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Protein

Mitochondrial tRNA-specific 2-thiouridylase 1

Gene

TRMU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei36 – 361ATP; via amide nitrogen and carbonyl oxygenBy similarity
Active sitei101 – 1011NucleophileBy similarity
Binding sitei126 – 1261ATP; via amide nitrogenBy similarity
Active sitei222 – 2221Cysteine persulfide intermediateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 178ATPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

tRNA processing

Keywords - Ligandi

ATP-binding, Nucleotide-binding, RNA-binding, tRNA-binding

Enzyme and pathway databases

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

HGNCiHGNC:25481. TRMU.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771Y → H in LFIT. 1 Publication
Corresponds to variant rs118203990 [ dbSNP | Ensembl ].
VAR_063429
Natural varianti272 – 2721G → D in LFIT. 1 Publication
Corresponds to variant rs118203991 [ dbSNP | Ensembl ].
VAR_063430

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi16 – 161D → A: Loss of activity. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiTRMU.
MIMi580000. phenotype.
613070. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 421421Mitochondrial tRNA-specific 2-thiouridylase 1PRO_0000121708Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi101 ↔ 222By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiO75648.
MaxQBiO75648.
PaxDbiO75648.
PeptideAtlasiO75648.
PRIDEiO75648.

PTM databases

iPTMnetiO75648.
PhosphoSiteiO75648.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000100416.
CleanExiHS_TRMT1.
HS_TRMU.
ExpressionAtlasiO75648. baseline and differential.
GenevisibleiO75648. HS.

Organism-specific databases

HPAiHPA035273.
HPA043300.

Interactioni

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei127 – 1271Interaction with tRNABy similarity
Sitei267 – 2671Interaction with tRNABy similarity
Sitei367 – 3671Interaction with tRNABy similarity

Protein-protein interaction databases

BioGridi120814. 6 interactions.
IntActiO75648. 2 interactions.
STRINGi9606.ENSP00000290846.

Structurei

3D structure databases

ProteinModelPortaliO75648.
SMRiO75648. Positions 7-383.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni96 – 983Interaction with target base in tRNABy similarity
Regioni171 – 1733Interaction with tRNABy similarity
Regioni334 – 3352Interaction with tRNABy similarity

Sequence similaritiesi

Belongs to the MnmA/TRMU family.Curated

Phylogenomic databases

eggNOGiKOG2805. Eukaryota.
COG0482. LUCA.
GeneTreeiENSGT00390000014323.
HOVERGENiHBG108157.
InParanoidiO75648.
KOiK00566.
OMAiLHKINFA.
OrthoDBiEOG091G0BKX.
PhylomeDBiO75648.
TreeFamiTF105611.

Family and domain databases

Gene3Di2.30.30.280. 1 hit.
3.40.50.620. 1 hit.
HAMAPiMF_00144. tRNA_thiouridyl_MnmA. 1 hit.
InterProiIPR023382. Adenine_a_hdrlase_dom.
IPR014729. Rossmann-like_a/b/a_fold.
IPR004506. tRNA-specific_2-thiouridylase.
[Graphical view]
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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti139 – 1391F → L in BAA91462 (PubMed:14702039).Curated
Isoform 3 (identifier: O75648-3)
Sequence conflicti14 – 141K → N in AAH80631 (PubMed:15489334).Curated

