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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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