POLG2: Difference between revisions

Jump to navigation Jump to search
← Older edit
VisualWikitext
imported>Trappist the monk
m →Further reading: cite repair;
 
Line 1: Line 1:
{{Infobox_gene}}
{{Infobox_gene}}'''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.<ref name="pmid91532132">{{cite journal | vauthors = Wang Y, Farr CL, Kaguni LS | title = Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos. Cloning, molecular analysis, and association in the native enzyme | journal = The Journal of Biological Chemistry | volume = 272 | issue = 21 | pages = 13640–6 | date = May 1997 | pmid = 9153213 | pmc =  | doi = 10.1074/jbc.272.21.13640 }}</ref><ref>{{cite journal | vauthors = Lim SE, Longley MJ, Copeland WC | title = The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance | journal = The Journal of Biological Chemistry | volume = 274 | issue = 53 | pages = 38197–203 | date = December 1999 | pmid = 10608893 | doi = 10.1074/jbc.274.53.38197 }}</ref> Mutations in this gene result in [[Dominance (genetics)|autosomal dominant]] [[progressive external ophthalmoplegia]] with mitochondrial DNA deletions.<ref name="entrez2">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11232|title=Entrez Gene: POLG2 polymerase (DNA directed), gamma 2, accessory subunit|access-date=}}{{PD-notice}}</ref>
'''DNA polymerase subunit gamma-2, mitochondrial''' is an [[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.<ref name="pmid9153213">{{cite journal |vauthors=Wang Y, Farr CL, Kaguni LS | title = Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos. Cloning, molecular analysis, and association in the native enzyme | journal = J Biol Chem | volume = 272 | issue = 21 | pages = 13640–6 |date=Jul 1997 | pmid = 9153213 | pmc =  | doi =10.1074/jbc.272.21.13640 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: POLG2 polymerase (DNA directed), gamma 2, accessory subunit| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11232| accessdate = }}</ref><ref>{{cite journal | last1 = Lim | first1 = SE | last2 = Longley | first2 = MJ | last3 = Copeland | first3 = WC |name-list-format=vanc | year = 1999 | title = The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance | url = | journal = J. Biol. Chem. | volume = 274 | issue = 53| pages = 38197–203 | doi = 10.1074/jbc.274.53.38197 | pmid = 10608893 }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{PBB_Summary
<i>POLG2</i> is located on the [[Locus (genetics)|q arm]] of [[chromosome 17]] in position 23.3 and has 8 [[Exon|exons]].<ref name="entrez2" /> 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 sheet|beta strands]], 21 [[Alpha helix|alpha helixes]], and 8 turns.<ref name=":1">{{Cite web|url=https://www.uniprot.org/uniprot/Q9UHN1|title=POLG2 - DNA polymerase subunit gamma-2, mitochondrial precursor - Homo sapiens (Human) - POLG2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-31}}{{CC-notice|cc=by4}}</ref><ref name=":0">{{cite journal | vauthors =  | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}</ref>
| section_title =  
| summary_text =  
}}


==References==
== 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 protein|DNA binding]], stimulates [[polymerase]] and [[exonuclease]] activity, and promotes processive [[DNA synthesis]].<ref name="entrez2" /><ref name=":1" /><ref name=":0" />
 
=== Catalytic activity ===
[[Nucleotide|Deoxynucleoside triphosphate]] + DNA(n) = [[diphosphate]] + DNA(n+1)<ref name=":1" /><ref name=":0" />
 
== Clinical significance ==
[[Mutation|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, [[Cataract|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.<ref name=":1" /><ref name=":0" /><ref>{{cite journal | vauthors = Longley MJ, Clark S, Yu Wai Man C, Hudson G, Durham SE, Taylor RW, Nightingale S, Turnbull DM, Copeland WC, Chinnery PF | title = Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia | journal = American Journal of Human Genetics | volume = 78 | issue = 6 | pages = 1026–34 | date = June 2006 | pmid = 16685652 | pmc = 1474082 | doi = 10.1086/504303 }}</ref>
 