Polymorphismi

The polymorphism Ser-10 aggravates the mitochondrial dysfunction associated with a mitochondrial 12S ribosomal RNA (rRNA) A1555G mutation that has been associated with aminoglycoside-induced and non-syndromic deafness [MIMi:580000].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101A → S Decreased activity. 2 Publications
Corresponds to variant rs11090865 [ dbSNP | Ensembl ].
VAR_027268
Natural varianti14 – 141G → S.1 Publication
Corresponds to variant rs751248771 [ dbSNP | Ensembl ].
VAR_063428
Natural varianti25 – 251R → S.
Corresponds to variant rs2272938 [ dbSNP | Ensembl ].
VAR_046380
Natural varianti77 – 771Y → H in LFIT. 1 Publication
Corresponds to variant rs118203990 [ dbSNP | Ensembl ].
VAR_063429
Natural varianti148 – 1481E → K.
Corresponds to variant rs34012206 [ dbSNP | Ensembl ].
VAR_046381
Natural varianti272 – 2721G → D in LFIT. 1 Publication
Corresponds to variant rs118203991 [ dbSNP | Ensembl ].
VAR_063430
Natural varianti279 – 2791V → M.1 Publication
Corresponds to variant rs387907022 [ dbSNP | Ensembl ].
VAR_063431
Natural varianti398 – 3981R → C.
Corresponds to variant rs34152016 [ dbSNP | Ensembl ].
VAR_046382

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 154154Missing in isoform 3 and isoform 4. 1 PublicationVSP_035391Add
BLAST
Alternative sequencei155 – 17925FEVRN…FFLSQ → MKKSLSRSTLRSPKGFSEIG LKLEM in isoform 3 and isoform 4. 1 PublicationVSP_035392Add
BLAST
Alternative sequencei161 – 1666VKLLQA → RFPRMP in isoform 5. 1 PublicationVSP_035393
Alternative sequencei167 – 421255Missing in isoform 5. 1 PublicationVSP_035394Add
BLAST
Alternative sequencei341 – 42181PCVLT…LSPLL → CCVLQGGRVPGQREDPAAGA VCLHAPEGPAQSWDGH in isoform 2 and isoform 3. 2 PublicationsVSP_035395Add
BLAST

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. Translation: CAB38414.1.
AL031588 Genomic DNA. Translation: CAP58845.1.
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]
GeneIDi55687.
KEGGihsa:55687.
UCSCiuc003bhp.4. human. [O75648-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAB38414.1.
AL031588 Genomic DNA. Translation: CAP58845.1.
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.
SMRiO75648. Positions 7-383.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120814. 6 interactions.
IntActiO75648. 2 interactions.
STRINGi9606.ENSP00000290846.

PTM databases

iPTMnetiO75648.
PhosphoSiteiO75648.

Polymorphism and mutation databases

BioMutaiTRMU.

Proteomic databases

EPDiO75648.
MaxQBiO75648.
PaxDbiO75648.
PeptideAtlasiO75648.
PRIDEiO75648.

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]
GeneIDi55687.
KEGGihsa:55687.
UCSCiuc003bhp.4. human. [O75648-1]

Organism-specific databases

CTDi55687.
GeneCardsiTRMU.
HGNCiHGNC:25481. TRMU.
HPAiHPA035273.
HPA043300.
MalaCardsiTRMU.
MIMi580000. phenotype.
610230. gene.
613070. phenotype.
neXtProtiNX_O75648.
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.
KOiK00566.
OMAiLHKINFA.
OrthoDBiEOG091G0BKX.
PhylomeDBiO75648.
TreeFamiTF105611.

Enzyme and pathway databases

BRENDAi2.1.1.61. 2681.
ReactomeiR-HSA-6787450. tRNA modification in the mitochondrion.

Miscellaneous databases

ChiTaRSiTRMU. human.
GeneWikiiTRMU.
GenomeRNAii55687.
PROiO75648.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100416.
CleanExiHS_TRMT1.
HS_TRMU.
ExpressionAtlasiO75648. baseline and differential.
GenevisibleiO75648. HS.

Family and domain databases

Gene3Di2.30.30.280. 1 hit.
3.40.50.620. 1 hit.
HAMAPiMF_00144. tRNA_thiouridyl_MnmA. 1 hit.
InterProiIPR023382. Adenine_a_hdrlase_dom.
IPR014729. Rossmann-like_a/b/a_fold.
IPR004506. tRNA-specific_2-thiouridylase.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: September 7, 2016
This is version 126 of the entry and version 2 of the sequence. [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

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.