MPV17_HUMAN
ID MPV17_HUMAN Reviewed; 176 AA.
AC P39210; D6W555; Q53SY2; Q96B08;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Protein Mpv17;
GN Name=MPV17;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Liver;
RX PubMed=8281143; DOI=10.1093/hmg/2.11.1829;
RA Karasawa M., Zwacka R.M., Reuter A., Fink T., Hsieh C.L., Lichter P.,
RA Francke U., Weiher H.;
RT "The human homolog of the glomerulosclerosis gene Mpv17: structure and
RT genomic organization.";
RL Hum. Mol. Genet. 2:1829-1834(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8427063;
RA Weiher H.;
RT "Glomerular sclerosis in transgenic mice: the Mpv-17 gene and its human
RT homologue.";
RL Adv. Nephrol. Necker Hosp. 22:37-42(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN MTDPS6.
RX PubMed=16582907; DOI=10.1038/ng1776;
RA Calvo S., Jain M., Xie X., Sheth S.A., Chang B., Goldberger O.A.,
RA Spinazzola A., Zeviani M., Carr S.A., Mootha V.K.;
RT "Systematic identification of human mitochondrial disease genes through
RT integrative genomics.";
RL Nat. Genet. 38:576-582(2006).
RN [8]
RP FUNCTION, MUTAGENESIS OF THR-80; ASP-92 AND CYS-99, AND CHARACTERIZATION OF
RP VARIANT MTDPS6 LEU-98.
RX PubMed=25861990; DOI=10.1074/jbc.m114.608083;
RA Antonenkov V.D., Isomursu A., Mennerich D., Vapola M.H., Weiher H.,
RA Kietzmann T., Hiltunen J.K.;
RT "The human mitochondrial DNA depletion syndrome gene MPV17 encodes a non-
RT selective channel that modulates membrane potential.";
RL J. Biol. Chem. 290:13840-13861(2015).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP FUNCTION.
RX PubMed=26760297; DOI=10.1371/journal.pgen.1005779;
RA Dalla Rosa I., Camara Y., Durigon R., Moss C.F., Vidoni S., Akman G.,
RA Hunt L., Johnson M.A., Grocott S., Wang L., Thorburn D.R., Hirano M.,
RA Poulton J., Taylor R.W., Elgar G., Marti R., Voshol P., Holt I.J.,
RA Spinazzola A.;
RT "MPV17 loss causes deoxynucleotide insufficiency and slow DNA replication
RT in mitochondria.";
RL PLoS Genet. 12:E1005779-E1005779(2016).
RN [11]
RP VARIANTS MTDPS6 TRP-50; GLN-50 AND LYS-166, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=16582910; DOI=10.1038/ng1765;
RA Spinazzola A., Viscomi C., Fernandez-Vizarra E., Carrara F., D'Adamo P.,
RA Calvo S., Marsano R.M., Donnini C., Weiher H., Strisciuglio P., Parini R.,
RA Sarzi E., Chan A., Dimauro S., Rotig A., Gasparini P., Ferrero I.,
RA Mootha V.K., Tiranti V., Zeviani M.;
RT "MPV17 encodes an inner mitochondrial membrane protein and is mutated in
RT infantile hepatic mitochondrial DNA depletion.";
RL Nat. Genet. 38:570-575(2006).
RN [12]
RP VARIANT MTDPS6 GLN-50.
RX PubMed=16909392; DOI=10.1086/506913;
RA Karadimas C.L., Vu T.H., Holve S.A., Chronopoulou P., Quinzii C.,
RA Johnsen S.D., Kurth J., Eggers E., Palenzuela L., Tanji K., Bonilla E.,
RA De Vivo D.C., DiMauro S., Hirano M.;
RT "Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.";
RL Am. J. Hum. Genet. 79:544-548(2006).
RN [13]
RP VARIANTS MTDPS6 TRP-50; 69-TRP--LEU-176 DEL; 79-GLY--THR-81 DEL AND LYS-88
RP DEL.
