O75648 · MTU1_HUMAN
- ProteinMitochondrial tRNA-specific 2-thiouridylase 1
- GeneTRMU
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids421 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
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 a nucleophile towards the activated C2 atom on U34. Subsequently, a transient disulfide bond is formed between the two active site cysteine residues (By similarity).
Catalytic activity
- 5-taurinomethyluridine34 in tRNA + AH2 + ATP + S-sulfanyl-L-cysteinyl-[protein] = 5-taurinomethyl-2-thiouridine34 in tRNA + A + AMP + diphosphate + H+ + L-cysteinyl-[protein]
RHEA-COMP:11732 CHEBI:87172 Position: 34+ CHEBI:17499 + CHEBI:30616 + RHEA-COMP:11726 = RHEA-COMP:11733 + CHEBI:13193 + CHEBI:456215 + CHEBI:33019 + CHEBI:15378 + RHEA-COMP:10131
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 10-17 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ALSGGVDS | ||||||
Binding site | 36 | ATP (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Active site | 101 | Nucleophile | ||||
Sequence: C | ||||||
Binding site | 126 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Site | 127 | Interaction with tRNA | ||||
Sequence: H | ||||||
Active site | 222 | Cysteine persulfide intermediate | ||||
Sequence: C | ||||||
Site | 267 | Interaction with tRNA | ||||
Sequence: R | ||||||
Site | 367 | Interaction with tRNA | ||||
Sequence: Q |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | tRNA binding | |
Molecular Function | tRNA-5-taurinomethyluridine 2-sulfurtransferase | |
Biological Process | tRNA wobble position uridine thiolation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMitochondrial tRNA-specific 2-thiouridylase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75648
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Deafness, aminoglycoside-induced (DFNI)
- Note
- DescriptionA form of sensorineural deafness characterized by moderate-to-profound hearing loss and mitochondrial inheritance. It is induced by exposure to aminoglycosides.
- See alsoMIM:580000
Liver failure, infantile, transient (LFIT)
- Note
- 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 alsoMIM:613070
Natural variants in LFIT
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_063429 | 77 | Y>H | in LFIT; dbSNP:rs118203990 | |
VAR_063430 | 272 | G>D | in LFIT; dbSNP:rs118203991 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_027268 | 10 | 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; dbSNP:rs11090865 | |||
Sequence: A → S | ||||||
Natural variant | VAR_063428 | 14 | in dbSNP:rs751248771 | |||
Sequence: G → S | ||||||
Mutagenesis | 16 | Loss of activity. | ||||
Sequence: D → A | ||||||
Natural variant | VAR_046380 | 25 | in dbSNP:rs2272938 | |||
Sequence: R → S | ||||||
Natural variant | VAR_063429 | 77 | in LFIT; dbSNP:rs118203990 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_046381 | 148 | in dbSNP:rs34012206 | |||
Sequence: E → K | ||||||
Natural variant | VAR_063430 | 272 | in LFIT; dbSNP:rs118203991 | |||
Sequence: G → D | ||||||
Natural variant | VAR_063431 | 279 | in dbSNP:rs387907022 | |||
Sequence: V → M | ||||||
Natural variant | VAR_046382 | 398 | in dbSNP:rs34152016 | |||
Sequence: R → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 614 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000121708 | 1-421 | Mitochondrial tRNA-specific 2-thiouridylase 1 | |||
Sequence: MQALRHVVCALSGGVDSAVAALLLRRRGYQVTGVFMKNWDSLDEHGVCTADKDCEDAYRVCQILDIPFHQVSYVKEYWNDVFSDFLNEYEKGRTPNPDIVCNKHIKFSCFFHYAVDNLGADAIATGHYARTSLEDEEVFEQKHVKKPEGLFRNRFEVRNAVKLLQAADSFKDQTFFLSQVSQDALRRTIFPLGGLTKEFVKKIAAENRLHHVLQKKESMGMCFIGKRNFEHFLLQYLQPRPGHFISIEDNKVLGTHKGWFLYTLGQRANIGGLREPWYVVEKDSVKGDVFVAPRTDHPALYRDLLRTSRVHWIAEEPPAALVRDKMMECHFRFRHQMALVPCVLTLNQDGTVWVTAVQAVRALATGQFAVFYKGDECLGSGKILRLGPSAYTLQKGQRRAGMATESPSDSPEDGPGLSPLL | ||||||
Disulfide bond | 101↔222 | |||||
Sequence: CNKHIKFSCFFHYAVDNLGADAIATGHYARTSLEDEEVFEQKHVKKPEGLFRNRFEVRNAVKLLQAADSFKDQTFFLSQVSQDALRRTIFPLGGLTKEFVKKIAAENRLHHVLQKKESMGMC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous. Abundantly expressed in tissues with high metabolic rates including heart, liver, kidney, and brain.
