Q96RR1 (PEO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Twinkle protein, mitochondrial
EC=3.6.4.12

Alternative name(s):
Progressive external ophthalmoplegia 1 protein
T7 gp4-like protein with intramitochondrial nucleoid localization
T7-like mitochondrial DNA helicase

Gene names

Name:	PEO1
Synonyms:	C10orf2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	684 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in mitochondrial DNA (mtDNA) metabolism. Could function as an adenine nucleotide-dependent DNA helicase. Function inferred to be critical for lifetime maintenance of mtDNA integrity. In vitro, forms in combination with POLG, a processive replication machinery, which can use double-stranded DNA (dsDNA) as template to synthesize single-stranded DNA (ssDNA) molecules. May be a key regulator of mtDNA copy number in mammals. Ref.8 Ref.9
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Forms multimers in vitro, including hexamers. Interacts with POLG in vitro. Ref.9
Subcellular location	Mitochondrion matrix › mitochondrion nucleoid. Note: Colocalizes with mtDNA in mitochondrial nucleoids, a nucleoproteins complex consisting of a number of copies of proteins associated with mtDNA, probably involved in mtDNA maintenance and expression. Ref.1
Tissue specificity	High relative levels in skeletal muscle, testis and pancreas. Lower levels of expression in the heart, brain, placenta, lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine, colon and leukocytes. Expression is coregulated with MRPL43. Ref.1 Ref.10
Involvement in disease	Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant 3 (PEOA3) [MIM:609286]: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.12 Ref.16 Ref.19 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]: A systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss. An atypical form of the disease is characterized by headaches and/or seizures manifesting in childhood or adolescence, followed by development of cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus in early adulthood. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Mitochondrial DNA depletion syndrome 7 (MTDPS7) [MIM:271245]: A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.20 Ref.21 Ref.27 Ref.30
Sequence similarities	Contains 1 SF4 helicase domain.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Mitochondrion Mitochondrion nucleoid
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Neurodegeneration Neuropathy Progressive external ophthalmoplegia
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA unwinding involved in replication Inferred from electronic annotation. Source: Compara cell death Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial DNA replication Inferred from mutant phenotype PubMed 18971204. Source: UniProtKB protein hexamerization Inferred from direct assay PubMed 18971204. Source: UniProtKB protein homooligomerization Inferred from direct assay PubMed 18971204. Source: UniProtKB transcription from mitochondrial promoter Inferred from mutant phenotype PubMed 18971204. Source: UniProtKB
Cellular_component	mitochondrial nucleoid Inferred from direct assay PubMed 18971204. Source: UniProtKB
Molecular_function	5'-3' DNA helicase activity Inferred from direct assay Ref.8PubMed 18971204. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW single-stranded DNA binding Inferred from direct assay PubMed 18971204. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96RR1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96RR1-2)

Also known as: Twinky;

The sequence of this isoform differs from the canonical sequence as follows:
     579-582: ASQE → VSGL
     583-684: Missing.