RX PubMed=17694548; DOI=10.1002/hep.21799;
RA Wong L.J., Brunetti-Pierri N., Zhang Q., Yazigi N., Bove K.E., Dahms B.B.,
RA Puchowicz M.A., Gonzalez-Gomez I., Schmitt E.S., Truong C.K., Hoppel C.L.,
RA Chou P.C., Wang J., Baldwin E.E., Adams D., Leslie N., Boles R.G.,
RA Kerr D.S., Craigen W.J.;
RT "Mutations in the MPV17 gene are responsible for rapidly progressive liver
RT failure in infancy.";
RL Hepatology 46:1218-1227(2007).
RN [14]
RP VARIANTS MTDPS6 TRP-24 AND 120-TRP--LEU-176 DEL.
RX PubMed=18695062; DOI=10.1001/archneur.65.8.1108;
RA Spinazzola A., Santer R., Akman O.H., Tsiakas K., Schaefer H., Ding X.,
RA Karadimas C.L., Shanske S., Ganesh J., Di Mauro S., Zeviani M.;
RT "Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17
RT mutations.";
RL Arch. Neurol. 65:1108-1113(2008).
RN [15]
RP VARIANT MTDPS6 PHE-170.
RX PubMed=19520594; DOI=10.1016/j.ymgme.2009.04.014;
RA Kaji S., Murayama K., Nagata I., Nagasaka H., Takayanagi M., Ohtake A.,
RA Iwasa H., Nishiyama M., Okazaki Y., Harashima H., Eitoku T., Yamamoto M.,
RA Matsushita H., Kitamoto K., Sakata S., Katayama T., Sugimoto S.,
RA Fujimoto Y., Murakami J., Kanzaki S., Shiraki K.;
RT "Fluctuating liver functions in siblings with MPV17 mutations and possible
RT improvement associated with dietary and pharmaceutical treatments targeting
RT respiratory chain complex II.";
RL Mol. Genet. Metab. 97:292-296(2009).
RN [16]
RP VARIANTS MTDPS6 GLN-50; GLU-88; LYS-88 DEL; LEU-91 DEL; ARG-94; LEU-98 AND
RP ASP-162.
RX PubMed=20074988; DOI=10.1016/j.ymgme.2009.10.003;
RA El-Hattab A.W., Li F.Y., Schmitt E., Zhang S., Craigen W.J., Wong L.J.;
RT "MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new
RT patients and novel mutations.";
RL Mol. Genet. Metab. 99:300-308(2010).
RN [17]
RP VARIANT CMT2EE LEU-98.
RX PubMed=22508010; DOI=10.1016/j.nmd.2012.03.006;
RA Blakely E.L., Butterworth A., Hadden R.D., Bodi I., He L., McFarland R.,
RA Taylor R.W.;
RT "MPV17 mutation causes neuropathy and leukoencephalopathy with multiple
RT mtDNA deletions in muscle.";
RL Neuromuscul. Disord. 22:587-591(2012).
RN [18]
RP VARIANT MTDPS6 ARG-64.
RX PubMed=23829229; DOI=10.1111/cge.12228;
RA Piekutowska-Abramczuk D., Pronicki M., Strawa K.,
RA Karkucinska-Wieckowska A., Szymanska-Debinska T., Fidzianska A.,
RA Wieckowski M.R., Jurkiewicz D., Ciara E., Jankowska I., Sykut-Cegielska J.,
RA Krajewska-Walasek M., Ploski R., Pronicka E.;
RT "Novel c.191C>G (p.Pro64Arg) MPV17 mutation identified in two pairs of
RT unrelated Polish siblings with mitochondrial hepatoencephalopathy.";
RL Clin. Genet. 85:573-577(2014).
RN [19]
RP VARIANTS MTDPS6 ARG-21; PRO-23; PRO-36; TRP-41; 44-GLN--LEU-176 DEL;
RP ARG-64; PRO-93 AND LEU-98.
