PEO1_MOUSE
ID PEO1_MOUSE Reviewed; 685 AA.
AC Q8CIW5; Q8K1Z1;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Twinkle mtDNA helicase {ECO:0000312|MGI:MGI:2137410};
DE EC=3.6.4.12 {ECO:0000250|UniProtKB:Q96RR1};
DE AltName: Full=Progressive external ophthalmoplegia 1 protein homolog;
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|MGI:MGI:2137410}; Synonyms=Peo1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fibroblast;
RA Spelbrink J.N.;
RT "Cloning of full length Mus musculus Twinkle cDNA.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Liver;
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 [4]
RP TISSUE SPECIFICITY, COREGULATION WITH MRPL43, AND FUNCTION.
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).
CC -!- FUNCTION: Mitochondrial helicase involved in mtDNA replication and
CC repair (By similarity). Might have a role in mtDNA repair (By
CC similarity). 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 (By similarity). Preferentially unwinds DNA substrates with pre-
CC existing 5'-and 3'- single-stranded tails but is also active on a
CC 5'- flap substrate (By similarity). Can dissociate the invading strand
CC of immobile or mobile D-loop DNA structures irrespective of the single
CC strand polarity of the third strand (By similarity). In addition to its
CC DNA strand separation activity, also has DNA strand annealing, DNA
CC strand-exchange and DNA branch migration activities (By similarity).
CC {ECO:0000250|UniProtKB:Q96RR1}.
CC -!- CATALYTIC ACTIVITY:
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:0000250|UniProtKB:Q96RR1};
CC -!- SUBUNIT: Homohexamer (via C-terminus) which assembled in a ring-like
CC structure. Homoheptamer which assembled in a ring-like structure.
CC Oligomerization is Mg(2+), nucleotide and DNA-independent, however,
CC Mg(2+) and nucleotide stabilize the homohexameric form. Interacts with
CC POLG in vitro. Interacts with LONP1. {ECO:0000250|UniProtKB:Q96RR1}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix, mitochondrion nucleoid
CC {ECO:0000250|UniProtKB:Q96RR1}. Note=Colocalizes with mtDNA in
CC mitochondrial nucleoids, a nucleoproteins complex consisting of a
CC number of copies of proteins associated with mtDNA, probably involved
CC in mtDNA maintenance and expression. {ECO:0000250|UniProtKB:Q96RR1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CIW5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CIW5-2; Sequence=VSP_015962, VSP_015963;
CC -!- TISSUE SPECIFICITY: Ubiquitous with the highest levels in the liver,
CC heart and kidneys. The skeletal muscle, brain and testis showed lower
CC but detectable expression. Expression is coregulated with MRPL43.
CC {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:0000250|UniProtKB:Q96RR1}.
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:0000250|UniProtKB:Q96RR1}.
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DR EMBL; AY059385; AAL27647.1; -; mRNA.
DR EMBL; AK146244; BAE27008.1; -; mRNA.
DR EMBL; BC034909; AAH34909.1; -; mRNA.
DR EMBL; BC071195; AAH71195.1; -; mRNA.
DR CCDS; CCDS29854.1; -. [Q8CIW5-1]
DR RefSeq; NP_001335188.1; NM_001348259.1. [Q8CIW5-2]
DR RefSeq; NP_722491.2; NM_153796.4. [Q8CIW5-1]
DR AlphaFoldDB; Q8CIW5; -.
DR SMR; Q8CIW5; -.
DR BioGRID; 230482; 2.
DR STRING; 10090.ENSMUSP00000026227; -.
DR iPTMnet; Q8CIW5; -.
DR PhosphoSitePlus; Q8CIW5; -.
DR EPD; Q8CIW5; -.
DR MaxQB; Q8CIW5; -.
DR PaxDb; Q8CIW5; -.
DR PeptideAtlas; Q8CIW5; -.
DR PRIDE; Q8CIW5; -.
DR ProteomicsDB; 301789; -. [Q8CIW5-1]
DR ProteomicsDB; 301790; -. [Q8CIW5-2]
DR Antibodypedia; 1261; 228 antibodies from 25 providers.
DR Ensembl; ENSMUST00000026227; ENSMUSP00000026227; ENSMUSG00000025209. [Q8CIW5-1]
DR GeneID; 226153; -.
DR KEGG; mmu:226153; -.