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.<ref>{{cite journal | vauthors = 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 | title = Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C | journal = Gastroenterology | volume = 130 | issue = 6 | pages = 1679–87 | date = May 2006 | pmid = 16697732 | doi = 10.1053/j.gastro.2006.02.032 }}</ref>
 
== Interactions ==
POLG2 has been shown to have 32 binary [[Protein–protein interaction|protein-protein interactions]] including 19 co-complex interactions. POLG2 appears to interact with [[POLG]].<ref>{{Cite web|url=https://www.ebi.ac.uk/intact/interactions?conversationContext=1|title=https://www.ebi.ac.uk/intact/interactions?conversationContext=1|last=IntAct|website=www.ebi.ac.uk|language=en|access-date=2018-08-31}}</ref>
== References ==
{{reflist}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Michiels S, Danoy P, Dessen P, Bera A, Boulet T, Bouchardy C, Lathrop M, Sarasin A, Benhamou S | title = Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers | journal = Carcinogenesis | volume = 28 | issue = 8 | pages = 1731–9 | date = August 2007 | pmid = 17494052 | doi = 10.1093/carcin/bgm111 }}
| citations =
* {{cite journal | vauthors = 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 | title = Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C | journal = Gastroenterology | volume = 130 | issue = 6 | pages = 1679–87 | date = May 2006 | pmid = 16697732 | doi = 10.1053/j.gastro.2006.02.032 }}
*{{cite journal   |vauthors=Michiels S, Danoy P, Dessen P, etal |title=Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers. |journal=Carcinogenesis |volume=28 |issue= 8 |pages= 1731–9 |year= 2007 |pmid= 17494052 |doi= 10.1093/carcin/bgm111 }}
* {{cite journal | vauthors = Longley MJ, Clark S, Yu Wai Man C, Hudson G, Durham SE, Taylor RW, Nightingale S, Turnbull DM, Copeland WC, Chinnery PF | title = Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia | journal = American Journal of Human Genetics | volume = 78 | issue = 6 | pages = 1026–34 | date = June 2006 | pmid = 16685652 | pmc = 1474082 | doi = 10.1086/504303 }}
*{{cite journal   |vauthors=Huang H, Shiffman ML, Cheung RC, etal |title=Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C. |journal=Gastroenterology |volume=130 |issue= 6 |pages= 1679–87 |year= 2006 |pmid= 16697732 |doi= 10.1053/j.gastro.2006.02.032 }}
* {{cite journal | vauthors = Yakubovskaya E, Chen Z, Carrodeguas JA, Kisker C, Bogenhagen DF | title = Functional human mitochondrial DNA polymerase gamma forms a heterotrimer | journal = The Journal of Biological Chemistry | volume = 281 | issue = 1 | pages = 374–82 | date = January 2006 | pmid = 16263719 | doi = 10.1074/jbc.M509730200 }}
*{{cite journal   |vauthors=Longley MJ, Clark S, Yu Wai Man C, etal |title=Mutant POLG2 Disrupts DNA Polymerase γ Subunits and Causes Progressive External Ophthalmoplegia |journal=Am. J. Hum. Genet. |volume=78 |issue= 6 |pages= 1026–34 |year= 2006 |pmid= 16685652 |doi= 10.1086/504303 | pmc=1474082 }}
* {{cite journal | vauthors = Carrodeguas JA, Pinz KG, Bogenhagen DF | title = DNA binding properties of human pol gammaB | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 50008–14 | date = December 2002 | pmid = 12379656 | doi = 10.1074/jbc.M207030200 }}
*{{cite journal   |vauthors=Yakubovskaya E, Chen Z, Carrodeguas JA, etal |title=Functional human mitochondrial DNA polymerase gamma forms a heterotrimer |journal=J. Biol. Chem. |volume=281 |issue= 1 |pages= 374–82 |year= 2006 |pmid= 16263719 |doi= 10.1074/jbc.M509730200 }}
* {{cite journal | vauthors = Johnson AA, Tsai Y, Graves SW, Johnson KA | title = Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization | journal = Biochemistry | volume = 39 | issue = 7 | pages = 1702–8 | date = February 2000 | pmid = 10677218 | doi = 10.1021/bi992104w }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
* {{cite journal | vauthors = Carrodeguas JA, Bogenhagen DF | title = Protein sequences conserved in prokaryotic aminoacyl-tRNA synthetases are important for the activity of the processivity factor of human mitochondrial DNA polymerase | journal = Nucleic Acids Research | volume = 28 | issue = 5 | pages = 1237–44 | date = March 2000 | pmid = 10666468 | pmc = 102604 | doi = 10.1093/nar/28.5.1237 }}
*{{cite journal  |vauthors=Carrodeguas JA, Pinz KG, Bogenhagen DF |title=DNA binding properties of human pol gammaB |journal=J. Biol. Chem. |volume=277 |issue= 51 |pages= 50008–14 |year= 2003 |pmid= 12379656 |doi= 10.1074/jbc.M207030200 }}
* {{cite journal | vauthors = Lim SE, Longley MJ, Copeland WC | title = The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance | journal = The Journal of Biological Chemistry | volume = 274 | issue = 53 | pages = 38197–203 | date = December 1999 | pmid = 10608893 | doi = 10.1074/jbc.274.53.38197 }}
*{{cite journal |vauthors=Johnson AA, Tsai Y, Graves SW, Johnson KA |title=Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization |journal=Biochemistry |volume=39 |issue= 7 |pages= 1702–8 |year= 2000 |pmid= 10677218 |doi=10.1021/bi992104w }}
*{{cite journal |vauthors=Carrodeguas JA, Bogenhagen DF |title=Protein sequences conserved in prokaryotic aminoacyl-tRNA synthetases are important for the activity of the processivity factor of human mitochondrial DNA polymerase |journal=Nucleic Acids Res. |volume=28 |issue= 5 |pages= 1237–44 |year= 2000 |pmid= 10666468 |doi=10.1093/nar/28.5.1237 | pmc=102604  }}
*{{cite journal |vauthors=Lim SE, Longley MJ, Copeland WC |title=The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance |journal=J. Biol. Chem. |volume=274 |issue= 53 |pages= 38197–203 |year= 1999 |pmid= 10608893 |doi=10.1074/jbc.274.53.38197 }}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=11232}}
{{PDB Gallery|geneid=11232}}


