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TRMU tRNA mitochondrial 2-thiouridylase [ Homo sapiens (human) ]

Gene ID: 55687, updated on 5-Mar-2024

Summary

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Official Symbol
TRMUprovided by HGNC
Official Full Name
tRNA mitochondrial 2-thiouridylaseprovided by HGNC
Primary source
HGNC:HGNC:25481
See related
Ensembl:ENSG00000100416 MIM:610230; AllianceGenome:HGNC:25481
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MTO2; MTU1; TRMT; LCAL3; TRMT1
Summary
This nuclear gene encodes a mitochondrial tRNA-modifying enzyme. The encoded protein catalyzes the 2-thiolation of uridine on the wobble positions of tRNA(Lys), tRNA(Glu), and tRNA(Gln), resulting in the formation of 5-taurinomethyl-2-thiouridine moieties. Mutations in this gene may cause transient infantile liver failure. Polymorphisms in this gene may also influence the severity of deafness caused by mitochondrial 12S ribosomal RNA mutations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
Expression
Ubiquitous expression in spleen (RPKM 4.2), skin (RPKM 3.8) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
22q13.31
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (46335714..46357340)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (46820411..46842039)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (46731611..46753237)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19234 Neighboring gene GTSE1 divergent transcript Neighboring gene G2 and S-phase expressed 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr22:46718535-46719734 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:46731701-46732200 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46757719-46758220 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46758221-46758720 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19236 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:46772879-46774078 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46777489-46777988 Neighboring gene cadherin EGF LAG seven-pass G-type receptor 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:46780176-46780359 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:46782038-46783237 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46787203-46788025 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46805763-46806264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13911 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19238 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19237 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46838653-46839604 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46849165-46849747 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46849748-46850331 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46851429-46851929 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:46858535-46859734 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46867173-46867992 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:46868263-46868432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46875081-46875610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19239 Neighboring gene family with sequence similarity 136 member A pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46896241-46897215 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46903004-46903964 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46907166-46907666 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:46910168-46911084 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46913033-46913798 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr22:46918799-46919299 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:46924113-46924614 Neighboring gene VISTA enhancer hs1924 Neighboring gene long intergenic non-protein coding RNA 2925

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. TRMU Deficiency. Adam MP, et al. , 1993. PMID 37184193
  2. Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants. Vogel GF, et al. Genet Med, 2023 Jun. PMID 36305855
  3. Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients. Chen C, et al. Hum Mol Genet, 2022 Sep 10. PMID 35467742
  4. TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation. Murali CN, et al. Mol Genet Metab, 2021 Feb. PMID 33485800, Free PMC Article
  5. Biochemical Evidence for a Nuclear Modifier Allele (A10S) in TRMU (Methylaminomethyl-2-thiouridylate-methyltransferase) Related to Mitochondrial tRNA Modification in the Phenotypic Manifestation of Deafness-associated 12S rRNA Mutation. Meng F, et al. J Biol Chem, 2017 Feb 17. PMID 28049726, Free PMC Article

See all (40) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Pathological mutations promote proteolysis of mitochondrial tRNA-specific 2-thiouridylase 1 (MTU1) via mitochondrial caseinolytic peptidase (CLPP).
    Title: Pathological mutations promote proteolysis of mitochondrial tRNA-specific 2-thiouridylase 1 (MTU1) via mitochondrial caseinolytic peptidase (CLPP).
  2. Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.
    Title: Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.
  3. Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients.
    Title: Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients.
  4. Mtu1 defects are correlated with reduced osteogenic differentiation.
    Title: Mtu1 defects are correlated with reduced osteogenic differentiation.
  5. TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.
    Title: TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.
  6. Heteroplasmic transition of A to G at position 1555 of MT-RNR1 gene was identified in all affected individuals co-existing with nuclear c.28G>T (p.A10S) variant in the TRMU gene, only in some patients with hereditary non-syndromic hearing loss of variable severity.
    Title: Whole exome sequencing identifies both nuclear and mitochondrial variations in an Iranian family with non-syndromic hearing loss.
  7. The A10S mutation caused marked decreases in 2-thiouridine modification of U34 of tRNA(Lys), tRNA(Glu) and tRNA(Gln) However, the A10S mutation mildly increased the aminoacylated efficiency of tRNAs
    Title: Biochemical Evidence for a Nuclear Modifier Allele (A10S) in TRMU (Methylaminomethyl-2-thiouridylate-methyltransferase) Related to Mitochondrial tRNA Modification in the Phenotypic Manifestation of Deafness-associated 12S rRNA Mutation.
  8. Results show that post-transcriptional expression of GTPBP3, MTO1 and TRMU genes is down-regulated, leading to mt-tRNA hypomodification and contributing to mitochondrial dysfunction in MELAS cybrids.
    Title: The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.
  9. An additional, heterozygous mutation was detected in TRMU/MTU1. Although subject myoblasts and myotubes contained half the normal levels of TRMU, thiolation of mitochondrial tRNAs was normal.
    Title: A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia.
  10. MTU1 is not required for mitochondrial translation.
    Title: The 2-thiouridylase function of the human MTU1 (TRMU) enzyme is dispensable for mitochondrial translation.
Submit: New GeneRIF Correction See all GeneRIFs (19)

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

Associated conditions

Description Tests
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
MedGen: C3278664 OMIM: 613070 GeneReviews: TRMU Deficiency
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Aminoglycoside antibacterials response
MedGen: CN184091 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
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Aminoglycoside-induced deafness
MedGen: C1838854 OMIM: 580000 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial, Genetic Hearing Loss Overview
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Gentamicin response
MedGen: CN184225 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
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Kanamycin response
MedGen: CN184547 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
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Streptomycin response
MedGen: C1154708 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
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Tobramycin response
MedGen: CN184545 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
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Aminoglycoside-induced deafness
MedGen: C1838854 OMIM: 580000 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial, Genetic Hearing Loss Overview
Compare labs

