROSITE-ProRule annotation
Contains 1 GATA-type zinc finger.PROSITE-ProRule annotation
Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri52 – 8231GATA-type; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 14957PHD-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG69419.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000246422.
HOVERGENiHBG051382.
InParanoidiQ9UJW3.
KOiK17400.
OMAiTVPVWKR.
TreeFamiTF329039.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR025766. ADD.
IPR030486. DNMT3L.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR23068:SF5. PTHR23068:SF5. 1 hit.
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti246 – 2461P → A in AAF05812 (PubMed:10857753).Curated
Sequence conflicti266 – 2661L → F in AAF05812 (PubMed:10857753).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti278 – 2781R → G.1 Publication
Corresponds to variant rs7354779 [ dbSNP | Ensembl ].
VAR_051962

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei332 – 3321S → SS in isoform 2. 1 PublicationVSP_041295

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]
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.2. human. [Q9UJW3-1]
uc002zeh.2. human. [Q9UJW3-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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]
RefSeqiNP_037501.2. NM_013369.3. [Q9UJW3-2]
NP_787063.1. NM_175867.2. [Q9UJW3-1]
UniGeneiHs.592165.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ9UJW3.
SMRiQ9UJW3. Positions 34-380.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118984. 12 interactions.
DIPiDIP-35238N.
IntActiQ9UJW3. 7 interactions.
MINTiMINT-1448248.
STRINGi9606.ENSP00000270172.

Chemistry

BindingDBiQ9UJW3.
ChEMBLiCHEMBL3137291.

Protein family/group databases

REBASEi4636. M.HsaDnmt3L.

PTM databases

PhosphoSiteiQ9UJW3.

Polymorphism and mutation databases

BioMutaiDNMT3L.
DMDMi334302913.

Proteomic databases

PaxDbiQ9UJW3.
PRIDEiQ9UJW3.

Protocols and materials databases

DNASUi29947.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000270172; ENSP00000270172; ENSG00000142182. [Q9UJW3-2]
ENST00000628202; ENSP00000486001; ENSG00000142182. [Q9UJW3-1]
GeneIDi29947.
KEGGihsa:29947.
UCSCiuc002zeg.2. human. [Q9UJW3-1]
uc002zeh.2. human. [Q9UJW3-2]

Organism-specific databases

CTDi29947.
GeneCardsiGC21M045666.
HGNCiHGNC:2980. DNMT3L.
HPAiHPA066780.
MIMi606588. gene.
neXtProtiNX_Q9UJW3.
PharmGKBiPA27447.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG69419.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000246422.
HOVERGENiHBG051382.
InParanoidiQ9UJW3.
KOiK17400.
OMAiTVPVWKR.
TreeFamiTF329039.

Enzyme and pathway databases

ReactomeiREACT_268237. DNA methylation.

Miscellaneous databases

ChiTaRSiDNMT3L. human.
EvolutionaryTraceiQ9UJW3.
GeneWikiiDNMT3L.
GenomeRNAii29947.
NextBioi52621.
PROiQ9UJW3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UJW3.
CleanExiHS_DNMT3L.
ExpressionAtlasiQ9UJW3. baseline.
GenevisibleiQ9UJW3. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR025766. ADD.
IPR030486. DNMT3L.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR23068:SF5. PTHR23068:SF5. 1 hit.
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiDNM3L_HUMAN
AccessioniPrimary (citable) accession number: Q9UJW3
Secondary accession number(s): E9PB42, Q9BUJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 31, 2011
Last modified: June 24, 2015
This is version 128 of the entry and version 3 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.