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    METTL6 methyltransferase 6, tRNA N3-cytidine [ Homo sapiens (human) ]

    Gene ID: 131965, updated on 5-Mar-2024

    Summary

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    Official Symbol
    METTL6provided by HGNC
    Official Full Name
    methyltransferase 6, tRNA N3-cytidineprovided by HGNC
    Primary source
    HGNC:HGNC:28343
    See related
    Ensembl:ENSG00000206562 MIM:618903; AllianceGenome:HGNC:28343
    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
    hMETTL6
    Summary
    Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in testis (RPKM 1.5), brain (RPKM 1.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3p25.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (15381275..15427643, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (15383684..15430055, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (15451267..15469051, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124909348 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14106 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19531 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19532 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19533 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:15469022-15469185 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19534 Neighboring gene RNA, U6 small nuclear 1024, pseudogene Neighboring gene ELL associated factor 1 Neighboring gene collagen like tail subunit of asymmetric acetylcholinesterase Neighboring gene microRNA 4270

    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
    • 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. Structural basis for METTL6-mediated m3C RNA methylation. Li S, et al. Biochem Biophys Res Commun, 2022 Jan 22. PMID 34922197
    2. Crystal structure of human METTL6, the m(3)C methyltransferase. Chen R, et al. Commun Biol, 2021 Dec 3. PMID 34862464, Free PMC Article
    3. A tRNA methyltransferase paralog is important for ribosome stability and cell division in Trypanosoma brucei. Fleming IM, et al. Sci Rep, 2016 Feb 18. PMID 26888608, Free PMC Article
    4. METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth. Ignatova VV, et al. Sci Adv, 2020 Aug. PMID 32923617, Free PMC Article
    5. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Mao XL, et al. Nucleic Acids Res, 2021 Aug 20. PMID 34268557, Free PMC Article

    See all (21) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth.
      Title: METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth.
    2. Structural basis for METTL6-mediated m3C RNA methylation.
      Title: Structural basis for METTL6-mediated m3C RNA methylation.
    3. Crystal structure of human METTL6, the m(3)C methyltransferase.
      Title: Crystal structure of human METTL6, the m(3)C methyltransferase.
    4. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6.
      Title: Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6.
    5. Data, including data from studies using mutant/knockout mice and cell lines from such mice, suggest that METTL2 and METTL6 (but not METTL8) contribute to post-transcriptional methylation of cytidine (formation of 3-methylcytidine) in tRNA; METTL2 methylates tRNA(Thr) and tRNA(Arg); METTL6 interacts with seryl-tRNA synthetase and methylates tRNA(Ser); METTL8 catalyzes post-transcriptional methylation of cytidine in mRNA.
      Title: Three distinct 3-methylcytidine (m(3)C) methyltransferases modify tRNA and mRNA in mice and humans.
    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
    Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish.
    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC24132

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables tRNA (cytidine-3-)-methyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in tRNA methylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tRNA modification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    tRNA N(3)-methylcytidine methyltransferase METTL6
    Names
    methyltransferase 6, RNA N3-cytidine
    methyltransferase 6, methylcytidine
    methyltransferase like 6
    methyltransferase-like protein 6
    NP_001288719.1
    NP_001288720.1
    NP_001288721.1
    NP_001317591.1
    NP_689609.2
    XP_005264924.1
    XP_006713033.1
    XP_006713035.1
    XP_011531659.1
    XP_016861207.1
    XP_016861208.1
    XP_016861212.1
    XP_016861213.1
    XP_047303406.1
    XP_047303407.1
    XP_047303408.1
    XP_047303409.1
    XP_047303410.1
    XP_047303411.1
    XP_047303412.1
    XP_054201222.1
    XP_054201223.1
    XP_054201224.1
    XP_054201225.1
    XP_054201226.1
    XP_054201227.1
    XP_054201228.1
    XP_054201229.1
    XP_054201230.1
    XP_054201231.1
    XP_054201232.1
    XP_054201233.1
    XP_054201234.1
    XP_054201235.1
    XP_054201236.1

    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_001301790.2 → NP_001288719.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform 2

      See identical proteins and their annotated locations for NP_001288719.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC027125, AK293370, BG701912, CX872865, Z44406
      Consensus CDS
      CCDS77706.1
      UniProtKB/TrEMBL
      B4DDX3
      Related
      ENSP00000410726.2, ENST00000450816.6
      Conserved Domains (1) summary
      cd02440
      Location:70 → 142
      AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

