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Protein

Mitochondrial tRNA-specific 2-thiouridylase 1

Gene

TRMU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base.3 Publications

Miscellaneous

During the reaction, ATP is used to activate the C2 atom of U34 by adenylation. After this, the persulfide sulfur on the catalytic cysteine is transferred to the C2 atom of the wobble base (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards the activated C2 atom on U34. Subsequently, a transient disulfide bond is formed between the two active site cysteine residues (By similarity).By similarity

Caution

Was originally thought to be a 5-methylaminomethyl-2-methyltransferase involved in tRNA modification.1 Publication

Catalytic activityi

A [protein]-S-sulfanyl-L-cysteine + 5-taurinomethyluridine(34) in tRNA + ATP + reduced acceptor = a [protein]-L-cysteine + 5-taurinomethyl-2-thiouridine(34) in tRNA + AMP + diphosphate + acceptor.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei36ATP; via amide nitrogen and carbonyl oxygenBy similarity1
Active sitei101NucleophileBy similarity1
Binding sitei126ATP; via amide nitrogenBy similarity1
Active sitei222Cysteine persulfide intermediateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17ATPBy similarity8

GO - Molecular functioni

GO - Biological processi

  • tRNA wobble position uridine thiolation Source: GO_Central

Keywordsi

Molecular functionRNA-binding, Transferase, tRNA-binding
Biological processtRNA processing
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000100416-MONOMER
BRENDAi2.1.1.61 2681
ReactomeiR-HSA-6787450 tRNA modification in the mitochondrion

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial tRNA-specific 2-thiouridylase 1 (EC:2.8.1.14By similarity)
Alternative name(s):
MTO2 homolog
Gene namesi
Name:TRMU
Synonyms:MTU1, TRMT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100416.12
HGNCiHGNC:25481 TRMU
MIMi610230 gene
neXtProtiNX_O75648

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Deafness, aminoglycoside-induced (DFNI)1 Publication
The gene represented in this entry acts as a disease modifier. DFNI is caused by mutations in mitochondrial rRNA genes, including homoplasmic A1555G and C1494T mutations in the highly conserved decoding site of the mitochondrial 12S rRNA. Mutated TRMU modulates the phenotypic manifestation of these mutations.1 Publication
Disease descriptionA form of sensorineural deafness characterized by moderate-to-profound hearing loss and mitochondrial inheritance. It is induced by exposure to aminoglycosides.
See also OMIM:580000
Liver failure, infantile, transient (LFIT)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA transient disorder of hepatic function characterized by elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, increased serum lactate. Patients who survive the initial acute episode can recover, show normal development and have no recurrence.
See also OMIM:613070
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06342977Y → H in LFIT. 1 PublicationCorresponds to variant dbSNP:rs118203990EnsemblClinVar.1
Natural variantiVAR_063430272G → D in LFIT. 1 PublicationCorresponds to variant dbSNP:rs118203991EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16D → A: Loss of activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi55687
MalaCardsiTRMU
MIMi580000 phenotype
613070 phenotype
OpenTargetsiENSG00000100416
Orphaneti217371 Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
254864 Mitochondrial myopathy with reversible cytochrome C oxidase deficiency
90641 Mitochondrial non-syndromic sensorineural deafness
168609 Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure
PharmGKBiPA142670701

Polymorphism and mutation databases

BioMutaiTRMU

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001217081 – 421Mitochondrial tRNA-specific 2-thiouridylase 1Add BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi101 ↔ 222By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiO75648
MaxQBiO75648
PaxDbiO75648
PeptideAtlasiO75648
PRIDEiO75648
ProteomicsDBi50138
50139 [O75648-2]
50140 [O75648-3]
50141 [O75648-4]
50142 [O75648-5]

PTM databases

iPTMnetiO75648
PhosphoSitePlusiO75648

Expressioni

Tissue specificityi

Ubiquitous. Abundantly expressed in tissues with high metabolic rates including heart, liver, kidney, and brain.1 Publication

Gene expression databases

BgeeiENSG00000100416 Expressed in 211 organ(s), highest expression level in adenohypophysis
CleanExiHS_TRMT1
HS_TRMU
ExpressionAtlasiO75648 baseline and differential
GenevisibleiO75648 HS

