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词条 GTPBP3
释义

  1. Structure

  2. Function

  3. Clinical Significance

  4. References

  5. Further reading

{{Infobox_gene}}tRNA modification GTPase GTPBP3, mitochondrial is an enzyme that in human is encoded by the GTPBP3 gene on chromosome 19.[1][2]

The GTPBP3 gene encodes a GTP-binding protein that is evolutionarily conserved from bacteria to mammals [3] and which is localized to the mitochondrion and functions in tRNA modification.[2] 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.[2]

Structure

The GTPBP3 gene contains 10 exons,[2] and encodes a ~44 kDa GTP-binding protein that is evolutionarily conserved from bacteria to mammals.[3] The N-terminal domain of mitochondrial tRNA modification GTPase mediates the dimerization of the protein in a potassium-independent manner,[4] 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.[4]

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.[5] 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.[3] 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.[5] Individuals with homozygous or compound heterozygous mutations in GTPBP3 present with combined deficiency of respiratory chain complexes in skeletal muscle,[5] 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.

References

1. ^{{cite journal | vauthors = Magrini SM, Papi MG, Marletta F, Tomaselli S, Cellai E, Mungai V, Biti G | title = Chordoma-natural history, treatment and prognosis. The Florence Radiotherapy Department experience (1956-1990) and a critical review of the literature | journal = Acta Oncologica | volume = 31 | issue = 8 | pages = 847–51 | date = Apr 1993 | pmid = 1290633 | pmc = | doi = 10.3109/02841869209089717 }}
2. ^1 2 3 {{cite web | title = Entrez Gene: GTPBP3 GTP binding protein 3 (mitochondrial)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84705| accessdate = }}
3. ^1 2 {{cite journal |vauthors=Li X, Guan MX |title=A human mitochondrial GTP binding protein related to tRNA modification may modulate phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation |journal=Mol. Cell. Biol. |volume=22 |issue=21 |pages=7701–11 |year=2002 |pmid=12370316 |pmc=135671 |doi= 10.1128/mcb.22.21.7701-7711.2002|url=}}
4. ^1 {{cite journal |vauthors=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 |title=Characterization of human GTPBP3, a GTP-binding protein involved in mitochondrial tRNA modification |journal=Mol. Cell. Biol. |volume=28 |issue=24 |pages=7514–31 |year=2008 |pmid=18852288 |pmc=2593442 |doi=10.1128/MCB.00946-08 |url=}}
5. ^1 2 {{cite journal |vauthors=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 |title=Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy |journal=Am. J. Hum. Genet. |volume=95 |issue=6 |pages=708–20 |year=2014 |pmid=25434004 |pmc=4259976 |doi=10.1016/j.ajhg.2014.10.017 |url=}}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Li X, Guan MX | title = A human mitochondrial GTP binding protein related to tRNA modification may modulate phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation | journal = Molecular and Cellular Biology | volume = 22 | issue = 21 | pages = 7701–11 | date = Nov 2002 | pmid = 12370316 | pmc = 135671 | doi = 10.1128/MCB.22.21.7701-7711.2002 }}
  • {{cite journal | vauthors = Li X, Guan MX | title = Identification and characterization of mouse GTPBP3 gene encoding a mitochondrial GTP-binding protein involved in tRNA modification | journal = Biochemical and Biophysical Research Communications | volume = 312 | issue = 3 | pages = 747–54 | date = Dec 2003 | pmid = 14680828 | doi = 10.1016/j.bbrc.2003.10.187 }}
  • {{cite journal | vauthors = Bykhovskaya Y, Mengesha E, Wang D, Yang H, Estivill X, Shohat M, Fischel-Ghodsian N | title = Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTO1 and GTPBP3 | journal = Molecular Genetics and Metabolism | volume = 83 | issue = 3 | pages = 199–206 | date = Nov 2004 | pmid = 15542390 | doi = 10.1016/j.ymgme.2004.07.009 }}
  • {{cite journal|authorlink30=Huda Zoghbi | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = Oct 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
  • {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 }}
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