POLG
entrez
5428
canonical
uniprot
P54098
canonical
ensembl
ENSG00000140521
resolver
ensp
ENSP00000268124
resolver
ensp
ENSP00000399851
resolver
ensp
ENSP00000516154
resolver
enst
ENST00000268124
resolver
enst
ENST00000442287
resolver
enst
ENST00000636937
resolver
genesymbol
POLG
resolver
genesymbol_syn
MDP1
resolver
genesymbol_syn
POLG1
resolver
genesymbol_syn
POLGA
resolver
hgnc
HGNC:9179
resolver
uniprot
E5KNU5
resolver
uniprot
Q8NFM2
resolver
uniprot
Q92515
resolver
uniprot_entry
DPOG1_HUMAN
resolver
uniprot_entry
E5KNU5_HUMAN
resolver
uniprot_sec
Q8NFM2
resolver
uniprot_sec
Q92515
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by dideoxynucleotides such as antiviral agent zalcitabine. {ECO:0000269|PubMed:26056153}.
uniprot
proteins
amino_acid_sequence
MSRLLWRKVAGATVGPGPVPAPGRWVSSSVPASDPSDGQRRRQQQQQQQQQQQQQPQQPQVLSSEGGQLRHNPLDIQMLSRGLHEQIFGQGGEMPGEAAVRRSVEHLQKHGLWGQPAVPLPDVELRLPPLYGDNLDQHFRLLAQKQSLPYLEAANLLLQAQLPPKPPAWAWAEGWTRYGPEGEAVPVAIPEERALVFDVEVCLAEGTCPTLAVAISPSAWYSWCSQRLVEERYSWTSQLSPADLIPLEVPTGASSPTQRDWQEQLVVGHNVSFDRAHIREQYLIQGSRMRFLDTMSMHMAISGLSSFQRSLWIAAKQGKHKVQPPTKQGQKSQRKARRGPAISSWDWLDISSVNSLAEVHRLYVGGPPLEKEPRELFVKGTMKDIRENFQDLMQYCAQDVWATHEVFQQQLPLFLERCPHPVTLAGMLEMGVSYLPVNQNWERYLAEAQGTYEELQREMKKSLMDLANDACQLLSGERYKEDPWLWDLEWDLQEFKQKKAKKVKKEPATASKLPIEGAGAPGDPMDQEDLGPCSEEEEFQQDVMARACLQKLKGTTELLPKRPQHLPGHPGWYRKLCPRLDDPAWTPGPSLLSLQMRVTPKLMALTWDGFPLHYSERHGWGYLVPGRRDNLAKLPTGTTLESAGVVCPYRAIESLYRKHCLEQGKQQLMPQEAGLAEEFLLTDNSAIWQTVEELDYLEVEAEAKMENLRAAVPGQPLALTARGGPKDTQPSYHHGNGPYNDVDIPGCWFFKLPHKDGNSCNVGSPFAKDFLPKMEDGTLQAGPGGASGPRALEINKMISFWRNAHKRISSQMVVWLPRSALPRAVIRHPDYDEEGLYGAILPQVVTAGTITRRAVEPTWLTASNARPDRVGSELKAMVQAPPGYTLVGADVDSQELWIAAVLGDAHFAGMHGCTAFGWMTLQGRKSRGTDLHSKTATTVGISREHAKIFNYGRIYGAGQPFAERLLMQFNHRLTQQEAAEKAQQMYAATKGLRWYRLSDEGEWLVRELNLPVDRTEGGWISLQDLRKVQRETARKSQWKKWEVVAERAWKGGTESEMFNKLESIATSDIPRTPVLGCCISRALEPSAVQEEFMTSRVNWVVQSSAVDYLHLMLVAMKWLFEEFAIDGRFCISIHDEVRYLVREEDRYRAALALQITNLLTRCMFAYKLGLNDLPQSVAFFSAVDIDRCLRKEVTMDCKTPSNPTGMERRYGIPQGEALDIYQIIELTKGSLEKRSQPGP
uniprot
proteins
disease_involvement
DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1 (PEOA1) [MIM:157640]: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. {ECO:0000269|PubMed:11897778, ECO:0000269|PubMed:12210792, ECO:0000269|PubMed:15351195, ECO:0000269|PubMed:15534189, ECO:0000269|PubMed:17420318, ECO:0000269|PubMed:17846414, ECO:0000269|PubMed:18575922}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 1 (PEOB1) [MIM:258450]: A severe form of progressive external ophthalmoplegia, a disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. It is clinically more heterogeneous than the autosomal dominant forms. {ECO:0000269|PubMed:11431686, ECO:0000269|PubMed:12210792, ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:12872260, ECO:0000269|PubMed:12975295, ECO:0000269|PubMed:14635118, ECO:0000269|PubMed:15349879, ECO:0000269|PubMed:15351195, ECO:0000269|PubMed:15477547, ECO:0000269|PubMed:15917273, ECO:0000269|PubMed:16401742, ECO:0000269|PubMed:16621917, ECO:0000269|PubMed:16634032, ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:21301859, ECO:0000269|PubMed:26095671}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]: A systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss. {ECO:0000269|PubMed:12565911, ECO:0000269|PubMed:14745080, ECO:0000269|PubMed:15477547, ECO:0000269|PubMed:15824347, ECO:0000269|PubMed:15917273, ECO:0000269|PubMed:16080118, ECO:0000269|PubMed:16621917, ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:16919951}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 4A (MTDPS4A) [MIM:203700]: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis. {ECO:0000269|PubMed:15122711, ECO:0000269|PubMed:15689359, ECO:0000269|PubMed:15929042, ECO:0000269|PubMed:16621917, ECO:0000269|PubMed:16639411, ECO:0000269|PubMed:18828154, ECO:0000269|PubMed:20400524, ECO:0000269|PubMed:22000311, ECO:0000269|PubMed:25129007}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 