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75648 | MBL2 P11226 | 3 | EBI-2876757, EBI-5325353 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 96-98 | Interaction with target base in tRNA | ||||
Sequence: NPD | ||||||
Region | 171-173 | Interaction with tRNA | ||||
Sequence: KDQ | ||||||
Region | 334-335 | Interaction with tRNA | ||||
Sequence: RH | ||||||
Region | 395-421 | Disordered | ||||
Sequence: KGQRRAGMATESPSDSPEDGPGLSPLL |
Sequence similarities
Belongs to the MnmA/TRMU family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
O75648-1
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.
- Name1
- Length421
- Mass (Da)47,745
- Last updated1999-05-01 v2
- ChecksumF06A57DED79BBE84
O75648-2
- Name2
- Differences from canonical
- 341-421: PCVLTLNQDGTVWVTAVQAVRALATGQFAVFYKGDECLGSGKILRLGPSAYTLQKGQRRAGMATESPSDSPEDGPGLSPLL → CCVLQGGRVPGQREDPAAGAVCLHAPEGPAQSWDGH
O75648-3
- Name3
O75648-4
- Name4
O75648-5
- Name5
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q2PPL5 | Q2PPL5_HUMAN | TRMU | 99 | ||
A0A2R8Y6L6 | A0A2R8Y6L6_HUMAN | TRMU | 341 | ||
A0A2R8Y4R7 | A0A2R8Y4R7_HUMAN | TRMU | 331 | ||
B4DZN5 | B4DZN5_HUMAN | TRMU | 131 | ||
A0A2R8YDK3 | A0A2R8YDK3_HUMAN | TRMU | 102 | ||
A0A2R8YFQ3 | A0A2R8YFQ3_HUMAN | TRMU | 207 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_035391 | 1-154 | in isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 14 | In isoform O75648-3; in Ref. 7; AAH80631 | ||||
Sequence: K → N | ||||||
Sequence conflict | 139 | in Ref. 4; BAA91462 | ||||
Sequence: F → L | ||||||
Alternative sequence | VSP_035392 | 155-179 | in isoform 3 and isoform 4 | |||
Sequence: FEVRNAVKLLQAADSFKDQTFFLSQ → MKKSLSRSTLRSPKGFSEIGLKLEM | ||||||
Alternative sequence | VSP_035393 | 161-166 | in isoform 5 | |||
Sequence: VKLLQA → RFPRMP | ||||||
Alternative sequence | VSP_035394 | 167-421 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_035395 | 341-421 | in isoform 2 and isoform 3 | |||
Sequence: PCVLTLNQDGTVWVTAVQAVRALATGQFAVFYKGDECLGSGKILRLGPSAYTLQKGQRRAGMATESPSDSPEDGPGLSPLL → CCVLQGGRVPGQREDPAAGAVCLHAPEGPAQSWDGH |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY062123 EMBL· GenBank· DDBJ | AAL38183.1 EMBL· GenBank· DDBJ | mRNA | ||
AF448221 EMBL· GenBank· DDBJ | AAL35970.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB178028 EMBL· GenBank· DDBJ | BAD66875.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456445 EMBL· GenBank· DDBJ | CAG30331.1 EMBL· GenBank· DDBJ | mRNA | ||
AK001002 EMBL· GenBank· DDBJ | BAA91462.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290712 EMBL· GenBank· DDBJ | BAF83401.1 EMBL· GenBank· DDBJ | mRNA | ||
AL031588 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471138 EMBL· GenBank· DDBJ | EAW73422.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471138 EMBL· GenBank· DDBJ | EAW73426.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC027991 EMBL· GenBank· DDBJ | AAH27991.1 EMBL· GenBank· DDBJ | mRNA | ||
BC080631 EMBL· GenBank· DDBJ | AAH80631.1 EMBL· GenBank· DDBJ | mRNA |