Isoform 3 (identifier: Q96RR1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     532-684: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 31	31	Mitochondrion Potential
	Chain	32 – 684	653	Twinkle protein, mitochondrial		PRO_0000042640
Regions
	Domain	384 – 635	252	SF4 helicase
	Nucleotide binding	415 – 422	8	ATP By similarity
Natural variations
	Alternative sequence	532 – 684	153	Missing in isoform 3.		VSP_015959
	Alternative sequence	579 – 582	4	ASQE → VSGL in isoform 2.		VSP_015960
	Alternative sequence	583 – 684	102	Missing in isoform 2.		VSP_015961
	Natural variant	303	1	R → Q in PEOA3. Ref.25 Ref.28		VAR_065102
	Natural variant	303	1	R → W in PEOA3; also detected in a case showing digenic inheritance. Ref.15 Ref.23 Ref.26 Ref.28		VAR_023647
	Natural variant	315	1	W → L in PEOA3. Ref.1		VAR_023648
	Natural variant	315	1	W → S in PEOA3. Ref.23		VAR_065103
	Natural variant	318	1	A → T in MTDPS7. Ref.21		VAR_065104
	Natural variant	319	1	K → E in SANDO; the phenotype highly overlaps with PEOA3. Ref.18		VAR_023649
	Natural variant	319	1	K → T in PEOA3. Ref.16		VAR_023650
	Natural variant	334	1	R → P in PEOA3. Ref.23		VAR_065105
	Natural variant	334	1	R → Q in PEO; sporadic case; the patient also carries the S-848 mutation in the POLG gene suggesting digenic inheritance. Ref.14 Ref.15 Ref.28 Corresponds to variant rs28937887 [ dbSNP | Ensembl ].		VAR_023651
	Natural variant	335	1	P → L in PEOA3. Ref.12		VAR_023652
	Natural variant	348	1	G → R. Ref.4		VAR_062268
	Natural variant	354	1	R → P in PEOA3. Ref.1 Ref.28		VAR_023653
	Natural variant	357	1	R → P in PEOA3. Ref.22 Ref.28		VAR_065106
	Natural variant	359	1	A → T in PEOA3. Ref.1 Ref.28		VAR_023654
	Natural variant	360	1	L → G in MTDPS7; patients manifest multi-organ failure; requires 2 nucleotide substitutions. Ref.27		VAR_065107
	Natural variant	362	1	A → P in PEOA3. Ref.28		VAR_065108
	Natural variant	363	1	W → L in PEOA3. Ref.28		VAR_065109
	Natural variant	367	1	I → T in PEOA3. Ref.1		VAR_023655
	Natural variant	368	1	V → I. Ref.1 Ref.4 Ref.13 Ref.19 Corresponds to variant rs17113613 [ dbSNP | Ensembl ].		VAR_023656
	Natural variant	369	1	S → P in PEOA3. Ref.1		VAR_023657
	Natural variant	369	1	S → Y in PEOA3. Ref.12		VAR_023658
	Natural variant	370	1	F → C in PEOA3. Ref.28		VAR_065110
	Natural variant	370	1	F → L in PEOA3. Ref.24		VAR_065111
	Natural variant	374	1	R → Q in PEOA3. Ref.1 Ref.19 Ref.28 Ref.29		VAR_023659
	Natural variant	381	1	L → P in PEOA3. Ref.1 Ref.28		VAR_023660
	Natural variant	426	1	S → N in PEOA3. Ref.23		VAR_065112
	Natural variant	427	1	E → G. Corresponds to variant rs11542126 [ dbSNP | Ensembl ].		VAR_051267
	Natural variant	456	1	L → V in MTDPS7; infantile spinocerebellar ataxia phenotype. Ref.30		VAR_067722
	Natural variant	457	1	T → I in MTDPS7; affects helicase activity. Ref.20		VAR_039045
	Natural variant	458	1	Q → H in PEOA3. Ref.28		VAR_065113
	Natural variant	460	1	A → P in PEOA3. Ref.28		VAR_065114
	Natural variant	474	1	W → C in PEOA3. Ref.1		VAR_023661
	Natural variant	474	1	W → S in PEOA3. Ref.23		VAR_065115
	Natural variant	475	1	A → D in PEOA3. Ref.28		VAR_065116
	Natural variant	475	1	A → P in PEOA3. Ref.1		VAR_023662
	Natural variant	478	1	F → I in PEOA3. Ref.23		VAR_065117
