DPOG1_HUMAN
ID DPOG1_HUMAN Reviewed; 1239 AA.
AC P54098; Q8NFM2; Q92515;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=DNA polymerase subunit gamma-1;
DE EC=2.7.7.7;
DE AltName: Full=Mitochondrial DNA polymerase catalytic subunit;
DE AltName: Full=PolG-alpha;
GN Name=POLG; Synonyms=MDP1, POLG1, POLGA;
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 [MRNA].
RX PubMed=8884268; DOI=10.1006/geno.1996.0490;
RA Ropp P.A., Copeland W.C.;
RT "Cloning and characterization of the human mitochondrial DNA polymerase,
RT DNA polymerase gamma.";
RL Genomics 36:449-458(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9034326; DOI=10.1016/s0378-1119(96)00663-4;
RA Lecrenier N.L., van der Bruggen P., Foury F.;
RT "Mitochondrial DNA polymerases from yeast to man: a new family of
RT polymerases.";
RL Gene 185:147-152(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-GLN-55 INS.
RC TISSUE=Brain;
RA Watanabe T.K., Shimizu F., Nishino N., Fujiwara T., Kanemoto N., Suzuki M.,
RA Nakamura Y., Hirai Y., Maekawa H., Takahashi E.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-55 INS; GLN-193;
RP CYS-546; LYS-662; TRP-1142; GLY-1143; CYS-1146 AND HIS-1236.
RG NIEHS SNPs program;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Testis;
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 [6]
RP SUBCELLULAR LOCATION, ASSOCIATION WITH MITOCHONDRIAL DNA, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18063578; DOI=10.1074/jbc.m708444200;
RA Bogenhagen D.F., Rousseau D., Burke S.;
RT "The layered structure of human mitochondrial DNA nucleoids.";
RL J. Biol. Chem. 283:3665-3675(2008).
RN [7]
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 [8]
RP INVOLVEMENT IN SCAE, AND VARIANTS SCAE THR-467; HIS-497 AND SER-748.
RX PubMed=26942291; DOI=10.1016/j.ajhg.2016.01.009;
RA Sandford E., Bird T.D., Li J.Z., Burmeister M.;
RT "PRICKLE2 mutations might not be involved in epilepsy.";
RL Am. J. Hum. Genet. 98:588-589(2016).
RN [9]
RP INTERACTION WITH TTC3.
RX PubMed=29290964; DOI=10.18632/oncotarget.22476;
RA Gong Y., Wang X., Shang X., Xiao S.P., Li W., Shang Y., Dou F.;
RT "Tetratricopeptide repeat domain 3 overexpression tends to form aggregates
RT and inhibit ubiquitination and degradation of DNA polymerase gamma.";
RL Oncotarget 8:106475-106485(2017).
RN [10]
RP VARIANTS PEOB1 PRO-3; ARG-304; THR-467 AND CYS-955.
RX PubMed=11431686; DOI=10.1038/90034;
RA Van Goethem G., Dermaut B., Loefgren A., Martin J.-J., Van Broeckhoven C.;
RT "Mutation of POLG is associated with progressive external ophthalmoplegia
RT characterized by mtDNA deletions.";
RL Nat. Genet. 28:211-212(2001).
RN [11]
RP VARIANTS PEOA1 ASP-923; HIS-943; CYS-955; SER-957 AND LEU-1176, AND
RP VARIANTS PEO ILE-251; LEU-309 AND SER-848.
RX PubMed=12210792; DOI=10.1002/ana.10278;
RA Lamantea E., Tiranti V., Bordoni A., Toscano A., Bono F., Servidei S.,
RA Papadimitriou A., Spelbrink H., Silvestri L., Casari G., Comi G.P.,
RA Zeviani M.;
RT "Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of
RT autosomal dominant or recessive progressive external ophthalmoplegia.";
RL Ann. Neurol. 52:211-219(2002).
RN [12]
RP CHARACTERIZATION OF VARIANT PEOA1 CYS-955.
RX PubMed=11897778; DOI=10.1074/jbc.c200100200;
RA Ponamarev M.V., Longley M.J., Nguyen D., Kunkel T.A., Copeland W.C.;
RT "Active site mutation in DNA polymerase gamma associated with progressive
RT external ophthalmoplegia causes error-prone DNA synthesis.";
RL J. Biol. Chem. 277:15225-15228(2002).
RN [13]
RP VARIANTS PEOB1 TRP-579; LEU-587; THR-889 AND VAL-1076, AND VARIANT
RP HIS-1236.
RX PubMed=12975295; DOI=10.1001/archneur.60.9.1279;
RA Filosto M., Mancuso M., Nishigaki Y., Pancrudo J., Harati Y., Gooch C.,
RA Mankodi A., Bayne L., Bonilla E., Shanske S., Hirano M., DiMauro S.;
RT "Clinical and genetic heterogeneity in progressive external ophthalmoplegia
RT due to mutations in polymerase gamma.";
RL Arch. Neurol. 60:1279-1284(2003).
RN [14]
RP VARIANTS MTDPS4B ILE-251; LEU-587 AND SER-864.
RX PubMed=12825077; DOI=10.1038/sj.ejhg.5201002;
RA Van Goethem G., Schwartz M., Loefgren A., Dermaut B., Van Broeckhoven C.,
RA Vissing J.;
RT "Novel POLG mutations in progressive external ophthalmoplegia mimicking
RT mitochondrial neurogastrointestinal encephalomyopathy.";
RL Eur. J. Hum. Genet. 11:547-549(2003).
RN [15]
RP VARIANT PEOB1 SER-848.
RX PubMed=12872260; DOI=10.1002/humu.10246;
RA Van Goethem G., Loefgren A., Dermaut B., Ceuterick C., Martin J.-J.,
RA Van Broeckhoven C.;
RT "Digenic progressive external ophthalmoplegia in a sporadic patient:
RT recessive mutations in POLG and C10orf2/Twinkle.";
RL Hum. Mutat. 22:175-176(2003).
RN [16]
RP VARIANTS PEOB1 ILE-251; ALA-268; ARG-312; THR-467; GLN-562; LEU-587;
RP PRO-807 AND TYR-932, AND VARIANTS GLY-1143 AND HIS-1236.
RX PubMed=14635118; DOI=10.1002/humu.9203;
RA Di Fonzo A., Bordoni A., Crimi M., Sara G., Del Bo R., Bresolin N.,
RA Comi G.P.;
RT "POLG mutations in sporadic mitochondrial disorders with multiple mtDNA
RT deletions.";
RL Hum. Mutat. 22:498-499(2003).
RN [17]
RP VARIANTS PEOB1 TRP-227; ILE-251; ARG-312; VAL-431; THR-467; GLN-1047;
RP CYS-1096 AND CYS-1104.
