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METTL8 methyltransferase 8, tRNA N3-cytidine [ Homo sapiens (human) ]

Gene ID: 79828, updated on 14-Nov-2024

Summary

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Official Symbol
METTL8provided by HGNC
Official Full Name
methyltransferase 8, tRNA N3-cytidineprovided by HGNC
Primary source
HGNC:HGNC:25856
See related
Ensembl:ENSG00000123600 MIM:609525; AllianceGenome:HGNC:25856
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
TIP
Summary
Enables mRNA methyltransferase activity and tRNA (cytidine-3-)-methyltransferase activity. Involved in RNA metabolic process and positive regulation of mitochondrial translation. Is active in mitochondrial matrix. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in skin (RPKM 2.5), esophagus (RPKM 2.0) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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See METTL8 in Genome Data Viewer
Location:
2q31.1
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (171315746..171434772, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (171792877..171911912, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (172172256..172291282, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107983995 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:172100813-172102012 Neighboring gene uncharacterized LOC105373737 Neighboring gene small integral membrane protein 26-like Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:172172370-172173192 Neighboring gene Sharpr-MPRA regulatory region 707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16746 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:172174870-172175072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16747 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:172175660-172176482 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16748 Neighboring gene Sharpr-MPRA regulatory region 8774 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16749 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16750 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:172183340-172183864 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12100 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16751 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:172242874-172243458 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:172243459-172244043 Neighboring gene ribosomal protein S26 pseudogene 20 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12101 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16752 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16753 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16754 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16755 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16756 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr2:172289881-172290441 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:172291003-172291562 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:172303768-172303972 Neighboring gene DDB1 and CUL4 associated factor 17 Neighboring gene CRISPRi-validated cis-regulatory element chr2.5458 Neighboring gene death associated protein 3 pseudogene 2 Neighboring gene ribosomal protein S15 pseudogene 4

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. Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8. Huang MH, et al. Nucleic Acids Res, 2022 Apr 22. PMID 35357504, Free PMC Article
  2. Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs. Lentini JM, et al. J Biol Chem, 2022 Apr. PMID 35247384, Free PMC Article
  3. The RNA methyltransferase METTL8 installs m(3)C(32) in mitochondrial tRNAs(Thr/Ser(UCN)) to optimise tRNA structure and mitochondrial translation. Kleiber N, et al. Nat Commun, 2022 Jan 11. PMID 35017528, Free PMC Article
  4. METTL8 links mt-tRNA m(3)C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity. Lee BWL, et al. Cell Death Dis, 2024 May 14. PMID 38744809, Free PMC Article
  5. Balancing of mitochondrial translation through METTL8-mediated m(3)C modification of mitochondrial tRNAs. Schöller E, et al. Mol Cell, 2021 Dec 2. PMID 34774131, Free PMC Article

See all (23) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. METTL8 links mt-tRNA m[3]C modification to the HIF1alpha/RTK/Akt axis to sustain GBM stemness and tumorigenicity.
    Title: METTL8 links mt-tRNA m(3)C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity.
  2. Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.
    Title: Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.
  3. Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs.
    Title: Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs.
  4. The RNA methyltransferase METTL8 installs m(3)C32 in mitochondrial tRNAs(Thr/Ser(UCN)) to optimise tRNA structure and mitochondrial translation.
    Title: The RNA methyltransferase METTL8 installs m(3)C(32) in mitochondrial tRNAs(Thr/Ser(UCN)) to optimise tRNA structure and mitochondrial translation.
  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
Multiple loci influencing hippocampal degeneration identified by genome scan.
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)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ13334, FLJ13984, FLJ31054, FLJ42098, FLJ77788

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NOT enables mRNA methyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables mRNA methyltransferase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables tRNA (cytidine-3-)-methyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in mRNA metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mitochondrial tRNA modification IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of mitochondrial translation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tRNA C3-cytosine methylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
NOT is_active_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
NOT is_active_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial
Names
mRNA N(3)-methylcytidine methyltransferase METTL8
methyltransferase 8, methylcytidine
methyltransferase like 8
methyltransferase-like protein 8
tension-induced/inhibited protein
NP_001308083.1
NP_001308084.1
NP_001308085.1
NP_001308086.1
NP_001308087.1
NP_001308088.1
NP_001308089.1
NP_001308090.1
NP_001308091.1
NP_079046.2