	Natural variant	479	1	E → K in PEOA3. Ref.23 Ref.28		VAR_065118
	Natural variant	508	1	Y → C in MTDPS7. Ref.17 Ref.21		VAR_043797
	Natural variant	634	1	N → K. Ref.4		VAR_062269
Experimental info
	Sequence conflict	351	1	N → D in CAE45905. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 58186043888234DA	FASTA	684	77,154
	10 20 30 40 50 60 MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI 70 80 90 100 110 120 RQYLRGHGIP FQDGHSCLRA LSPFAESSQL KGQTGVTTSF SLFIDKTTGH FLCMTSLAEG 130 140 150 160 170 180 SWEDFQASVE GRGDGAREGF LLSKAPEFED SEEVRRIWNR AIPLWELPDQ EEVQLADTMF 190 200 210 220 230 240 GLTKVTDDTL KRFSVRYLRP ARSLVFPWFS PGGSGLRGLK LLEAKCQGDG VSYEETTIPR 250 260 270 280 290 300 PSAYHNLFGL PLISRRDAEV VLTSRELDSL ALNQSTGLPT LTLPRGTTCL PPALLPYLEQ 310 320 330 340 350 360 FRRIVFWLGD DLRSWEAAKL FARKLNPKRC FLVRPGDQQP RPLEALNGGF NLSRILRTAL 370 380 390 400 410 420 PAWHKSIVSF RQLREEVLGE LSNVEQAAGL RWSRFPDLNR ILKGHRKGEL TVFTGPTGSG 430 440 450 460 470 480 KTTFISEYAL DLCSQGVNTL WGSFEISNVR LARVMLTQFA EGRLEDQLDK YDHWADRFED 490 500 510 520 530 540 LPLYFMTFHG QQSIRTVIDT MQHAVYVYDI CHVIIDNLQF MMGHEQLSTD RIAAQDYIIG 550 560 570 580 590 600 VFRKFATDNN CHVTLVIHPR KEDDDKELQT ASIFGSAKAS QEADNVLILQ DRKLVTGPGK 610 620 630 640 650 660 RYLQVSKNRF DGDVGVFPLE FNKNSLTFSI PPKNKARLKK IKDDTGPVAK KPSSGKKGAT 670 680 TQNSEICSGQ APTPDQPDTS KRSK
	Isoform 2 (Twinky) [UniParc]. Checksum: 8A6A46BDCD5B8C3F	FASTA	582	66,016
	10 20 30 40 50 60 MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI 70 80 90 100 110 120 RQYLRGHGIP FQDGHSCLRA LSPFAESSQL KGQTGVTTSF SLFIDKTTGH FLCMTSLAEG 130 140 150 160 170 180 SWEDFQASVE GRGDGAREGF LLSKAPEFED SEEVRRIWNR AIPLWELPDQ EEVQLADTMF 190 200 210 220 230 240 GLTKVTDDTL KRFSVRYLRP ARSLVFPWFS PGGSGLRGLK LLEAKCQGDG VSYEETTIPR 250 260 270 280 290 300 PSAYHNLFGL PLISRRDAEV VLTSRELDSL ALNQSTGLPT LTLPRGTTCL PPALLPYLEQ 310 320 330 340 350 360 FRRIVFWLGD DLRSWEAAKL FARKLNPKRC FLVRPGDQQP RPLEALNGGF NLSRILRTAL 370 380 390 400 410 420 PAWHKSIVSF RQLREEVLGE LSNVEQAAGL RWSRFPDLNR ILKGHRKGEL TVFTGPTGSG 430 440 450 460 470 480 KTTFISEYAL DLCSQGVNTL WGSFEISNVR LARVMLTQFA EGRLEDQLDK YDHWADRFED 490 500 510 520 530 540 LPLYFMTFHG QQSIRTVIDT MQHAVYVYDI CHVIIDNLQF MMGHEQLSTD RIAAQDYIIG 550 560 570 580 VFRKFATDNN CHVTLVIHPR KEDDDKELQT ASIFGSAKVS GL
	Isoform 3 [UniParc]. Checksum: B7B4246EC5B6502A	FASTA	531	60,400
	10 20 30 40 50 60 MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI 70 80 90 100 110 120 RQYLRGHGIP FQDGHSCLRA LSPFAESSQL KGQTGVTTSF SLFIDKTTGH FLCMTSLAEG 130 140 150 160 170 180 SWEDFQASVE GRGDGAREGF LLSKAPEFED SEEVRRIWNR AIPLWELPDQ EEVQLADTMF 190 200 210 220 230 240 GLTKVTDDTL KRFSVRYLRP ARSLVFPWFS PGGSGLRGLK LLEAKCQGDG VSYEETTIPR 250 260 270 280 290 300 PSAYHNLFGL PLISRRDAEV VLTSRELDSL ALNQSTGLPT LTLPRGTTCL PPALLPYLEQ 310 320 330 340 350 360 FRRIVFWLGD DLRSWEAAKL FARKLNPKRC FLVRPGDQQP RPLEALNGGF NLSRILRTAL 370 380 390 400 410 420 PAWHKSIVSF RQLREEVLGE LSNVEQAAGL RWSRFPDLNR ILKGHRKGEL TVFTGPTGSG 430 440 450 460 470 480 KTTFISEYAL DLCSQGVNTL WGSFEISNVR LARVMLTQFA EGRLEDQLDK YDHWADRFED 490 500 510 520 530 LPLYFMTFHG QQSIRTVIDT MQHAVYVYDI CHVIIDNLQF MMGHEQLSTD R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human mitochondrial DNA deletions associated with mutations in the gene for Twinkle, a phage T7 gene 4-like protein localized in mitochondria." Spelbrink J.N., Li F.