Organism-specific databases

HPAiHPA000824
HPA035273
HPA043300

Interactioni

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei127Interaction with tRNABy similarity1
Sitei267Interaction with tRNABy similarity1
Sitei367Interaction with tRNABy similarity1

Protein-protein interaction databases

BioGridi120814, 16 interactors
IntActiO75648, 2 interactors
STRINGi9606.ENSP00000290846

Structurei

3D structure databases

ProteinModelPortaliO75648
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni96 – 98Interaction with target base in tRNABy similarity3
Regioni171 – 173Interaction with tRNABy similarity3
Regioni334 – 335Interaction with tRNABy similarity2

Sequence similaritiesi

Belongs to the MnmA/TRMU family.Curated

Phylogenomic databases

eggNOGiKOG2805 Eukaryota
COG0482 LUCA
GeneTreeiENSGT00390000014323
HOVERGENiHBG108157
InParanoidiO75648
KOiK21027
OMAiAVCTGHY
OrthoDBiEOG091G0BKX
PhylomeDBiO75648
TreeFamiTF105611

Family and domain databases

CDDicd01998 tRNA_Me_trans, 1 hit
Gene3Di2.30.30.280, 1 hit
3.40.50.620, 1 hit
HAMAPiMF_00144 tRNA_thiouridyl_MnmA, 1 hit
InterProiView protein in InterPro
IPR023382 Adenine_a_hdrlase_dom
IPR014729 Rossmann-like_a/b/a_fold
IPR004506 tRNA-specific_2-thiouridylase
PANTHERiPTHR11933 PTHR11933, 1 hit
TIGRFAMsiTIGR00420 trmU, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O75648-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MQALRHVVCA LSGGVDSAVA ALLLRRRGYQ VTGVFMKNWD SLDEHGVCTA
60 70 80 90 100
DKDCEDAYRV CQILDIPFHQ VSYVKEYWND VFSDFLNEYE KGRTPNPDIV
110 120 130 140 150
CNKHIKFSCF FHYAVDNLGA DAIATGHYAR TSLEDEEVFE QKHVKKPEGL
160 170 180 190 200
FRNRFEVRNA VKLLQAADSF KDQTFFLSQV SQDALRRTIF PLGGLTKEFV
210 220 230 240 250
KKIAAENRLH HVLQKKESMG MCFIGKRNFE HFLLQYLQPR PGHFISIEDN
260 270 280 290 300
KVLGTHKGWF LYTLGQRANI GGLREPWYVV EKDSVKGDVF VAPRTDHPAL
310 320 330 340 350
YRDLLRTSRV HWIAEEPPAA LVRDKMMECH FRFRHQMALV PCVLTLNQDG
360 370 380 390 400
TVWVTAVQAV RALATGQFAV FYKGDECLGS GKILRLGPSA YTLQKGQRRA
410 420
GMATESPSDS PEDGPGLSPL L
Length:421
Mass (Da):47,745
Last modified:May 1, 1999 - v2
Checksum:iF06A57DED79BBE84
GO
Isoform 2 (identifier: O75648-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     341-421: PCVLTLNQDG...EDGPGLSPLL → CCVLQGGRVP...EGPAQSWDGH

Show »
Length:376
Mass (Da):42,950
Checksum:iCDD44D61E0426DFD
GO
Isoform 3 (identifier: O75648-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-154: Missing.
     155-179: FEVRNAVKLLQAADSFKDQTFFLSQ → MKKSLSRSTLRSPKGFSEIGLKLEM
     341-421: PCVLTLNQDG...EDGPGLSPLL → CCVLQGGRVP...EGPAQSWDGH

Show »
Length:222
Mass (Da):25,237
Checksum:i9EFE17BA0DD15B9C
GO
Isoform 4 (identifier: O75648-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-154: Missing.
     155-179: FEVRNAVKLLQAADSFKDQTFFLSQ → MKKSLSRSTLRSPKGFSEIGLKLEM

Show »
Length:267
Mass (Da):30,032
Checksum:i02B847B0EE43234A
GO
Isoform 5 (identifier: O75648-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-166: VKLLQA → RFPRMP
     167-421: Missing.

