DNA polymerase subunit gamma-1
Details
- Name
- DNA polymerase subunit gamma-1
- Kind
- protein
- Synonyms
- 2.7.7.7
- 3'-5' exodeoxyribonuclease
- 5'-deoxyribose-phosphate lyase
- MDP1
- Mitochondrial DNA polymerase catalytic subunit
- PolG-alpha
- POLG1
- POLGA
- Gene Name
- POLG
- UniProtKB Entry
- P54098Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0054052|DNA polymerase subunit gamma-1 MSRLLWRKVAGATVGPGPVPAPGRWVSSSVPASDPSDGQRRRQQQQQQQQQQQQQPQQPQ VLSSEGGQLRHNPLDIQMLSRGLHEQIFGQGGEMPGEAAVRRSVEHLQKHGLWGQPAVPL PDVELRLPPLYGDNLDQHFRLLAQKQSLPYLEAANLLLQAQLPPKPPAWAWAEGWTRYGP EGEAVPVAIPEERALVFDVEVCLAEGTCPTLAVAISPSAWYSWCSQRLVEERYSWTSQLS PADLIPLEVPTGASSPTQRDWQEQLVVGHNVSFDRAHIREQYLIQGSRMRFLDTMSMHMA ISGLSSFQRSLWIAAKQGKHKVQPPTKQGQKSQRKARRGPAISSWDWLDISSVNSLAEVH RLYVGGPPLEKEPRELFVKGTMKDIRENFQDLMQYCAQDVWATHEVFQQQLPLFLERCPH PVTLAGMLEMGVSYLPVNQNWERYLAEAQGTYEELQREMKKSLMDLANDACQLLSGERYK EDPWLWDLEWDLQEFKQKKAKKVKKEPATASKLPIEGAGAPGDPMDQEDLGPCSEEEEFQ QDVMARACLQKLKGTTELLPKRPQHLPGHPGWYRKLCPRLDDPAWTPGPSLLSLQMRVTP KLMALTWDGFPLHYSERHGWGYLVPGRRDNLAKLPTGTTLESAGVVCPYRAIESLYRKHC LEQGKQQLMPQEAGLAEEFLLTDNSAIWQTVEELDYLEVEAEAKMENLRAAVPGQPLALT ARGGPKDTQPSYHHGNGPYNDVDIPGCWFFKLPHKDGNSCNVGSPFAKDFLPKMEDGTLQ AGPGGASGPRALEINKMISFWRNAHKRISSQMVVWLPRSALPRAVIRHPDYDEEGLYGAI LPQVVTAGTITRRAVEPTWLTASNARPDRVGSELKAMVQAPPGYTLVGADVDSQELWIAA VLGDAHFAGMHGCTAFGWMTLQGRKSRGTDLHSKTATTVGISREHAKIFNYGRIYGAGQP FAERLLMQFNHRLTQQEAAEKAQQMYAATKGLRWYRLSDEGEWLVRELNLPVDRTEGGWI SLQDLRKVQRETARKSQWKKWEVVAERAWKGGTESEMFNKLESIATSDIPRTPVLGCCIS RALEPSAVQEEFMTSRVNWVVQSSAVDYLHLMLVAMKWLFEEFAIDGRFCISIHDEVRYL VREEDRYRAALALQITNLLTRCMFAYKLGLNDLPQSVAFFSAVDIDRCLRKEVTMDCKTP SNPTGMERRYGIPQGEALDIYQIIELTKGSLEKRSQPGP
- Number of residues
- 1239
- Molecular Weight
- 139561.06
- Theoretical pI
- Not Available
- GO Classification
- Functions5'-deoxyribose-5-phosphate lyase activity / single-stranded DNA 3'-5' DNA exonuclease activityProcessesbase-excision repair / DNA replication proofreading
- General 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)
- Specific Function
- 3'-5' exonuclease activity
- Pfam Domain Function
- DNApol_Exo (PF18136)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion
- Gene sequence