-Y., Tiranti V., Nikali K., Yuan Q.-P., Tariq M., Wanrooij S., Garrido N., Comi G., Morandi L., Santoro L., Toscano A., Fabrizi G.-M., Somer H., Croxen R., Beeson D., Poulton J., Suomalainen A. , Jacobs H.T., Zeviani M., Larsson C. Nat. Genet. 28:223-231(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT ILE-368, VARIANTS PEOA3 LEU-315; PRO-354; THR-359; THR-367; PRO-369; GLN-374; PRO-381; CYS-474 AND PRO-475.
[2]	Erratum Spelbrink J.N., Li F.-Y., Tiranti V., Nikali K., Yuan Q.-P., Tariq M., Wanrooij S., Garrido N., Comi G., Morandi L., Santoro L., Toscano A., Fabrizi G.-M., Somer H., Croxen R., Beeson D., Poulton J., Suomalainen A. , Jacobs H.T., Zeviani M., Larsson C. Nat. Genet. 29:100-100(2001)
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Fetal brain.
[4]	NIEHS SNPs program Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-348; ILE-368 AND LYS-634.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 132-582 (ISOFORM 2). Tissue: Skin.
[8]	"TWINKLE has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein." Korhonen J.A., Gaspari M., Falkenberg M. J. Biol. Chem. 278:48627-48632(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROBABLE FUNCTION.
[9]	"Reconstitution of a minimal mtDNA replisome in vitro." Korhonen J.A., Pham X.H., Pellegrini M., Falkenberg M. EMBO J. 23:2423-2429(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH POLG.
[10]	"Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number." Tyynismaa H., Sembongi H., Bokori-Brown M., Granycome C., Ashley N., Poulton J., Jalanko A., Spelbrink J.N., Holt I.J., Suomalainen A. Hum. Mol. Genet. 13:3219-3227(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, COREGULATION WITH MRPL43.
[11]	"Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA." Wanrooij S., Luoma P., van Goethem G., van Broeckhoven C., Suomalainen A., Spelbrink J.N. Nucleic Acids Res. 32:3053-3064(2004) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE MECHANISM OF DELETION FORMATION.
[12]	"Clinical and molecular features of adPEO due to mutations in the Twinkle gene." Lewis S., Hutchison W., Thyagarajan D., Dahl H.-H.M. J. Neurol. Sci. 201:39-44(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PEOA3 LEU-335 AND TYR-369.
[13]	"The V368I mutation in Twinkle does not segregate with AdPEO." Arenas J., Briem E., Dahl H.-H.M., Hutchison W., Lewis S., Martin M.A., Spelbrink H., Tiranti V., Jacobs H., Zeviani M. Ann. Neurol. 53:278-278(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-368.
[14]	"Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle." Van Goethem G., Loefgren A., Dermaut B., Ceuterick C., Martin J.-J., Van Broeckhoven C. Hum. Mutat. 22:175-176(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEO GLN-334.
[15]	"Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)." Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F., Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M. Neurology 60:1354-1356(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PEO TRP-303 AND GLN-334.
[16]	"A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia." Deschauer M., Kiefer R., Blakely E.L., He L., Zierz S., Turnbull D.M., Taylor R.W. Neuromuscul. Disord. 13:568-572(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 THR-319.
