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METTL4 methyltransferase 4, N6-adenosine [ Homo sapiens (human) ]

Gene ID: 64863, updated on 2-Nov-2024

Summary

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Official Symbol
METTL4provided by HGNC
Official Full Name
methyltransferase 4, N6-adenosineprovided by HGNC
Primary source
HGNC:HGNC:24726
See related
Ensembl:ENSG00000101574 MIM:619626; AllianceGenome:HGNC:24726
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HsT661
Summary
Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in regulation of gene expression; regulation of mitochondrial DNA replication; and snRNA (adenine-N6)-methylation. Located in cytosol; mitochondrial matrix; and nucleus. Part of RNA N6-methyladenosine methyltransferase complex and oxidoreductase complex. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in lymph node (RPKM 4.0), thyroid (RPKM 3.9) and 25 other tissues See more
Orthologs
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Genomic context

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See METTL4 in Genome Data Viewer
Location:
18p11.32
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (2537530..2571505, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (2693282..2727252, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (2537529..2571504, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr18:2350584-2351783 Neighboring gene uncharacterized LOC105371961 Neighboring gene MPRA-validated peak3044 silencer Neighboring gene MPRA-validated peak3045 silencer Neighboring gene uncharacterized LOC124904235 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr18:2535575-2536114 Neighboring gene small nucleolar RNA U109 Neighboring gene ubiquitin-conjugating enzyme E2 variant 1-like Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:2570597-2571519 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr18:2589133-2590332 Neighboring gene NDC80 kinetochore complex component Neighboring gene katanin regulatory subunit B1 like 1 pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13024 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13026 Neighboring gene RNA, U6 small nuclear 340, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4. van den Homberg DAL, et al. Int J Mol Sci, 2022 Jan 19. PMID 35162982, Free PMC Article
  2. METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing. Goh YT, et al. Nucleic Acids Res, 2020 Sep 18. PMID 32813009, Free PMC Article
  3. N(6)-Deoxyadenosine Methylation in Mammalian Mitochondrial DNA. Hao Z, et al. Mol Cell, 2020 May 7. PMID 32183942, Free PMC Article
  4. METTL4 is an snRNA m(6)Am methyltransferase that regulates RNA splicing. Chen H, et al. Cell Res, 2020 Jun. PMID 31913360, Free PMC Article
  5. Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. Wang P, et al. Mol Cell, 2016 Jul 21. PMID 27373337, Free PMC Article

See all (15) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4.
    Title: N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4.
  2. METTL4 is an snRNA m(6)Am methyltransferase that regulates RNA splicing.
    Title: METTL4 is an snRNA m(6)Am methyltransferase that regulates RNA splicing.
  3. METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing.
    Title: METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing.
  4. N(6)-Deoxyadenosine Methylation in Mammalian Mitochondrial DNA.
    Title: N(6)-Deoxyadenosine Methylation in Mammalian Mitochondrial DNA.
  5. METTL4 methylates U2 snRNA Am at position 30 to generate m6Am in vivo. 'HMAGKD', where H = A/C/U, M = A/C, K = G/U, D = A/G/U, and A is the methylation site, is METTL4's in vivo preferred target motif.
    Title: METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing.
  6. For the methylation of adenosine in RNA, Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition.
    Title: Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases.
  7. associations revealed between genetic polymorphisms located in the flanking region of the ARID1B genes and hypoesthesia
    Title: Genome-wide association study of sensory disturbances in the inferior alveolar nerve after bilateral sagittal split ramus osteotomy.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

General gene information

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Markers

Homology

Clone Names

  • FLJ23017, MGC117235

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA methyltransferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA methyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables U2 snRNA 2'-O-methyladenosine m6 methyltransferase activity IEA
Inferred from Electronic Annotation
more info
  
enables nucleic acid binding IEA
Inferred from Electronic Annotation
more info
  
enables site-specific DNA-methyltransferase (adenine-specific) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables site-specific DNA-methyltransferase (adenine-specific) activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in mRNA modification IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in methylation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of gene expression, epigenetic ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of RNA splicing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of mitochondrial DNA replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of mitochondrial transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in snRNA (adenine-N6)-methylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of RNA N6-methyladenosine methyltransferase complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of oxidoreductase complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 

General protein information

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Preferred Names
N(6)-adenine-specific methyltransferase METTL4
Names
N(6)-adenine-specific DNA methyltransferase METTL4
methyltransferase like 4
methyltransferase-like protein 4
snRNA (2'-O-methyladenosine-N(6)-)-methyltransferase METTL4
NP_001295330.1
NP_073751.3
XP_005258189.1
XP_005258190.1
XP_011524032.1
XP_047293697.1
XP_047293698.1
XP_054174957.1
XP_054174958.1
XP_054174959.1
XP_054174960.1
XP_054174961.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001308401.2 → NP_001295330.1  N(6)-adenine-specific methyltransferase METTL4 isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 3' coding region, resulting in a frameshift compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.
    Source sequence(s)
    AP005136
    Consensus CDS
    CCDS77144.1
    UniProtKB/TrEMBL
    A8K1T6, J3KNJ7
    Related
    ENSP00000320349.6, ENST00000319888.10
    Conserved Domains (1) summary
    cl01947
    Location:281 → 383
    MT-A70

  2. NM_022840.5 → NP_073751.3  N(6)-adenine-specific methyltransferase METTL4 isoform 1

    See identical proteins and their annotated locations for NP_073751.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AP005136, BC111020, BU741018, HY026088
    Consensus CDS
    CCDS11826.1
    UniProtKB/Swiss-Prot
    B2RNA1, Q2TAA7, Q8N3J2, Q9H5U9
    UniProtKB/TrEMBL
    A8K1T6
    Related
    ENSP00000458290.1, ENST00000574538.2
    Conserved Domains (1) summary
    cl01947
    Location:281 → 455
    MT-A70

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    2537530..2571505 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005258133.4 → XP_005258190.1  N(6)-adenine-specific methyltransferase METTL4 isoform X4

    UniProtKB/TrEMBL
    I6L9E3
    Conserved Domains (1) summary
    cl01947
    Location:134 → 308
    MT-A70

  2. XM_011525730.4 → XP_011524032.1  N(6)-adenine-specific methyltransferase METTL4 isoform X3

    Conserved Domains (1) summary
    cl01947
    Location:281 → 300
    MT-A70

  3. XM_005258132.5 → XP_005258189.1  N(6)-adenine-specific methyltransferase METTL4 isoform X2

    Conserved Domains (1) summary
    cl01947
    Location:281 → 358
    MT-A70

  4. XM_047437741.1 → XP_047293697.1  N(6)-adenine-specific methyltransferase METTL4 isoform X1

  5. XM_047437742.1 → XP_047293698.1  N(6)-adenine-specific methyltransferase METTL4 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    2693282..2727252 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318985.1 → XP_054174960.1  N(6)-adenine-specific methyltransferase METTL4 isoform X4

  2. XM_054318984.1 → XP_054174959.1  N(6)-adenine-specific methyltransferase METTL4 isoform X3

  3. XM_054318983.1 → XP_054174958.1  N(6)-adenine-specific methyltransferase METTL4 isoform X2

  4. XM_054318982.1 → XP_054174957.1  N(6)-adenine-specific methyltransferase METTL4 isoform X1

  5. XM_054318986.1 → XP_054174961.1  N(6)-adenine-specific methyltransferase METTL4 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8N3J2.3 GenPept UniProtKB/Swiss-Prot:Q8N3J2

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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