| IED ID | IndEnz0002000419 |
| Enzyme Type ID | protease000419 |
| Protein Name |
Twinkle mtDNA helicase EC 3.6.4.12 Progressive external ophthalmoplegia 1 protein T7 gp4-like protein with intramitochondrial nucleoid localization T7-like mitochondrial DNA helicase Twinkle protein, mitochondrial |
| Gene Name | TWNK C10orf2 PEO1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MWVLLRSGYPLRILLPLRGEWMGRRGLPRNLAPGPPRRRYRKETLQALDMPVLPVTATEIRQYLRGHGIPFQDGHSCLRALSPFAESSQLKGQTGVTTSFSLFIDKTTGHFLCMTSLAEGSWEDFQASVEGRGDGAREGFLLSKAPEFEDSEEVRRIWNRAIPLWELPDQEEVQLADTMFGLTKVTDDTLKRFSVRYLRPARSLVFPWFSPGGSGLRGLKLLEAKCQGDGVSYEETTIPRPSAYHNLFGLPLISRRDAEVVLTSRELDSLALNQSTGLPTLTLPRGTTCLPPALLPYLEQFRRIVFWLGDDLRSWEAAKLFARKLNPKRCFLVRPGDQQPRPLEALNGGFNLSRILRTALPAWHKSIVSFRQLREEVLGELSNVEQAAGLRWSRFPDLNRILKGHRKGELTVFTGPTGSGKTTFISEYALDLCSQGVNTLWGSFEISNVRLARVMLTQFAEGRLEDQLDKYDHWADRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAQDYIIGVFRKFATDNNCHVTLVIHPRKEDDDKELQTASIFGSAKASQEADNVLILQDRKLVTGPGKRYLQVSKNRFDGDVGVFPLEFNKNSLTFSIPPKNKARLKKIKDDTGPVAKKPSSGKKGATTQNSEICSGQAPTPDQPDTSKRSK |
| Enzyme Length | 684 |
| Uniprot Accession Number | Q96RR1 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: [Isoform 1]: Strand annealing activity is inhibited by 150 mM NaCl (in vitro). {ECO:0000269|PubMed:22383523}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [Isoform 1]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={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}; |
| DNA Binding | |
| EC Number | 3.6.4.12 |
| Enzyme Function | FUNCTION: [Isoform 1]: Mitochondrial helicase involved in mtDNA replication and repair (PubMed:12975372, PubMed:15167897, PubMed:17324440, PubMed:18039713, PubMed:18971204, PubMed:25824949, PubMed:26887820, PubMed:27226550). Might have a role in mtDNA repair (PubMed:27226550). Has DNA strand separation activity needed to form a processive replication fork for leading strand synthesis which is catalyzed by the formation of a replisome complex with POLG and mtSDB (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand (PubMed:27226550). In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities (PubMed:22383523, PubMed:26887820, PubMed:27226550). {ECO:0000269|PubMed:12975372, ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:17324440, ECO:0000269|PubMed:18039713, ECO:0000269|PubMed:18971204, ECO:0000269|PubMed:22383523, ECO:0000269|PubMed:25824949, ECO:0000269|PubMed:26887820, ECO:0000269|PubMed:27226550}.; FUNCTION: [Isoform 2]: Lack DNA unwinding and ATP hydrolysis activities (PubMed:18039713). Does not bind single-stranded or double-stranded DNA (PubMed:18039713). {ECO:0000269|PubMed:18039713}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 415..422; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00596 |
| Features | Alternative sequence (3); Chain (1); Compositional bias (1); Domain (1); Mutagenesis (1); Natural variant (43); Nucleotide binding (1); Region (5); Sequence conflict (1); Transit peptide (1) |
| Keywords | ATP-binding;Alternative splicing;DNA replication;Deafness;Disease variant;Helicase;Hydrolase;Mitochondrion;Mitochondrion nucleoid;Neurodegeneration;Neuropathy;Nucleotide-binding;Primary mitochondrial disease;Progressive external ophthalmoplegia;Reference proteome;Transit peptide |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269|PubMed:11431692, ECO:0000269|PubMed:18971204}. 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. {ECO:0000269|PubMed:11431692}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12686611; 16169070; 16385451; 17420318; 17614276; 17620490; 18973250; 18989381; 19425506; 19513767; 19951946; 20181062; 20186120; 20562859; 20659899; 20877624; 21540127; 21689831; 22580846; 22653443; 22952820; 23375728; 24018892; 24218554; 24524965; 24816431; 25193669; 25609649; 25665578; 26496610; 26689116; 26838077; 27112570; 27600867; 28178980; 29316893; 30715486; 31455269; 31455392; 32161153; 32213598; 32387964; 33087282; 33396418; 33847968; |
| Motif | |
| Gene Encoded By | |
| Mass | 77,154 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]: Kinetic parameters: KM=1.7 mM for UTP (using ssM13mp18 as DNA substrate) {ECO:0000269|PubMed:22383523}; KM=1.6 mM for UTP (using ssDNA as DNA substrate) {ECO:0000269|PubMed:22383523}; KM=1.4 mM for UTP (using forked dsDNA as DNA substrate) {ECO:0000269|PubMed:22383523}; KM=3.4 mM for UTP (using no DNA as substrate) {ECO:0000269|PubMed:22383523}; |
| Metal Binding | |
| Rhea ID | RHEA:13065 |
| Cross Reference Brenda | 3.6.4.12; |