METTL4 Gene (Protein Coding)

Methyltransferase Like 4

GC18M002527
GIFtS:
33
See more...

Aliases for METTL4 Gene

Aliases for METTL4 Gene

  • Methyltransferase Like 4 2 3 5
  • SnRNA (2'-O-Methyladenosine-N(6)-)-Methyltransferase METTL4 3 4
  • N(6)-Adenine-Specific DNA Methyltransferase METTL4 3 4
  • N(6)-Adenine-Specific Methyltransferase METTL4 3 4
  • Methyltransferase-Like Protein 4 3 4
  • HsT661 2 3
  • EC 2.1.1.72 4
  • EC 2.1.1.- 4
  • FLJ23017 2
  • METTL4 5

External Ids for METTL4 Gene

Previous GeneCards Identifiers for METTL4 Gene

  • GC18M002528

Summaries for METTL4 Gene

GeneCards Summary for METTL4 Gene

METTL4 (Methyltransferase Like 4) is a Protein Coding gene. Diseases associated with METTL4 include Chromosome 18P Deletion Syndrome and Facioscapulohumeral Muscular Dystrophy 2. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and methyltransferase activity.

UniProtKB/Swiss-Prot Summary for METTL4 Gene

  • N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA (PubMed:31913360). Acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA): methylates the 6th position of adenine residues with a pre-deposited 2'-O-methylation (PubMed:31913360). Internal m6A(m) methylation of snRNAs regulates RNA splicing (PubMed:31913360). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine), a modification that regulates Polycomb silencing (By similarity). N(6)-methyladenosine deposition by METTL4 triggers ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing (By similarity).

Additional gene information for METTL4 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for METTL4 Gene

Genomics for METTL4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for METTL4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around METTL4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for METTL4

Top Transcription factor binding sites by QIAGEN in the METTL4 gene promoter:
  • AML1a
  • Bach1
  • CREB
  • deltaCREB
  • GR
  • GR-alpha
  • IRF-1
  • ISGF-3
  • Pax-5
  • STAT5B

Genomic Locations for METTL4 Gene

Genomic Locations for METTL4 Gene
chr18:2,537,525-2,571,509
(GRCh38/hg38)
Size:
33,985 bases
Orientation:
Minus strand
chr18:2,537,524-2,571,508
(GRCh37/hg19)
Size:
33,985 bases
Orientation:
Minus strand

Genomic View for METTL4 Gene

Genes around METTL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
METTL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for METTL4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for METTL4 Gene

Proteins for METTL4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for METTL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N3J2-METL4_HUMAN
    Recommended name:
    N(6)-adenine-specific methyltransferase METTL4
    Protein Accession:
    Q8N3J2
    Secondary Accessions:
    • B2RNA1
    • Q2TAA7
    • Q9H5U9

    Protein attributes for METTL4 Gene

    Size:
    472 amino acids
    Molecular mass:
    54041 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAB15520.1; Type=Frameshift; Evidence={ECO:0000305};

neXtProt entry for METTL4 Gene

Protein Expression for METTL4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for METTL4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for METTL4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for METTL4 Gene

Domains & Families for METTL4 Gene

Gene Families for METTL4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for METTL4 Gene

InterPro:
Blocks:
  • N-6 Adenine-specific DNA methylase
  • MT-A70
ProtoNet:

Suggested Antigen Peptide Sequences for METTL4 Gene

GenScript: Design optimal peptide antigens:
  • Methyltransferase-like protein 4 (METL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N3J2

UniProtKB/Swiss-Prot:

METL4_HUMAN :
  • Belongs to the MT-A70-like family.
Family:
  • Belongs to the MT-A70-like family.
genes like me logo Genes that share domains with METTL4: view

Function for METTL4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for METTL4 Gene

UniProtKB/Swiss-Prot Function:
N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA (PubMed:31913360). Acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA): methylates the 6th position of adenine residues with a pre-deposited 2'-O-methylation (PubMed:31913360). Internal m6A(m) methylation of snRNAs regulates RNA splicing (PubMed:31913360). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine), a modification that regulates Polycomb silencing (By similarity). N(6)-methyladenosine deposition by METTL4 triggers ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a 2'-O-methyladenosine in U2 snRNA + S-adenosyl-L-methionine = an N(6)-methyl-2'-O-methyladenosine in U2 snRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:62672, Rhea:RHEA-COMP:16150, Rhea:RHEA-COMP:16151, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74477, ChEBI:CHEBI:145853; Evidence={ECO:0000269|PubMed:31913360};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=a 2'-deoxyadenosine in DNA + S-adenosyl-L-methionine = an N(6)-methyl-2'-deoxyadenosine in DNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:15197, Rhea:RHEA-COMP:12418, Rhea:RHEA-COMP:12419, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:90615, ChEBI:CHEBI:90616; EC=2.1.1.72; Evidence={ECO:0000250|UniProtKB:Q3U034};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.43 uM for U2 snRNA {ECO:0000269|PubMed:31913360};

Enzyme Numbers (IUBMB) for METTL4 Gene

Phenotypes From GWAS Catalog for METTL4 Gene

Gene Ontology (GO) - Molecular Function for METTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0008168 methyltransferase activity IBA 21873635
GO:0008173 RNA methyltransferase activity IDA 31913360
GO:0009007 site-specific DNA-methyltransferase (adenine-specific) activity IBA,ISS --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with METTL4: view
genes like me logo Genes that share phenotypes with METTL4: view

Animal Model Products

CRISPR Products

miRNA for METTL4 Gene

miRTarBase miRNAs that target METTL4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for METTL4

