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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
    		Compare labs
    Aminoglycoside antibacterials response
    MedGen: CN184091 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
    		Compare labs
    Aminoglycoside-induced deafness
    MedGen: C1838854 OMIM: 580000 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial, Genetic Hearing Loss Overview
    		Compare labs
    Gentamicin response
    MedGen: CN184225 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
    		Compare labs
    Kanamycin response
    MedGen: CN184547 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
    		Compare labs
    Streptomycin response
    MedGen: C1154708 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
    		Compare labs
    Tobramycin response
    MedGen: CN184545 GeneReviews: Nonsyndromic Hearing Loss and Deafness, Mitochondrial
    		Compare labs
    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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    NEW Try the new Transcript table

    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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