DNMT3L

Protein identityUniProt · HPA

UniProt accession

Q9UJW3

Gene

DNMT3L

Ensembl

ENSG00000142182

Chromosome

21

Canonical length

386 aa

Protein class

Metabolic proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nuclear speckles

Quaternary structure

Homodimer

OverviewNCBI Gene

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a nuclear protein with similarity to DNA methyltransferases, but is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, it does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

Canonical amino-acid sequenceUniProt

386 residues, UniProt reviewed canonical sequence.

>Q9UJW3|DNMT3L
     1  MAAIPALDPE AEPSMDVILV GSSELSSSVS PGTGRDLIAY EVKANQRNIE DICICCGSLQ
    61  VHTQHPLFEG GICAPCKDKF LDALFLYDDD GYQSYCSICC SGETLLICGN PDCTRCYCFE
   121  CVDSLVGPGT SGKVHAMSNW VCYLCLPSSR SGLLQRRRKW RSQLKAFYDR ESENPLEMFE
   181  TVPVWRRQPV RVLSLFEDIK KELTSLGFLE SGSDPGQLKH VVDVTDTVRK DVEEWGPFDL
   241  VYGATPPLGH TCDRPPSWYL FQFHRLLQYA RPKPGSPRPF FWMFVDNLVL NKEDLDVASR
   301  FLEMEPVTIP DVHGGSLQNA VRVWSNIPAI RSRHWALVSE EELSLLAQNK QSSKLAAKWP
   361  TKLVKNCFLP LREYFKYFST ELTSSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DNMT3L can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

1.8 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.3

gnomAD pLI

0

gnomAD missense Z

0.1

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autosome genomic imprinting
• chorionic trophoblast cell differentiation
• DNA methylation-dependent constitutive heterochromatin formation
• epigenetic programing of female pronucleus
• genomic imprinting
• male meiosis I
• methylation
• negative regulation of DNA methylation-dependent heterochromatin formation
• negative regulation of DNA-templated transcription
• negative regulation of gene expression via chromosomal CpG island methylation
• negative regulation of gene expression, epigenetic
• oocyte development
• placenta development
• post-embryonic development
• spermatogenesis
• stem cell differentiation
• transposable element silencing by heterochromatin formation
• transposable element silencing by piRNA-mediated DNA methylation

Molecular functions

• enzyme activator activity
• enzyme binding
• zinc ion binding

Cellular components

• catalytic complex
• condensed nuclear chromosome
• cytoplasm
• cytosol
• ESC/E(Z) complex
• heterochromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Zinc finger, FYVE/PHD-type
• Zinc finger, RING/FYVE/PHD-type
• ADD domain
• S-adenosyl-L-methionine-dependent methyltransferase superfamily
• DNMT3, cysteine rich ADD domain, GATA1-like zinc finger
• DNMT3, ADD domain, PHD zinc finger
• DNA Cytosine-5 Methyltransferase
• DNMT3, cysteine rich ADD domain, GATA1-like zinc finger
• DNMT3, ADD PHD zinc finger

KeywordsUniProt

• Differentiation
• Metal-binding
• Nucleus
• Spermatogenesis
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of DNMT3L in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EZH2
• SPOCD1
• HDAC1