GTPBP3

tRNA modification GTPase GTPBP3, mitochondrial is an enzyme that in human is encoded by the GTPBP3 gene on chromosome 19.^[5][6]

GTPBP3
Identifiers
Aliases	GTPBP3, GTPBG3, MSS1, MTGP1, THDF1, COXPD23, GTP binding protein 3 (mitochondrial), GTP binding protein 3, mitochondrial
External IDs	OMIM: 608536; MGI: 1917609; HomoloGene: 6600; GeneCards: GTPBP3; OMA:GTPBP3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 17,334,920 bp[1] End 17,342,731 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B3.3 Start 71,488,103 bp[2] End 71,499,583 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell tendon of biceps brachii right adrenal gland right adrenal cortex left adrenal cortex right uterine tube skin of leg skin of abdomen body of pancreas granulocyte Top expressed in otic vesicle Rostral migratory stream epiblast muscle of thigh ventricular zone superior frontal gyrus granulocyte primary visual cortex dentate gyrus of hippocampal formation granule cell embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding GTPase activity GTP binding Cellular component intracellular anatomical structure nucleus mitochondrion cytoplasm Biological process tRNA modification tRNA processing tRNA wobble uridine modification tRNA methylation embryonic organ development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84705 70359 Ensembl ENSG00000130299 ENSMUSG00000007610 UniProt Q969Y2 Q923K4 RefSeq (mRNA) NM_133644 NM_001128855 NM_001195422 NM_032620 NM_032544 RefSeq (protein) NP_001122327 NP_001182351 NP_116009 NP_598399 NP_115933 Location (UCSC) Chr 19: 17.33 – 17.34 Mb Chr 8: 71.49 – 71.5 Mb PubMed search [3] [4]
Wikidata
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The GTPBP3 gene encodes a GTP-binding protein that is evolutionarily conserved from bacteria to mammals ^[7] and which is localized to the mitochondrion and functions in tRNA modification.^[6] At least two major isoforms due to alternative splicing are known In addition, a polymorphism on valine 250 is known and may influence aminoglydoside-induced deafness.^[6]

Structure

The GTPBP3 gene contains 10 exons,^[6] and encodes a ~44 kDa GTP-binding protein that is evolutionarily conserved from bacteria to mammals.^[7] The N-terminal domain of mitochondrial tRNA modification GTPase mediates the dimerization of the protein in a potassium-independent manner,^[8] which is thought to be related to the construction of the binding site for the one-carbon-unit donor in its tRNA modification reaction function.^[8]

Function

Mitochondrial tRNA modification GTPase is thought to catalyze the formation of 5-taurinomethyluridine (τm(5)U) in the anticodon wobble position of five mitochondrial tRNA.^[9] The gene was first discovered yeast where the mutation of the yeast homolog of human GTPBP3, MSS1, is found to elicit respiratory defect in yeast only when the mitochondrial 155 rRNA P(R)454 is present. The latter is equivalent to the human 12 rRNA A1555G mutation which has been found to associate with deafness. Hence GTPBP3 and its yeast homolog function in modification of mitochondrial function. In human, GTPBP3 is ubiquitously expressed in multiple tissues in multiple transcripts.^[7] As a tRNA modification enzyme, it is thought to function to modify codon-anticodon interaction, which is consistent with its modification of the severity of phenotypes in 12S rRNA A1555G mutation..

Clinical Significance

Mutations in GTPBP3 are known to cause hypertrophic cardiomyopathy and mitochondrial defects.^[9] Individuals with homozygous or compound heterozygous mutations in GTPBP3 present with combined deficiency of respiratory chain complexes in skeletal muscle,^[9] which require mitochondrial translation of mitochondrial-encoded complex subunits to assemble. GTPBP3 mutations cause severe mitochondrial translation defect. The majority of characterized subjects presented with lactic acidosis and hypertrophic cardiomyopathy.

The valine 250 polymorphisms on GTPBP3 is associated with severity of aminoglycoside-induced deafness in human, a disease associated with homoplasmic A1555G mutation in the mitochondrial-encoded 12S rRNA and is characterized by deafness, varying from profond congenital hearing loss to normal hearing.