POLG2

Protein identityUniProt · HPA

UniProt accession

Q9UHN1

Gene

POLG2

Ensembl

ENSG00000256525

Chromosome

17

Canonical length

485 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nuclear bodies,Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the processivity subunit of the mitochondrial DNA polymerase gamma. The encoded protein forms a heterotrimer containing one catalytic subunit and two processivity subunits. This protein enhances DNA binding and promotes processive DNA synthesis. Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

485 residues, UniProt reviewed canonical sequence.

>Q9UHN1|POLG2
     1  MRSRVAVRAC HKVCRCLLSG FGGRVDAGQP ELLTERSSPK GGHVKSHAEL EGNGEHPEAP
    61  GSGEGSEALL EICQRRHFLS GSKQQLSRDS LLSGCHPGFG PLGVELRKNL AAEWWTSVVV
   121  FREQVFPVDA LHHKPGPLLP GDSAFRLVSA ETLREILQDK ELSKEQLVAF LENVLKTSGK
   181  LRENLLHGAL EHYVNCLDLV NKRLPYGLAQ IGVCFHPVFD TKQIRNGVKS IGEKTEASLV
   241  WFTPPRTSNQ WLDFWLRHRL QWWRKFAMSP SNFSSSDCQD EEGRKGNKLY YNFPWGKELI
   301  ETLWNLGDHE LLHMYPGNVS KLHGRDGRKN VVPCVLSVNG DLDRGMLAYL YDSFQLTENS
   361  FTRKKNLHRK VLKLHPCLAP IKVALDVGRG PTLELRQVCQ GLFNELLENG ISVWPGYLET
   421  MQSSLEQLYS KYDEMSILFT VLVTETTLEN GLIHLRSRDT TMKEMMHISK LKDFLIKYIS
   481  SAKNV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against POLG2 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)

0.33

Highest tissue expression

11 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about POLG2.

Disease | AllUniProt

Conditions POLG2 is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 4 (PEOA4) MIM:610131
• Mitochondrial DNA depletion syndrome 16, hepatic type (MTDPS16) MIM:618528
• Mitochondrial DNA depletion syndrome 16B, neuroophthalmic type (MTDPS16B) MIM:619425

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 573 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4
• POLG2-related disorder
• Mitochondrial DNA depletion syndrome 16 (hepatic type)
• Mitochondrial dna depletion syndrome 16B (neuroophthalmic type)

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)

1.06

gnomAD pLI

0

gnomAD missense Z

-0.35

DepMap mean gene effect

-0.32

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA-templated DNA replication
• in utero embryonic development
• mitochondrial DNA replication
• mitochondrion organization
• positive regulation of DNA-directed DNA polymerase activity

Molecular functions

• DNA polymerase binding
• DNA polymerase processivity factor activity
• DNA-directed DNA polymerase activity
• double-stranded DNA binding
• identical protein binding

Cellular components

• cytoplasm
• gamma DNA polymerase complex
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Anticodon-binding
• Glycyl-tRNA synthetase/DNA polymerase subunit gamma-2
• Anticodon-binding domain superfamily
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Anticodon binding domain
• POLG2, C-terminal

KeywordsUniProt

• DNA replication
• DNA-binding
• Mitochondrion
• Mitochondrion nucleoid
• Phosphoprotein
• Primary mitochondrial disease
• Progressive external ophthalmoplegia
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of POLG2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• POLG