    2. NM_001301791.2 → NP_001288720.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) contains multiple coding region differences, including an alternate 3' terminal exon, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC027125, BG701912, BU183521, CA430635
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 178
      Methyltransf_12; Methyltransferase domain

    3. NM_001301792.2 → NP_001288721.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and lacks an exon in the 3' coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (4) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC027125, BC022400, BG701912, BI913767, CX872865, Z44406
      UniProtKB/Swiss-Prot
      Q8TCB7
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 177
      Methyltransf_12; Methyltransferase domain

    4. NM_001330662.2 → NP_001317591.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform 5

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains an alternate exon in the 3' coding region and includes an alternate 3' terminal exon, compared to variant 1. It encodes isoform 5, which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC027125, BX114702
      Consensus CDS
      CCDS87051.1
      UniProtKB/Swiss-Prot
      Q8TCB7
      Related
      ENSP00000373299.5, ENST00000383789.9
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 178
      Methyltransf_12; Methyltransferase domain

    5. NM_152396.4 → NP_689609.2  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform 1

      See identical proteins and their annotated locations for NP_689609.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC027125, BC022400, BG701912, CX872865, Z44406
      Consensus CDS
      CCDS43056.1
      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4
      Related
      ENSP00000373300.3, ENST00000383790.8
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 182
      Methyltransf_12; Methyltransferase domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      15381275..15427643 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017005719.2 → XP_016861208.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X3

      UniProtKB/TrEMBL
      B4DDX3
      Conserved Domains (1) summary
      cd02440
      Location:70 → 142
      AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

    2. XM_017005723.2 → XP_016861212.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X9

      Conserved Domains (1) summary
      cd02440
      Location:70 → 132
      AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

    3. XM_005264867.5 → XP_005264924.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      See identical proteins and their annotated locations for XP_005264924.1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4
      Related
      ENSP00000407613.1, ENST00000443029.5
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 182
      Methyltransf_12; Methyltransferase domain

    4. XM_006712972.5 → XP_006713035.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X4

      Conserved Domains (1) summary
      pfam08242
      Location:84 → 178
      Methyltransf_12; Methyltransferase domain

    5. XM_047447450.1 → XP_047303406.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4

    6. XM_017005718.3 → XP_016861207.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 182
      Methyltransf_12; Methyltransferase domain

    7. XM_047447456.1 → XP_047303412.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X11

    8. XM_011533357.4 → XP_011531659.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X5

      Conserved Domains (1) summary
      pfam08242
      Location:84 → 178
      Methyltransf_12; Methyltransferase domain

    9. XM_006712970.5 → XP_006713033.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      See identical proteins and their annotated locations for XP_006713033.1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4
      Conserved Domains (1) summary
      pfam08242
      Location:84 → 182
      Methyltransf_12; Methyltransferase domain

    10. XM_047447452.1 → XP_047303408.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X5

    11. XM_047447454.1 → XP_047303410.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X7

    12. XM_047447455.1 → XP_047303411.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X8

    13. XM_047447451.1 → XP_047303407.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X2

    14. XM_047447453.1 → XP_047303409.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X6

    15. XM_017005724.3 → XP_016861213.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X10

      Conserved Domains (1) summary
      pfam08242
      Location:84 → 178
      Methyltransf_12; Methyltransferase domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      15383684..15430055 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054345252.1 → XP_054201227.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X3

      UniProtKB/TrEMBL
      B4DDX3

    2. XM_054345259.1 → XP_054201234.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X9

    3. XM_054345247.1 → XP_054201222.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4

    4. XM_054345253.1 → XP_054201228.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X4

    5. XM_054345250.1 → XP_054201225.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4

    6. XM_054345249.1 → XP_054201224.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4

    7. XM_054345261.1 → XP_054201236.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X11

    8. XM_054345254.1 → XP_054201229.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X5

    9. XM_054345248.1 → XP_054201223.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X1

      UniProtKB/Swiss-Prot
      Q8TCB7, Q96LU4

    10. XM_054345255.1 → XP_054201230.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X5

    11. XM_054345257.1 → XP_054201232.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X7

    12. XM_054345258.1 → XP_054201233.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X8

    13. XM_054345251.1 → XP_054201226.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X2

    14. XM_054345256.1 → XP_054201231.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X6

    15. XM_054345260.1 → XP_054201235.1  tRNA N(3)-methylcytidine methyltransferase METTL6 isoform X10

    RNA

    1. XR_008486658.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TCB7.2 GenPept UniProtKB/Swiss-Prot:Q8TCB7

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