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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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