RX PubMed=23714749; DOI=10.1038/ejhg.2013.112;
RA Uusimaa J., Evans J., Smith C., Butterworth A., Craig K., Ashley N.,
RA Liao C., Carver J., Diot A., Macleod L., Hargreaves I., Al-Hussaini A.,
RA Faqeih E., Asery A., Al Balwi M., Eyaid W., Al-Sunaid A., Kelly D.,
RA van Mourik I., Ball S., Jarvis J., Mulay A., Hadzic N., Samyn M., Baker A.,
RA Rahman S., Stewart H., Morris A.A., Seller A., Fratter C., Taylor R.W.,
RA Poulton J.;
RT "Clinical, biochemical, cellular and molecular characterization of
RT mitochondrial DNA depletion syndrome due to novel mutations in the MPV17
RT gene.";
RL Eur. J. Hum. Genet. 22:184-191(2014).
RN [20]
RP VARIANTS MTDPS6 LEU-98 AND 136-TYR--LEU-176 DEL.
RX PubMed=25129007; DOI=10.1007/s13312-014-0475-z;
RA Bijarnia-Mahay S., Mohan N., Goyal D., Verma I.C.;
RT "Mitochondrial DNA depletion syndrome causing liver failure.";
RL Indian Pediatr. 51:666-668(2014).
RN [21]
RP VARIANT CMT2EE LEU-98.
RX PubMed=24190800; DOI=10.1007/8904_2013_267;
RA Mendelsohn B.A., Mehta N., Hameed B., Pekmezci M., Packman S., Ralph J.;
RT "Adult-onset fatal neurohepatopathy in a woman caused by MPV17 mutation.";
RL JIMD Rep. 13:37-41(2014).
RN [22]
RP VARIANT CMT2EE GLN-41, AND INVOLVEMENT IN CMT2EE.
RX PubMed=26437932; DOI=10.1186/s12883-015-0430-1;
RA Choi Y.R., Hong Y.B., Jung S.C., Lee J.H., Kim Y.J., Park H.J., Lee J.,
RA Koo H., Lee J.S., Jwa D.H., Jung N., Woo S.Y., Kim S.B., Chung K.W.,
RA Choi B.O.;
RT "A novel homozygous MPV17 mutation in two families with axonal sensorimotor
RT polyneuropathy.";
RL BMC Neurol. 15:179-179(2015).
RN [23]
RP VARIANTS MTDPS6 GLU-66; ARG-94 AND LEU-98.
RX PubMed=27536553; DOI=10.1016/j.ymgmr.2016.06.006;
RA Kim J., Kang E., Kim Y., Kim J.M., Lee B.H., Murayama K., Kim G.H.,
RA Choi I.H., Kim K.M., Yoo H.W.;
RT "MPV17 mutations in patients with hepatocerebral mitochondrial DNA
RT depletion syndrome.";
RL Mol. Genet. Metab. Rep. 8:74-76(2016).
RN [24]
RP VARIANT MTDPS6 LEU-98.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
RN [25]
RP CHARACTERIZATION OF VARIANTS MTDPS6 PRO-23 AND PRO-93.
RX PubMed=28207748; DOI=10.1371/journal.pgen.1006628;
RA Berglund A.K., Navarrete C., Engqvist M.K., Hoberg E., Szilagyi Z.,
RA Taylor R.W., Gustafsson C.M., Falkenberg M., Clausen A.R.;
RT "Nucleotide pools dictate the identity and frequency of ribonucleotide
RT incorporation in mitochondrial DNA.";
RL PLoS Genet. 13:E1006628-E1006628(2017).
RN [26]
RP VARIANTS MTDPS6 ARG-21; TRP-50; LYS-88 DEL; LEU-91 DEL; GLY-92; PRO-93;
RP ASP-95; LEU-98; 99-CYS--LEU-176 DEL AND MET-154.