RX PubMed=12707443; DOI=10.1212/01.wnl.0000056088.09408.3c;
RA Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F.,
RA Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M.;
RT "Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external
RT ophthalmoplegia (PEO).";
RL Neurology 60:1354-1356(2003).
RN [18]
RP VARIANT MERRF THR-467.
RX PubMed=14694057; DOI=10.1212/01.wnl.0000098997.23471.65;
RA Van Goethem G., Mercelis R., Loefgren A., Seneca S., Ceuterick C.,
RA Martin J.-J., Van Broeckhoven C.;
RT "Patient homozygous for a recessive POLG mutation presents with features of
RT MERRF.";
RL Neurology 61:1811-1813(2003).
RN [19]
RP VARIANTS PEOB1 PRO-3; ARG-304; THR-467 AND CYS-955, AND VARIANT SANDO
RP TRP-627.
RX PubMed=12565911; DOI=10.1016/s0960-8966(02)00216-x;
RA Van Goethem G., Martin J.-J., Dermaut B., Loefgren A., Wibail A.,
RA Ververken D., Tack P., Dehaene I., Van Zandijcke M., Moonen M.,
RA Ceuterick C., De Jonghe P., Van Broeckhoven C.;
RT "Recessive POLG mutations presenting with sensory and ataxic neuropathy in
RT compound heterozygote patients with progressive external ophthalmoplegia.";
RL Neuromuscul. Disord. 13:133-142(2003).
RN [20]
RP VARIANT MTDPS4A THR-467.
RX PubMed=15122711; DOI=10.1002/ana.20079;
RA Naviaux R.K., Nguyen K.V.;
RT "POLG mutations associated with Alpers' syndrome and mitochondrial DNA
RT depletion.";
RL Ann. Neurol. 55:706-712(2004).
RN [21]
RP VARIANTS PEOB1 TRP-227; ILE-251 LEU-309; LEU-587; SER-848 ILE-1106 AND
RP LEU-1176.
RX PubMed=15349879; DOI=10.1002/ana.20219;
RA Lamantea E., Zeviani M.;
RT "Sequence analysis of familial PEO shows additional mutations associated
RT with the 752C-->T and 3527C-->T changes in the POLG1 gene.";
RL Ann. Neurol. 56:454-455(2004).
RN [22]
RP VARIANT PEOA1 CYS-831.
RX PubMed=15534189; DOI=10.1001/archneur.61.11.1777;
RA Mancuso M., Filosto M., Oh S.J., DiMauro S.;
RT "A novel polymerase gamma mutation in a family with ophthalmoplegia,
RT neuropathy, and parkinsonism.";
RL Arch. Neurol. 61:1777-1779(2004).
RN [23]
RP VARIANTS PEOA1 CYS-953 AND CYS-955, AND VARIANTS PEOB1 ASP-468 AND
RP THR-1105.
RX PubMed=15351195; DOI=10.1016/s0140-6736(04)16983-3;
RA Luoma P., Melberg A., Rinne J.O., Kaukonen J.A., Nupponen N.N.,
RA Chalmers R.M., Oldfors A., Rautakorpi I., Peltonen L., Majamaa K.,
RA Somer H., Suomalainen A.;
RT "Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma
RT mutations: clinical and molecular genetic study.";
RL Lancet 364:875-882(2004).
RN [24]
RP VARIANTS SANDO TYR-932 AND ARG-1051.
RX PubMed=14745080; DOI=10.1212/wnl.62.2.316;
RA Mancuso M., Filosto M., Bellan M., Liguori R., Montagna P., Baruzzi A.,
RA DiMauro S., Carelli V.;
RT "POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy,
RT ataxia, and deafness.";
RL Neurology 62:316-318(2004).
RN [25]
RP VARIANT PEOB1 THR-467, VARIANT SANDO SER-748, AND VARIANT GLY-1143.
RX PubMed=15477547; DOI=10.1212/01.wnl.0000140494.58732.83;
RA Van Goethem G., Luoma P., Rantamaeki M., Al-Memar A., Kaakkola S.,
RA Hackman P., Krahe R., Loefgren A., Martin J.-J., De Jonghe P.,
RA Suomalainen A., Udd B., Van Broeckhoven C.;
RT "POLG mutations in neurodegenerative disorders with ataxia but no muscle
RT involvement.";
RL Neurology 63:1251-1257(2004).
RN [26]
RP VARIANT SANDO SER-748, AND VARIANT GLY-1143.
RX PubMed=16080118; DOI=10.1086/444548;
RA Hakonen A.H., Heiskanen S., Juvonen V., Lappalainen I., Luoma P.T.,
RA Rantamaeki M., Van Goethem G., Loefgren A., Hackman P., Paetau A.,
RA Kaakkola S., Majamaa K., Varilo T., Udd B., Kaeaeriaeinen H., Bindoff L.A.,
RA Suomalainen A.;
RT "Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal
RT recessive ataxia with ancient European origin.";
RL Am. J. Hum. Genet. 77:430-441(2005).
RN [27]
RP VARIANTS MTDPS4A SER-748 AND SER-848.
RX PubMed=15929042; DOI=10.1002/ana.20498;
RA Davidzon G., Mancuso M., Ferraris S., Quinzii C., Hirano M., Peters H.L.,
RA Kirby D., Thorburn D.R., DiMauro S.;
RT "POLG mutations and Alpers syndrome.";
RL Ann. Neurol. 57:921-923(2005).
RN [28]
RP VARIANTS MTDPS4A GLY-232; PRO-244; ILE-251 THR-467; LEU-587; SER-748
RP SER-848 AND PRO-957, AND VARIANT GLY-1143.
RX PubMed=15689359; DOI=10.1093/brain/awh410;
RA Ferrari G., Lamantea E., Donati A., Filosto M., Briem E., Carrara F.,
RA Parini R., Simonati A., Santer R., Zeviani M.;
RT "Infantile hepatocerebral syndromes associated with mutations in the
RT mitochondrial DNA polymerase-gammaA.";
RL Brain 128:723-731(2005).
RN [29]
RP VARIANT PEOB1 THR-467, VARIANT SANDO GLN-627, VARIANT HIS-1236,
RP CHARACTERIZATION OF VARIANT PEOB1 THR-467, AND CHARACTERIZATION OF VARIANT
RP SANDO GLN-627.
RX PubMed=15917273; DOI=10.1093/hmg/ddi196;
RA Luoma P.T., Luo N., Loescher W.N., Farr C.L., Horvath R., Wanschitz J.,
RA Kiechl S., Kaguni L.S., Suomalainen A.;
RT "Functional defects due to spacer-region mutations of human mitochondrial
RT DNA polymerase in a family with an ataxia-myopathy syndrome.";
RL Hum. Mol. Genet. 14:1907-1920(2005).
RN [30]
RP VARIANTS SANDO THR-467; HIS-497 AND SER-748.
