位置:首页 > 蛋白库 > PEO1_HUMAN
PEO1_HUMAN
ID   PEO1_HUMAN              Reviewed;         684 AA.
AC   Q96RR1; B2CQL2; Q6MZX2; Q6PJP5; Q96RR0;
DT   25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 176.
DE   RecName: Full=Twinkle mtDNA helicase {ECO:0000312|HGNC:HGNC:1160};
DE            EC=3.6.4.12 {ECO:0000269|PubMed:12975372, ECO:0000269|PubMed:17324440, ECO:0000269|PubMed:18039713, ECO:0000269|PubMed:18971204, ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949, ECO:0000269|PubMed:27226550};
DE   AltName: Full=Progressive external ophthalmoplegia 1 protein;
DE   AltName: Full=T7 gp4-like protein with intramitochondrial nucleoid localization;
DE   AltName: Full=T7-like mitochondrial DNA helicase;
DE   AltName: Full=Twinkle protein, mitochondrial {ECO:0000305};
DE   Flags: Precursor;
GN   Name=TWNK {ECO:0000312|HGNC:HGNC:1160}; Synonyms=C10orf2, PEO1;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP   SUBCELLULAR LOCATION, VARIANT ILE-368, AND VARIANTS PEOA3 LEU-315; PRO-354;
RP   THR-359; THR-367; PRO-369; GLN-374; PRO-381; CYS-474 AND PRO-475.
RX   PubMed=11431692; DOI=10.1038/90058;
RA   Spelbrink J.N., Li F.-Y., Tiranti V., Nikali K., Yuan Q.-P., Tariq M.,
RA   Wanrooij S., Garrido N., Comi G., Morandi L., Santoro L., Toscano A.,
RA   Fabrizi G.-M., Somer H., Croxen R., Beeson D., Poulton J., Suomalainen A.,
RA   Jacobs H.T., Zeviani M., Larsson C.;
RT   "Human mitochondrial DNA deletions associated with mutations in the gene
RT   for Twinkle, a phage T7 gene 4-like protein localized in mitochondria.";
RL   Nat. Genet. 28:223-231(2001).
RN   [2]
RP   ERRATUM OF PUBMED:11431692.
RA   Spelbrink J.N., Li F.-Y., Tiranti V., Nikali K., Yuan Q.-P., Tariq M.,
RA   Wanrooij S., Garrido N., Comi G., Morandi L., Santoro L., Toscano A.,
RA   Fabrizi G.-M., Somer H., Croxen R., Beeson D., Poulton J., Suomalainen A.,
RA   Jacobs H.T., Zeviani M., Larsson C.;
RL   Nat. Genet. 29:100-100(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Fetal brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-348; ILE-368 AND
RP   LYS-634.
RG   NIEHS SNPs program;
RL   Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [6]
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 132-582 (ISOFORM 2).
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   [8]
RP   FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY (ISOFORM 1).
RX   PubMed=12975372; DOI=10.1074/jbc.m306981200;
RA   Korhonen J.A., Gaspari M., Falkenberg M.;
RT   "TWINKLE has 5' -> 3' DNA helicase activity and is specifically stimulated
RT   by mitochondrial single-stranded DNA-binding protein.";
RL   J. Biol. Chem. 278:48627-48632(2003).
RN   [9]
RP   FUNCTION (ISOFORM 1), AND INTERACTION WITH POLG (ISOFORM 1).
RX   PubMed=15167897; DOI=10.1038/sj.emboj.7600257;
RA   Korhonen J.A., Pham X.H., Pellegrini M., Falkenberg M.;
RT   "Reconstitution of a minimal mtDNA replisome in vitro.";
RL   EMBO J. 23:2423-2429(2004).
RN   [10]
RP   TISSUE SPECIFICITY, AND COREGULATION WITH MRPL43.
RX   PubMed=15509589; DOI=10.1093/hmg/ddh342;
RA   Tyynismaa H., Sembongi H., Bokori-Brown M., Granycome C., Ashley N.,
RA   Poulton J., Jalanko A., Spelbrink J.N., Holt I.J., Suomalainen A.;
RT   "Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA
RT   copy number.";
RL   Hum. Mol. Genet. 13:3219-3227(2004).
RN   [11]
RP   INTERACTION WITH LONP1.
RX   PubMed=14739292; DOI=10.1074/jbc.m309642200;
RA   Liu T., Lu B., Lee I., Ondrovicova G., Kutejova E., Suzuki C.K.;
RT   "DNA and RNA binding by the mitochondrial lon protease is regulated by
RT   nucleotide and protein substrate.";
RL   J. Biol. Chem. 279:13902-13910(2004).
RN   [12]
RP   POSSIBLE MECHANISM OF DELETION FORMATION.
RX   PubMed=15181170; DOI=10.1093/nar/gkh634;
RA   Wanrooij S., Luoma P., van Goethem G., van Broeckhoven C., Suomalainen A.,
RA   Spelbrink J.N.;
RT   "Twinkle and POLG defects enhance age-dependent accumulation of mutations
RT   in the control region of mtDNA.";
RL   Nucleic Acids Res. 32:3053-3064(2004).
RN   [13]
RP   FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), AND SUBUNIT (ISOFORM
RP   1).
RX   PubMed=17324440; DOI=10.1016/j.jmb.2007.01.079;
RA   Ziebarth T.D., Farr C.L., Kaguni L.S.;
RT   "Modular architecture of the hexameric human mitochondrial DNA helicase.";
RL   J. Mol. Biol. 367:1382-1391(2007).
