POLG

Protein identityUniProt · HPA

UniProt accession

P54098

Gene

POLG

Ensembl

ENSG00000140521

Chromosome

15

Canonical length

1239 aa

Protein class

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

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1239 residues, UniProt reviewed canonical sequence.

>P54098|POLG
     1  MSRLLWRKVA GATVGPGPVP APGRWVSSSV PASDPSDGQR RRQQQQQQQQ QQQQQPQQPQ
    61  VLSSEGGQLR HNPLDIQMLS RGLHEQIFGQ GGEMPGEAAV RRSVEHLQKH GLWGQPAVPL
   121  PDVELRLPPL YGDNLDQHFR LLAQKQSLPY LEAANLLLQA QLPPKPPAWA WAEGWTRYGP
   181  EGEAVPVAIP EERALVFDVE VCLAEGTCPT LAVAISPSAW YSWCSQRLVE ERYSWTSQLS
   241  PADLIPLEVP TGASSPTQRD WQEQLVVGHN VSFDRAHIRE QYLIQGSRMR FLDTMSMHMA
   301  ISGLSSFQRS LWIAAKQGKH KVQPPTKQGQ KSQRKARRGP AISSWDWLDI SSVNSLAEVH
   361  RLYVGGPPLE KEPRELFVKG TMKDIRENFQ DLMQYCAQDV WATHEVFQQQ LPLFLERCPH
   421  PVTLAGMLEM GVSYLPVNQN WERYLAEAQG TYEELQREMK KSLMDLANDA CQLLSGERYK
   481  EDPWLWDLEW DLQEFKQKKA KKVKKEPATA SKLPIEGAGA PGDPMDQEDL GPCSEEEEFQ
   541  QDVMARACLQ KLKGTTELLP KRPQHLPGHP GWYRKLCPRL DDPAWTPGPS LLSLQMRVTP
   601  KLMALTWDGF PLHYSERHGW GYLVPGRRDN LAKLPTGTTL ESAGVVCPYR AIESLYRKHC
   661  LEQGKQQLMP QEAGLAEEFL LTDNSAIWQT VEELDYLEVE AEAKMENLRA AVPGQPLALT
   721  ARGGPKDTQP SYHHGNGPYN DVDIPGCWFF KLPHKDGNSC NVGSPFAKDF LPKMEDGTLQ
   781  AGPGGASGPR ALEINKMISF WRNAHKRISS QMVVWLPRSA LPRAVIRHPD YDEEGLYGAI
   841  LPQVVTAGTI TRRAVEPTWL TASNARPDRV GSELKAMVQA PPGYTLVGAD VDSQELWIAA
   901  VLGDAHFAGM HGCTAFGWMT LQGRKSRGTD LHSKTATTVG ISREHAKIFN YGRIYGAGQP
   961  FAERLLMQFN HRLTQQEAAE KAQQMYAATK GLRWYRLSDE GEWLVRELNL PVDRTEGGWI
  1021  SLQDLRKVQR ETARKSQWKK WEVVAERAWK GGTESEMFNK LESIATSDIP RTPVLGCCIS
  1081  RALEPSAVQE EFMTSRVNWV VQSSAVDYLH LMLVAMKWLF EEFAIDGRFC ISIHDEVRYL
  1141  VREEDRYRAA LALQITNLLT RCMFAYKLGL NDLPQSVAFF SAVDIDRCLR KEVTMDCKTP
  1201  SNPTGMERRY GIPQGEALDI YQIIELTKGS LEKRSQPGP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against POLG 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

22 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about POLG.

Disease | AllUniProt

Conditions POLG is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1 (PEOA1) MIM:157640
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 1 (PEOB1) MIM:258450
• Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) MIM:607459
• Mitochondrial DNA depletion syndrome 4A (MTDPS4A) MIM:203700
• Mitochondrial DNA depletion syndrome 4B (MTDPS4B) MIM:613662
• Leigh syndrome (LS) MIM:256000
• Spinocerebellar ataxia with epilepsy (SCAE) MIM:607459

Disease | GeneticClinVar

375 pathogenic / likely-pathogenic of 3,347 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive sclerosing poliodystrophy
• Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
• Mitochondrial DNA depletion syndrome 4b
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1

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

gnomAD missense Z

-0.74

DepMap mean gene effect

-0.29

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• base-excision repair
• base-excision repair, gap-filling
• DNA metabolic process
• DNA replication proofreading
• DNA-templated DNA replication
• mitochondrial DNA replication

Molecular functions

• 3'-5' exonuclease activity
• 5'-deoxyribose-5-phosphate lyase activity
• chromatin binding
• DNA binding
• DNA-directed DNA polymerase activity
• protease binding
• single-stranded DNA 3'-5' DNA exonuclease activity

Cellular components

• gamma DNA polymerase complex
• mitochondrial chromosome
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• DNA-directed DNA polymerase, family A, palm domain
• Ribonuclease H-like superfamily
• DNA-directed DNA polymerase, family A, conserved site
• DNA/RNA polymerase superfamily
• DNA-directed DNA-polymerase, family A, mitochondria
• DNA mitochondrial polymerase, exonuclease domain
• DNA polymerase gamma, palm domain
• DNA mitochondrial polymerase exonuclease domain

KeywordsUniProt

• DNA replication
• DNA-binding
• DNA-directed DNA polymerase
• Epilepsy
• Hydrolase
• Leigh syndrome
• Lyase
• Magnesium
• Mitochondrion
• Mitochondrion nucleoid
• Neurodegeneration
• Neuropathy
• Nucleotidyltransferase
• Primary mitochondrial disease
• Progressive external ophthalmoplegia
• Transferase

InteractionsUniProt · HPA

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

• LIG3
• TTC3
• TWNK
• MTG2
• POLG2