Protein: Mitochondrial DNA helicase (EC 5.6.2.3) (Twinkle mtDNA helicase) (Twinkle protein, mitochondrial) (Q9VL76)
Organism: Drosophila melanogaster (Fruit fly)
Function: Mitochondrial helicase involved in mtDNA replication. Might have a role in mtDNA repair (By similarity). 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 (By similarity). Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate (By similarity). Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand (By similarity). In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities (By similarity).
Subcellular location: Mitochondrion {ECO:0000269|PubMed:17272269}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000250|UniProtKB:Q96RR1}. Mitochondrion inner membrane {ECO:0000303|PubMed:34950192}; Peripheral membrane protein {ECO:0000269|PubMed:34950192}. 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 (By similarity). Associates with phospholipid membranes via electrostatic binding (PubMed:34950192). Preferentially associates with membranes enriched with cardiolipin, a lipid abundant in the mitochondrial inner membrane (PubMed:34950192). ATPase and helicase activity may be enhanced by binding to lipid membranes (By similarity). {ECO:0000250|UniProtKB:Q96RR1, ECO:0000269|PubMed:34950192}.
Sequence: MRRAGLIKPLLRINNEKQRVWRKNYATQVVSGLEECSLDPKEYVDFKRQLRQLNLPHKDGHTCLQLECRLCDRNRQPVTNAQKGTDHGLLAYVNKRTGAFICPNCDVKTSLTSALLSYQLPKPVGYKQPLQRQPVYESRFPHLAVVTPEACAALGIKGLKEDQLNAIGAQWEPQQQLLHFKLRNAAQVEVGEKVLYLGDRREEIFQSSSSSGLLIHGAMNKTKAVLVSNLIDFIVLATQNIETHCVVCLPYELKTLPQECLPALERFKELIFWLHYDASHSWDAARAFALKLDERRCLLIRPTETEPAPHLALRRRLNLRHILAKATPVQHKAITTFGAMRNDILSELQNIEKVNGVKWKRFPVLNKLLKGHRRGELTILTGPTGSGKTTFMSEYSLDLAMQGVNTLWGSFEIRNTRLAATLLRQYVGYPLDDRLHEFNHWAAEFERLPLYFMTFHGQQPLKPVLEAIEHASYVHDVMHVIIDNLQFMMGVSTFRGDKFFEQDSIIAAFRSFATKHNVHVTLVMHPRKERQEDELTTSSVFGTAKATQEADNVLIIQDKRLTSVRGKKYLQIAKNRYSGDLGIMPLEFDKDGLSYSTQIQNAKRKREKTPSEN
InterPro domains: - IPR027032: Twinkle-like protein (family) [46-604]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [341-596]
- IPR007694: DNA helicase, DnaB-like, C-terminal (domain) [351-602]
Interaction partners: - Single-stranded DNA-binding protein, mitochondrial
- DNA polymerase subunit gamma-1, mitochondrial
- Mitochondrial transcription factor A, isoform B
- DNA-directed RNA polymerase
- DNA polymerase subunit gamma-2, mitochondrial
- DNA replication ATP-dependent helicase/nuclease
- Iron-sulfur cluster transfer protein Nubpl
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0140657 (ATP-dependent activity), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0004386 (helicase activity), GO:0008094 (ATP-dependent activity, acting on DNA), GO:0140097 (catalytic activity, acting on DNA), GO:0003678 (DNA helicase activity), GO:0043138 (3'-5' DNA helicase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0044085 (cellular component biogenesis), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0016043 (cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0006259 (DNA metabolic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0043933 (protein-containing complex organization), GO:0006996 (organelle organization), GO:0010467 (gene expression), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0022607 (cellular component assembly), GO:0007005 (mitochondrion organization), GO:0006260 (DNA replication), GO:0016070 (RNA metabolic process), GO:0032042 (mitochondrial DNA metabolic process), GO:0065003 (protein-containing complex assembly), GO:0140053 (mitochondrial gene expression), GO:0032774 (RNA biosynthetic process), GO:0097659 (nucleic acid-templated transcription), GO:0006390 (mitochondrial transcription), GO:0006261 (DNA-templated DNA replication), GO:0051259 (protein complex oligomerization), GO:0000959 (mitochondrial RNA metabolic process), GO:0006264 (mitochondrial DNA replication), GO:0006351 (DNA-templated transcription), GO:0000002 (mitochondrial genome maintenance), GO:0034214 (protein hexamerization), GO:0006268 (DNA unwinding involved in DNA replication), GO:0032392 (DNA geometric change), GO:0032508 (DNA duplex unwinding)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)