Show »
Length:166
Mass (Da):19,154
Checksum:i2591018317F58C96
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q2PPL5Q2PPL5_HUMAN
Mitochondrial 5-methylaminomethyl-2...
TRMU
99Annotation score:
B4DZN5B4DZN5_HUMAN
Mitochondrial tRNA-specific 2-thiou...
TRMU
131Annotation score:
A0A2R8Y6L6A0A2R8Y6L6_HUMAN
Mitochondrial tRNA-specific 2-thiou...
TRMU
341Annotation score:
A0A2R8Y4R7A0A2R8Y4R7_HUMAN
Mitochondrial tRNA-specific 2-thiou...
TRMU
331Annotation score:
A0A2R8YFQ3A0A2R8YFQ3_HUMAN
Mitochondrial tRNA-specific 2-thiou...
TRMU
207Annotation score:
A0A2R8YDK3A0A2R8YDK3_HUMAN
Mitochondrial tRNA-specific 2-thiou...
TRMU
102Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139F → L in BAA91462 (PubMed:14702039).Curated1
Isoform 3 (identifier: O75648-3)
Sequence conflicti14K → N in AAH80631 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02726810A → S Polymorphism; acts as a disease modifier in patients with aminoglycoside-induced deafness and a mutation in mitochondrial 12S rRNA; affects tRNA processing by decreasing thiolation and increasing aminoacylation of tRNAs; the mutant has lower thermal stability than wild-type; does not affect import in the mitochondria. 3 PublicationsCorresponds to variant dbSNP:rs11090865EnsemblClinVar.1
Natural variantiVAR_06342814G → S1 PublicationCorresponds to variant dbSNP:rs751248771EnsemblClinVar.1
Natural variantiVAR_04638025R → S. Corresponds to variant dbSNP:rs2272938EnsemblClinVar.1
Natural variantiVAR_06342977Y → H in LFIT. 1 PublicationCorresponds to variant dbSNP:rs118203990EnsemblClinVar.1
Natural variantiVAR_046381148E → K. Corresponds to variant dbSNP:rs34012206EnsemblClinVar.1
Natural variantiVAR_063430272G → D in LFIT. 1 PublicationCorresponds to variant dbSNP:rs118203991EnsemblClinVar.1
Natural variantiVAR_063431279V → M1 PublicationCorresponds to variant dbSNP:rs387907022EnsemblClinVar.1
Natural variantiVAR_046382398R → C. Corresponds to variant dbSNP:rs34152016EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0353911 – 154Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST154
Alternative sequenceiVSP_035392155 – 179FEVRN…FFLSQ → MKKSLSRSTLRSPKGFSEIG LKLEM in isoform 3 and isoform 4. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_035393161 – 166VKLLQA → RFPRMP in isoform 5. 1 Publication6
Alternative sequenceiVSP_035394167 – 421Missing in isoform 5. 1 PublicationAdd BLAST255
Alternative sequenceiVSP_035395341 – 421PCVLT…LSPLL → CCVLQGGRVPGQREDPAAGA VCLHAPEGPAQSWDGH in isoform 2 and isoform 3. 2 PublicationsAdd BLAST81

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY062123 mRNA Translation: AAL38183.1
AF448221 Genomic DNA Translation: AAL35970.1
AB178028 mRNA Translation: BAD66875.1
CR456445 mRNA Translation: CAG30331.1
AK001002 mRNA Translation: BAA91462.1
AK290712 mRNA Translation: BAF83401.1
AL031588 Genomic DNA No translation available.
CH471138 Genomic DNA Translation: EAW73422.1
CH471138 Genomic DNA Translation: EAW73426.1
BC027991 mRNA Translation: AAH27991.1
BC080631 mRNA Translation: AAH80631.1
CCDSiCCDS14075.1 [O75648-1]
CCDS63510.1 [O75648-2]
RefSeqiNP_001269712.1, NM_001282783.1
NP_001269713.1, NM_001282784.1
NP_001269714.1, NM_001282785.1 [O75648-2]
NP_060476.2, NM_018006.4 [O75648-1]
UniGeneiHs.439524