RX PubMed=15824347; DOI=10.1212/01.wnl.0000156516.77696.5a;
RA Winterthun S., Ferrari G., He L., Taylor R.W., Zeviani M., Turnbull D.M.,
RA Engelsen B.A., Moen G., Bindoff L.A.;
RT "Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial
RT polymerase gamma mutations.";
RL Neurology 64:1204-1208(2005).
RN [31]
RP VARIANTS PEOB1 ARG-737 AND TRP-853.
RX PubMed=16634032; DOI=10.1002/ana.20831;
RA Davidzon G., Greene P., Mancuso M., Klos K.J., Ahlskog J.E., Hirano M.,
RA DiMauro S.;
RT "Early-onset familial parkinsonism due to POLG mutations.";
RL Ann. Neurol. 59:859-862(2006).
RN [32]
RP VARIANTS PEOB1 LEU-603; TRP-853; CYS-1146 AND ASN-1184.
RX PubMed=16401742; DOI=10.1001/archneur.63.1.107;
RA Gonzalez-Vioque E., Blazquez A., Fernandez-Moreira D., Bornstein B.,
RA Bautista J., Arpa J., Navarro C., Campos Y., Fernandez-Moreno M.A.,
RA Garesse R., Arenas J., Martin M.A.;
RT "Association of novel POLG mutations and multiple mitochondrial DNA
RT deletions with variable clinical phenotypes in a Spanish population.";
RL Arch. Neurol. 63:107-111(2006).
RN [33]
RP VARIANTS PEOB1 HIS-308; TRP-574 AND ARG-648, VARIANT SANDO VAL-517, AND
RP VARIANTS MTDPS4A ASP-767; HIS-879; SER-885; PRO-914; HIS-1096 AND ASN-1191.
RX PubMed=16621917; DOI=10.1093/brain/awl088;
RA Horvath R., Hudson G., Ferrari G., Fuetterer N., Ahola S., Lamantea E.,
RA Prokisch H., Lochmueller H., McFarland R., Ramesh V., Klopstock T.,
RA Freisinger P., Salvi F., Mayr J.A., Santer R., Tesarova M., Zeman J.,
RA Udd B., Taylor R.W., Turnbull D., Hanna M., Fialho D., Suomalainen A.,
RA Zeviani M., Chinnery P.F.;
RT "Phenotypic spectrum associated with mutations of the mitochondrial
RT polymerase gamma gene.";
RL Brain 129:1674-1684(2006).
RN [34]
RP VARIANTS PEOB1 ARG-304; ASP-380 AND THR-467, VARIANT SANDO SER-748, VARIANT
RP MTDPS4A PRO-914, AND VARIANTS GLY-1143 AND HIS-1236.
RX PubMed=16639411; DOI=10.1038/sj.ejhg.5201627;
RA Naiemi M., Bannwarth S., Procaccio V., Pouget J., Desnuelle C.,
RA Pellissier J.-F., Roetig A., Munnich A., Calvas P., Richelme C.,
RA Jonveaux P., Castelnovo G., Simon M., Clanet M., Wallace D.,
RA Paquis-Flucklinger V.;
RT "Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple
RT deletions or depletion of mitochondrial DNA by a dHPLC-based assay.";
RL Eur. J. Hum. Genet. 14:917-922(2006).
RN [35]
RP ERRATUM OF PUBMED:16639411.
RA Naiemi M., Bannwarth S., Procaccio V., Pouget J., Desnuelle C.,
RA Pellissier J.-F., Roetig A., Munnich A., Calvas P., Richelme C.,
RA Jonveaux P., Castelnovo G., Simon M., Clanet M., Wallace D.,
RA Paquis-Flucklinger V.;
RL Eur. J. Hum. Genet. 15:607-607(2006).
RN [36]
RP VARIANTS SANDO ARG-648 AND CYS-807.
RX PubMed=16919951; DOI=10.1016/j.nmd.2006.05.016;
RA Gago M.F., Rosas M.J., Guimaraes J., Ferreira M., Vilarinho L., Castro L.,
RA Carpenter S.;
RT "SANDO: two novel mutations in POLG1 gene.";
RL Neuromuscul. Disord. 16:507-509(2006).
RN [37]
RP VARIANT PEOA1 ASN-511, AND VARIANT PHE-463.
RX PubMed=17420318; DOI=10.1001/archneur.64.4.553;
RA Hudson G., Schaefer A.M., Taylor R.W., Tiangyou W., Gibson A., Venables G.,
RA Griffiths P., Burn D.J., Turnbull D.M., Chinnery P.F.;
RT "Mutation of the linker region of the polymerase gamma-1 (POLG1) gene
RT associated with progressive external ophthalmoplegia and Parkinsonism.";
RL Arch. Neurol. 64:553-557(2007).
RN [38]
RP VARIANT PEOA1 CYS-831.
RX PubMed=17846414; DOI=10.1212/01.wnl.0000276955.23735.eb;
RA Luoma P.T., Eerola J., Ahola S., Hakonen A.H., Hellstroem O.,
RA Kivistoe K.T., Tienari P.J., Suomalainen A.;
RT "Mitochondrial DNA polymerase gamma variants in idiopathic sporadic
RT Parkinson disease.";
RL Neurology 69:1152-1159(2007).
RN [39]
RP VARIANT PEOA1 HIS-1186.
RX PubMed=18575922; DOI=10.1007/s00415-008-0926-3;
RA Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F.,
RA Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S.,
RA Papadimitriou A., Bresolin N., Comi G.P.;
RT "Novel Twinkle (PEO1) gene mutations in Mendelian progressive external
RT ophthalmoplegia.";
RL J. Neurol. 255:1384-1391(2008).
RN [40]
RP VARIANTS LS HIS-232 AND SER-848, VARIANTS MTDPS4A ILE-251; THR-467;
RP LEU-587; SER-748; CYS-831; SER-848; PRO-914; TYR-1110; ARG-1134 AND
RP LYS-1136, AND VARIANTS GLY-1143 AND HIS-1236.
RX PubMed=18828154; DOI=10.1002/humu.20852;
RA Taanman J.-W., Rahman S., Pagnamenta A.T., Morris A.A.M.,
RA Bitner-Glindzicz M., Wolf N.I., Leonard J.V., Clayton P.T.,
RA Schapira A.H.V.;
RT "Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA
RT depletion.";
RL Hum. Mutat. 30:248-254(2009).
RN [41]
RP VARIANTS MTDPS4B TRP-227 AND SER-848.
RX PubMed=19307547; DOI=10.1212/01.wnl.0000345002.47396.e1;
RA Giordano C., Powell H., Leopizzi M., de Curtis M., Travaglini C.,
RA Sebastiani M., Gallo P., Taylor R.W., d'Amati G.;
RT "Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to
RT POLG1 mutations.";
RL Neurology 72:1103-1105(2009).