[17]	"Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky." Nikali K., Suomalainen A., Saharinen J., Kuokkanen M., Spelbrink J.N., Loennqvist T., Peltonen L. Hum. Mol. Genet. 14:2981-2990(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS7 CYS-508.
[18]	"Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism." Hudson G., Deschauer M., Busse K., Zierz S., Chinnery P.F. Neurology 64:371-373(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SANDO GLU-319.
[19]	"Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay." Naiemi M., Bannwarth S., Procaccio V., Pouget J., Desnuelle C., Pellissier J.-F., Roetig A., Munnich A., Calvas P., Richelme C., Jonveaux P., Castelnovo G., Simon M., Clanet M., Wallace D., Paquis-Flucklinger V. Eur. J. Hum. Genet. 14:917-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 GLN-374, VARIANT ILE-368.
[20]	"Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion." Sarzi E., Goffart S., Serre V., Chretien D., Slama A., Munnich A., Spelbrink J.N., Roetig A. Ann. Neurol. 62:579-587(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS7 ILE-457, CHARACTERIZATION OF VARIANT MTDPS7 ILE-457.
[21]	"Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion." Hakonen A.H., Isohanni P., Paetau A., Herva R., Suomalainen A., Lonnqvist T. Brain 130:3032-3040(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS7 THR-318 AND CYS-508.
[22]	"Mild ocular myopathy associated with a novel mutation in mitochondrial twinkle helicase." Rivera H., Blazquez A., Carretero J., Alvarez-Cermeno J.C., Campos Y., Cabello A., Gonzalez-Vioque E., Borstein B., Garesse R., Arenas J., Martin M.A. Neuromuscul. Disord. 17:677-680(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 PRO-357.
[23]	"Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia." Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F., Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S., Papadimitriou A., Bresolin N., Comi G.P. J. Neurol. 255:1384-1391(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PEOA3 TRP-303; SER-315; PRO-334; ASN-426; SER-474; ILE-478 AND LYS-479.
[24]	"Phenotype and clinical course in a family with a new de novo Twinkle gene mutation." Jeppesen T.D., Schwartz M., Colding-Jorgensen E., Krag T., Hauerslev S., Vissing J. Neuromuscul. Disord. 18:306-309(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 LEU-370.
[25]	"Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease." Van Hove J.L., Cunningham V., Rice C., Ringel S.P., Zhang Q., Chou P.C., Truong C.K., Wong L.J. Am. J. Med. Genet. A 149:861-867(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 GLN-303.
[26]	"Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia." Negro R., Zoccolella S., Dell'aglio R., Amati A., Artuso L., Bisceglia L., Lavolpe V., Papa S., Serlenga L., Petruzzella V. Neuromuscul. Disord. 19:423-426(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 TRP-303.
[27]	"Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure." Bohlega S., Van Goethem G., Al Semari A., Lofgren A., Al Hamed M., Van Broeckhoven C., Kambouris M. Neuromuscul. Disord. 19:845-848(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS7 GLY-360.