4B (MTDPS4B) [MIM:613662]: An autosomal recessive progressive multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness. {ECO:0000269|PubMed:12825077, ECO:0000269|PubMed:19307547}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:18828154, ECO:0000269|PubMed:26095671}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia with epilepsy (SCAE) [MIM:607459]: An autosomal recessive syndrome characterized by headaches and/or seizures manifesting in childhood or adolescence, cerebellar and sensory ataxia, dysarthria, and myoclonus manifesting in early adulthood. Neuropathological findings include spinocerebellar degeneration associated with cortical neuronal degeneration in advanced cases. {ECO:0000269|PubMed:14694057, ECO:0000269|PubMed:20400524, ECO:0000269|PubMed:26942291}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.7.7
uniprot
proteins
ec_number
3.1.11.-
uniprot
proteins
ec_number
4.2.99.-
uniprot
proteins
function
FUNCTION: Catalytic subunit of DNA polymerase gamma solely responsible for replication of mitochondrial DNA (mtDNA). Replicates both heavy and light strands of the circular mtDNA genome using a single-stranded DNA template, RNA primers and the four deoxyribonucleoside triphosphates as substrates (PubMed:11477093, PubMed:11897778, PubMed:15917273, PubMed:19837034, PubMed:9558343). Has 5' -> 3' polymerase activity. Functionally interacts with TWNK and SSBP1 at the replication fork to form a highly processive replisome, where TWNK unwinds the double-stranded DNA template prior to replication and SSBP1 covers the parental heavy strand to enable continuous replication of the entire mitochondrial genome. A single nucleotide incorporation cycle includes binding of the incoming nucleotide at the insertion site, a phosphodiester bond formation reaction that extends the 3'-end of the primer DNA, and translocation of the primer terminus to the post-insertion site. After completing replication of a mtDNA strand, mediates 3' -> 5' exonucleolytic degradation at the nick to enable proper ligation (PubMed:11477093, PubMed:11897778, PubMed:15167897, PubMed:15917273, PubMed:19837034, PubMed:26095671, PubMed:9558343). Highly accurate due to high nucleotide selectivity and 3' -> 5' exonucleolytic proofreading. Proficiently corrects base substitutions, single-base additions and deletions in non-repetitive sequences and short repeats, but displays lower proofreading activity when replicating longer homopolymeric stretches. Exerts exonuclease activity toward single-stranded DNA and double-stranded DNA containing 3'-terminal mispairs. When a misincorporation occurs, transitions from replication to a pro-nucleolytic editing mode and removes the missincorporated nucleoside in the exonuclease active site. Proceeds via an SN2 nucleolytic mechanism in which Asp-198 catalyzes phosphodiester bond hydrolysis and Glu-200 stabilizes the leaving group. As a result the primer strand becomes one nucleotide shorter and is positioned in the post-insertion site, ready to resume DNA synthesis (PubMed:10827171, PubMed:11477094, PubMed:11504725, PubMed:37202477). Exerts 5'-deoxyribose phosphate (dRP) lyase activity and mediates repair-associated mtDNA synthesis (gap filling) in base-excision repair pathway. Catalyzes the release of the 5'-terminal 2-deoxyribose-5-phosphate sugar moiety from incised apurinic/apyrimidinic (AP) sites to produce a substrate for DNA ligase. The dRP lyase reaction does not require divalent metal ions and likely proceeds via a Schiff base intermediate in a beta-elimination reaction mechanism (PubMed:9770471). {ECO:0000269|PubMed:10827171, ECO:0000269|PubMed:11477093, ECO:0000269|PubMed:11477094, ECO:0000269|PubMed:11504725, ECO:0000269|PubMed:11897778, ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:15917273, ECO:0000269|PubMed:19837034, ECO:0000269|PubMed:26095671, ECO:0000269|PubMed:37202477, ECO:0000269|PubMed:9558343, ECO:0000269|PubMed:9770471}.