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_001321154.2 → NP_001308083.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK024046, AK124092, BC025250, BM930105
    Consensus CDS
    CCDS2242.2
    UniProtKB/TrEMBL
    A0A9K3Y8H4, A8K7U3, B3KW44, D3DPD3, E7ETE0
    Related
    ENSP00000364407.4, ENST00000375258.9
    Conserved Domains (1) summary
    pfam13649
    Location:200 → 303
    Methyltransf_25; Methyltransferase domain

  2. NM_001321155.2 → NP_001308084.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK024046, AK124092, BC025250, BM930105
    Consensus CDS
    CCDS2242.2
    UniProtKB/TrEMBL
    A0A9K3Y8H4, A8K7U3, B3KW44, D3DPD3, E7ETE0
    Conserved Domains (1) summary
    pfam13649
    Location:200 → 303
    Methyltransf_25; Methyltransferase domain

  3. NM_001321156.2 → NP_001308085.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK124092, BM930105
    Consensus CDS
    CCDS2242.2
    UniProtKB/TrEMBL
    A0A9K3Y8H4, A8K7U3, B3KW44, D3DPD3, E7ETE0
    Conserved Domains (1) summary
    pfam13649
    Location:200 → 303
    Methyltransf_25; Methyltransferase domain

  4. NM_001321157.2 → NP_001308086.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 2 precursor

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK124092, AK297141, BC025250, BM930105
    UniProtKB/TrEMBL
    A8K7U3
    Conserved Domains (1) summary
    pfam13649
    Location:248 → 351
    Methyltransf_25; Methyltransferase domain

  5. NM_001321158.2 → NP_001308087.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 3

    Status: VALIDATED

    Source sequence(s)
    AC007739, AC008065, AK297141, BM930105
    UniProtKB/TrEMBL
    A8K7U3, B4DLT0
    Conserved Domains (1) summary
    pfam13649
    Location:155 → 258
    Methyltransf_25; Methyltransferase domain

  6. NM_001321159.2 → NP_001308088.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 4

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK124092, BC025250, BM930105
    UniProtKB/TrEMBL
    A8K7U3
    Conserved Domains (1) summary
    pfam13649
    Location:150 → 253
    Methyltransf_25; Methyltransferase domain

  7. NM_001321160.2 → NP_001308089.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 5

    Status: VALIDATED

    Source sequence(s)
    AC007739, AC008065, BC025250, BM930105
    Consensus CDS
    CCDS82532.1
    UniProtKB/Swiss-Prot
    Q53TM9, Q53TQ0, Q9H825
    Related
    ENSP00000376382.2, ENST00000392604.6
    Conserved Domains (1) summary
    pfam13649
    Location:200 → 286
    Methyltransf_25; Methyltransferase domain

  8. NM_001321161.2 → NP_001308090.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 6

    Status: VALIDATED

    Source sequence(s)
    AC007739, AC007969, AC008065, BM930105, KF459614
    Conserved Domains (1) summary
    pfam13649
    Location:155 → 241
    Methyltransf_25; Methyltransferase domain

  9. NM_001321162.2 → NP_001308091.1  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 7

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK024046, BM930105
    Consensus CDS
    CCDS82531.1
    UniProtKB/Swiss-Prot
    Q9H825
    Related
    ENSP00000409025.1, ENST00000447486.5
    Conserved Domains (1) summary
    pfam13649
    Location:150 → 236
    Methyltransf_25; Methyltransferase domain

  10. NM_024770.5 → NP_079046.2  tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial isoform 1

    See identical proteins and their annotated locations for NP_079046.2

    Status: VALIDATED

    Source sequence(s)
    AC007739, AK124092, AK292108, BM930105
    Consensus CDS
    CCDS2242.2
    UniProtKB/TrEMBL
    A0A9K3Y8H4, A8K7U3, B3KW44, D3DPD3, E7ETE0
    Related
    ENSP00000480056.1, ENST00000612742.5
    Conserved Domains (1) summary
    pfam13649
    Location:200 → 303
    Methyltransf_25; Methyltransferase domain

RNA

  1. NR_135568.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC007739, AC008065, BM930105, DB031573, KF459614

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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    171315746..171434772 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    171792877..171911912 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H825.2 GenPept UniProtKB/Swiss-Prot:Q9H825

Gene LinkOut

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