[28]	"The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO." Fratter C., Gorman G.S., Stewart J.D., Buddles M., Smith C., Evans J., Seller A., Poulton J., Roberts M., Hanna M.G., Rahman S., Omer S.E., Klopstock T., Schoser B., Kornblum C., Czermin B., Lecky B., Blakely E.L. , Craig K., Chinnery P.F., Turnbull D.M., Horvath R., Taylor R.W. Neurology 74:1619-1626(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PEOA3 GLN-303; TRP-303; GLN-334; PRO-354; PRO-357; THR-359; PRO-362; LEU-363; CYS-370; GLN-374; PRO-381; HIS-458; PRO-460; ASP-475 AND LYS-479.
[29]	"TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review." Martin-Negrier M.L., Sole G., Jardel C., Vital C., Ferrer X., Vital A. Eur. J. Neurol. 18:436-441(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PEOA3 GLN-374.
[30]	"Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing." Dundar H., Ozgul R.K., Yalnizoglu D., Erdem S., Oguz K.K., Tuncel D., Temucin C.M., Dursun A. Pediatr. Neurol. 46:172-177(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS7 VAL-456.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF292004 mRNA. Translation: AAK69558.1. AF292005 mRNA. Translation: AAK69559.1. BX640829 mRNA. Translation: CAE45905.1. AL133215 Genomic DNA. Translation: CAI10924.1. EU543650 Genomic DNA. Translation: ACB21043.1. AL133215 Genomic DNA. Translation: CAI10925.1. CH471066 Genomic DNA. Translation: EAW49794.1. BC013349 mRNA. Translation: AAH13349.1.
IPI	IPI00102660. IPI00640641. IPI00654621.
RefSeq	NP_001157284.1. NM_001163812.1. NP_068602.2. NM_021830.4.
UniGene	Hs.22678.
3D structure databases
ProteinModelPortal	Q96RR1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96RR1. 3 interactions.
MINT	MINT-1385725.
STRING	9606.ENSP00000309595.
PTM databases
PhosphoSite	Q96RR1.
Polymorphism databases
DMDM	74752111.
Proteomic databases
PaxDb	Q96RR1.
PRIDE	Q96RR1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000311916; ENSP00000309595; ENSG00000107815. ENST00000370228; ENSP00000359248; ENSG00000107815.
GeneID	56652.
KEGG	hsa:56652.
UCSC	uc001ksf.2. human. uc001ksg.2. human.
Organism-specific databases
CTD	56652.
GeneCards	GC10P102738.
HGNC	HGNC:1160. C10orf2.
HPA	HPA002532.
MIM	271245. phenotype. 606075. gene. 607459. phenotype. 609286. phenotype.
neXtProt	NX_Q96RR1.
Orphanet	254892. Autosomal dominant progressive external ophthalmoplegia. 1186. Infantile onset spinocerebellar ataxia.
PharmGKB	PA162377675.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG29349.
HOGENOM	HOG000273872.
HOVERGEN	HBG059782.
InParanoid	Q96RR1.
OMA	GSWEDFQ.
OrthoDB	EOG434W5N.
PhylomeDB	Q96RR1.
Gene expression databases
ArrayExpress	Q96RR1.
Bgee	Q96RR1.
CleanEx	HS_C10orf2.
Genevestigator	Q96RR1.
GermOnline	ENSG00000107815. Homo sapiens.
Family and domain databases
InterPro	IPR007694. DNA_helicase_DnaB-like_C. IPR027032. Twinkle. [Graphical view]
PANTHER	PTHR12873. PTHR12873. 1 hit.
PROSITE	PS51199. SF4_HELICASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	56652.
NextBio	62113.
SOURCE	Search...

Entry information

Entry name

PEO1_HUMAN

Accession

Primary (citable) accession number: Q96RR1
Secondary accession number(s): B2CQL2 , Q6MZX2, Q6PJP5, Q96RR0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.