mitochondrial tRNA-specific 2-thiouridylase 1; MTO2 homolog (TRMU, MTU1)

Function

• catalyzes 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), mt-tRNA(Glu) & mt-tRNA(Gln)
• required for formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), mt-tRNA(Glu), & mt-tRNA(Gln) at the wobble position
• ATP is required to activate the C2 atom of the wobble base

Structure

belongs to the mnmA/TRMU family

Compartment

mitochondria

Alternative splicing

named isoforms=5

Expression

• ubiquitous
• abundantly expressed in tissues with high metabolic rates including heart, liver, kidney, & brain

Pathology

• defects in TRMU are a cause of acute infantile liver failure

Polymorphism

• polymorphism Ser-10 aggravates mitochondrial dysfunction associated with a mitochondrial 12S ribosomal RNA A1555G mutation associated with aminoglycoside-induced deafness

Mechanism of action

• 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), mt-tRNA(Glu) & mt-tRNA(Gln)
• the reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate & that acts as nucleophile towards the activated C2 atom on U34
• subsequently, a transient disulfide bond is formed between the two active site Cys (putative)

More general terms

• N-methyltransferase
• mitochondrial protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=55687
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:55687
• OMIM: https://mirror.omim.org/entry/580000
• OMIM: https://mirror.omim.org/entry/610230
• OMIM: https://mirror.omim.org/entry/613070
• UniProt: http://www.uniprot.org/uniprot/O75648.html