>lcl|BSEQ0054053|DNA polymerase subunit gamma-1 (POLG) ATGAGCCGCCTGCTCTGGAGGAAGGTGGCCGGCGCCACCGTCGGGCCAGGGCCGGTTCCA GCTCCGGGGCGCTGGGTCTCCAGCTCCGTCCCCGCGTCCGACCCCAGCGACGGGCAGCGG CGGCGGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAACAGCAGCCTCAGCAGCCGCAA GTGCTATCCTCGGAGGGCGGGCAGCTGCGGCACAACCCATTGGACATCCAGATGCTCTCG AGAGGGCTGCACGAGCAAATCTTCGGGCAAGGAGGGGAGATGCCTGGCGAGGCCGCGGTG CGCCGCAGCGTCGAGCACCTGCAGAAGCACGGGCTCTGGGGGCAGCCAGCCGTGCCCTTG CCCGACGTGGAGCTGCGCCTGCCGCCCCTCTACGGGGACAACCTGGACCAGCACTTCCGC CTCCTGGCCCAGAAGCAGAGCCTGCCCTACCTGGAGGCGGCCAACTTGCTGTTGCAGGCC CAGCTGCCCCCGAAGCCCCCGGCTTGGGCCTGGGCGGAGGGCTGGACCCGGTACGGCCCC GAGGGGGAGGCCGTACCCGTGGCCATCCCCGAGGAGCGGGCCCTGGTGTTCGACGTGGAG GTCTGCTTGGCAGAGGGAACTTGCCCCACATTGGCGGTGGCCATATCCCCCTCGGCCTGG TATTCCTGGTGCAGCCAGCGGCTGGTGGAAGAGCGTTACTCTTGGACCAGCCAGCTGTCG CCGGCTGACCTCATCCCCCTGGAGGTCCCTACTGGTGCCAGCAGCCCCACCCAGAGAGAC TGGCAGGAGCAGTTAGTGGTGGGGCACAATGTTTCCTTTGACCGAGCTCATATCAGGGAG CAGTACCTGATCCAGGGTTCCCGCATGCGTTTCCTGGACACCATGAGCATGCACATGGCC ATCTCAGGGCTAAGCAGCTTCCAGCGCAGTCTGTGGATAGCAGCCAAGCAGGGCAAACAC AAGGTCCAGCCCCCCACAAAGCAAGGCCAGAAGTCCCAGAGGAAAGCCAGAAGAGGCCCA GCGATCTCATCCTGGGACTGGCTGGACATCAGCAGTGTCAACAGTCTGGCAGAGGTGCAC AGACTTTATGTAGGGGGGCCTCCCTTAGAGAAGGAGCCTCGAGAACTGTTTGTGAAGGGC ACCATGAAGGACATTCGTGAGAACTTCCAGGACCTGATGCAGTACTGTGCCCAGGACGTG TGGGCCACCCATGAGGTTTTCCAGCAGCAGCTACCGCTCTTCTTGGAGAGGTGTCCCCAC CCAGTGACTCTGGCCGGCATGCTGGAGATGGGTGTCTCCTACCTGCCTGTCAACCAGAAC TGGGAGCGTTACCTGGCAGAGGCACAGGGCACTTATGAGGAGCTCCAGCGGGAGATGAAG AAGTCGTTGATGGATCTGGCCAATGATGCCTGCCAGCTGCTCTCAGGAGAGAGGTACAAA GAAGACCCCTGGCTCTGGGACCTGGAGTGGGACCTGCAAGAATTTAAGCAGAAGAAAGCT AAGAAGGTGAAGAAGGAACCAGCCACAGCCAGCAAGTTGCCCATCGAGGGGGCTGGGGCC CCTGGTGATCCCATGGATCAGGAAGACCTCGGCCCCTGCAGTGAGGAGGAGGAGTTTCAA CAAGATGTCATGGCCCGCGCCTGCTTGCAGAAGCTGAAGGGGACCACAGAGCTCCTGCCC AAGCGGCCCCAGCACCTTCCTGGACACCCTGGATGGTACCGGAAGCTCTGCCCCCGGCTA GACGACCCTGCATGGACCCCGGGCCCCAGCCTCCTCAGCCTGCAGATGCGGGTCACACCT AAACTCATGGCACTTACCTGGGATGGCTTCCCTCTGCACTACTCAGAGCGTCATGGCTGG GGCTACTTGGTGCCTGGGCGGCGGGACAACCTGGCCAAGCTGCCGACAGGTACCACCCTG GAGTCAGCTGGGGTGGTCTGCCCCTACAGAGCCATCGAGTCCCTGTACAGGAAGCACTGT CTCGAACAGGGGAAGCAGCAGCTGATGCCCCAGGAGGCCGGCCTGGCGGAGGAGTTCCTG