RN   [14]
RP   FUNCTION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY (ISOFORM 1), SUBUNIT
RP   (ISOFORMS 1 AND 2), AND DOMAIN.
RX   PubMed=18039713; DOI=10.1093/nar/gkm1025;
RA   Farge G., Holmlund T., Khvorostova J., Rofougaran R., Hofer A.,
RA   Falkenberg M.;
RT   "The N-terminal domain of TWINKLE contributes to single-stranded DNA
RT   binding and DNA helicase activities.";
RL   Nucleic Acids Res. 36:393-403(2008).
RN   [15]
RP   FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), SUBUNIT (ISOFORM 1),
RP   SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS LEU-315; GLU-319;
RP   THR-359; PRO-369; GLN-374 AND CYS-474.
RX   PubMed=18971204; DOI=10.1093/hmg/ddn359;
RA   Goffart S., Cooper H.M., Tyynismaa H., Wanrooij S., Suomalainen A.,
RA   Spelbrink J.N.;
RT   "Twinkle mutations associated with autosomal dominant progressive external
RT   ophthalmoplegia lead to impaired helicase function and in vivo mtDNA
RT   replication stalling.";
RL   Hum. Mol. Genet. 18:328-340(2009).
RN   [16]
RP   FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), ACTIVITY REGULATION
RP   (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM 1), SUBUNIT (ISOFORM
RP   1), AND MUTAGENESIS OF LYS-421.
RX   PubMed=22383523; DOI=10.1074/jbc.m111.309468;
RA   Sen D., Nandakumar D., Tang G.Q., Patel S.S.;
RT   "Human mitochondrial DNA helicase TWINKLE is both an unwinding and
RT   annealing helicase.";
RL   J. Biol. Chem. 287:14545-14556(2012).
RN   [17]
RP   FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), AND SUBUNIT (ISOFORM
RP   1).
RX   PubMed=25824949; DOI=10.1093/nar/gkv189;
RA   Fernandez-Millan P., Lazaro M., Cansiz-Arda S., Gerhold J.M., Rajala N.,
RA   Schmitz C.A., Silva-Espina C., Gil D., Bernado P., Valle M.,
RA   Spelbrink J.N., Sola M.;
RT   "The hexameric structure of the human mitochondrial replicative helicase
RT   Twinkle.";
RL   Nucleic Acids Res. 43:4284-4295(2015).
RN   [18]
RP   FUNCTION (ISOFORM 1).
RX   PubMed=26887820; DOI=10.1093/nar/gkw098;
RA   Sen D., Patel G., Patel S.S.;
RT   "Homologous DNA strand exchange activity of the human mitochondrial DNA
RT   helicase TWINKLE.";
RL   Nucleic Acids Res. 44:4200-4210(2016).
RN   [19]
RP   FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY (ISOFORM 1).
RX   PubMed=27226550; DOI=10.1074/jbc.m115.712026;
RA   Khan I., Crouch J.D., Bharti S.K., Sommers J.A., Carney S.M.,
RA   Yakubovskaya E., Garcia-Diaz M., Trakselis M.A., Brosh R.M. Jr.;
RT   "Biochemical Characterization of the Human Mitochondrial Replicative
RT   Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY
RT   TO OVERCOME BLOCKADES TO DNA UNWINDING.";
RL   J. Biol. Chem. 291:14324-14339(2016).
RN   [20]
RP   SUBUNIT (ISOFORM 1), AND CHARACTERIZATION OF PEOA3 LEU-314; GLN-334;
RP   LEU-335; PRO-369 AND PRO-381.
RX   PubMed=30496414; DOI=10.1093/hmg/ddy415;
RA   Peter B., Farge G., Pardo-Hernandez C., Taangefjord S., Falkenberg M.;
RT   "Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE
RT   helicase.";
RL   Hum. Mol. Genet. 28:1090-1099(2019).
RN   [21]
RP   VARIANTS PEOA3 LEU-335 AND TYR-369.
RX   PubMed=12163192; DOI=10.1016/s0022-510x(02)00190-9;
RA   Lewis S., Hutchison W., Thyagarajan D., Dahl H.-H.M.;
RT   "Clinical and molecular features of adPEO due to mutations in the Twinkle
RT   gene.";
RL   J. Neurol. Sci. 201:39-44(2002).
RN   [22]
RP   VARIANT ILE-368.
RX   PubMed=12557300; DOI=10.1002/ana.10430;
RA   Arenas J., Briem E., Dahl H.-H.M., Hutchison W., Lewis S., Martin M.A.,
RA   Spelbrink H., Tiranti V., Jacobs H., Zeviani M.;
RT   "The V368I mutation in Twinkle does not segregate with AdPEO.";
RL   Ann. Neurol. 53:278-278(2003).
RN   [23]
RP   VARIANT PEO GLN-334.
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   [24]
RP   VARIANTS PEO TRP-303 AND GLN-334.
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   [25]
RP   VARIANT PEOA3 THR-319.
RX   PubMed=12921794; DOI=10.1016/s0960-8966(03)00071-3;
RA   Deschauer M., Kiefer R., Blakely E.L., He L., Zierz S., Turnbull D.M.,
RA   Taylor R.W.;
RT   "A novel Twinkle gene mutation in autosomal dominant progressive external
RT   ophthalmoplegia.";
RL   Neuromuscul. Disord. 13:568-572(2003).
RN   [26]
RP   VARIANT MTDPS7 CYS-508.