RN [42]
RP VARIANT MTDPS4A CYS-1096.
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).
CC -!- FUNCTION: Involved in the replication of mitochondrial DNA. Associates
CC with mitochondrial DNA.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Heterotrimer composed of a catalytic subunit and a homodimer
CC of accessory subunits (By similarity). Interacts with TTC3
CC (PubMed:29290964). {ECO:0000250|UniProtKB:Q27607,
CC ECO:0000269|PubMed:29290964}.
CC -!- INTERACTION:
CC P54098; Q9UHN1: POLG2; NbExp=11; IntAct=EBI-852624, EBI-852642;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:18063578}.
CC Mitochondrion matrix, mitochondrion nucleoid
CC {ECO:0000269|PubMed:18063578}.
CC -!- POLYMORPHISM: The poly-Gln region seems to be polymorphic.
CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC deletions, autosomal dominant, 1 (PEOA1) [MIM:157640]: A disorder
CC characterized by progressive weakness of ocular muscles and levator
CC muscle of the upper eyelid. In a minority of cases, it is associated
CC with skeletal myopathy, which predominantly involves axial or proximal
CC muscles and which causes abnormal fatigability and even permanent
CC muscle weakness. Ragged-red fibers and atrophy are found on muscle
CC biopsy. A large proportion of chronic ophthalmoplegias are associated
CC with other symptoms, leading to a multisystemic pattern of this
CC disease. Additional symptoms are variable, and may include cataracts,
CC hearing loss, sensory axonal neuropathy, ataxia, depression,
CC hypogonadism, and parkinsonism. {ECO:0000269|PubMed:11897778,
CC ECO:0000269|PubMed:12210792, ECO:0000269|PubMed:15351195,
CC ECO:0000269|PubMed:15534189, ECO:0000269|PubMed:17420318,
CC ECO:0000269|PubMed:17846414, ECO:0000269|PubMed:18575922}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC deletions, autosomal recessive, 1 (PEOB1) [MIM:258450]: A severe form
CC of progressive external ophthalmoplegia, a disorder characterized by
CC progressive weakness of ocular muscles and levator muscle of the upper
CC eyelid. It is clinically more heterogeneous than the autosomal dominant
CC forms. {ECO:0000269|PubMed:11431686, ECO:0000269|PubMed:12565911,
CC ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:12872260,
CC ECO:0000269|PubMed:12975295, ECO:0000269|PubMed:14635118,
CC ECO:0000269|PubMed:15349879, ECO:0000269|PubMed:15351195,
CC ECO:0000269|PubMed:15477547, ECO:0000269|PubMed:15917273,
CC ECO:0000269|PubMed:16401742, ECO:0000269|PubMed:16621917,
CC ECO:0000269|PubMed:16634032, ECO:0000269|PubMed:16639411}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Sensory ataxic neuropathy dysarthria and ophthalmoparesis
CC (SANDO) [MIM:607459]: A systemic disorder resulting from mitochondrial
CC dysfunction associated with mitochondrial depletion in skeletal muscle
CC and peripheral nerve tissue. The clinical triad of symptoms consists of
CC sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However,
CC the phenotype varies widely, even within the same family, and can also
CC include myopathy, seizures, and hearing loss.
CC {ECO:0000269|PubMed:12565911, ECO:0000269|PubMed:14745080,
CC ECO:0000269|PubMed:15477547, ECO:0000269|PubMed:15824347,
CC ECO:0000269|PubMed:15917273, ECO:0000269|PubMed:16080118,
CC ECO:0000269|PubMed:16621917, ECO:0000269|PubMed:16639411,
CC ECO:0000269|PubMed:16919951}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 4A (MTDPS4A)
CC [MIM:203700]: An autosomal recessive hepatocerebral syndrome due to
CC mitochondrial dysfunction. The typical course of the disease includes
CC severe developmental delay, intractable seizures, liver failure, and
CC death in childhood. Refractory seizures, cortical blindness,
CC progressive liver dysfunction, and acute liver failure after exposure
CC to valproic acid are considered diagnostic features. The
CC neuropathological hallmarks are neuronal loss, spongiform degeneration,
CC and astrocytosis of the visual cortex. Liver biopsy results show
CC steatosis, often progressing to cirrhosis.
CC {ECO:0000269|PubMed:15122711, ECO:0000269|PubMed:15689359,
CC ECO:0000269|PubMed:15929042, ECO:0000269|PubMed:16621917,
CC ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:18828154,
CC ECO:0000269|PubMed:25129007}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 4B (MTDPS4B)
CC [MIM:613662]: An autosomal recessive progressive multisystem disorder
CC due to mitochondrial dysfunction. It is clinically characterized by
CC chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia,
CC progressive external ophthalmoplegia, axonal sensory ataxic neuropathy,
CC and muscle weakness. {ECO:0000269|PubMed:12825077,
CC ECO:0000269|PubMed:19307547}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive
CC neurodegenerative disorder characterized by the presence of focal,
CC bilateral lesions in one or more areas of the central nervous system
CC including the brainstem, thalamus, basal ganglia, cerebellum and spinal
CC cord. Clinical features depend on which areas of the central nervous
CC system are involved and include subacute onset of psychomotor
CC retardation, hypotonia, ataxia, weakness, vision loss, eye movement
CC abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:18828154}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Spinocerebellar ataxia with epilepsy (SCAE) [MIM:607459]: An
CC autosomal recessive syndrome characterized by headaches and/or seizures
CC manifesting in childhood or adolescence, cerebellar and sensory ataxia,
CC dysarthria, and myoclonus manifesting in early adulthood.
CC Neuropathological findings include spinocerebellar degeneration
CC associated with cortical neuronal degeneration in advanced cases.
CC {ECO:0000269|PubMed:26942291}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/polg/";
CC ---------------------------------------------------------------------------
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DR EMBL; U60325; AAC50712.1; -; mRNA.
DR EMBL; X98093; CAA66719.1; -; mRNA.
DR EMBL; D84103; BAA12223.1; -; mRNA.
DR EMBL; AF497906; AAM77583.1; -; Genomic_DNA.
DR EMBL; BC042571; AAH42571.1; -; mRNA.
DR EMBL; BC050559; AAH50559.1; -; mRNA.
DR CCDS; CCDS10350.1; -.
DR PIR; G02750; G02750.
DR RefSeq; NP_001119603.1; NM_001126131.1.
DR RefSeq; NP_002684.1; NM_002693.2.
DR PDB; 3IKM; X-ray; 3.24 A; A/D=70-1239.
DR PDB; 4ZTU; X-ray; 3.30 A; A=30-1239.
DR PDB; 4ZTZ; X-ray; 3.44 A; A=30-1239.
