Protein MPV17 is a protein that in humans is encoded by the MPV17gene.[5][6][7] It is a mitochondrial inner membrane protein, which has a so far largely unknown role in mtDNA maintenance. Protein MPV17 is expressed in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart.[8] Human MPV17 is the orthologue of the mouse kidney disease gene, Mpv17. Loss of function has been shown to cause hepatocerebral mtDNA depletion syndromes (MDS) with oxidative phosphorylation failure and mtDNA depletion both in affected individuals and in Mpv17−/− mice.[6][9]
This protein was first thought to be a peroxisomal protein, but in 2006, Spinazzola et al. demonstrated that it is a mitochondrial inner membrane protein that is implicated in the formation of reactive oxygen species (ROS).[6]
Restoration of Mpv17 expression in Mpv17-/- mice restores mtDNA copy number, suggesting MPV17 is involved in mtDNA copy number, and in mtDNA maintenance.[10]
MPV17 seems to be also involved in apoptosis in podocytes, and involved in ROS.[11]
MPV17 belongs to a family of integral membrane proteins consisting of four members (PXMP2, MPV17, MP-L, and FKSG24 (MPV17L2)) in mammals and two members (Sym1 and Yor292) in yeast. The amino acid sequence of MPV17 (176 amino acids) contains four cysteine residues and three putative phosphorylation sites implies that this protein may act as a redox- and ATP-sensitive channel.[12]
Clinical significanceedit
Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS), a mutation in this protein leads to an mtDNA (mitochondrial DNA) copy number decrease.[7] By 2013, MDS caused by MPV17 mutations had been reported in 32 patients with the clinical manifestations including early progressive liver failure, neurological abnormalities, hypoglycaemia and raised blood lactate.[8] In addition, MPV17 mutations have also been associated with autosomal recessive adult-onset neuropathy and leukoencephalopathy with multiple mtDNA deletions in skeletal muscle.[13] Thus, MPV17 mutations can lead to recessive MDS or recessive multiple mtDNA deletion disorders.
^ abcGRCh38: Ensembl release 89: ENSG00000115204 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000107283 - 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.
^Karasawa M, Zwacka RM, Reuter A, Fink T, Hsieh CL, Lichter P, Francke U, Weiher H (Nov 1993). "The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization". Human Molecular Genetics. 2 (11): 1829–34. doi:10.1093/hmg/2.11.1829. PMID 8281143.
^ abcSpinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, D'Adamo P, Calvo S, Marsano RM, Donnini C, Weiher H, Strisciuglio P, Parini R, Sarzi E, Chan A, DiMauro S, Rötig A, Gasparini P, Ferrero I, Mootha VK, Tiranti V, Zeviani M (May 2006). "MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion". Nature Genetics. 38 (5): 570–5. doi:10.1038/ng1765. hdl:11577/3321860. PMID 16582910. S2CID 17999433.
^ abUusimaa J, Evans J, Smith C, Butterworth A, Craig K, Ashley N, Liao C, Carver J, Diot A, Macleod L, Hargreaves I, Al-Hussaini A, Faqeih E, Asery A, Al Balwi M, Eyaid W, Al-Sunaid A, Kelly D, van Mourik I, Ball S, Jarvis J, Mulay A, Hadzic N, Samyn M, Baker A, Rahman S, Stewart H, Morris AA, Seller A, Fratter C, Taylor RW, Poulton J (Feb 2014). "Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene". European Journal of Human Genetics. 22 (2): 184–91. doi:10.1038/ejhg.2013.112. PMC3895632. PMID 23714749.
^Viscomi C, Spinazzola A, Maggioni M, Fernandez-Vizarra E, Massa V, Pagano C, Vettor R, Mora M, Zeviani M (Jan 2009). "Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice". Human Molecular Genetics. 18 (1): 12–26. doi:10.1093/hmg/ddn309. PMC2644642. PMID 18818194.
^Bottani E, Giordano C, Civiletto G, Di Meo I, Auricchio A, Ciusani E, Marchet S, Lamperti C, d'Amati G, Viscomi C, Zeviani M (Jan 2014). "AAV-mediated liver-specific MPV17 expression restores mtDNA levels and prevents diet-induced liver failure". Molecular Therapy. 22 (1): 10–7. doi:10.1038/mt.2013.230. PMC3880585. PMID 24247928.
^Casalena G, Krick S, Daehn I, Yu L, Ju W, Shi S, Tsai SY, D'Agati V, Lindenmeyer M, Cohen CD, Schlondorff D, Bottinger EP (Jun 2014). "Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro". American Journal of Physiology. Renal Physiology. 306 (11): F1372-80. doi:10.1152/ajprenal.00608.2013. PMC4042102. PMID 24598802.