RX   PubMed=16135556; DOI=10.1093/hmg/ddi328;
RA   Nikali K., Suomalainen A., Saharinen J., Kuokkanen M., Spelbrink J.N.,
RA   Loennqvist T., Peltonen L.;
RT   "Infantile onset spinocerebellar ataxia is caused by recessive mutations in
RT   mitochondrial proteins Twinkle and Twinky.";
RL   Hum. Mol. Genet. 14:2981-2990(2005).
RN   [27]
RP   VARIANT PEOA3 GLU-319.
RX   PubMed=15668446; DOI=10.1212/01.wnl.0000149767.51152.83;
RA   Hudson G., Deschauer M., Busse K., Zierz S., Chinnery P.F.;
RT   "Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable
RT   germline mosaicism.";
RL   Neurology 64:371-373(2005).
RN   [28]
RP   VARIANT PEOA3 GLN-374, AND VARIANT ILE-368.
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   [29]
RP   VARIANT MTDPS7 ILE-457, AND CHARACTERIZATION OF VARIANT MTDPS7 ILE-457.
RX   PubMed=17722119; DOI=10.1002/ana.21207;
RA   Sarzi E., Goffart S., Serre V., Chretien D., Slama A., Munnich A.,
RA   Spelbrink J.N., Roetig A.;
RT   "Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA
RT   depletion.";
RL   Ann. Neurol. 62:579-587(2007).
RN   [30]
RP   VARIANTS MTDPS7 THR-318 AND CYS-508.
RX   PubMed=17921179; DOI=10.1093/brain/awm242;
RA   Hakonen A.H., Isohanni P., Paetau A., Herva R., Suomalainen A.,
RA   Lonnqvist T.;
RT   "Recessive Twinkle mutations in early onset encephalopathy with mtDNA
RT   depletion.";
RL   Brain 130:3032-3040(2007).
RN   [31]
RP   VARIANT PEOA3 PRO-357.
RX   PubMed=17614277; DOI=10.1016/j.nmd.2007.05.006;
RA   Rivera H., Blazquez A., Carretero J., Alvarez-Cermeno J.C., Campos Y.,
RA   Cabello A., Gonzalez-Vioque E., Borstein B., Garesse R., Arenas J.,
RA   Martin M.A.;
RT   "Mild ocular myopathy associated with a novel mutation in mitochondrial
RT   twinkle helicase.";
RL   Neuromuscul. Disord. 17:677-680(2007).
RN   [32]
RP   VARIANTS PEOA3 TRP-303; SER-315; PRO-334; ASN-426; SER-474; ILE-478 AND
RP   LYS-479.
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   [33]
RP   VARIANT PEOA3 LEU-370.
RX   PubMed=18396044; DOI=10.1016/j.nmd.2007.10.007;
RA   Jeppesen T.D., Schwartz M., Colding-Jorgensen E., Krag T., Hauerslev S.,
RA   Vissing J.;
RT   "Phenotype and clinical course in a family with a new de novo Twinkle gene
RT   mutation.";
RL   Neuromuscul. Disord. 18:306-309(2008).
RN   [34]
RP   VARIANT PEOA3 GLN-303.
RX   PubMed=19353676; DOI=10.1002/ajmg.a.32731;
RA   Van Hove J.L., Cunningham V., Rice C., Ringel S.P., Zhang Q., Chou P.C.,
RA   Truong C.K., Wong L.J.;
RT   "Finding twinkle in the eyes of a 71-year-old lady: a case report and
RT   review of the genotypic and phenotypic spectrum of TWINKLE-related dominant
RT   disease.";
RL   Am. J. Med. Genet. A 149:861-867(2009).
RN   [35]
RP   VARIANT PEOA3 TRP-303.
RX   PubMed=19428252; DOI=10.1016/j.nmd.2009.04.008;
RA   Negro R., Zoccolella S., Dell'aglio R., Amati A., Artuso L., Bisceglia L.,
RA   Lavolpe V., Papa S., Serlenga L., Petruzzella V.;
RT   "Molecular analysis in a family presenting with a mild form of late-onset
RT   autosomal dominant chronic progressive external ophthalmoplegia.";
RL   Neuromuscul. Disord. 19:423-426(2009).
RN   [36]
RP   VARIANT MTDPS7 GLY-360.
RX   PubMed=19853444; DOI=10.1016/j.nmd.2009.10.002;
RA   Bohlega S., Van Goethem G., Al Semari A., Lofgren A., Al Hamed M.,
RA   Van Broeckhoven C., Kambouris M.;
RT   "Novel Twinkle gene mutation in autosomal dominant progressive external
RT   ophthalmoplegia and multisystem failure.";
RL   Neuromuscul. Disord. 19:845-848(2009).
RN   [37]
RP   VARIANTS PEOA3 GLN-303; TRP-303; GLN-334; PRO-354; PRO-357; THR-359;
RP   PRO-362; LEU-363; CYS-370; GLN-374; PRO-381; HIS-458; PRO-460; ASP-475 AND
RP   LYS-479.
RX   PubMed=20479361; DOI=10.1212/wnl.0b013e3181df099f;
RA   Fratter C., Gorman G.S., Stewart J.D., Buddles M., Smith C., Evans J.,
RA   Seller A., Poulton J., Roberts M., Hanna M.G., Rahman S., Omer S.E.,
RA   Klopstock T., Schoser B., Kornblum C., Czermin B., Lecky B., Blakely E.L.,
RA   Craig K., Chinnery P.F., Turnbull D.M., Horvath R., Taylor R.W.;
RT   "The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-
RT   linked adPEO.";
RL   Neurology 74:1619-1626(2010).