RX PubMed=29282788; DOI=10.1002/humu.23387;
RA El-Hattab A.W., Wang J., Dai H., Almannai M., Staufner C., Alfadhel M.,
RA Gambello M.J., Prasun P., Raza S., Lyons H.J., Afqi M., Saleh M.A.M.,
RA Faqeih E.A., Alzaidan H.I., Alshenqiti A., Flore L.A., Hertecant J.,
RA Sacharow S., Barbouth D.S., Murayama K., Shah A.A., Lin H.C., Wong L.C.;
RT "MPV17-related mitochondrial DNA maintenance defect: New cases and review
RT of clinical, biochemical, and molecular aspects.";
RL Hum. Mutat. 39:461-470(2018).
RN [27]
RP VARIANT CMT2EE GLN-41, AND INVOLVEMENT IN CMT2EE.
RX PubMed=30298599; DOI=10.1111/cge.13462;
RA Baumann M., Schreiber H., Schlotter-Weigel B., Loescher W.N., Stucka R.,
RA Karall D., Strom T.M., Bauer P., Krabichler B., Fauth C., Glaeser D.,
RA Senderek J.;
RT "MPV17 mutations in juvenile- and adult-onset axonal sensorimotor
RT polyneuropathy.";
RL Clin. Genet. 95:182-186(2019).
RN [28]
RP CHARACTERIZATION OF VARIANT MTDPS6 GLN-50.
RX PubMed=30833296; DOI=10.1242/dmm.037226;
RA Martorano L., Peron M., Laquatra C., Lidron E., Facchinello N.,
RA Meneghetti G., Tiso N., Rasola A., Ghezzi D., Argenton F.;
RT "The zebrafish orthologue of the human hepatocerebral disease gene MPV17
RT plays pleiotropic roles in mitochondria.";
RL Dis. Model. Mech. 12:0-0(2019).
CC -!- FUNCTION: Non-selective channel that modulates the membrane potential
CC under normal conditions and oxidative stress, and is involved in
CC mitochondrial homeostasis (PubMed:25861990). Involved in mitochondrial
CC deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial
CC DNA (mtDNA) maintenance (PubMed:26760297). May be involved in the
CC regulation of reactive oxygen species metabolism and the control of
CC oxidative phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:P19258, ECO:0000269|PubMed:25861990,
CC ECO:0000269|PubMed:26760297}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:16582907, ECO:0000269|PubMed:16582910}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:16582907,
CC ECO:0000269|PubMed:16582910}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in pancreas, kidney, muscle,
CC liver, lung, placenta, brain and heart. {ECO:0000269|PubMed:16582910}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 6 (MTDPS6) [MIM:256810]:
CC A disease due to mitochondrial dysfunction. It is characterized by
CC infantile onset of progressive liver failure, often leading to death in
CC the first year of life, peripheral neuropathy, corneal scarring, acral
CC ulceration and osteomyelitis leading to autoamputation, cerebral
CC leukoencephalopathy, failure to thrive, and recurrent metabolic
CC acidosis with intercurrent infections. {ECO:0000269|PubMed:16582907,
CC ECO:0000269|PubMed:16582910, ECO:0000269|PubMed:16909392,
CC ECO:0000269|PubMed:17694548, ECO:0000269|PubMed:18695062,
CC ECO:0000269|PubMed:19520594, ECO:0000269|PubMed:20074988,
CC ECO:0000269|PubMed:23714749, ECO:0000269|PubMed:23829229,
CC ECO:0000269|PubMed:25129007, ECO:0000269|PubMed:25861990,
CC ECO:0000269|PubMed:26741492, ECO:0000269|PubMed:27536553,
CC ECO:0000269|PubMed:28207748, ECO:0000269|PubMed:29282788,
CC ECO:0000269|PubMed:30833296}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2EE (CMT2EE)
CC [MIM:618400]: A recessive axonal form of Charcot-Marie-Tooth disease, a
CC disorder of the peripheral nervous system, characterized by progressive
CC weakness and atrophy, initially of the peroneal muscles and later of
CC the distal muscles of the arms. Charcot-Marie-Tooth disease is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies (designated CMT1 when they are dominantly inherited) and
CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2
CC group are characterized by signs of axonal degeneration in the absence
CC of obvious myelin alterations, normal or slightly reduced nerve
CC conduction velocities, and progressive distal muscle weakness and
CC atrophy. CMT2EE is a slowly progressive, sensorimotor peripheral axonal
CC neuropathy with onset in the first or second decades of life. The
CC disorder primarily affects the lower limbs, sometimes resulting in loss
CC of ambulation, with later onset of upper limb involvement.