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

  • MGC99627

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables tRNA binding IEA
Inferred from Electronic Annotation
more info
  
enables tRNA-5-taurinomethyluridine 2-sulfurtransferase IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in tRNA wobble position uridine thiolation IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
mitochondrial tRNA-specific 2-thiouridylase 1
Names
MTO2 homolog
lung cancer associated lncRNA 3
mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase
tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase
NP_001269711.1
NP_001269712.1
NP_001269713.1
NP_001269714.1
NP_060476.2
XP_011528574.1
XP_011528575.1
XP_047297400.1
XP_047297401.1
XP_047297402.1
XP_054181765.1
XP_054181766.1
XP_054181767.1
XP_054181768.1
XP_054181769.1

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.

Genomic

  1. NG_012173.1 RefSeqGene

    Range
    5314..26940
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001282782.2 → NP_001269711.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform d

    See identical proteins and their annotated locations for NP_001269711.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the 5' coding region and initiates translation at an alternate downstream start codon, compared to variant 1. The encoded isoform (d) is shorter and has a distinct N-terminus, compared to isoform a.
    Source sequence(s)
    BC066593, DQ309999
    UniProtKB/TrEMBL
    Q2PPL5
    Conserved Domains (1) summary
    cd01998
    Location:5 → 269
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...

  2. NM_001282783.2 → NP_001269712.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform e

    See identical proteins and their annotated locations for NP_001269712.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains multiple differences in the coding region, including initiation of translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (e) is shorter than isoform a.
    Source sequence(s)
    AL031588, AY062123, BC027991, BC066593
    UniProtKB/Swiss-Prot
    O75648
    Conserved Domains (1) summary
    cd01998
    Location:37 → 243
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...

  3. NM_001282784.2 → NP_001269713.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains multiple differences in the coding region, including initiation of translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (f) is shorter and has a distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AL031588, AY062123, BC066593, DQ310000
    UniProtKB/Swiss-Prot
    O75648
    UniProtKB/TrEMBL
    Q2PPL4
    Conserved Domains (1) summary
    cl00292
    Location:37 → 204
    AANH_like; Adenine nucleotide alpha hydrolases superfamily including N type ATP PPases, ATP sulphurylases Universal Stress Response protein and electron transfer flavoprotein (ETF). The domain forms a apha/beta/apha fold which binds to Adenosine nucleotide.

  4. NM_001282785.2 → NP_001269714.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform g

    See identical proteins and their annotated locations for NP_001269714.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (g) is shorter and has a distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AY062123, BC066593, CR456445
    Consensus CDS
    CCDS63510.1
    UniProtKB/TrEMBL
    A0A2R8Y6L6
    Related
    ENSP00000370407.3, ENST00000381019.3
    Conserved Domains (2) summary
    cd01998
    Location:6 → 344
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...
    pfam03054
    Location:5 → 344
    tRNA_Me_trans; tRNA methyl transferase

  5. NM_018006.5 → NP_060476.2  mitochondrial tRNA-specific 2-thiouridylase 1 isoform a

    See identical proteins and their annotated locations for NP_060476.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AY062123, BC066593
    Consensus CDS
    CCDS14075.1
    UniProtKB/Swiss-Prot
    A8K3U7, O75648, Q05C99, Q5W9C8, Q66K31, Q6ICC3, Q9NWC1
    Related
    ENSP00000496496.1, ENST00000645190.1
    Conserved Domains (2) summary
    cd01998
    Location:6 → 383
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...
    pfam03054
    Location:5 → 383
    tRNA_Me_trans; tRNA methyl transferase

RNA

  1. NR_104240.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site at an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AK000212, AK001002, BC066593, CN365141
    Related
    ENST00000457572.5

  2. NR_104241.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an internal exon and uses an alternate splice site at an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    BC066593, DQ309998
    Related
    ENST00000453630.5

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_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    46335714..46357340
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011530272.3 → XP_011528574.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X1

    Conserved Domains (1) summary
    cd01998
    Location:6 → 258
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...

  2. XM_011530273.3 → XP_011528575.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X2

    Conserved Domains (1) summary
    cd01998
    Location:6 → 258
    tRNA_Me_trans; tRNA methyl transferase. This family represents tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine present in the wobble position of some tRNAs. ...

  3. XM_047441445.1 → XP_047297401.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X4

  4. XM_047441444.1 → XP_047297400.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X3

  5. XM_047441446.1 → XP_047297402.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    46820411..46842039
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325790.1 → XP_054181765.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X1

  2. XM_054325791.1 → XP_054181766.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X2

  3. XM_054325793.1 → XP_054181768.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X4

  4. XM_054325792.1 → XP_054181767.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X3

  5. XM_054325794.1 → XP_054181769.1  mitochondrial tRNA-specific 2-thiouridylase 1 isoform X5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001008569.2: Suppressed sequence

    Description
    NM_001008569.2: This RefSeq was permanently suppressed because it is based on DQ309999 which is a nonsense-mediated mRNA decay (NMD) candidate and the related publication with PMID 16513084 does not provide functional evidence.

  2. NM_001008571.2: Suppressed sequence

    Description
    NM_001008571.2: This RefSeq was permanently suppressed because it is based on BC027991.1 which is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75648.2 GenPept UniProtKB/Swiss-Prot:O75648

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