RN   [38]
RP   VARIANT PEOA3 GLN-374.
RX   PubMed=20880070; DOI=10.1111/j.1468-1331.2010.03171.x;
RA   Martin-Negrier M.L., Sole G., Jardel C., Vital C., Ferrer X., Vital A.;
RT   "TWINKLE gene mutation: report of a French family with an autosomal
RT   dominant progressive external ophthalmoplegia and literature review.";
RL   Eur. J. Neurol. 18:436-441(2011).
RN   [39]
RP   VARIANT MTDPS7 VAL-456.
RX   PubMed=22353293; DOI=10.1016/j.pediatrneurol.2011.12.006;
RA   Dundar H., Ozgul R.K., Yalnizoglu D., Erdem S., Oguz K.K., Tuncel D.,
RA   Temucin C.M., Dursun A.;
RT   "Identification of a novel Twinkle mutation in a family with infantile
RT   onset spinocerebellar ataxia by whole exome sequencing.";
RL   Pediatr. Neurol. 46:172-177(2012).
RN   [40]
RP   INVOLVEMENT IN PRLTS5, AND VARIANTS PRLTS5 HIS-391; GLY-441; ILE-507 AND
RP   SER-585.
RX   PubMed=25355836; DOI=10.1212/wnl.0000000000001036;
RA   Morino H., Pierce S.B., Matsuda Y., Walsh T., Ohsawa R., Newby M.,
RA   Hiraki-Kamon K., Kuramochi M., Lee M.K., Klevit R.E., Martin A.,
RA   Maruyama H., King M.C., Kawakami H.;
RT   "Mutations in Twinkle primase-helicase cause Perrault syndrome with
RT   neurologic features.";
RL   Neurology 83:2054-2061(2014).
CC   -!- FUNCTION: [Isoform 1]: Mitochondrial helicase involved in mtDNA
CC       replication and repair (PubMed:12975372, PubMed:15167897,
CC       PubMed:17324440, PubMed:18039713, PubMed:18971204, PubMed:25824949,
CC       PubMed:26887820, PubMed:27226550). Might have a role in mtDNA repair
CC       (PubMed:27226550). Has DNA strand separation activity needed to form a
CC       processive replication fork for leading strand synthesis which is
CC       catalyzed by the formation of a replisome complex with POLG and mtSDB
CC       (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523,
CC       PubMed:26887820, PubMed:27226550). Preferentially unwinds DNA
CC       substrates with pre-existing 5'-and 3'- single-stranded tails but is
CC       also active on a 5'- flap substrate (PubMed:12975372, PubMed:15167897,
CC       PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550).
CC       Can dissociate the invading strand of immobile or mobile D-loop DNA
CC       structures irrespective of the single strand polarity of the third
CC       strand (PubMed:27226550). In addition to its DNA strand separation
CC       activity, also has DNA strand annealing, DNA strand-exchange and DNA
CC       branch migration activities (PubMed:22383523, PubMed:26887820,
CC       PubMed:27226550). {ECO:0000269|PubMed:12975372,
CC       ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:17324440,
CC       ECO:0000269|PubMed:18039713, ECO:0000269|PubMed:18971204,
CC       ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949,
CC       ECO:0000269|PubMed:26887820, ECO:0000269|PubMed:27226550}.
CC   -!- FUNCTION: [Isoform 2]: Lack DNA unwinding and ATP hydrolysis activities
CC       (PubMed:18039713). Does not bind single-stranded or double-stranded DNA
CC       (PubMed:18039713). {ECO:0000269|PubMed:18039713}.
CC   -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC         Evidence={ECO:0000269|PubMed:12975372, ECO:0000269|PubMed:17324440,
CC         ECO:0000269|PubMed:18039713, ECO:0000269|PubMed:18971204,
CC         ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949,
CC         ECO:0000269|PubMed:27226550};
CC   -!- ACTIVITY REGULATION: [Isoform 1]: Strand annealing activity is
CC       inhibited by 150 mM NaCl (in vitro). {ECO:0000269|PubMed:22383523}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC       Kinetic parameters:
CC         KM=1.7 mM for UTP (using ssM13mp18 as DNA substrate)
CC         {ECO:0000269|PubMed:22383523};
CC         KM=1.6 mM for UTP (using ssDNA as DNA substrate)
CC         {ECO:0000269|PubMed:22383523};
CC         KM=1.4 mM for UTP (using forked dsDNA as DNA substrate)
CC         {ECO:0000269|PubMed:22383523};
CC         KM=3.4 mM for UTP (using no DNA as substrate)
CC         {ECO:0000269|PubMed:22383523};
CC   -!- SUBUNIT: Interacts with LONP1. {ECO:0000269|PubMed:14739292}.
CC   -!- SUBUNIT: [Isoform 1]: Homohexamer (via C-terminus) which assembled in a
CC       ring-like structure (PubMed:18039713, PubMed:17324440, PubMed:22383523,
CC       PubMed:25824949, PubMed:30496414, PubMed:18971204). Homoheptamer which
CC       assembled in a ring-like structure (PubMed:25824949, PubMed:30496414).
CC       Oligomerization is Mg(2+), nucleotide and DNA-independent, however,
CC       Mg(2+) and nucleotide stabilize the homohexameric form
CC       (PubMed:18039713). Interacts with POLG in vitro (PubMed:15167897).