CC {ECO:0000269|PubMed:22508010, ECO:0000269|PubMed:24190800,
CC ECO:0000269|PubMed:26437932, ECO:0000269|PubMed:30298599}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peroxisomal membrane protein PXMP2/4 family.
CC {ECO:0000305}.
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DR EMBL; S68430; AAD14014.1; -; Genomic_DNA.
DR EMBL; S68417; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; S68418; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; S68419; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; S68420; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; S68421; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; S68422; AAD14014.1; JOINED; Genomic_DNA.
DR EMBL; X76538; CAA54047.1; -; mRNA.
DR EMBL; HQ205986; ADP91854.1; -; Genomic_DNA.
DR EMBL; HQ205987; ADP91855.1; -; Genomic_DNA.
DR EMBL; HQ205988; ADP91856.1; -; Genomic_DNA.
DR EMBL; HQ205989; ADP91857.1; -; Genomic_DNA.
DR EMBL; HQ205990; ADP91858.1; -; Genomic_DNA.
DR EMBL; HQ205991; ADP91859.1; -; Genomic_DNA.
DR EMBL; HQ205992; ADP91860.1; -; Genomic_DNA.
DR EMBL; HQ205993; ADP91861.1; -; Genomic_DNA.
DR EMBL; HQ205994; ADP91862.1; -; Genomic_DNA.
DR EMBL; HQ205995; ADP91863.1; -; Genomic_DNA.
DR EMBL; HQ205996; ADP91864.1; -; Genomic_DNA.
DR EMBL; HQ205997; ADP91865.1; -; Genomic_DNA.
DR EMBL; HQ205998; ADP91866.1; -; Genomic_DNA.
DR EMBL; HQ205999; ADP91867.1; -; Genomic_DNA.
DR EMBL; HQ206000; ADP91868.1; -; Genomic_DNA.
DR EMBL; HQ206001; ADP91869.1; -; Genomic_DNA.
DR EMBL; HQ206002; ADP91870.1; -; Genomic_DNA.
DR EMBL; HQ206003; ADP91871.1; -; Genomic_DNA.
DR EMBL; HQ206004; ADP91872.1; -; Genomic_DNA.
DR EMBL; HQ206005; ADP91873.1; -; Genomic_DNA.
DR EMBL; HQ206006; ADP91874.1; -; Genomic_DNA.
DR EMBL; HQ206007; ADP91875.1; -; Genomic_DNA.
DR EMBL; HQ206008; ADP91876.1; -; Genomic_DNA.
DR EMBL; HQ206009; ADP91877.1; -; Genomic_DNA.
DR EMBL; HQ206010; ADP91878.1; -; Genomic_DNA.
DR EMBL; HQ206011; ADP91879.1; -; Genomic_DNA.
DR EMBL; HQ206012; ADP91880.1; -; Genomic_DNA.
DR EMBL; HQ206013; ADP91881.1; -; Genomic_DNA.
DR EMBL; HQ206014; ADP91882.1; -; Genomic_DNA.
DR EMBL; HQ206015; ADP91883.1; -; Genomic_DNA.
DR EMBL; HQ206016; ADP91884.1; -; Genomic_DNA.
DR EMBL; HQ206017; ADP91885.1; -; Genomic_DNA.
DR EMBL; HQ206018; ADP91886.1; -; Genomic_DNA.
DR EMBL; HQ206019; ADP91887.1; -; Genomic_DNA.
DR EMBL; HQ206020; ADP91888.1; -; Genomic_DNA.