CTCACTGACAATAGTGCCATATGGCAAACGGTAGAAGAACTGGATTACTTAGAAGTGGAG GCTGAGGCCAAGATGGAGAACTTGCGAGCTGCAGTGCCAGGTCAACCCCTAGCTCTGACT GCCCGTGGTGGCCCCAAGGACACCCAGCCCAGCTATCACCATGGCAATGGACCTTACAAC GACGTGGACATCCCTGGCTGCTGGTTTTTCAAGCTGCCTCACAAGGATGGTAATAGCTGT AATGTGGGAAGCCCCTTTGCCAAGGACTTCCTGCCCAAGATGGAGGATGGCACCCTGCAG GCTGGCCCAGGAGGTGCCAGTGGGCCCCGTGCTCTGGAAATCAACAAAATGATTTCTTTC TGGAGGAACGCCCATAAACGTATCAGCTCCCAGATGGTGGTGTGGCTGCCCAGGTCAGCT CTGCCCCGTGCTGTGATCAGGCACCCCGACTATGATGAGGAAGGCCTCTATGGGGCCATC CTGCCCCAAGTGGTGACTGCCGGCACCATCACTCGCCGGGCTGTGGAGCCCACATGGCTC ACCGCCAGCAATGCCCGGCCTGACCGAGTAGGCAGTGAGTTGAAAGCCATGGTGCAGGCC CCACCTGGCTACACCCTTGTGGGTGCTGATGTGGACTCCCAAGAGCTGTGGATTGCAGCT GTGCTTGGAGACGCCCACTTTGCCGGCATGCATGGCTGCACAGCCTTTGGGTGGATGACA CTGCAGGGCAGGAAGAGCAGGGGCACTGATCTACACAGTAAGACAGCCACTACTGTGGGC ATCAGCCGTGAGCATGCCAAAATCTTCAACTACGGCCGCATCTATGGTGCTGGGCAGCCC TTTGCTGAGCGCTTACTAATGCAGTTTAACCACCGGCTCACACAGCAGGAGGCAGCTGAG AAGGCCCAGCAGATGTACGCTGCCACCAAGGGCCTCCGCTGGTATCGGCTGTCGGATGAG GGCGAGTGGCTGGTGAGGGAGTTGAACCTCCCAGTGGACAGGACTGAGGGTGGCTGGATT TCCCTGCAGGATCTGCGCAAGGTCCAGAGAGAAACTGCAAGGAAGTCACAGTGGAAGAAG TGGGAGGTGGTTGCTGAACGGGCATGGAAGGGGGGCACAGAGTCAGAAATGTTCAATAAG CTTGAGAGCATTGCTACGTCTGACATACCACGTACCCCGGTGCTGGGCTGCTGCATCAGC CGAGCCCTGGAGCCCTCGGCTGTCCAGGAAGAGTTTATGACCAGCCGTGTGAATTGGGTG GTACAGAGCTCTGCTGTTGACTACTTACACCTCATGCTTGTGGCCATGAAGTGGCTGTTT GAAGAGTTTGCCATAGATGGGCGCTTCTGCATCAGCATCCATGACGAGGTTCGCTACCTG GTGCGGGAGGAGGACCGCTACCGCGCTGCCCTGGCCTTGCAGATCACCAACCTCTTGACC AGGTGCATGTTTGCCTACAAGCTGGGTCTGAATGACTTGCCCCAGTCAGTCGCCTTTTTC AGTGCAGTCGATATTGACCGGTGCCTCAGGAAGGAAGTGACCATGGATTGTAAAACCCCT TCCAACCCAACTGGGATGGAAAGGAGATACGGGATTCCCCAGGGTGAAGCGCTGGATATT TACCAGATAATTGAACTCACCAAAGGCTCCTTGGAAAAACGAAGCCAGCCTGGACCATAG
- Chromosome Location
- 15
- Locus
- 15q26.1
- External Identifiers
Resource Link UniProtKB ID P54098 UniProtKB Entry Name DPOG1_HUMAN GeneCard ID POLG HGNC ID HGNC:9179 PDB ID(s) 3IKM, 4ZTU, 4ZTZ, 5C51, 5C52, 5C53, 8D33, 8D37, 8D3R, 8D42, 8G5I, 8G5J, 8G5K, 8G5L, 8G5M, 8G5N, 8G5O, 8G5P, 8T7E KEGG ID hsa:5428 NCBI Gene ID 5428 - General References
- Not Available
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Brincidofovir approved, investigational yes target inhibitor Details