CC       {ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:17324440,
CC       ECO:0000269|PubMed:18039713, ECO:0000269|PubMed:18971204,
CC       ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949,
CC       ECO:0000269|PubMed:30496414}.
CC   -!- SUBUNIT: [Isoform 2]: Monomer (PubMed:18039713). Does not form
CC       oligomers (PubMed:18039713). {ECO:0000269|PubMed:18039713}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix, mitochondrion nucleoid
CC       {ECO:0000269|PubMed:11431692, ECO:0000269|PubMed:18971204}.
CC       Note=Colocalizes with mtDNA in mitochondrial nucleoids, a
CC       nucleoproteins complex consisting of a number of copies of proteins
CC       associated with mtDNA, probably involved in mtDNA maintenance and
CC       expression. {ECO:0000269|PubMed:11431692}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q96RR1-1; Sequence=Displayed;
CC       Name=2; Synonyms=Twinky;
CC         IsoId=Q96RR1-2; Sequence=VSP_015960, VSP_015961;
CC       Name=3;
CC         IsoId=Q96RR1-3; Sequence=VSP_015959;
CC   -!- TISSUE SPECIFICITY: High relative levels in skeletal muscle, testis and
CC       pancreas. Lower levels of expression in the heart, brain, placenta,
CC       lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine,
CC       colon and leukocytes. Expression is coregulated with MRPL43.
CC       {ECO:0000269|PubMed:11431692, ECO:0000269|PubMed:15509589}.
CC   -!- DOMAIN: N-terminus enhances protein stability and hexamer formation,
CC       which is important for DNA binding, and is required for DNA helicase
CC       activity and, ultimately, for mtDNA replisome processivity.
CC       {ECO:0000269|PubMed:18039713}.
CC   -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC       deletions, autosomal dominant, 3 (PEOA3) [MIM:609286]: 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:11431692,
CC       ECO:0000269|PubMed:12163192, ECO:0000269|PubMed:12921794,
CC       ECO:0000269|PubMed:15668446, ECO:0000269|PubMed:16639411,
CC       ECO:0000269|PubMed:17614277, ECO:0000269|PubMed:18396044,
CC       ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:19353676,
CC       ECO:0000269|PubMed:19428252, ECO:0000269|PubMed:20479361,
CC       ECO:0000269|PubMed:20880070}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Mitochondrial DNA depletion syndrome 7 (MTDPS7) [MIM:271245]:
CC       A severe disease associated with mitochondrial dysfunction. Some
CC       patients are affected by progressive atrophy of the cerebellum, brain
CC       stem, the spinal cord, and sensory axonal neuropathy. Clinical features
CC       include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural
CC       hearing deficit, sensory axonal neuropathy, epileptic encephalopathy
CC       and female hypogonadism. In some individuals liver dysfunction and
CC       multi-organ failure is present. {ECO:0000269|PubMed:16135556,
CC       ECO:0000269|PubMed:17722119, ECO:0000269|PubMed:17921179,
CC       ECO:0000269|PubMed:19853444, ECO:0000269|PubMed:22353293}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Perrault syndrome 5 (PRLTS5) [MIM:616138]: A form of Perrault
CC       syndrome, a sex-influenced disorder characterized by sensorineural
CC       deafness in both males and females, and ovarian dysgenesis in females.
CC       Affected females have primary amenorrhea, streak gonads, and
CC       infertility, whereas affected males show normal pubertal development
CC       and are fertile. {ECO:0000269|PubMed:25355836}. Note=The disease is
CC       caused by variants affecting the gene represented in this entry.
CC   -!- CAUTION: The N-terminus contains a putative primase-like domain;
CC       however the absence of the zinc binding domain and other motifs
CC       important for catalysis suggests that TWNK lacks primase activity.
CC       {ECO:0000305|PubMed:25824949}.
CC   -!- CAUTION: In vitro, can catalyze the hydrolysis of different nucleotide
CC       triphosphate (NTP) substrates with different efficiency.
CC       {ECO:0000269|PubMed:12975372, ECO:0000269|PubMed:18971204,
CC       ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/peo1/";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF292004; AAK69558.1; -; mRNA.
DR   EMBL; AF292005; AAK69559.1; -; mRNA.
DR   EMBL; BX640829; CAE45905.1; -; mRNA.
DR   EMBL; AL133215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; EU543650; ACB21043.1; -; Genomic_DNA.
DR   EMBL; CH471066; EAW49794.1; -; Genomic_DNA.
DR   EMBL; BC013349; AAH13349.1; -; mRNA.
DR   CCDS; CCDS53570.1; -. [Q96RR1-2]
DR   CCDS; CCDS7506.1; -. [Q96RR1-1]
DR   RefSeq; NP_001157284.1; NM_001163812.1. [Q96RR1-2]
DR   RefSeq; NP_068602.2; NM_021830.4. [Q96RR1-1]
DR   AlphaFoldDB; Q96RR1; -.
DR   SMR; Q96RR1; -.
DR   BioGRID; 121166; 128.
DR   IntAct; Q96RR1; 44.
DR   MINT; Q96RR1; -.
DR   STRING; 9606.ENSP00000309595; -.
DR   iPTMnet; Q96RR1; -.
DR   PhosphoSitePlus; Q96RR1; -.
DR   BioMuta; TWNK; -.
DR   DMDM; 74752111; -.
DR   EPD; Q96RR1; -.
DR   jPOST; Q96RR1; -.
DR   MassIVE; Q96RR1; -.
DR   MaxQB; Q96RR1; -.
DR   PaxDb; Q96RR1; -.