^Antonenkov VD, Isomursu A, Mennerich D, Vapola MH, Weiher H, Kietzmann T, Hiltunen JK (May 2015). "The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential". The Journal of Biological Chemistry. 290 (22): 13840–61. doi:10.1074/jbc.M114.608083. PMC4447960. PMID 25861990.
^Blakely EL, Butterworth A, Hadden RD, Bodi I, He L, McFarland R, Taylor RW (Jul 2012). "MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle". Neuromuscular Disorders. 22 (7): 587–91. doi:10.1016/j.nmd.2012.03.006. PMC3387382. PMID 22508010.
^Papeta N, Zheng Z, Schon EA, Brosel S, Altintas MM, Nasr SH, Reiser J, D'Agati VD, Gharavi AG (Nov 2010). "Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin-induced nephropathy in mice". The Journal of Clinical Investigation. 120 (11): 4055–64. doi:10.1172/JCI43721. PMC2964992. PMID 20978358.
Further readingedit
Schenkel J, Zwacka RM, Rutenberg C, Reuter A, Waldherr R, Weiher H (Jul 1995). "Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue" (PDF). Kidney International. 48 (1): 80–4. doi:10.1038/ki.1995.270. PMID 7564095.
Weiher H (1993). "Glomerular sclerosis in transgenic mice: the Mpv-17 gene and its human homologue". Advances in Nephrology from the Necker Hospital. 22: 37–42. PMID 8427063.
Iida R, Yasuda T, Tsubota E, Takatsuka H, Masuyama M, Matsuki T, Kishi K (Feb 2003). "M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up-regulates expression of the manganese superoxide dismutase gene". The Journal of Biological Chemistry. 278 (8): 6301–6. doi:10.1074/jbc.M210886200. PMID 12471025.
Calvo S, Jain M, Xie X, Sheth SA, Chang B, Goldberger OA, Spinazzola A, Zeviani M, Carr SA, Mootha VK (May 2006). "Systematic identification of human mitochondrial disease genes through integrative genomics". Nature Genetics. 38 (5): 576–82. doi:10.1038/ng1776. PMID 16582907. S2CID 11573946.
Iida R, Yasuda T, Tsubota E, Takatsuka H, Matsuki T, Kishi K (Jun 2006). "Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes". Biochemical and Biophysical Research Communications. 344 (3): 948–54. doi:10.1016/j.bbrc.2006.04.008. PMID 16631601.
Karadimas CL, Vu TH, Holve SA, Chronopoulou P, Quinzii C, Johnsen SD, Kurth J, Eggers E, Palenzuela L, Tanji K, Bonilla E, De Vivo DC, DiMauro S, Hirano M (Sep 2006). "Navajo neurohepatopathy is caused by a mutation in the MPV17 gene". American Journal of Human Genetics. 79 (3): 544–8. doi:10.1086/506913. PMC1559552. PMID 16909392.
Wong LJ, Brunetti-Pierri N, Zhang Q, Yazigi N, Bove KE, Dahms BB, Puchowicz MA, Gonzalez-Gomez I, Schmitt ES, Truong CK, Hoppel CL, Chou PC, Wang J, Baldwin EE, Adams D, Leslie N, Boles RG, Kerr DS, Craigen WJ (Oct 2007). "Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy". Hepatology. 46 (4): 1218–27. doi:10.1002/hep.21799. hdl:2027.42/142478. PMID 17694548. S2CID 6198280.
This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it.
