GTPBP3

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
Gene location (Human)
Chr.	Chromosome 19 (human)
End	17,342,731 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	71,499,583 bp
RNA expression pattern
	Top expressed in
	Right adrenal gland; ; right uterine tube; ; skin of abdomen; ; body of pancreas; ; body of stomach; ; minor salivary gland; ; right lobe of liver; ; spleen; ; right lobe of thyroid gland; ; vagina;
	Top expressed in
	superior frontal gyrus; ; otic placode; ; endocardial cushion; ; saccule; ; cerebellar cortex; ; yolk sac; ; abdominal wall; ; thymus; ; lip; ; mirror;
	More reference expression data
	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
	84705
	70359
	ENSG00000130299
	ENSMUSG00000007610
	Q969Y2
	Q923K4
	NM_133644 ; NM_001128855 ; NM_001195422 ; NM_032620
	NM_032544
	NP_001122327 ; NP_001182351 ; NP_116009 ; NP_598399
	NP_115933
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated September 30, 2022

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

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.

Related Research Articles

Mitochondrially encoded 12S ribosomal RNA, also known as Mitochondrial-derived peptide MOTS-c or Mitochondrial open reading frame of the 12S rRNA-c is the SSU rRNA of the mitochondrial ribosome. In humans, 12S is encoded by the MT-RNR1 gene and is 959 nucleotides long. MT-RNR1 is one of the 37 genes contained in animal mitochondria genomes. Their 2 rRNA, 22 tRNA and 13 mRNA genes are very useful in phylogenetic studies, in particular the 12S and 16S rRNAs. The 12S rRNA is the mitochondrial homologue of the prokaryotic 16S and eukaryotic nuclear 18S ribosomal RNAs. Mutations in the MT-RNR1 gene may be associated with hearing loss.

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. This isoform is expressed exclusively in heart muscle during human and mouse development, and is distinct from those expressed in slow skeletal muscle (MYBPC1) and fast skeletal muscle (MYBPC2).

Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the RANGAP1 gene.

Ran-specific binding protein 1 is an enzyme that in humans is encoded by the RANBP1 gene.

SCO2 cytochrome c oxidase assembly is a protein that in humans is encoded by the SCO2 gene. The encoded protein is one of the cytochrome c oxidase (COX)(Complex IV) assembly factors. Human COX is a multimeric protein complex that requires several assembly factors. Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6.

Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene. The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation. There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function. Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.

NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial (NDUFV2) is an enzyme that in humans is encoded by the NDUFV2 gene. The encoded protein, NDUFV2, is a subunit of complex I of the mitochondrial respiratory chain, which is located on the inner mitochondrial membrane and involved in oxidative phosphorylation. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy.

Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the COX6B1 gene. Cytochrome c oxidase 6B1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).

Nucleolar GTP-binding protein 1 is a protein that in humans is encoded by the GTPBP4 gene.

Mitochondrial tRNA-specific 2-thiouridylase 1 is an enzyme that in humans is encoded by the TRMU gene.

Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene. This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X.

ATP-dependent metalloprotease YME1L1 is an enzyme that in humans is encoded by the YME1L1 gene. YME1L1 belongs to the AAA family of ATPases and mainly functions in the maintenance of mitochondrial morphology. Mutations in this gene would cause infantile-onset mitochondriopathy.

Protein MTO1 homolog, mitochondrial is a protein that in humans is encoded by the MTO1 gene.

Interferon-induced guanylate-binding protein 2 is a protein that in humans is encoded by the GBP2 gene. GBP2 is a gene related to the superfamily of large GTPases which can be induced mainly by interferon gamma.

Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene.

Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene.

Mitochondrial ribosomal protein L3 is a protein that in humans is encoded by the MRPL3 gene.

Myosin binding protein C, fast type is a protein that in humans is encoded by the MYBPC2 gene.

Cytochrome c oxidase assembly factor 5 is a protein that in humans is encoded by the COA5 gene. This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000130299 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000007610 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Magrini SM, Papi MG, Marletta F, Tomaselli S, Cellai E, Mungai V, Biti G (Apr 1993). "Chordoma-natural history, treatment and prognosis. The Florence Radiotherapy Department experience (1956-1990) and a critical review of the literature". Acta Oncologica. 31 (8): 847–51. doi:10.3109/02841869209089717. PMID 1290633.
1 2 3 4 "Entrez Gene: GTPBP3 GTP binding protein 3 (mitochondrial)".
1 2 3 Li X, Guan MX (2002). "A human mitochondrial GTP binding protein related to tRNA modification may modulate phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation". Mol. Cell. Biol. 22 (21): 7701–11. doi:10.1128/mcb.22.21.7701-7711.2002. PMC 135671 . PMID 12370316.
1 2 Villarroya M, Prado S, Esteve JM, Soriano MA, Aguado C, Pérez-Martínez D, Martínez-Ferrandis JI, Yim L, Victor VM, Cebolla E, Montaner A, Knecht E, Armengod ME (2008). "Characterization of human GTPBP3, a GTP-binding protein involved in mitochondrial tRNA modification". Mol. Cell. Biol. 28 (24): 7514–31. doi:10.1128/MCB.00946-08. PMC 2593442 . PMID 18852288.
1 2 3 Kopajtich R, Nicholls TJ, Rorbach J, Metodiev MD, Freisinger P, Mandel H, Vanlander A, Ghezzi D, Carrozzo R, Taylor RW, Marquard K, Murayama K, Wieland T, Schwarzmayr T, Mayr JA, Pearce SF, Powell CA, Saada A, Ohtake A, Invernizzi F, Lamantea E, Sommerville EW, Pyle A, Chinnery PF, Crushell E, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Assouline Z, Rio M, Feillet F, Mousson de Camaret B, Chretien D, Munnich A, Menten B, Sante T, Smet J, Régal L, Lorber A, Khoury A, Zeviani M, Strom TM, Meitinger T, Bertini ES, Van Coster R, Klopstock T, Rötig A, Haack TB, Minczuk M, Prokisch H (2014). "Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy". Am. J. Hum. Genet. 95 (6): 708–20. doi:10.1016/j.ajhg.2014.10.017. PMC 4259976 . PMID 25434004.