DR   PeptideAtlas; Q96RR1; -.
DR   PRIDE; Q96RR1; -.
DR   ProteomicsDB; 78006; -. [Q96RR1-1]
DR   ProteomicsDB; 78007; -. [Q96RR1-2]
DR   ProteomicsDB; 78008; -. [Q96RR1-3]
DR   Antibodypedia; 1261; 228 antibodies from 25 providers.
DR   DNASU; 56652; -.
DR   Ensembl; ENST00000311916.8; ENSP00000309595.2; ENSG00000107815.10. [Q96RR1-1]
DR   Ensembl; ENST00000370228.2; ENSP00000359248.1; ENSG00000107815.10. [Q96RR1-2]
DR   Ensembl; ENST00000643860.1; ENSP00000494389.1; ENSG00000107815.10. [Q96RR1-3]
DR   GeneID; 56652; -.
DR   KEGG; hsa:56652; -.
DR   MANE-Select; ENST00000311916.8; ENSP00000309595.2; NM_021830.5; NP_068602.2.
DR   UCSC; uc001ksf.3; human. [Q96RR1-1]
DR   CTD; 56652; -.
DR   DisGeNET; 56652; -.
DR   GeneCards; TWNK; -.
DR   GeneReviews; TWNK; -.
DR   HGNC; HGNC:1160; TWNK.
DR   HPA; ENSG00000107815; Low tissue specificity.
DR   MalaCards; TWNK; -.
DR   MIM; 271245; phenotype.
DR   MIM; 606075; gene.
DR   MIM; 609286; phenotype.
DR   MIM; 616138; phenotype.
DR   neXtProt; NX_Q96RR1; -.
DR   OpenTargets; ENSG00000107815; -.
DR   Orphanet; 254892; Autosomal dominant progressive external ophthalmoplegia.
DR   Orphanet; 1186; Infantile-onset spinocerebellar ataxia.
DR   Orphanet; 363534; Mitochondrial DNA depletion syndrome, hepatocerebrorenal form.
DR   Orphanet; 2855; Perrault syndrome.
DR   Orphanet; 70595; Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome.
DR   PharmGKB; PA162377675; -.
DR   VEuPathDB; HostDB:ENSG00000107815; -.
DR   eggNOG; KOG2373; Eukaryota.
DR   GeneTree; ENSGT00390000004495; -.
DR   HOGENOM; CLU_012336_1_0_1; -.
DR   InParanoid; Q96RR1; -.
DR   OMA; RPGAYHN; -.
DR   PhylomeDB; Q96RR1; -.
DR   TreeFam; TF105994; -.
DR   BRENDA; 3.6.4.12; 2681.
DR   PathwayCommons; Q96RR1; -.
DR   Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR   SignaLink; Q96RR1; -.
DR   BioGRID-ORCS; 56652; 325 hits in 1071 CRISPR screens.
DR   ChiTaRS; TWNK; human.
DR   GeneWiki; PEO1; -.
DR   GenomeRNAi; 56652; -.
DR   Pharos; Q96RR1; Tbio.
DR   PRO; PR:Q96RR1; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q96RR1; protein.
DR   Bgee; ENSG00000107815; Expressed in gastrocnemius and 137 other tissues.
DR   ExpressionAtlas; Q96RR1; baseline and differential.
DR   Genevisible; Q96RR1; HS.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0003678; F:DNA helicase activity; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR   GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR   GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:FlyBase.
DR   GO; GO:0006264; P:mitochondrial DNA replication; IMP:UniProtKB.
DR   GO; GO:0006390; P:mitochondrial transcription; IMP:UniProtKB.
DR   GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB.
DR   CDD; cd01029; TOPRIM_primases; 1.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR007694; DNA_helicase_DnaB-like_C.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR034154; TOPRIM_DnaG/twinkle.
DR   InterPro; IPR027032; Twinkle-like.
