POLG2

Last updated
POLG2
Protein POLG2 PDB 2g4c.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases POLG2 , HP55, MTPOLB, PEOA4, POLB, POLG-BETA, POLGB, polymerase (DNA) gamma 2, accessory subunit, DNA polymerase gamma 2, accessory subunit, MTDPS16, MTDPS16A, MTDPS16B
External IDs OMIM: 604983 MGI: 1354947 HomoloGene: 5221 GeneCards: POLG2
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 Mb Chr 11: 106.66 – 106.67 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

Structure

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

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

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

Clinical significance

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

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

Related Research Articles

<span class="mw-page-title-main">HADHB</span> Protein-coding gene in the species Homo sapiens

Trifunctional enzyme subunit beta, mitochondrial (TP-beta) also known as 3-ketoacyl-CoA thiolase, acetyl-CoA acyltransferase, or beta-ketothiolase is an enzyme that in humans is encoded by the HADHB gene.

<span class="mw-page-title-main">PPP2R5C</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform is an enzyme that in humans is encoded by the PPP2R5C gene.

<span class="mw-page-title-main">POLG</span> Protein-coding gene in the species Homo sapiens

DNA polymerase subunit gamma is an enzyme that in humans is encoded by the POLG 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. 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).

<span class="mw-page-title-main">GNB1</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.

<span class="mw-page-title-main">TCEA1</span> Human protein-coding gene

Transcription elongation factor A protein 1 is a protein that in humans is encoded by the TCEA1 gene.

<span class="mw-page-title-main">GNB2</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 is a protein that in humans is encoded by the GNB2 gene.

<span class="mw-page-title-main">RFC3</span> Protein-coding gene in the species Homo sapiens

Replication factor C subunit 3 is a protein that in humans is encoded by the RFC3 gene.

<span class="mw-page-title-main">GNGT1</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(T) subunit gamma-T1 is a protein that in humans is encoded by the GNGT1 gene.

<span class="mw-page-title-main">REV3L</span> Protein-coding gene in the species Homo sapiens

Protein reversionless 3-like (REV3L) also known as DNA polymerase zeta catalytic subunit (POLZ) is an enzyme that in humans is encoded by the REV3L gene.

<span class="mw-page-title-main">SSBP1</span> Protein-coding gene in the species Homo sapiens

Single-stranded DNA-binding protein, mitochondrial is a protein that in humans is encoded by the SSBP1 gene.

<span class="mw-page-title-main">GNB4</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit beta-4 is a protein that in humans is encoded by the GNB4 gene.

<span class="mw-page-title-main">ATP5G2</span> Protein-coding gene in humans

The ATP5MC2 gene is one of three human paralogs that encode membrane subunit c of the mitochondrial ATP synthase.

<span class="mw-page-title-main">POLD3</span> Protein-coding gene in the species Homo sapiens

DNA polymerase delta subunit 3 is an enzyme that in humans is encoded by the POLD3 gene. It is a component of the DNA polymerase delta complex.

<span class="mw-page-title-main">POLDIP2</span> Protein-coding gene in the species Homo sapiens

Polymerase delta-interacting protein 2 also known as Polymerase delta-interacting protein of 38 kDa (PDIP38) is encoded by the POLDIP2 gene in humans.

<span class="mw-page-title-main">Mitochondrial ribosomal protein L12</span> Protein-coding gene in the species Homo sapiens

39S ribosomal protein L12, mitochondrial is a protein that in humans is encoded by the MRPL12 gene.

<span class="mw-page-title-main">SNAPC2</span> Protein-coding gene in the species Homo sapiens

snRNA-activating protein complex subunit 2 is a protein that in humans is encoded by the SNAPC2 gene.

<span class="mw-page-title-main">POLRMT</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase, mitochondrial is an enzyme that in humans is encoded by the POLRMT gene.

<span class="mw-page-title-main">Mitochondrial ribosomal protein L41</span> Protein-coding gene in the species Homo sapiens

39S ribosomal protein L41, mitochondrial is a protein that in humans is encoded by the MRPL41 gene.

<span class="mw-page-title-main">MRPS26</span> Protein-coding gene in the species Homo sapiens

28S ribosomal protein S26, mitochondrial is a protein that in humans is encoded by the MRPS26 gene.

<span class="mw-page-title-main">POLE4</span> Protein-coding gene in the species Homo sapiens

Polymerase (DNA-directed), epsilon 4, accessory subunit is a protein that in humans is encoded by the POLE4 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000256525 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 "Entrez Gene: POLG2 polymerase (DNA directed), gamma 2, accessory subunit".PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 3 4 "POLG2 - DNA polymerase subunit gamma-2, mitochondrial precursor - Homo sapiens (Human) - POLG2 gene & protein". www.uniprot.org. Retrieved 2018-08-31. CC BY icon-80x15.png  This article incorporates text available under the CC BY 4.0 license.
  9. 1 2 3 4 "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

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

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