TWNK

Protein identityUniProt · HPA

UniProt accession

Q96RR1

Gene

TWNK

Ensembl

ENSG00000107815

Chromosome

10

Canonical length

684 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Quaternary structure

Homooctamer

OverviewNCBI Gene

This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]

Canonical amino-acid sequenceUniProt

684 residues, UniProt reviewed canonical sequence.

>Q96RR1|TWNK
     1  MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI
    61  RQYLRGHGIP FQDGHSCLRA LSPFAESSQL KGQTGVTTSF SLFIDKTTGH FLCMTSLAEG
   121  SWEDFQASVE GRGDGAREGF LLSKAPEFED SEEVRRIWNR AIPLWELPDQ EEVQLADTMF
   181  GLTKVTDDTL KRFSVRYLRP ARSLVFPWFS PGGSGLRGLK LLEAKCQGDG VSYEETTIPR
   241  PSAYHNLFGL PLISRRDAEV VLTSRELDSL ALNQSTGLPT LTLPRGTTCL PPALLPYLEQ
   301  FRRIVFWLGD DLRSWEAAKL FARKLNPKRC FLVRPGDQQP RPLEALNGGF NLSRILRTAL
   361  PAWHKSIVSF RQLREEVLGE LSNVEQAAGL RWSRFPDLNR ILKGHRKGEL TVFTGPTGSG
   421  KTTFISEYAL DLCSQGVNTL WGSFEISNVR LARVMLTQFA EGRLEDQLDK YDHWADRFED
   481  LPLYFMTFHG QQSIRTVIDT MQHAVYVYDI CHVIIDNLQF MMGHEQLSTD RIAAQDYIIG
   541  VFRKFATDNN CHVTLVIHPR KEDDDKELQT ASIFGSAKAS QEADNVLILQ DRKLVTGPGK
   601  RYLQVSKNRF DGDVGVFPLE FNKNSLTFSI PPKNKARLKK IKDDTGPVAK KPSSGKKGAT
   661  TQNSEICSGQ APTPDQPDTS KRSK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TWNK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TWNK.

Disease | AllUniProt

Conditions TWNK is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) MIM:609286
• Mitochondrial DNA depletion syndrome 7 (MTDPS7) MIM:271245
• Perrault syndrome 5 (PRLTS5) MIM:616138

Disease | GeneticClinVar

84 pathogenic / likely-pathogenic of 674 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
• Infantile onset spinocerebellar ataxia
• Perrault syndrome 5
• Mitochondrial disease
• Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0

DepMap mean gene effect

-0.37

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA-templated DNA replication
• mitochondrial DNA replication
• mitochondrial transcription
• protein hexamerization

Molecular functions

• 5'-3' DNA helicase activity
• ATP binding
• ATP hydrolysis activity
• DNA helicase activity
• identical protein binding
• lipid binding
• protease binding
• single-stranded DNA binding

Cellular components

• mitochondrial chromosome
• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• P-loop containing nucleoside triphosphate hydrolase
• DNA helicase, DnaB-like, C-terminal
• Twinkle-like protein
• Archaeal primase DnaG/twinkle-like, TOPRIM domain
• AAA domain

KeywordsUniProt

• ATP-binding
• Deafness
• DNA replication
• Helicase
• Hydrolase
• Isomerase
• Lipid-binding
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Mitochondrion nucleoid
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Primary mitochondrial disease
• Progressive external ophthalmoplegia
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of TWNK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LONP1
• POLG