mpv17, protein, protein, that, humans, encoded, gene, mitochondrial, inner, membrane, protein, which, largely, unknown, role, mtdna, maintenance, protein, expressed, human, pancreas, kidney, muscle, liver, lung, placenta, brain, heart, human, orthologue, mouse. Protein MPV17 is a protein that in humans is encoded by the MPV17 gene 5 6 7 It is a mitochondrial inner membrane protein which has a so far largely unknown role in mtDNA maintenance Protein MPV17 is expressed in human pancreas kidney muscle liver lung placenta brain and heart 8 Human MPV17 is the orthologue of the mouse kidney disease gene Mpv17 Loss of function has been shown to cause hepatocerebral mtDNA depletion syndromes MDS with oxidative phosphorylation failure and mtDNA depletion both in affected individuals and in Mpv17 mice 6 9 MPV17IdentifiersAliasesMPV17 MTDPS6 SYM1 mitochondrial inner membrane protein mitochondrial inner membrane protein CMT2EEExternal IDsOMIM 137960 MGI 97138 HomoloGene 39746 GeneCards MPV17Gene location Human Chr Chromosome 2 human 1 Band2p23 3Start27 309 492 bp 1 End27 325 680 bp 1 Gene location Mouse Chr Chromosome 5 mouse 2 Band5 5 B1Start31 297 998 bp 2 End31 311 595 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright adrenal glandleft adrenal glandright lobe of thyroid glandanterior pituitaryleft lobe of thyroid glandislet of Langerhansstromal cell of endometriumbody of pancreascanal of the cervixleft uterine tubeTop expressed inyolk sacproximal tubuleright ventriclesuperior frontal gyruscarotid bodyendocardial cushionkidneyatrioventricular valvemyocardium of ventriclebrown adipose tissueMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionmolecular functionCellular componentintegral component of membrane mitochondrial inner membrane peroxisome membrane mitochondrion peroxisomal membrane cytosol cytoplasmBiological processinner ear development regulation of reactive oxygen species metabolic process mitochondrial genome maintenance glomerular basement membrane development homeostatic process cellular response to reactive oxygen species protein targeting to peroxisomeSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez435817527EnsemblENSG00000115204ENSMUSG00000107283UniProtP39210P19258RefSeq mRNA NM 002437NM 001294322NM 001294324NM 008622NM 001310527NM 001310528RefSeq protein NP 002428NP 001281251NP 001281253NP 001297456NP 001297457NP 032648Location UCSC Chr 2 27 31 27 33 MbChr 5 31 3 31 31 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Structure 2 1 Gene 2 2 Protein 3 Clinical significance 4 Interactions 5 See also 6 References 7 Further readingFunction editThis protein was first thought to be a peroxisomal protein but in 2006 Spinazzola et al demonstrated that it is a mitochondrial inner membrane protein that is implicated in the formation of reactive oxygen species ROS 6 Restoration of Mpv17 expression in Mpv17 mice restores mtDNA copy number suggesting MPV17 is involved in mtDNA copy number and in mtDNA maintenance 10 MPV17 seems to be also involved in apoptosis in podocytes and involved in ROS 11 Structure editGene edit The human MPV17 gene is located on chromosome 2 at p21 23 comprising eight exons encoding 176 amino acids 7 Protein edit MPV17 belongs to a family of integral membrane proteins consisting of four members PXMP2 MPV17 MP L and FKSG24 MPV17L2 in mammals and two members Sym1 and Yor292 in yeast The amino acid sequence of MPV17 176 amino acids contains four cysteine residues and three putative phosphorylation sites implies that this protein may act as a redox and ATP sensitive channel 12 Clinical significance editMutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome MDS a mutation in this protein leads to an mtDNA mitochondrial DNA copy number decrease 7 By 2013 MDS caused by MPV17 mutations had been reported in 32 patients with the clinical manifestations including early progressive liver failure neurological abnormalities hypoglycaemia and raised blood lactate 8 In addition MPV17 mutations have also been associated with autosomal recessive adult onset neuropathy and leukoencephalopathy with multiple mtDNA deletions in skeletal muscle 13 Thus MPV17 mutations can lead to recessive MDS or recessive multiple mtDNA deletion disorders Interactions editMPV17 has been shown to interact with Prkdc protein during Adriamycin induced nephropathy in mice 14 See also editNavajo neurohepatopathyReferences edit a b c GRCh38 Ensembl release 89 ENSG00000115204 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000107283 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 Karasawa M Zwacka RM Reuter A Fink T Hsieh CL Lichter P Francke U Weiher H Nov 1993 The human homolog of the glomerulosclerosis gene Mpv17 structure and genomic organization