DR EMBL; HQ206021; ADP91889.1; -; Genomic_DNA.
DR EMBL; HQ206022; ADP91890.1; -; Genomic_DNA.
DR EMBL; HQ206023; ADP91891.1; -; Genomic_DNA.
DR EMBL; HQ206024; ADP91892.1; -; Genomic_DNA.
DR EMBL; HQ206025; ADP91893.1; -; Genomic_DNA.
DR EMBL; AC013413; AAY24298.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00600.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00602.1; -; Genomic_DNA.
DR EMBL; BC001115; AAH01115.1; -; mRNA.
DR EMBL; BC016289; AAH16289.2; -; mRNA.
DR CCDS; CCDS1748.1; -.
DR PIR; S45343; S45343.
DR RefSeq; NP_002428.1; NM_002437.4.
DR RefSeq; XP_005264383.1; XM_005264326.3.
DR AlphaFoldDB; P39210; -.
DR BioGRID; 110498; 53.
DR IntAct; P39210; 2.
DR STRING; 9606.ENSP00000369383; -.
DR TCDB; 1.A.126.1.1; the mpv17/pmp22 4 tms putative channel (mpv17) family.
DR iPTMnet; P39210; -.
DR PhosphoSitePlus; P39210; -.
DR SwissPalm; P39210; -.
DR BioMuta; MPV17; -.
DR EPD; P39210; -.
DR jPOST; P39210; -.
DR MassIVE; P39210; -.
DR MaxQB; P39210; -.
DR PaxDb; P39210; -.
DR PeptideAtlas; P39210; -.
DR PRIDE; P39210; -.
DR ProteomicsDB; 55316; -.
DR TopDownProteomics; P39210; -.
DR Antibodypedia; 28381; 182 antibodies from 28 providers.
DR DNASU; 4358; -.
DR Ensembl; ENST00000233545.6; ENSP00000233545.2; ENSG00000115204.15.
DR Ensembl; ENST00000380044.6; ENSP00000369383.1; ENSG00000115204.15.
DR GeneID; 4358; -.
DR KEGG; hsa:4358; -.
DR MANE-Select; ENST00000380044.6; ENSP00000369383.1; NM_002437.5; NP_002428.1.
DR UCSC; uc002rjr.3; human.
DR CTD; 4358; -.
DR DisGeNET; 4358; -.
DR GeneCards; MPV17; -.
DR GeneReviews; MPV17; -.
DR HGNC; HGNC:7224; MPV17.
DR HPA; ENSG00000115204; Low tissue specificity.
DR MalaCards; MPV17; -.
DR MIM; 137960; gene.
DR MIM; 256810; phenotype.
DR MIM; 618400; phenotype.
DR neXtProt; NX_P39210; -.
DR OpenTargets; ENSG00000115204; -.
DR Orphanet; 255229; Navajo neurohepatopathy.
DR PharmGKB; PA30929; -.
DR VEuPathDB; HostDB:ENSG00000115204; -.
DR eggNOG; KOG1944; Eukaryota.
DR GeneTree; ENSGT00940000160891; -.
DR InParanoid; P39210; -.
DR OMA; TYLSWKT; -.
DR OrthoDB; 1324608at2759; -.
DR PhylomeDB; P39210; -.
DR TreeFam; TF324070; -.
DR PathwayCommons; P39210; -.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SignaLink; P39210; -.
DR BioGRID-ORCS; 4358; 12 hits in 1078 CRISPR screens.
DR ChiTaRS; MPV17; human.
DR GeneWiki; MPV17; -.
DR GenomeRNAi; 4358; -.
DR Pharos; P39210; Tbio.
DR PRO; PR:P39210; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P39210; protein.
DR Bgee; ENSG00000115204; Expressed in right adrenal gland and 194 other tissues.
DR ExpressionAtlas; P39210; baseline and differential.
DR Genevisible; P39210; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005778; C:peroxisomal membrane; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; NAS:UniProtKB.