DR UCSC; uc008hqh.1; mouse. [Q8CIW5-2]
DR UCSC; uc008hqi.1; mouse. [Q8CIW5-1]
DR CTD; 56652; -.
DR MGI; MGI:2137410; Twnk.
DR VEuPathDB; HostDB:ENSMUSG00000025209; -.
DR eggNOG; KOG2373; Eukaryota.
DR GeneTree; ENSGT00390000004495; -.
DR HOGENOM; CLU_012336_1_0_1; -.
DR InParanoid; Q8CIW5; -.
DR OMA; RPGAYHN; -.
DR PhylomeDB; Q8CIW5; -.
DR TreeFam; TF105994; -.
DR BRENDA; 3.6.4.12; 3474.
DR BioGRID-ORCS; 226153; 27 hits in 78 CRISPR screens.
DR ChiTaRS; Twnk; mouse.
DR PRO; PR:Q8CIW5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8CIW5; protein.
DR Bgee; ENSMUSG00000025209; Expressed in epiblast (generic) and 180 other tissues.
DR ExpressionAtlas; Q8CIW5; baseline and differential.
DR Genevisible; Q8CIW5; MM.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; ISS: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; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS: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:MGI.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:UniProtKB.
DR GO; GO:0006390; P:mitochondrial transcription; ISO:MGI.
DR GO; GO:0034214; P:protein hexamerization; ISO:MGI.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Coiled coil; DNA replication; Helicase;
KW Hydrolase; Mitochondrion; Mitochondrion nucleoid; Nucleotide-binding;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 32..685
FT /note="Twinkle mtDNA helicase"
FT /id="PRO_0000042641"
FT DOMAIN 385..636
FT /note="SF4 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00596"
FT REGION 1..122
FT /note="Contributes to single strand DNA binding activity"
FT /evidence="ECO:0000250|UniProtKB:Q96RR1"
FT REGION 122..373
FT /note="Required for hexamers formation and DNA helicase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q96RR1"
FT REGION 406..591
FT /note="Maybe required for stable oligomeric structure"
FT /evidence="ECO:0000250|UniProtKB:Q96RR1"
FT REGION 641..685
FT /note="Might negatively regulate ATPase activity"
FT /evidence="ECO:0000250|UniProtKB:Q96RR1"
FT REGION 642..685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 454..482
FT /evidence="ECO:0000255"
FT BINDING 416..423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00596"
FT VAR_SEQ 1..398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015962"
FT VAR_SEQ 399..415
FT /note="LNRLLKGHRKGELTVFT -> MCCQTLLLTQSFVRPPI (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015963"
SQ SEQUENCE 685 AA; 76993 MW; F9CF69BDC4DCF838 CRC64;
MWLLLRRAYP LRILLPLRGE WVGRRGLPRS LAPGPPRRRY RKEALPALEM PVSPVTTTEI
RQYLRAHGIP FQDGHSCLRA PSPFVVSSDI KNEKKDAPTS FCLFIDKTTG HFLCMTSLAE
GSWEDLQASV EGRGDGAKEG VLLREGPEAE VREEVLRIWN RAIPLWELPD PEEAQLARVM
FGLTKVTDDT LRRFSVRYLR SARSLVFPWF TPGSSGLRGL KLLGAEGQEN GVQYVETTIP
RPGVYHNLFG LPLISRRDTE VVVTSRELDS LALSQSTGLP TLSLPRGTVC LPPALLPYLE
QFRRIVFWLG DDLRSWEAAK LFARKLNPKR CSLVRPGNQQ PRPLEALNQG LSLPRILRTA
LPAWHKSIVS FRQLREEVLG ELSNVEQAAG VRWSRFPDLN RLLKGHRKGE LTVFTGPTGS
GKTTFISEYA LDLCTQGVNT LWGSFEISNV RLARVMLTQF AVTRLEEQLD KYEEWADRFE
DLPLYFMTFH GQQSIRSVID TMQHAVYVYD VCHVVIDNLQ FMMGHEQLSS DRIAAQDYIV
GAFRKFATDN SCHVTLVIHP RKEDDDKELQ TASIFGSAKA SQEADNVLIL QDRKLVTGPG
KRYLQVSKNR FDGDVGVFPL EFNKNSLTFS IPPKSKARLK KIKDDNGLVA KKSSSGKKGA
AHQNPEICLG QDPSPAQPDT SKSSG