DR   PANTHER; PTHR12873; PTHR12873; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   PROSITE; PS51199; SF4_HELICASE; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Deafness; Disease variant;
KW   DNA replication; Helicase; Hydrolase; Mitochondrion;
KW   Mitochondrion nucleoid; Neurodegeneration; Neuropathy; Nucleotide-binding;
KW   Primary mitochondrial disease; Progressive external ophthalmoplegia;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..31
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           32..684
FT                   /note="Twinkle mtDNA helicase"
FT                   /id="PRO_0000042640"
FT   DOMAIN          384..635
FT                   /note="SF4 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00596"
FT   REGION          1..121
FT                   /note="Contributes to single strand DNA binding activity"
FT                   /evidence="ECO:0000269|PubMed:18039713"
FT   REGION          121..372
FT                   /note="Required for hexamers formation and DNA helicase
FT                   activity"
FT                   /evidence="ECO:0000269|PubMed:18039713"
FT   REGION          405..590
FT                   /note="Maybe required for stable oligomeric structure"
FT                   /evidence="ECO:0000269|PubMed:17324440"
FT   REGION          637..684
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          640..684
FT                   /note="Might negatively regulate ATPase activity"
FT                   /evidence="ECO:0000269|PubMed:17324440"
FT   COMPBIAS        655..678
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         415..422
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00596"
FT   VAR_SEQ         532..684
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_015959"
FT   VAR_SEQ         579..582
FT                   /note="ASQE -> VSGL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11431692,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_015960"
FT   VAR_SEQ         583..684
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11431692,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_015961"
FT   VARIANT         303
FT                   /note="R -> Q (in PEOA3; dbSNP:rs137852956)"
FT                   /evidence="ECO:0000269|PubMed:19353676,
FT                   ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065102"
FT   VARIANT         303
FT                   /note="R -> W (in PEOA3; also detected in a case showing
FT                   digenic inheritance; dbSNP:rs1159929268)"
FT                   /evidence="ECO:0000269|PubMed:12707443,
FT                   ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:19428252,
FT                   ECO:0000269|PubMed:20479361"
FT                   /id="VAR_023647"
FT   VARIANT         315
FT                   /note="W -> L (in PEOA3; reduced single-strand DNA binding;
FT                   increased heptamer oligomerization; dbSNP:rs111033575)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:30496414"
FT                   /id="VAR_023648"
FT   VARIANT         315
FT                   /note="W -> S (in PEOA3; reduces helicase activity; reduced
FT                   single-strand DNA binding)"
FT                   /evidence="ECO:0000269|PubMed:18575922,
FT                   ECO:0000269|PubMed:18971204"
FT                   /id="VAR_065103"
FT   VARIANT         318
FT                   /note="A -> T (in MTDPS7; dbSNP:rs80356542)"
FT                   /evidence="ECO:0000269|PubMed:17921179"
FT                   /id="VAR_065104"
FT   VARIANT         319
FT                   /note="K -> E (in PEOA3; the phenotype highly overlaps with
FT                   sensory ataxic neuropathy dysarthria and ophthalmoparesis;
FT                   reduces helicase activity and single-strand DNA binding;
FT                   dbSNP:rs80356543)"
FT                   /evidence="ECO:0000269|PubMed:15668446,
FT                   ECO:0000269|PubMed:18971204"
FT                   /id="VAR_023649"
FT   VARIANT         319
FT                   /note="K -> T (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:12921794"
FT                   /id="VAR_023650"
FT   VARIANT         334
FT                   /note="R -> P (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:18575922"
FT                   /id="VAR_065105"
FT   VARIANT         334
FT                   /note="R -> Q (in PEO; sporadic case; the patient also
FT                   carries the S-848 mutation in the POLG gene suggesting
FT                   digenic inheritance; retains hexamer and heptamer
FT                   formation; dbSNP:rs28937887)"
FT                   /evidence="ECO:0000269|PubMed:12707443,
FT                   ECO:0000269|PubMed:12872260, ECO:0000269|PubMed:20479361,
FT                   ECO:0000269|PubMed:30496414"
FT                   /id="VAR_023651"
FT   VARIANT         335
FT                   /note="P -> L (in PEOA3; displays unusual oligomeric
FT                   forms)"
FT                   /evidence="ECO:0000269|PubMed:12163192,
FT                   ECO:0000269|PubMed:30496414"
FT                   /id="VAR_023652"
FT   VARIANT         348
FT                   /note="G -> R (in dbSNP:rs62626271)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_062268"
FT   VARIANT         354
FT                   /note="R -> P (in PEOA3; dbSNP:rs111033576)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:20479361"
FT                   /id="VAR_023653"
FT   VARIANT         357
FT                   /note="R -> P (in PEOA3; dbSNP:rs758026634)"
FT                   /evidence="ECO:0000269|PubMed:17614277,
FT                   ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065106"
FT   VARIANT         359
FT                   /note="A -> T (in PEOA3; reduces helicase activity;
FT                   dbSNP:rs111033573)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:18971204, ECO:0000269|PubMed:20479361"
FT                   /id="VAR_023654"
FT   VARIANT         360
FT                   /note="L -> G (in MTDPS7; patients manifest multi-organ
FT                   failure; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:19853444"
FT                   /id="VAR_065107"
FT   VARIANT         362
FT                   /note="A -> P (in PEOA3; dbSNP:rs1554887075)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065108"
FT   VARIANT         363
FT                   /note="W -> L (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065109"
FT   VARIANT         367