DR GO; GO:0015267; F:channel activity; IMP:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISS:UniProtKB.
DR GO; GO:0042592; P:homeostatic process; IMP:UniProtKB.
DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:UniProtKB.
DR GO; GO:1901858; P:regulation of mitochondrial DNA metabolic process; IMP:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR InterPro; IPR007248; Mpv17_PMP22.
DR PANTHER; PTHR11266; PTHR11266; 1.
DR Pfam; PF04117; Mpv17_PMP22; 1.
PE 1: Evidence at protein level;
KW Charcot-Marie-Tooth disease; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Neurodegeneration; Neuropathy;
KW Primary mitochondrial disease; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..176
FT /note="Protein Mpv17"
FT /id="PRO_0000218927"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT SITE 92
FT /note="Determines ion selectivity"
FT /evidence="ECO:0000269|PubMed:25861990"
FT VARIANT 21
FT /note="L -> R (in MTDPS6; unknown pathological
FT significance; dbSNP:rs976220715)"
FT /evidence="ECO:0000269|PubMed:23714749,
FT ECO:0000269|PubMed:29282788"
FT /id="VAR_082226"
FT VARIANT 23
FT /note="A -> P (in MTDPS6; results in altered ribonucleotide
FT incorporation in mtDNA from patient fibroblasts)"
FT /evidence="ECO:0000269|PubMed:23714749,
FT ECO:0000269|PubMed:28207748"
FT /id="VAR_082227"
FT VARIANT 24
FT /note="G -> W (in MTDPS6; unknown pathological
FT significance; dbSNP:rs121909725)"
FT /evidence="ECO:0000269|PubMed:18695062"
FT /id="VAR_082228"
FT VARIANT 36
FT /note="Q -> P (in MTDPS6; unknown pathological
FT significance; dbSNP:rs762327729)"
FT /evidence="ECO:0000269|PubMed:23714749"
FT /id="VAR_082229"
FT VARIANT 41
FT /note="R -> Q (in CMT2EE; dbSNP:rs140992482)"
FT /evidence="ECO:0000269|PubMed:26437932,
FT ECO:0000269|PubMed:30298599"
FT /id="VAR_082230"
FT VARIANT 41
FT /note="R -> W (in MTDPS6; dbSNP:rs863224072)"
FT /evidence="ECO:0000269|PubMed:23714749"
FT /id="VAR_082231"
FT VARIANT 44..176
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:23714749"
FT /id="VAR_082232"
FT VARIANT 50
FT /note="R -> Q (in MTDPS6; does not completely rescue
FT iridophores loss in zebrafish 'tra' mutants; may cause
FT protein instability and decay; dbSNP:rs121909721)"
FT /evidence="ECO:0000269|PubMed:16582910,
FT ECO:0000269|PubMed:16909392, ECO:0000269|PubMed:20074988,
FT ECO:0000269|PubMed:30833296"
FT /id="VAR_026217"
FT VARIANT 50
FT /note="R -> W (in MTDPS6; dbSNP:rs121909723)"
FT /evidence="ECO:0000269|PubMed:16582910,
FT ECO:0000269|PubMed:17694548, ECO:0000269|PubMed:29282788"
FT /id="VAR_026218"
FT VARIANT 64
FT /note="P -> R (in MTDPS6; dbSNP:rs375401970)"
FT /evidence="ECO:0000269|PubMed:23714749,
FT ECO:0000269|PubMed:23829229"
FT /id="VAR_082233"
FT VARIANT 66
FT /note="V -> E (in MTDPS6; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27536553"
FT /id="VAR_082234"
FT VARIANT 69..176
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:17694548"
FT /id="VAR_082235"
FT VARIANT 79..81
FT /note="Missing (in MTDPS6; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17694548"