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


{{NLM content}}


{{gene-17-stub}}
{{Portal bar|Mitochondria|Gene Wiki|border=no}}

Latest revision as of 11:10, 5 September 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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.[1][2] Mutations in this gene result in autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions.[3]

Structure

POLG2 is located on the q arm of chromosome 17 in position 23.3 and has 8 exons.[3] 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.[4][5]

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.[3][4][5]

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)[4][5]

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.[4][5][6]

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.[7]

Interactions

POLG2 has been shown to have 32 binary protein-protein interactions including 19 co-complex interactions. POLG2 appears to interact with POLG.[8]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 3.0 3.1 3.2 "Entrez Gene: POLG2 polymerase (DNA directed), gamma 2, accessory subunit". This article incorporates text from this source, which is in the public domain.
  4. ↑ 4.0 4.1 4.2 4.3 "POLG2 - DNA polymerase subunit gamma-2, mitochondrial precursor - Homo sapiens (Human) - POLG2 gene & protein". www.uniprot.org. Retrieved 2018-08-31.File:CC-BY-icon-80x15.png This article incorporates text available under the CC BY 4.0 license.
  5. ↑ 5.0 5.1 5.2 5.3 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ IntAct. "https://www.ebi.ac.uk/intact/interactions?conversationContext=1". www.ebi.ac.uk. Retrieved 2018-08-31. External link in |title= (help)

Further reading


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

Retrieved from "https://www.wikidoc.org/index.php?title=POLG2&oldid=1529187"