DR PDB; 5C51; X-ray; 3.43 A; A=25-1239.
DR PDB; 5C52; X-ray; 3.64 A; A=25-1239.
DR PDB; 5C53; X-ray; 3.57 A; A=25-1239.
DR PDBsum; 3IKM; -.
DR PDBsum; 4ZTU; -.
DR PDBsum; 4ZTZ; -.
DR PDBsum; 5C51; -.
DR PDBsum; 5C52; -.
DR PDBsum; 5C53; -.
DR AlphaFoldDB; P54098; -.
DR SMR; P54098; -.
DR BioGRID; 111424; 109.
DR ComplexPortal; CPX-2093; Mitochondrial DNA polymerase gamma complex.
DR IntAct; P54098; 27.
DR MINT; P54098; -.
DR STRING; 9606.ENSP00000268124; -.
DR BindingDB; P54098; -.
DR ChEMBL; CHEMBL2732; -.
DR DrugCentral; P54098; -.
DR iPTMnet; P54098; -.
DR PhosphoSitePlus; P54098; -.
DR BioMuta; POLG; -.
DR DMDM; 1706507; -.
DR EPD; P54098; -.
DR jPOST; P54098; -.
DR MassIVE; P54098; -.
DR MaxQB; P54098; -.
DR PaxDb; P54098; -.
DR PeptideAtlas; P54098; -.
DR PRIDE; P54098; -.
DR ProteomicsDB; 56642; -.
DR Antibodypedia; 28558; 218 antibodies from 33 providers.
DR DNASU; 5428; -.
DR Ensembl; ENST00000268124.11; ENSP00000268124.5; ENSG00000140521.17.
DR Ensembl; ENST00000442287.6; ENSP00000399851.2; ENSG00000140521.17.
DR GeneID; 5428; -.
DR KEGG; hsa:5428; -.
DR MANE-Select; ENST00000268124.11; ENSP00000268124.5; NM_002693.3; NP_002684.1.
DR UCSC; uc002bnr.5; human.
DR CTD; 5428; -.
DR DisGeNET; 5428; -.
DR GeneCards; POLG; -.
DR GeneReviews; POLG; -.
DR HGNC; HGNC:9179; POLG.
DR HPA; ENSG00000140521; Low tissue specificity.
DR MalaCards; POLG; -.
DR MIM; 157640; phenotype.
DR MIM; 174763; gene.
DR MIM; 203700; phenotype.
DR MIM; 256000; phenotype.
DR MIM; 258450; phenotype.
DR MIM; 607459; phenotype.
DR MIM; 613662; phenotype.
DR neXtProt; NX_P54098; -.
DR OpenTargets; ENSG00000140521; -.
DR Orphanet; 726; Alpers-Huttenlocher syndrome.
DR Orphanet; 254892; Autosomal dominant progressive external ophthalmoplegia.
DR Orphanet; 254886; Autosomal recessive progressive external ophthalmoplegia.
DR Orphanet; 298; Mitochondrial neurogastrointestinal encephalomyopathy.
DR Orphanet; 402082; Progressive myoclonic epilepsy type 5.
DR Orphanet; 94125; Recessive mitochondrial ataxia syndrome.
DR Orphanet; 70595; Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome.
DR Orphanet; 254881; Spinocerebellar ataxia with epilepsy.
DR PharmGKB; PA33500; -.
DR VEuPathDB; HostDB:ENSG00000140521; -.
DR eggNOG; KOG3657; Eukaryota.
DR GeneTree; ENSGT00390000000453; -.
DR HOGENOM; CLU_001524_2_2_1; -.
DR InParanoid; P54098; -.
DR OMA; LWLWDED; -.
DR OrthoDB; 86850at2759; -.
DR PhylomeDB; P54098; -.
DR PathwayCommons; P54098; -.
DR SignaLink; P54098; -.
DR SIGNOR; P54098; -.
DR BioGRID-ORCS; 5428; 207 hits in 1081 CRISPR screens.
DR ChiTaRS; POLG; human.
DR GeneWiki; POLG; -.
DR GenomeRNAi; 5428; -.
DR Pharos; P54098; Tchem.
DR PRO; PR:P54098; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P54098; protein.
DR Bgee; ENSG00000140521; Expressed in granulocyte and 210 other tissues.
DR ExpressionAtlas; P54098; baseline and differential.
DR Genevisible; P54098; HS.
DR GO; GO:0005760; C:gamma DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:ComplexPortal.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:FlyBase.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0006287; P:base-excision repair, gap-filling; IDA:MGI.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:UniProtKB.
DR GO; GO:0006264; P:mitochondrial DNA replication; IDA:ComplexPortal.
DR InterPro; IPR019760; DNA-dir_DNA_pol_A_CS.
DR InterPro; IPR002297; DNA-dir_DNA_pol_A_mt.
DR InterPro; IPR001098; DNA-dir_DNA_pol_A_palm_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR041336; DNApol_Exo.
DR InterPro; IPR012337; RNaseH-like_sf.
DR PANTHER; PTHR10267; PTHR10267; 1.
DR Pfam; PF00476; DNA_pol_A; 1.
DR Pfam; PF18136; DNApol_Exo; 1.
DR PIRSF; PIRSF000797; DNA_pol_mt; 1.
DR PRINTS; PR00867; DNAPOLG.
DR SMART; SM00482; POLAc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS00447; DNA_POLYMERASE_A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; DNA replication; DNA-binding;
KW DNA-directed DNA polymerase; Epilepsy; Leigh syndrome; Magnesium;
KW Mitochondrion; Mitochondrion nucleoid; Neurodegeneration; Neuropathy;
KW Nucleotidyltransferase; Primary mitochondrial disease;
KW Progressive external ophthalmoplegia; Reference proteome; Transferase.