FT /id="VAR_082236"
FT VARIANT 88
FT /note="K -> E (in MTDPS6; dbSNP:rs267607256)"
FT /evidence="ECO:0000269|PubMed:20074988"
FT /id="VAR_076199"
FT VARIANT 88
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:17694548,
FT ECO:0000269|PubMed:20074988, ECO:0000269|PubMed:29282788"
FT /id="VAR_076200"
FT VARIANT 91
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:20074988,
FT ECO:0000269|PubMed:29282788"
FT /id="VAR_076201"
FT VARIANT 92
FT /note="D -> G (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:29282788"
FT /id="VAR_082237"
FT VARIANT 93
FT /note="Q -> P (in MTDPS6; results in altered ribonucleotide
FT incorporation in mtDNA from patient fibroblasts)"
FT /evidence="ECO:0000269|PubMed:23714749,
FT ECO:0000269|PubMed:29282788"
FT /id="VAR_082238"
FT VARIANT 94
FT /note="G -> R (in MTDPS6; dbSNP:rs267607257)"
FT /evidence="ECO:0000269|PubMed:20074988,
FT ECO:0000269|PubMed:27536553"
FT /id="VAR_076202"
FT VARIANT 95
FT /note="G -> D (in MTDPS6; unknown pathological
FT significance; dbSNP:rs1260392202)"
FT /evidence="ECO:0000269|PubMed:29282788"
FT /id="VAR_082239"
FT VARIANT 98
FT /note="P -> L (in MTDPS6 and CMT2EE; results in incomplete
FT closing of the channel; dbSNP:rs267607258)"
FT /evidence="ECO:0000269|PubMed:20074988,
FT ECO:0000269|PubMed:22508010, ECO:0000269|PubMed:23714749,
FT ECO:0000269|PubMed:24190800, ECO:0000269|PubMed:25129007,
FT ECO:0000269|PubMed:25861990, ECO:0000269|PubMed:26741492,
FT ECO:0000269|PubMed:27536553, ECO:0000269|PubMed:29282788"
FT /id="VAR_076203"
FT VARIANT 99..176
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:29282788"
FT /id="VAR_082240"
FT VARIANT 120..176
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:18695062"
FT /id="VAR_082241"
FT VARIANT 136..176
FT /note="Missing (in MTDPS6)"
FT /evidence="ECO:0000269|PubMed:25129007"
FT /id="VAR_082242"
FT VARIANT 154
FT /note="R -> M (in MTDPS6; dbSNP:rs886044113)"
FT /evidence="ECO:0000269|PubMed:29282788"
FT /id="VAR_082243"
FT VARIANT 162
FT /note="A -> D (in MTDPS6; dbSNP:rs267607259)"
FT /evidence="ECO:0000269|PubMed:20074988"
FT /id="VAR_076204"
FT VARIANT 166
FT /note="N -> K (in MTDPS6; dbSNP:rs121909722)"
FT /evidence="ECO:0000269|PubMed:16582910"
FT /id="VAR_026219"
FT VARIANT 170
FT /note="S -> F (in MTDPS6; dbSNP:rs267607260)"
FT /evidence="ECO:0000269|PubMed:19520594"
FT /id="VAR_082244"
FT MUTAGEN 80
FT /note="T->A: Does not affect gating properties of the
FT channel."
FT /evidence="ECO:0000269|PubMed:25861990"
FT MUTAGEN 92
FT /note="D->K: Affects ion selectivity of the channel."
FT /evidence="ECO:0000269|PubMed:25861990"
FT MUTAGEN 99
FT /note="C->A: Does not affect conductance and gating
FT properties of the channel."
FT /evidence="ECO:0000269|PubMed:25861990"
SQ SEQUENCE 176 AA; 19733 MW; 5CD9A46F4498C4AB CRC64;
MALWRAYQRA LAAHPWKVQV LTAGSLMGLG DIISQQLVER RGLQEHQRGR TLTMVSLGCG
FVGPVVGGWY KVLDRFIPGT TKVDALKKML LDQGGFAPCF LGCFLPLVGA LNGLSAQDNW
AKLQRDYPDA LITNYYLWPA VQLANFYLVP LHYRLAVVQC VAVIWNSYLS WKAHRL