Human Molecular Genetics 2 11 1829 34 doi 10 1093 hmg 2 11 1829 PMID 8281143 a b c Spinazzola A Viscomi C Fernandez Vizarra E Carrara F D Adamo P Calvo S Marsano RM Donnini C Weiher H Strisciuglio P Parini R Sarzi E Chan A DiMauro S Rotig A Gasparini P Ferrero I Mootha VK Tiranti V Zeviani M May 2006 MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion Nature Genetics 38 5 570 5 doi 10 1038 ng1765 hdl 11577 3321860 PMID 16582910 S2CID 17999433 a b c Entrez Gene MPV17 MpV17 mitochondrial inner membrane protein a b Uusimaa J Evans J Smith C Butterworth A Craig K Ashley N Liao C Carver J Diot A Macleod L Hargreaves I Al Hussaini A Faqeih E Asery A Al Balwi M Eyaid W Al Sunaid A Kelly D van Mourik I Ball S Jarvis J Mulay A Hadzic N Samyn M Baker A Rahman S Stewart H Morris AA Seller A Fratter C Taylor RW Poulton J Feb 2014 Clinical biochemical cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene European Journal of Human Genetics 22 2 184 91 doi 10 1038 ejhg 2013 112 PMC 3895632 PMID 23714749 Viscomi C Spinazzola A Maggioni M Fernandez Vizarra E Massa V Pagano C Vettor R Mora M Zeviani M Jan 2009 Early onset liver mtDNA depletion and late onset proteinuric nephropathy in Mpv17 knockout mice Human Molecular Genetics 18 1 12 26 doi 10 1093 hmg ddn309 PMC 2644642 PMID 18818194 Bottani E Giordano C Civiletto G Di Meo I Auricchio A Ciusani E Marchet S Lamperti C d Amati G Viscomi C Zeviani M Jan 2014 AAV mediated liver specific MPV17 expression restores mtDNA levels and prevents diet induced liver failure Molecular Therapy 22 1 10 7 doi 10 1038 mt 2013 230 PMC 3880585 PMID 24247928 Casalena G Krick S Daehn I Yu L Ju W Shi S Tsai SY D Agati V Lindenmeyer M Cohen CD Schlondorff D Bottinger EP Jun 2014 Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro American Journal of Physiology Renal Physiology 306 11 F1372 80 doi 10 1152 ajprenal 00608 2013 PMC 4042102 PMID 24598802 Antonenkov VD Isomursu A Mennerich D Vapola MH Weiher H Kietzmann T Hiltunen JK May 2015 The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non selective Channel That Modulates Membrane Potential The Journal of Biological Chemistry 290 22 13840 61 doi 10 1074 jbc M114 608083 PMC 4447960 PMID 25861990 Blakely EL Butterworth A Hadden RD Bodi I He L McFarland R Taylor RW Jul 2012 MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle Neuromuscular Disorders 22 7 587 91 doi 10 1016 j nmd 2012 03 006 PMC 3387382 PMID 22508010 Papeta N Zheng Z Schon EA Brosel S Altintas MM Nasr SH Reiser J D Agati VD Gharavi AG Nov 2010 Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin induced nephropathy in mice The Journal of Clinical Investigation 120 11 4055 64 doi 10 1172 JCI43721 PMC 2964992 PMID 20978358 Further reading editSchenkel J Zwacka RM Rutenberg C Reuter A Waldherr R Weiher H Jul 1995 Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue PDF Kidney International 48 1 80 4 doi 10 1038 ki 1995 270 PMID 7564095 Weiher H 1993 Glomerular sclerosis in transgenic mice the Mpv 17 gene and its human homologue Advances in Nephrology from the Necker Hospital 22 37 42 PMID 8427063 Iida R Yasuda T Tsubota E Takatsuka H Masuyama M Matsuki T Kishi K Feb 2003 M LP Mpv17 like protein has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up regulates expression of the manganese superoxide dismutase gene The Journal of Biological Chemistry 278 8 6301 6 doi 10 1074 jbc M210886200 PMID 12471025 Calvo S Jain M Xie X Sheth SA Chang B Goldberger OA Spinazzola A Zeviani M Carr SA Mootha VK May 2006 Systematic identification of human mitochondrial disease genes through integrative genomics Nature Genetics 38 5 576 82 doi 10 1038 ng1776 PMID 16582907 S2CID 11573946 Iida R Yasuda T Tsubota E Takatsuka H Matsuki T Kishi K Jun 2006 Human Mpv17 like protein is localized in peroxisomes and regulates expression of antioxidant enzymes Biochemical and Biophysical Research Communications 344 3 948 54 doi 10 1016 j bbrc 2006 04 008 PMID 16631601 Karadimas CL Vu TH Holve SA Chronopoulou P Quinzii C Johnsen SD Kurth J Eggers E Palenzuela L Tanji K Bonilla E De Vivo DC DiMauro S Hirano M Sep 2006 Navajo neurohepatopathy is caused by a mutation in the MPV17 gene American Journal of Human Genetics 79 3 544 8 doi 10 1086 506913 PMC 1559552 PMID 16909392 Wong LJ Brunetti Pierri N Zhang Q Yazigi N Bove KE Dahms BB Puchowicz MA Gonzalez Gomez I Schmitt ES Truong CK Hoppel CL Chou PC Wang J Baldwin EE Adams D Leslie N Boles RG Kerr DS Craigen WJ Oct 2007 Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy Hepatology 46 4 1218 27 doi 10 1002 hep 21799 hdl 2027 42 142478 PMID 17694548 S2CID 6198280 nbsp This article on a gene on human chromosome 2 is a stub You can help Wikipedia 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