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for METTL4 Gene

Localization for METTL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for METTL4 Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for METTL4 gene
Compartment Confidence
nucleus 5
mitochondrion 2
extracellular 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for METTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 31913360
genes like me logo Genes that share ontologies with METTL4: view

Pathways & Interactions for METTL4 Gene

PathCards logo

SuperPathways for METTL4 Gene

No Data Available

Interacting Proteins for METTL4 Gene

Selected Interacting proteins: Q8N3J2-METL4_HUMAN for METTL4 Gene via IID

Symbol External ID(s) Details
SMCHD1
GPS-Prot Interaction Network for METTL4

Gene Ontology (GO) - Biological Process for METTL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001510 RNA methylation IEA --
GO:0006325 chromatin organization IEA --
GO:0032259 methylation IEA --
GO:0032775 DNA methylation on adenine ISS --
GO:0043484 regulation of RNA splicing IMP 31913360
genes like me logo Genes that share ontologies with METTL4: view

No data available for Pathways by source and SIGNOR curated interactions for METTL4 Gene

Drugs & Compounds for METTL4 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for METTL4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for METTL4 Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for METTL4

Alternative Splicing Database (ASD) splice patterns (SP) for METTL4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b
SP1:
SP2: - - -
SP3: - -
SP4: -
SP5:

Relevant External Links for METTL4 Gene

GeneLoc Exon Structure for
METTL4

Expression for METTL4 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for METTL4 Gene

mRNA expression in normal human tissues for METTL4 Gene
mRNA expression by GTEx for METTL4 GenemRNA expression by BioGPS for METTL4 Gene

Protein differential expression in normal tissues from HIPED for METTL4 Gene

This gene is overexpressed in Adipocyte (66.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for METTL4 Gene



Protein tissue co-expression partners for METTL4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for METTL4

SOURCE GeneReport for Unigene cluster for METTL4 Gene:

Hs.126888

Evidence on tissue expression from TISSUES for METTL4 Gene

  • Nervous system(4.3)
  • Lung(4.1)
genes like me logo Genes that share expression patterns with METTL4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for METTL4 Gene

Orthologs for METTL4 Gene

This gene was present in the common ancestor of animals.

Orthologs for METTL4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia METTL4 30 31
  • 99.29 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia METTL4 30 31
  • 88.96 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia METTL4 30 31
  • 86.99 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Mettl4 30 17 31
  • 80.78 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Mettl4 30
  • 80.64 (n)
Oppossum
(Monodelphis domestica)
 Mammalia METTL4 31
  • 64 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia METTL4 31
  • 62 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves METTL4 30 31
  • 67.62 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia METTL4 31
  • 52 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia mettl4 30
  • 61.3 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.19454 30
Zebrafish
(Danio rerio)
 Actinopterygii LOC560686 30
  • 55.62 (n)
METTL4 31
  • 42 (a)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta CG14906 30 31
  • 47.81 (n)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP008665 30
  • 47.33 (n)
Worm
(Caenorhabditis elegans)
 Secernentea C18A3.1 31
  • 28 (a)
 OneToOne
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 46 (a)
 OneToOne
Species where no ortholog for METTL4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for METTL4 Gene

ENSEMBL:
Gene Tree for METTL4 (if available)
TreeFam:
Gene Tree for METTL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for METTL4: view image

Paralogs for METTL4 Gene

No data available for Paralogs for METTL4 Gene

Variants for METTL4 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for METTL4 Gene

SNP ID Clinical significance and condition Chr 18 pos Variation AA Info Type
rs12606220 - p.Leu163Phe
rs2677879 - p.Gln310Lys
rs34143130 - p.Glu230Asp
rs8084295 - p.Val468Leu
VAR_064731 - p.Ser42Phe

Additional dbSNP identifiers (rs#s) for METTL4 Gene

Structural Variations from Database of Genomic Variants (DGV) for METTL4 Gene

Variant ID Type Subtype PubMed ID
esv2761986 CNV gain 21179565
esv3446409 CNV duplication 20981092
esv3641561 CNV loss 21293372
esv3641562 CNV gain 21293372
esv3893063 CNV loss 25118596
nsv1061548 CNV gain 25217958
nsv1065830 CNV gain 25217958
nsv1066735 CNV gain 25217958
nsv132209 CNV deletion 16902084
nsv482935 CNV loss 15286789
nsv576251 CNV gain 21841781
nsv576310 CNV gain 21841781
nsv576311 CNV gain 21841781

Variation tolerance for METTL4 Gene

Residual Variation Intolerance Score: 52.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.01; 80.10% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for METTL4 Gene

Human Gene Mutation Database (HGMD)
METTL4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
METTL4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for METTL4 Gene

Disorders for METTL4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for METTL4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
chromosome 18p deletion syndrome
  • 18p- syndrome
facioscapulohumeral muscular dystrophy 2
  • fshd2
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for METTL4

Genetic Association Database
(GAD)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with METTL4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for METTL4 Gene

Publications for METTL4 Gene

  1. METTL4 is an snRNA m6Am methyltransferase that regulates RNA splicing. (PMID: 31913360) Chen H … Shi Y (Cell research 2020) 2 3 4
  2. An Adversarial DNA N6-Methyladenine-Sensor Network Preserves Polycomb Silencing. (PMID: 30982744) Kweon SM … Feldman DE (Molecular cell 2019) 2 3
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. (PMID: 27373337) Wang P … Nam Y (Molecular cell 2016) 3

ExternalLinks

View latest publications for METTL4 gene in Mastermind

Products for METTL4 Gene

Sources for METTL4 Gene