POLG Knowpia

POLG
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3IKM, 4ZTU, 4ZTZ, 5C53, 5C52, 5C51
Identifiers
Aliases	POLG, MDP1, MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA, SANDO, SCAE, polymerase (DNA) gamma, catalytic subunit, DNA polymerase gamma, catalytic subunit, ORF-Y, POLGARF
External IDs	OMIM: 174763 MGI: 1196389 HomoloGene: 2016 GeneCards: POLG
Gene location (Human)
Chr.	Chromosome 15 (human)
End	89,334,861 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	79,116,110 bp
RNA expression pattern
	Top expressed in
	tibial nerve; ; transverse colon; ; body of stomach; ; right lobe of thyroid gland; ; body of pancreas; ; spleen; ; minor salivary gland; ; cardia; ; skin of abdomen; ; fundus;
	Top expressed in
	spermatocyte; ; spermatid; ; yolk sac; ; superior frontal gyrus; ; thymus; ; seminiferous tubule; ; lip; ; cerebellar cortex; ; renal corpuscle; ; primitive streak;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein binding; transferase activity; 3'-5' exonuclease activity; nucleotidyltransferase activity; chromatin binding; protease binding; DNA binding; DNA-directed DNA polymerase activity;
Cellular component	terminal bouton; gamma DNA polymerase complex; mitochondrial nucleoid; mitochondrion; protein-containing complex;
Biological process	DNA replication; response to gamma radiation; cellular response to glucose stimulus; DNA metabolic process; response to light stimulus; DNA-dependent DNA replication; human ageing; response to hyperoxia; base-excision repair, gap-filling; nucleic acid phosphodiester bond hydrolysis; DNA biosynthetic process; mitochondrial DNA replication;
	Sources:Amigo / QuickGO
Orthologs
	5428
	18975
	ENSG00000140521
	ENSMUSG00000039176
	P54098
	P54099
	NM_002693; NM_001126131
	NM_017462; NM_001360095; NM_001360096
	NP_001119603; NP_002684
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

DNA polymerase subunit gamma (POLG or POLG1) is an enzyme that in humans is encoded by the POLG gene.^[5] 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).^[6]

Structure edit

POLG is located on the q arm of chromosome 15 in position 26.1 and has 23 exons. The POLG gene produces a 140 kDa protein composed of 1239 amino acids.^[7]^[8] POLG, the protein encoded by this gene, is a member of the DNA polymerase type-A family. It is a mitochondrion nucleiod with an Mg2+ cofactor and 15 turns, 52 beta strands, and 39 alpha helixes.^[9]^[10] POLG contains a polyglutamine tract near its N-terminus that may be polymorphic. Two transcript variants encoding the same protein have been found for this gene.^[6]

Function edit

POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma.^[6] The human POLG cDNA and gene were cloned and mapped to chromosome band 15q25.^[11] In eukaryotic cells, the mitochondrial DNA is replicated by DNA polymerase gamma, a trimeric protein complex composed of a catalytic subunit, POLG, and a dimeric accessory subunit of 55 kDa encoded by the POLG2 gene.^[12] The catalytic subunit contains three enzymatic activities, a DNA polymerase activity, a 3’-5’ exonuclease activity that proofreads misincorporated nucleotides, and a 5’-dRP lyase activity required for base excision repair.

Catalytic activity edit

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).^[9]^[10]

Clinical significance edit

Mutations in the POLG gene are associated with several mitochondrial diseases, 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).^[6] Pathogenic variants have also been linked with fatal congenital myopathy and gastrointestinal pseudo-obstruction and fatal infantile hepatic failure.^[13]^[14] A list of all published mutations in the POLG coding region and their associated disease can be found at the Human DNA Polymerase Gamma Mutation Database.

Mice heterozygous for a Polg mutation are only able to replicate their mitochondrial DNA inaccurately, so that they sustain a 500-fold higher mutation burden than normal mice. These mice show no clear features of rapidly accelerated aging, indicating that mitochondrial mutations do not have a causal role in natural aging.^[15]

Interactions edit

POLG has been shown to have 50 binary protein-protein interactions including 32 co-complex interactions. POLG appears to interact with POLG2, Dlg4, Tp53, and Sod2.^[16]

References edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000140521 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039176 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Zullo SJ, Butler L, Zahorchak RJ, Macville M, Wilkes C, Merril CR (Mar 1998). "Localization by fluorescence in situ hybridization (FISH) of human mitochondrial polymerase gamma (POLG) to human chromosome band 15q24-->q26, and of mouse mitochondrial polymerase gamma (Polg) to mouse chromosome band 7E, with confirmation by direct sequence analysis of bacterial artificial chromosomes (BACs)". Cytogenetics and Cell Genetics. 78 (3–4): 281–4. doi:10.1159/000134672. PMID 9465903.
^ ^a ^b ^c ^d Entrez Gene: POLG polymerase (DNA directed), gamma, catalytic subunit This article incorporates text from this source, which is in the public domain.
^ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Archived from the original on 2018-08-29. Retrieved 2018-08-28.
^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
^ ^a ^b "POLG - DNA polymerase subunit gamma-1 - Homo sapiens (Human) - POLG gene & protein". www.uniprot.org. Retrieved 2018-08-28. This article incorporates text available under the CC BY 4.0 license.
^ ^a ^b "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
^ Ropp PA, Copeland WC (September 1996). "Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma". Genomics. 36 (3): 449–58. doi:10.1006/geno.1996.0490. PMID 8884268.
^ Graziewicz MA, Longley MJ, Copeland WC (February 2006). "DNA polymerase gamma in mitochondrial DNA replication and repair". Chemical Reviews. 106 (2): 383–405. doi:10.1021/cr040463d. PMID 16464011.
^ Giordano C, Powell H, Leopizzi M, De Curtis M, de Curtis M, Travaglini C, Sebastiani M, Gallo P, Taylor RW, d'Amati G (March 2009). "Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations". Neurology. 72 (12): 1103–5. doi:10.1212/01.wnl.0000345002.47396.e1. PMC 2821839. PMID 19307547.
^ Müller-Höcker J, Horvath R, Schäfer S, Hessel H, Müller-Felber W, Kühr J, Copeland WC, Seibel P (February 2011). "Mitochondrial DNA depletion and fatal infantile hepatic failure due to mutations in the mitochondrial polymerase γ (POLG) gene: a combined morphological/enzyme histochemical and immunocytochemical/biochemical and molecular genetic study". Journal of Cellular and Molecular Medicine. 15 (2): 445–56. doi:10.1111/j.1582-4934.2009.00819.x. PMC 3822808. PMID 19538466.
^ Vermulst M, Bielas JH, Kujoth GC, Ladiges WC, Rabinovitch PS, Prolla TA, Loeb LA (April 2007). "Mitochondrial point mutations do not limit the natural lifespan of mice". Nature Genetics. 39 (4): 540–3. doi:10.1038/ng1988. PMID 17334366. S2CID 291780.
^ "50 binary interactions found for search term POLG". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-29.