GTPBP3

tRNA modification GTPase GTPBP3, mitochondrial is an is_associated_with::enzyme that in human is encoded by the GTPBP3 is_associated_with::gene on chromosome 19.

The GTPBP3 gene contains 10 exons, and encodes a ~44 kDa is_associated_with::GTP-binding protein that is evolutionarily conserved from bacteria to mammals and which is localized to the is_associated_with::mitochondrion and functions in is_associated_with::tRNA modification. At least two major isoforms due to is_associated_with::alternative splicing are known In addition, a is_associated_with::polymorphism on is_associated_with::valine 250 is known and may influence aminoglydoside-induced deafness.

Structure
The N-terminal domain of mitochondrial tRNA modification GTPase mediates the dimerization of the protein in a potassium-independent manner, which is thought to be related to the construction of the binding site for the one-carbon-unit donor in its is_associated_with::tRNA modification reaction function.

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. 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 is_associated_with::rRNA P(R)454 is present. The latter is equivalent to the human 12 is_associated_with::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. 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 is_associated_with::hypertrophic cardiomyopathy and mitochondrial defects. Individuals with is_associated_with::homozygous or is_associated_with::compound heterozygous mutations in GTPBP3 present with combined deficiency of is_associated_with::respiratory chain complexes in skeletal muscle, 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 is_associated_with::lactic acidosis and is_associated_with::hypertrophic cardiomyopathy.

The valine 250 polymorphisms on GTPBP3 is associated with severity of aminoglycoside-induced deafness in human, a disease associated with is_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.