FT CHAIN 1..1239
FT /note="DNA polymerase subunit gamma-1"
FT /id="PRO_0000101270"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 3
FT /note="R -> P (in PEOB1; dbSNP:rs121918045)"
FT /evidence="ECO:0000269|PubMed:11431686,
FT ECO:0000269|PubMed:12565911"
FT /id="VAR_012153"
FT VARIANT 18
FT /note="P -> S (in dbSNP:rs3087373)"
FT /id="VAR_014904"
FT VARIANT 55
FT /note="Q -> QQ"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_019265"
FT VARIANT 55
FT /note="Q -> QQQ"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019266"
FT VARIANT 193
FT /note="R -> Q (in dbSNP:rs3176162)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_019267"
FT VARIANT 227
FT /note="R -> W (in PEOB1 and MTDPS4B; dbSNP:rs121918056)"
FT /evidence="ECO:0000269|PubMed:12707443,
FT ECO:0000269|PubMed:15349879, ECO:0000269|PubMed:19307547"
FT /id="VAR_023663"
FT VARIANT 232
FT /note="R -> G (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:15689359"
FT /id="VAR_058870"
FT VARIANT 232
FT /note="R -> H (in LS; dbSNP:rs113994093)"
FT /evidence="ECO:0000269|PubMed:18828154"
FT /id="VAR_058871"
FT VARIANT 244
FT /note="L -> P (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:15689359"
FT /id="VAR_058872"
FT VARIANT 251
FT /note="T -> I (in PEOB1, MTDPS4A and MTDPS4B;
FT dbSNP:rs113994094)"
FT /evidence="ECO:0000269|PubMed:12210792,
FT ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:12825077,
FT ECO:0000269|PubMed:14635118, ECO:0000269|PubMed:18828154,
FT ECO:0000269|PubMed:26942291"
FT /id="VAR_023664"
FT VARIANT 268
FT /note="G -> A (in PEOB1; sporadic case; dbSNP:rs61752784)"
FT /evidence="ECO:0000269|PubMed:14635118"
FT /id="VAR_058873"
FT VARIANT 304
FT /note="L -> R (in PEOB1; also found in SANDO;
FT dbSNP:rs121918044)"
FT /evidence="ECO:0000269|PubMed:11431686,
FT ECO:0000269|PubMed:12565911, ECO:0000269|PubMed:16639411"
FT /id="VAR_012154"
FT VARIANT 304
FT /note="L -> SANDO (in PEOB1)"
FT /id="VAR_058874"
FT VARIANT 308
FT /note="Q -> H (in PEOB1; sporadic case; dbSNP:rs745539599)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058875"
FT VARIANT 309
FT /note="R -> L (in PEOB1)"
FT /evidence="ECO:0000269|PubMed:12210792,
FT ECO:0000269|PubMed:15349879"
FT /id="VAR_023665"
FT VARIANT 312
FT /note="W -> R (in PEOB1; sporadic case)"
FT /evidence="ECO:0000269|PubMed:12707443,
FT ECO:0000269|PubMed:14635118"
FT /id="VAR_023666"
FT VARIANT 324
FT /note="P -> S (in dbSNP:rs2307437)"
FT /id="VAR_014905"
FT VARIANT 380
FT /note="G -> D (in PEOB1)"
FT /evidence="ECO:0000269|PubMed:16639411"
FT /id="VAR_058876"
FT VARIANT 431
FT /note="G -> V (in PEOB1; sporadic case)"
FT /evidence="ECO:0000269|PubMed:12707443"
FT /id="VAR_023667"
FT VARIANT 463
FT /note="L -> F (in dbSNP:rs150828914)"
FT /evidence="ECO:0000269|PubMed:17420318"
FT /id="VAR_058877"
FT VARIANT 467
FT /note="A -> T (in PEOB1, SANDO, SCAE and MTDPS4A; results
FT in clearly decreased activity, DNA binding and processivity
FT of the polymerase; dbSNP:rs113994095)"
FT /evidence="ECO:0000269|PubMed:11431686,
FT ECO:0000269|PubMed:12565911, ECO:0000269|PubMed:12707443,
FT ECO:0000269|PubMed:14635118, ECO:0000269|PubMed:14694057,
FT ECO:0000269|PubMed:15122711, ECO:0000269|PubMed:15477547,
FT ECO:0000269|PubMed:15689359, ECO:0000269|PubMed:15824347,
FT ECO:0000269|PubMed:15917273, ECO:0000269|PubMed:16639411,
FT ECO:0000269|PubMed:18828154, ECO:0000269|PubMed:26942291"
FT /id="VAR_012155"
FT VARIANT 468
FT /note="N -> D (in PEOB1; dbSNP:rs145843073)"
FT /evidence="ECO:0000269|PubMed:15351195"
FT /id="VAR_023668"
FT VARIANT 497
FT /note="Q -> H (in SANDO and SCAE; dbSNP:rs121918052)"
FT /evidence="ECO:0000269|PubMed:15824347,
FT ECO:0000269|PubMed:26942291"
FT /id="VAR_023669"
FT VARIANT 511
FT /note="S -> N (in PEOA1; dbSNP:rs121918055)"
FT /evidence="ECO:0000269|PubMed:17420318"
FT /id="VAR_058878"
FT VARIANT 517
FT /note="G -> V (in SANDO; dbSNP:rs61752783)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058879"
FT VARIANT 546
FT /note="R -> C (in dbSNP:rs2307447)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014906"
FT VARIANT 562
FT /note="R -> Q (in PEOB1; sporadic case; dbSNP:rs781168350)"
FT /evidence="ECO:0000269|PubMed:14635118"
FT /id="VAR_058880"
FT VARIANT 574
FT /note="R -> W (in PEOB1; sporadic case; dbSNP:rs774474723)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058881"
FT VARIANT 579
FT /note="R -> W (in PEOB1; dbSNP:rs556925652)"
FT /evidence="ECO:0000269|PubMed:12975295"
FT /id="VAR_023670"
FT VARIANT 587
FT /note="P -> L (in PEOB1, MTDPS4A and MTDPS4B;
FT dbSNP:rs113994096)"
FT /evidence="ECO:0000269|PubMed:12825077,
FT ECO:0000269|PubMed:12975295, ECO:0000269|PubMed:14635118,
FT ECO:0000269|PubMed:15349879, ECO:0000269|PubMed:15689359,
FT ECO:0000269|PubMed:18828154"
FT /id="VAR_023671"
FT VARIANT 603
FT /note="M -> L (in PEOB1)"
FT /evidence="ECO:0000269|PubMed:16401742"
FT /id="VAR_058882"
FT VARIANT 627
FT /note="R -> Q (in SANDO; shows DNA binding affinity and
FT processivities similar to the controls; dbSNP:rs375305567)"
FT /evidence="ECO:0000269|PubMed:15917273"
FT /id="VAR_058883"
FT VARIANT 627
FT /note="R -> W (in SANDO; sporadic case; dbSNP:rs121918046)"
FT /evidence="ECO:0000269|PubMed:12565911"
FT /id="VAR_023672"
FT VARIANT 648
FT /note="P -> R (in PEOB1; sporadic case; also in SANDO;
FT dbSNP:rs796052906)"
FT /evidence="ECO:0000269|PubMed:16621917,
FT ECO:0000269|PubMed:16919951"
FT /id="VAR_058884"
FT VARIANT 662
FT /note="E -> K (in dbSNP:rs2307450)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014907"
FT VARIANT 737
FT /note="G -> R (in PEOB1; with absence of progressive
FT external ophthalmoplegia; dbSNP:rs121918054)"
FT /evidence="ECO:0000269|PubMed:16634032"
FT /id="VAR_058885"
FT VARIANT 748
FT /note="W -> S (in SANDO, SCAE and MTDPS4A; unknown
FT pathological significance; dbSNP:rs113994097)"
FT /evidence="ECO:0000269|PubMed:15477547,
FT ECO:0000269|PubMed:15824347, ECO:0000269|PubMed:15929042,
FT ECO:0000269|PubMed:16080118, ECO:0000269|PubMed:16639411,
FT ECO:0000269|PubMed:18828154"
FT /id="VAR_023673"
FT VARIANT 767