uniprot
proteins
mass_dalton
139562
uniprot
proteins
mutagenesis
MUTAGEN 198; /note="D->A: Abolishes exonuclease activity; when associated with A-200. Decreases polymerase exonucleolytic proofreading by 30-fold for the T:G mismatch and by 14-fold for the A:A mismatch; when associated with A-200. Significantly increases mitochondrial DNA mutation frequency. Does not affect DNA polymerase activity."; /evidence="ECO:0000269|PubMed:10827171, ECO:0000269|PubMed:11504725, ECO:0000269|PubMed:37202477"; MUTAGEN 200; /note="E->A: Abolishes exonuclease activity; when associated with A-198. Decreases polymerase exonucleolytic proofreading by 30-fold for the T:G mismatch and by 14-fold for the A:A mismatch; when associated with A-198."; /evidence="ECO:0000269|PubMed:11477093, ECO:0000269|PubMed:11504725, ECO:0000269|PubMed:37202477"; MUTAGEN 274; /note="D->A: Unable to idle at the 5'-end of the nascent DNA strand. Continues DNA synthesis into double-stranded DNA past the 5'-end creating a flap structure that cannot be ligated."; /evidence="ECO:0000269|PubMed:26095671"; MUTAGEN 498; /note="K->C: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:26056153"; MUTAGEN 499; /note="K->C: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:26056153"; MUTAGEN 501; /note="K->C: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:26056153"; MUTAGEN 543..558; /note="Missing: Markedly decreases the stimulation by POLG2, resulting in impaired processive DNA synthesis."; /evidence="ECO:0000269|PubMed:19837034"; MUTAGEN 549; /note="L->N: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:19837034"; MUTAGEN 552; /note="L->N: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:19837034"; MUTAGEN 553; /note="K->N: Decreases processive DNA synthesis."; /evidence="ECO:0000269|PubMed:19837034"; MUTAGEN 853; /note="R->A: Abolishes primer DNA extention in the presence of dNTPs. Impairs intrinsic polymerase processivity. Enhances exonuclease activity leading to primer DNA degradation."; /evidence="ECO:0000269|PubMed:37202477"; MUTAGEN 890; /note="D->N: Abolishes DNA polymerase activity."; /evidence="ECO:0000269|PubMed:10827171"; MUTAGEN 1135; /note="D->N: Abolishes DNA polymerase activity."; /evidence="ECO:0000269|PubMed:10827171
uniprot
proteins
protein_family
DNA polymerase type-A family
uniprot
proteins
pubmed
10827171
uniprot
proteins
pubmed
11431686
uniprot
proteins
pubmed
11477093
uniprot
proteins
pubmed
11477094
uniprot
proteins
pubmed
11504725
uniprot
proteins
pubmed
11897778
uniprot
proteins
pubmed
12210792
uniprot
proteins
pubmed
12565911
uniprot
proteins
pubmed
12707443
uniprot
proteins
pubmed
12825077
uniprot
proteins
pubmed
12872260
uniprot
proteins
pubmed
12975295
uniprot
proteins
pubmed
14635118
uniprot
proteins
pubmed
14694057
uniprot
proteins
pubmed
14745080
uniprot
proteins
pubmed
15122711
uniprot
proteins
pubmed
15167897
uniprot
proteins
pubmed
15189144
uniprot
proteins
pubmed
15349879
uniprot
proteins
pubmed
15351195
uniprot
proteins
pubmed
15477547
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15534189
uniprot
proteins
pubmed
15689359
uniprot
proteins
pubmed
15824347
uniprot
proteins
pubmed
15917273
uniprot
proteins
pubmed
15929042
uniprot
proteins
pubmed
16080118
uniprot
proteins
pubmed
16401742
uniprot
proteins
pubmed
16621917
uniprot
proteins
pubmed
16634032
uniprot
proteins
pubmed
16639411
uniprot
proteins
pubmed
16919951
uniprot
proteins
pubmed
17420318
uniprot
proteins
pubmed
17846414
uniprot
proteins
pubmed
18063578
uniprot
proteins
pubmed
18575922
uniprot
proteins
pubmed
18828154
uniprot
proteins
pubmed
19307547
uniprot
proteins
pubmed
19837034
uniprot
proteins
pubmed
20400524
uniprot
proteins
pubmed
21301859
uniprot
proteins
pubmed
22000311
uniprot
proteins
pubmed
25129007
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26056153
uniprot
proteins
pubmed
26095671
uniprot
proteins
pubmed
26942291
uniprot
proteins
pubmed
29290964
uniprot
proteins
pubmed
30552426
uniprot
proteins
pubmed
33855352
uniprot
proteins
pubmed
37202477
uniprot
proteins
pubmed
8884268
uniprot
proteins
pubmed
9034326
uniprot
proteins
pubmed
9558343
uniprot
proteins
pubmed
9770471
uniprot
proteins
sequence_length
1239
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10827171, ECO:0000269|PubMed:18063578}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269|PubMed:18063578}.
uniprot
proteins