FT                   /note="I -> T (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:11431692"
FT                   /id="VAR_023655"
FT   VARIANT         368
FT                   /note="V -> I (in dbSNP:rs17113613)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:12557300, ECO:0000269|PubMed:16639411,
FT                   ECO:0000269|Ref.4"
FT                   /id="VAR_023656"
FT   VARIANT         369
FT                   /note="S -> P (in PEOA3; reduces helicase activity;
FT                   increases single strand DNA affinity; reduces closed-ring
FT                   quaternary structure formation)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:18971204, ECO:0000269|PubMed:30496414"
FT                   /id="VAR_023657"
FT   VARIANT         369
FT                   /note="S -> Y (in PEOA3; dbSNP:rs111033579)"
FT                   /evidence="ECO:0000269|PubMed:12163192"
FT                   /id="VAR_023658"
FT   VARIANT         370
FT                   /note="F -> C (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065110"
FT   VARIANT         370
FT                   /note="F -> L (in PEOA3; dbSNP:rs863223920)"
FT                   /evidence="ECO:0000269|PubMed:18396044"
FT                   /id="VAR_065111"
FT   VARIANT         374
FT                   /note="R -> Q (in PEOA3; reduces helicase activity and
FT                   alters nucleoid structure; dbSNP:rs1554887097)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:18971204,
FT                   ECO:0000269|PubMed:20479361, ECO:0000269|PubMed:20880070"
FT                   /id="VAR_023659"
FT   VARIANT         381
FT                   /note="L -> P (in PEOA3; reduces closed-ring quaternary
FT                   structure formation; dbSNP:rs111033577)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:20479361, ECO:0000269|PubMed:30496414"
FT                   /id="VAR_023660"
FT   VARIANT         391
FT                   /note="R -> H (in PRLTS5; dbSNP:rs556445621)"
FT                   /evidence="ECO:0000269|PubMed:25355836"
FT                   /id="VAR_072657"
FT   VARIANT         426
FT                   /note="S -> N (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:18575922"
FT                   /id="VAR_065112"
FT   VARIANT         427
FT                   /note="E -> G (in dbSNP:rs11542126)"
FT                   /id="VAR_051267"
FT   VARIANT         441
FT                   /note="W -> G (in PRLTS5; dbSNP:rs672601361)"
FT                   /evidence="ECO:0000269|PubMed:25355836"
FT                   /id="VAR_072658"
FT   VARIANT         456
FT                   /note="L -> V (in MTDPS7; infantile spinocerebellar ataxia
FT                   phenotype; dbSNP:rs386834145)"
FT                   /evidence="ECO:0000269|PubMed:22353293"
FT                   /id="VAR_067722"
FT   VARIANT         457
FT                   /note="T -> I (in MTDPS7; affects helicase activity;
FT                   dbSNP:rs80356544)"
FT                   /evidence="ECO:0000269|PubMed:17722119"
FT                   /id="VAR_039045"
FT   VARIANT         458
FT                   /note="Q -> H (in PEOA3; dbSNP:rs1554887213)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065113"
FT   VARIANT         460
FT                   /note="A -> P (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065114"
FT   VARIANT         474
FT                   /note="W -> C (in PEOA3; reduces helicase activity and
FT                   alters nucleoid structure; dbSNP:rs111033574)"
FT                   /evidence="ECO:0000269|PubMed:11431692,
FT                   ECO:0000269|PubMed:18971204"
FT                   /id="VAR_023661"
FT   VARIANT         474
FT                   /note="W -> S (in PEOA3; dbSNP:rs11542127)"
FT                   /evidence="ECO:0000269|PubMed:18575922"
FT                   /id="VAR_065115"
FT   VARIANT         475
FT                   /note="A -> D (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065116"
FT   VARIANT         475
FT                   /note="A -> P (in PEOA3; dbSNP:rs111033572)"
FT                   /evidence="ECO:0000269|PubMed:11431692"
FT                   /id="VAR_023662"
FT   VARIANT         478
FT                   /note="F -> I (in PEOA3)"
FT                   /evidence="ECO:0000269|PubMed:18575922"
FT                   /id="VAR_065117"
FT   VARIANT         479
FT                   /note="E -> K (in PEOA3; dbSNP:rs1085307937)"
FT                   /evidence="ECO:0000269|PubMed:18575922,
FT                   ECO:0000269|PubMed:20479361"
FT                   /id="VAR_065118"
FT   VARIANT         507
FT                   /note="V -> I (in PRLTS5; dbSNP:rs369588002)"
FT                   /evidence="ECO:0000269|PubMed:25355836"
FT                   /id="VAR_072659"
FT   VARIANT         508
FT                   /note="Y -> C (in MTDPS7; dbSNP:rs80356540)"
FT                   /evidence="ECO:0000269|PubMed:16135556,
FT                   ECO:0000269|PubMed:17921179"
FT                   /id="VAR_043797"
FT   VARIANT         585
FT                   /note="N -> S (in PRLTS5; dbSNP:rs672601360)"
FT                   /evidence="ECO:0000269|PubMed:25355836"
FT                   /id="VAR_072660"
FT   VARIANT         634
FT                   /note="N -> K (in dbSNP:rs62626293)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_062269"
FT   MUTAGEN         421
FT                   /note="K->A: Loss of helicase activity on 5'-tailed
FT                   substrate."
FT                   /evidence="ECO:0000269|PubMed:22383523"
FT   CONFLICT        351
FT                   /note="N -> D (in Ref. 3; CAE45905)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   684 AA;  77154 MW;  58186043888234DA CRC64;
     MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI
     RQYLRGHGIP FQDGHSCLRA LSPFAESSQL KGQTGVTTSF SLFIDKTTGH FLCMTSLAEG
     SWEDFQASVE GRGDGAREGF LLSKAPEFED SEEVRRIWNR AIPLWELPDQ EEVQLADTMF
     GLTKVTDDTL KRFSVRYLRP ARSLVFPWFS PGGSGLRGLK LLEAKCQGDG VSYEETTIPR
     PSAYHNLFGL PLISRRDAEV VLTSRELDSL ALNQSTGLPT LTLPRGTTCL PPALLPYLEQ
     FRRIVFWLGD DLRSWEAAKL FARKLNPKRC FLVRPGDQQP RPLEALNGGF NLSRILRTAL
     PAWHKSIVSF RQLREEVLGE LSNVEQAAGL RWSRFPDLNR ILKGHRKGEL TVFTGPTGSG
     KTTFISEYAL DLCSQGVNTL WGSFEISNVR LARVMLTQFA EGRLEDQLDK YDHWADRFED
     LPLYFMTFHG QQSIRTVIDT MQHAVYVYDI CHVIIDNLQF MMGHEQLSTD RIAAQDYIIG
     VFRKFATDNN CHVTLVIHPR KEDDDKELQT ASIFGSAKAS QEADNVLILQ DRKLVTGPGK
     RYLQVSKNRF DGDVGVFPLE FNKNSLTFSI PPKNKARLKK IKDDTGPVAK KPSSGKKGAT
     TQNSEICSGQ APTPDQPDTS KRSK
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024