FT /note="A -> D (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058886"
FT VARIANT 807
FT /note="R -> C (in SANDO; dbSNP:rs769827124)"
FT /evidence="ECO:0000269|PubMed:16919951"
FT /id="VAR_058887"
FT VARIANT 807
FT /note="R -> P (in PEOB1; sporadic case)"
FT /evidence="ECO:0000269|PubMed:14635118"
FT /id="VAR_058888"
FT VARIANT 831
FT /note="Y -> C (in PEOA1 and MTDPS4A; unknown pathological
FT significance; dbSNP:rs41549716)"
FT /evidence="ECO:0000269|PubMed:15534189,
FT ECO:0000269|PubMed:17846414, ECO:0000269|PubMed:18828154"
FT /id="VAR_023674"
FT VARIANT 848
FT /note="G -> S (in PEOB1, MTDPS4A, MTDPS4B and LS;
FT dbSNP:rs113994098)"
FT /evidence="ECO:0000269|PubMed:12210792,
FT ECO:0000269|PubMed:12872260, ECO:0000269|PubMed:15689359,
FT ECO:0000269|PubMed:15929042, ECO:0000269|PubMed:18828154,
FT ECO:0000269|PubMed:19307547"
FT /id="VAR_023675"
FT VARIANT 853
FT /note="R -> W (in PEOB1; with absence of progressive
FT external ophthalmoplegia; dbSNP:rs121918053)"
FT /evidence="ECO:0000269|PubMed:16401742,
FT ECO:0000269|PubMed:16634032"
FT /id="VAR_058889"
FT VARIANT 864
FT /note="N -> S (in MTDPS4B; dbSNP:rs121918050)"
FT /evidence="ECO:0000269|PubMed:12825077"
FT /id="VAR_023676"
FT VARIANT 879
FT /note="Q -> H (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058890"
FT VARIANT 885
FT /note="T -> S (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058891"
FT VARIANT 889
FT /note="A -> T (in PEOB1; dbSNP:rs763393580)"
FT /evidence="ECO:0000269|PubMed:12975295"
FT /id="VAR_023677"
FT VARIANT 914
FT /note="T -> P (in MTDPS4A; dbSNP:rs139590686)"
FT /evidence="ECO:0000269|PubMed:16621917,
FT ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:18828154"
FT /id="VAR_058892"
FT VARIANT 923
FT /note="G -> D (in PEOA1)"
FT /evidence="ECO:0000269|PubMed:12210792"
FT /id="VAR_023678"
FT VARIANT 932
FT /note="H -> Y (in SANDO and PEOB1; sporadic case;
FT dbSNP:rs121918048)"
FT /evidence="ECO:0000269|PubMed:14635118,
FT ECO:0000269|PubMed:14745080"
FT /id="VAR_023679"
FT VARIANT 943
FT /note="R -> H (in PEOA1)"
FT /evidence="ECO:0000269|PubMed:12210792"
FT /id="VAR_023680"
FT VARIANT 953
FT /note="R -> C (in PEOA1; dbSNP:rs11546842)"
FT /evidence="ECO:0000269|PubMed:15351195"
FT /id="VAR_023681"
FT VARIANT 955
FT /note="Y -> C (in PEOA1; can underlie parkinsonism; 45-fold
FT decrease in apparent binding affinity for the incoming
FT nucleoside triphosphate; 2-fold less accurate for basepair
FT substitutions than wild-type; dbSNP:rs113994099)"
FT /evidence="ECO:0000269|PubMed:11431686,
FT ECO:0000269|PubMed:11897778, ECO:0000269|PubMed:12210792,
FT ECO:0000269|PubMed:12565911, ECO:0000269|PubMed:15351195"
FT /id="VAR_012156"
FT VARIANT 957
FT /note="A -> P (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:15689359"
FT /id="VAR_058893"
FT VARIANT 957
FT /note="A -> S (in PEOA1; dbSNP:rs121918051)"
FT /evidence="ECO:0000269|PubMed:12210792"
FT /id="VAR_023682"
FT VARIANT 1047
FT /note="R -> Q (in PEOB1; sporadic case; dbSNP:rs768028281)"
FT /evidence="ECO:0000269|PubMed:12707443"
FT /id="VAR_023683"
FT VARIANT 1051
FT /note="G -> R (in SANDO; dbSNP:rs121918049)"
FT /evidence="ECO:0000269|PubMed:14745080"
FT /id="VAR_023684"
FT VARIANT 1076
FT /note="G -> V (in PEOB1)"
FT /evidence="ECO:0000269|PubMed:12975295"
FT /id="VAR_023685"
FT VARIANT 1096
FT /note="R -> C (in PEOB1 and MTDPS4A; dbSNP:rs201732356)"
FT /evidence="ECO:0000269|PubMed:12707443,
FT ECO:0000269|PubMed:25129007"
FT /id="VAR_023686"
FT VARIANT 1096
FT /note="R -> H (in MTDPS4A; dbSNP:rs368435864)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058894"
FT VARIANT 1104
FT /note="S -> C (in PEOB1; sporadic case;
FT dbSNP:rs1010372555)"
FT /evidence="ECO:0000269|PubMed:12707443"
FT /id="VAR_023687"
FT VARIANT 1105
FT /note="A -> T (in PEOB1; dbSNP:rs753410045)"
FT /evidence="ECO:0000269|PubMed:15351195"
FT /id="VAR_023688"
FT VARIANT 1106
FT /note="V -> I (in PEOB1)"
FT /evidence="ECO:0000269|PubMed:15349879"
FT /id="VAR_023689"
FT VARIANT 1110
FT /note="H -> Y (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:18828154"
FT /id="VAR_058895"
FT VARIANT 1134
FT /note="H -> R (in MTDPS4A)"
FT /evidence="ECO:0000269|PubMed:18828154"
FT /id="VAR_058896"
FT VARIANT 1136
FT /note="E -> K (in MTDPS4A; dbSNP:rs56047213)"
FT /evidence="ECO:0000269|PubMed:18828154"
FT /id="VAR_065092"
FT VARIANT 1142
FT /note="R -> W (in dbSNP:rs2307442)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014908"
FT VARIANT 1143
FT /note="E -> G (in dbSNP:rs2307441)"
FT /evidence="ECO:0000269|PubMed:14635118,
FT ECO:0000269|PubMed:15477547, ECO:0000269|PubMed:15689359,
FT ECO:0000269|PubMed:16080118, ECO:0000269|PubMed:16639411,
FT ECO:0000269|PubMed:18828154, ECO:0000269|Ref.4"
FT /id="VAR_014909"
FT VARIANT 1146
FT /note="R -> C (in PEOB1; unknown pathological significance;
FT dbSNP:rs2307440)"
FT /evidence="ECO:0000269|PubMed:16401742, ECO:0000269|Ref.4"
FT /id="VAR_014910"
FT VARIANT 1176
FT /note="S -> L (in PEOA1; dbSNP:rs776031396)"
FT /evidence="ECO:0000269|PubMed:12210792,
FT ECO:0000269|PubMed:15349879"
FT /id="VAR_023690"
FT VARIANT 1184
FT /note="D -> N (in PEOB1; dbSNP:rs1131691575)"
FT /evidence="ECO:0000269|PubMed:16401742"
FT /id="VAR_058897"
FT VARIANT 1186
FT /note="D -> H (in PEOA1)"
FT /evidence="ECO:0000269|PubMed:18575922"
FT /id="VAR_065119"
FT VARIANT 1191
FT /note="K -> N (in MTDPS4A; dbSNP:rs1085307741)"
FT /evidence="ECO:0000269|PubMed:16621917"
FT /id="VAR_058898"
FT VARIANT 1236
FT /note="Q -> H (in dbSNP:rs3087374)"
FT /evidence="ECO:0000269|PubMed:12975295,
FT ECO:0000269|PubMed:14635118, ECO:0000269|PubMed:15917273,
FT ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:18828154,
FT ECO:0000269|Ref.4"
FT /id="VAR_014911"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 97..105
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 106..111
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:5C51"
FT HELIX 135..159
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 224..227
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 243..247
