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POLG2

From Wikipedia, the free encyclopedia
POLG2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPOLG2, HP55, MTPOLB, PEOA4, POLB, POLG-BETA, POLGB, polymerase (DNA) gamma 2, accessory subunit, DNA polymerase gamma 2, accessory subunit, MTDPS16, MTDPS16A, MTDPS16B
External IDsOMIM: 604983; MGI: 1354947; HomoloGene: 5221; GeneCards: POLG2; OMA:POLG2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

11232

50776

Ensembl

ENSG00000256525

ENSMUSG00000020718

UniProt

Q9UHN1

Q9QZM2

RefSeq (mRNA)

NM_007215

NM_015810
NM_001353435

RefSeq (protein)

NP_009146

NP_056625
NP_001340364

Location (UCSC)Chr 17: 64.48 – 64.5 MbChr 11: 106.66 – 106.67 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA polymerase subunit gamma-2, mitochondrial is a protein that in humans is encoded by the POLG2 gene. The POLG2 gene encodes a 55 kDa accessory subunit protein that imparts high processivity and salt tolerance to the catalytic subunit of DNA polymerase gamma, encoded by the POLG gene.[5][6] Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[7]

Structure

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POLG2 is located on the q arm of chromosome 17 in position 23.3 and has 8 exons.[7] POLG2, the protein encoded by this gene, contains a phosphoserine modified residue at p. 38 and a transit peptide. Its structure consists of 25 beta strands, 21 alpha helixes, and 8 turns.[8][9]

Function

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POLG2 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, stimulates polymerase and exonuclease activity, and promotes processive DNA synthesis.[7][8][9]

Catalytic activity

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Deoxynucleoside triphosphate DNA(n) = diphosphate DNA(n 1)[8][9]

Clinical significance

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Mutations in POLG2 have been associated with progressive external ophthalmoplegia with mitochondrial DNA deletions. This disease results in progressive weakness of ocular muscles and levator muscle of the upper eyelid and patients with it may also manifest skeletal myopathy, ragged-red fibers and atrophy shown on muscle biopsy, cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. This mutlisystemic disease has been linked to a G451E mutation that disrupts the DNA polymerase gamma subunits.[8][9][10]

In patients with chronic hepatitis C, those carrying the DDX5 minor allele or DDX5-POLG2 haplotypes are thought to be at an increased risk of advanced fibrosis. It is important to note, however, that those carrying the CPT1A minor allele are believed to be at a decreased risk.[11]

Interactions

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POLG2 has been shown to have 39 binary protein-protein interactions including 19 co-complex interactions. POLG2 appears to interact with POLG.[12]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000256525 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020718 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Wang Y, Farr CL, Kaguni LS (May 1997). "Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos. Cloning, molecular analysis, and association in the native enzyme". The Journal of Biological Chemistry. 272 (21): 13640–6. doi:10.1074/jbc.272.21.13640. PMID 9153213.
  6. ^ Lim SE, Longley MJ, Copeland WC (December 1999). "The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance". The Journal of Biological Chemistry. 274 (53): 38197–203. doi:10.1074/jbc.274.53.38197. PMID 10608893.
  7. ^ a b c "Entrez Gene: POLG2 polymerase (DNA directed), gamma 2, accessory subunit".Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ a b c d "POLG2 - DNA polymerase subunit gamma-2, mitochondrial precursor - Homo sapiens (Human) - POLG2 gene & protein". www.uniprot.org. Retrieved 2018-08-31. This article incorporates text available under the CC BY 4.0 license.
  9. ^ a b c d "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  10. ^ Longley MJ, Clark S, Yu Wai Man C, Hudson G, Durham SE, Taylor RW, Nightingale S, Turnbull DM, Copeland WC, Chinnery PF (June 2006). "Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia". American Journal of Human Genetics. 78 (6): 1026–34. doi:10.1086/504303. PMC 1474082. PMID 16685652.
  11. ^ Huang H, Shiffman ML, Cheung RC, Layden TJ, Friedman S, Abar OT, Yee L, Chokkalingam AP, Schrodi SJ, Chan J, Catanese JJ, Leong DU, Ross D, Hu X, Monto A, McAllister LB, Broder S, White T, Sninsky JJ, Wright TL (May 2006). "Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C". Gastroenterology. 130 (6): 1679–87. doi:10.1053/j.gastro.2006.02.032. PMID 16697732.
  12. ^ "39 binary interactions found for search term POLG2". IntAct. EMBL-EBI. Retrieved 2019-09-04.

Further reading

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  • Overview of all the structural information available in the PDB for UniProt: Q9UHN1 (Human DNA polymerase subunit gamma-2, mitochondrial) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q9QZM2 (Mouse DNA polymerase subunit gamma-2, mitochondrial) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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