Genome annotation databases

EnsembliENST00000290846; ENSP00000290846; ENSG00000100416 [O75648-1]
ENST00000381019; ENSP00000370407; ENSG00000100416 [O75648-2]
ENST00000457572; ENSP00000407700; ENSG00000100416 [O75648-5]
ENST00000645190; ENSP00000496496; ENSG00000100416 [O75648-1]
GeneIDi55687
KEGGihsa:55687
UCSCiuc003bhp.4 human [O75648-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY062123 mRNA Translation: AAL38183.1
AF448221 Genomic DNA Translation: AAL35970.1
AB178028 mRNA Translation: BAD66875.1
CR456445 mRNA Translation: CAG30331.1
AK001002 mRNA Translation: BAA91462.1
AK290712 mRNA Translation: BAF83401.1
AL031588 Genomic DNA No translation available.
CH471138 Genomic DNA Translation: EAW73422.1
CH471138 Genomic DNA Translation: EAW73426.1
BC027991 mRNA Translation: AAH27991.1
BC080631 mRNA Translation: AAH80631.1
CCDSiCCDS14075.1 [O75648-1]
CCDS63510.1 [O75648-2]
RefSeqiNP_001269712.1, NM_001282783.1
NP_001269713.1, NM_001282784.1
NP_001269714.1, NM_001282785.1 [O75648-2]
NP_060476.2, NM_018006.4 [O75648-1]
UniGeneiHs.439524

3D structure databases

ProteinModelPortaliO75648
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120814, 16 interactors
IntActiO75648, 2 interactors
STRINGi9606.ENSP00000290846

PTM databases

iPTMnetiO75648
PhosphoSitePlusiO75648

Polymorphism and mutation databases

BioMutaiTRMU

Proteomic databases

EPDiO75648
MaxQBiO75648
PaxDbiO75648
PeptideAtlasiO75648
PRIDEiO75648
ProteomicsDBi50138
50139 [O75648-2]
50140 [O75648-3]
50141 [O75648-4]
50142 [O75648-5]

Protocols and materials databases

DNASUi55687
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000290846; ENSP00000290846; ENSG00000100416 [O75648-1]
ENST00000381019; ENSP00000370407; ENSG00000100416 [O75648-2]
ENST00000457572; ENSP00000407700; ENSG00000100416 [O75648-5]
ENST00000645190; ENSP00000496496; ENSG00000100416 [O75648-1]
GeneIDi55687
KEGGihsa:55687
UCSCiuc003bhp.4 human [O75648-1]

Organism-specific databases

CTDi55687
DisGeNETi55687
EuPathDBiHostDB:ENSG00000100416.12
GeneCardsiTRMU
HGNCiHGNC:25481 TRMU
HPAiHPA000824
HPA035273
HPA043300
MalaCardsiTRMU
MIMi580000 phenotype
610230 gene
613070 phenotype
neXtProtiNX_O75648
OpenTargetsiENSG00000100416
Orphaneti217371 Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
254864 Mitochondrial myopathy with reversible cytochrome C oxidase deficiency
90641 Mitochondrial non-syndromic sensorineural deafness
168609 Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure
PharmGKBiPA142670701
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2805 Eukaryota
COG0482 LUCA
GeneTreeiENSGT00390000014323
HOVERGENiHBG108157
InParanoidiO75648
KOiK21027
OMAiAVCTGHY
OrthoDBiEOG091G0BKX
PhylomeDBiO75648
TreeFamiTF105611

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000100416-MONOMER
BRENDAi2.1.1.61 2681
ReactomeiR-HSA-6787450 tRNA modification in the mitochondrion

Miscellaneous databases

ChiTaRSiTRMU human
GeneWikiiTRMU
GenomeRNAii55687
PROiPR:O75648
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100416 Expressed in 211 organ(s), highest expression level in adenohypophysis
CleanExiHS_TRMT1
HS_TRMU
ExpressionAtlasiO75648 baseline and differential
GenevisibleiO75648 HS

Family and domain databases

CDDicd01998 tRNA_Me_trans, 1 hit
Gene3Di2.30.30.280, 1 hit
3.40.50.620, 1 hit
HAMAPiMF_00144 tRNA_thiouridyl_MnmA, 1 hit
InterProiView protein in InterPro
IPR023382 Adenine_a_hdrlase_dom
IPR014729 Rossmann-like_a/b/a_fold
IPR004506 tRNA-specific_2-thiouridylase
PANTHERiPTHR11933 PTHR11933, 1 hit
TIGRFAMsiTIGR00420 trmU, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMTU1_HUMAN
AccessioniPrimary (citable) accession number: O75648
Secondary accession number(s): A8K3U7
, Q05C99, Q5W9C8, Q66K31, Q6ICC3, Q9NWC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
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