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 306..317
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 356..360
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 385..415
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 422..431
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 435..438
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 440..473
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 478..480
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 483..490
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:5C51"
FT STRAND 519..521
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 537..540
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 541..558
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 559..561
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 563..568
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 571..575
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 592..595
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 597..604
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 607..610
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 616..618
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 627..629
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 636..644
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 647..671
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 716..721
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 738..740
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 743..745
FT /evidence="ECO:0007829|PDB:4ZTU"
FT TURN 755..757
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 770..775
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 776..778
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 784..786
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 787..810
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 818..821
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 822..829
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 833..835
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 837..840
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 845..848
FT /evidence="ECO:0007829|PDB:4ZTU"
FT TURN 849..851
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 853..855
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 859..861
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 867..869
FT /evidence="ECO:0007829|PDB:4ZTU"
FT TURN 870..873
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 875..878
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 884..890
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 894..906
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 907..909
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 914..919
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 924..926
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 929..937
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 944..955
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 960..969
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 974..990
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 992..995
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 997..999
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1001..1009
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1010..1013
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1027..1030
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1033..1035
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1037..1040
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 1041..1046
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1047..1058
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1061..1065
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1068..1070
FT /evidence="ECO:0007829|PDB:3IKM"
FT TURN 1073..1075
FT /evidence="ECO:0007829|PDB:5C51"
FT TURN 1081..1083
FT /evidence="ECO:0007829|PDB:4ZTU"
FT HELIX 1093..1121
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1122..1124
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1130..1133
FT /evidence="ECO:0007829|PDB:4ZTU"
FT STRAND 1136..1143
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1146..1168
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1175..1178
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1184..1188
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1193..1195
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1200..1203
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1207..1209
FT /evidence="ECO:0007829|PDB:3IKM"
FT HELIX 1220..1227
FT /evidence="ECO:0007829|PDB:3IKM"
FT STRAND 1232..1235
FT /evidence="ECO:0007829|PDB:3IKM"
SQ SEQUENCE 1239 AA; 139562 MW; 2D9ECCD75AD6E01E CRC64;
MSRLLWRKVA GATVGPGPVP APGRWVSSSV PASDPSDGQR RRQQQQQQQQ QQQQQPQQPQ
VLSSEGGQLR HNPLDIQMLS RGLHEQIFGQ GGEMPGEAAV RRSVEHLQKH GLWGQPAVPL
PDVELRLPPL YGDNLDQHFR LLAQKQSLPY LEAANLLLQA QLPPKPPAWA WAEGWTRYGP
EGEAVPVAIP EERALVFDVE VCLAEGTCPT LAVAISPSAW YSWCSQRLVE ERYSWTSQLS
PADLIPLEVP TGASSPTQRD WQEQLVVGHN VSFDRAHIRE QYLIQGSRMR FLDTMSMHMA
ISGLSSFQRS LWIAAKQGKH KVQPPTKQGQ KSQRKARRGP AISSWDWLDI SSVNSLAEVH
RLYVGGPPLE KEPRELFVKG TMKDIRENFQ DLMQYCAQDV WATHEVFQQQ LPLFLERCPH
PVTLAGMLEM GVSYLPVNQN WERYLAEAQG TYEELQREMK KSLMDLANDA CQLLSGERYK
EDPWLWDLEW DLQEFKQKKA KKVKKEPATA SKLPIEGAGA PGDPMDQEDL GPCSEEEEFQ
QDVMARACLQ KLKGTTELLP KRPQHLPGHP GWYRKLCPRL DDPAWTPGPS LLSLQMRVTP
KLMALTWDGF PLHYSERHGW GYLVPGRRDN LAKLPTGTTL ESAGVVCPYR AIESLYRKHC
LEQGKQQLMP QEAGLAEEFL LTDNSAIWQT VEELDYLEVE AEAKMENLRA AVPGQPLALT
ARGGPKDTQP SYHHGNGPYN DVDIPGCWFF KLPHKDGNSC NVGSPFAKDF LPKMEDGTLQ
AGPGGASGPR ALEINKMISF WRNAHKRISS QMVVWLPRSA LPRAVIRHPD YDEEGLYGAI
LPQVVTAGTI TRRAVEPTWL TASNARPDRV GSELKAMVQA PPGYTLVGAD VDSQELWIAA
VLGDAHFAGM HGCTAFGWMT LQGRKSRGTD LHSKTATTVG ISREHAKIFN YGRIYGAGQP
FAERLLMQFN HRLTQQEAAE KAQQMYAATK GLRWYRLSDE GEWLVRELNL PVDRTEGGWI
SLQDLRKVQR ETARKSQWKK WEVVAERAWK GGTESEMFNK LESIATSDIP RTPVLGCCIS
RALEPSAVQE EFMTSRVNWV VQSSAVDYLH LMLVAMKWLF EEFAIDGRFC ISIHDEVRYL
VREEDRYRAA LALQITNLLT RCMFAYKLGL NDLPQSVAFF SAVDIDRCLR KEVTMDCKTP
SNPTGMERRY GIPQGEALDI YQIIELTKGS LEKRSQPGP
