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POLG

Protein FULL name:

DNA polymerase subunit gamma-1 [Homo sapiens].


POLG (Homo sapiens) is product of expression of POLG gene.

Human diseases related to this protein:


Keywords:



FUNCTION: Involved in the replication of mitochondrial DNA.

CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

COFACTOR: Magnesium.

SUBUNIT: Heterotrimer composed of a catalytic subunit and an homodimer of accessory subunits.

INTERACTION: Q9UHN1:POLG2; NbExp=3; IntAct=EBI-852624, EBI-852642;

SUBCELLULAR LOCATION: Mitochondrion.

POLYMORPHISM: The poly-Gln region seems to be polymorphic.

DISEASE: Defects in POLG are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 1 (PEOA1) [MIM:157640]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.

DISEASE: Defects in POLG are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB) [MIM:258450]. PEOB is a severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the autosomal dominant forms. Can be more severe.

DISEASE: Defects in POLG are a cause of sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]. SANDO is a clinically heterogeneous systemic disorder with variable features resulting from mitochondrial dysfunction. It shares phenotypic characteristics with autosomal recessive progressive external ophthalmoplegia and mitochondrial neurogastrointestinal encephalopathy syndrome. The clinical triad of symptoms consists of sensory ataxic, neuropathy, dysarthria, and ophthalmoparesis.

DISEASE: Defects in POLG are a cause of Alpers-Huttenlocher syndrome (AHS) [MIM:203700]; also called Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis. AHS is an autosomal recessive hepatocerebral syndrome. The typical course of AHS includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks of AHS are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.

DISEASE: Defects in POLG are a cause of mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) [MIM:603041]; also known as myoneurogastrointestinal encephalomyopathy. MNGIE is an autosomal recessive disease associated with multiple deletions of skeletal muscle mitochondrial DNA (MtDNA). It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, thin body habitus, peripheral neuropathy, and myopathy.

DISEASE: Defects in POLG are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.

SIMILARITY: Belongs to the DNA polymerase type-A family.

WEB RESOURCE: Name=GeneReviews; [LINK]

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 4505937
187171277
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P54098 P54098
PFAM: - P54098 (Link - using uniprot id)
InterPro: - P54098 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MSRLLWRKVAGATVGPGPVPAPGRWVSSSVPASDPSDGQRRRQQQQQQQQ
QQQQQPQQPQVLSSEGGQLRHNPLDIQMLSRGLHEQIFGQGGEMPGEAAV
RRSVEHLQKHGLWGQPAVPLPDVELRLPPLYGDNLDQHFRLLAQKQSLPY
LEAANLLLQAQLPPKPPAWAWAEGWTRYGPEGEAVPVAIPEERALVFDVE
VCLAEGTCPTLAVAISPSAWYSWCSQRLVEERYSWTSQLSPADLIPLEVP
TGASSPTQRDWQEQLVVGHNVSFDRAHIREQYLIQGSRMRFLDTMSMHMA
ISGLSSFQRSLWIAAKQGKHKVQPPTKQGQKSQRKARRGPAISSWDWLDI
SSVNSLAEVHRLYVGGPPLEKEPRELFVKGTMKDIRENFQDLMQYCAQDV
WATHEVFQQQLPLFLERCPHPVTLAGMLEMGVSYLPVNQNWERYLAEAQG
TYEELQREMKKSLMDLANDACQLLSGERYKEDPWLWDLEWDLQEFKQKKA
KKVKKEPATASKLPIEGAGAPGDPMDQEDLGPCSEEEEFQQDVMARACLQ
KLKGTTELLPKRPQHLPGHPGWYRKLCPRLDDPAWTPGPSLLSLQMRVTP
KLMALTWDGFPLHYSERHGWGYLVPGRRDNLAKLPTGTTLESAGVVCPYR
AIESLYRKHCLEQGKQQLMPQEAGLAEEFLLTDNSAIWQTVEELDYLEVE
AEAKMENLRAAVPGQPLALTARGGPKDTQPSYHHGNGPYNDVDIPGCWFF
KLPHKDGNSCNVGSPFAKDFLPKMEDGTLQAGPGGASGPRALEINKMISF
WRNAHKRISSQMVVWLPRSALPRAVIRHPDYDEEGLYGAILPQVVTAGTI
TRRAVEPTWLTASNARPDRVGSELKAMVQAPPGYTLVGADVDSQELWIAA
VLGDAHFAGMHGCTAFGWMTLQGRKSRGTDLHSKTATTVGISREHAKIFN
YGRIYGAGQPFAERLLMQFNHRLTQQEAAEKAQQMYAATKGLRWYRLSDE
GEWLVRELNLPVDRTEGGWISLQDLRKVQRETARKSQWKKWEVVAERAWK
GGTESEMFNKLESIATSDIPRTPVLGCCISRALEPSAVQEEFMTSRVNWV
VQSSAVDYLHLMLVAMKWLFEEFAIDGRFCISIHDEVRYLVREEDRYRAA
LALQITNLLTRCMFAYKLGLNDLPQSVAFFSAVDIDRCLRKEVTMDCKTP
SNPTGMERRYGIPQGEALDIYQIIELTKGSLEKRSQPGP

POLG (Homo sapiens) is able to recognize following damages:
References:

Title Authors Journal
Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma. Ropp PA, Copeland WC Genomics Sept. 15, 1996
Mitochondrial DNA polymerases from yeast to man: a new family of polymerases. Lecrenier N, Van Der Bruggen P, Foury F Gene Feb. 1, 1997
Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Van Goethem G, Dermaut B, Lofgren A, Martin JJ, Van Broeckhoven C Nat Genet July 1, 2001
Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis. Ponamarev MV, Longley MJ, Nguyen D, Kunkel TA, Copeland WC J Biol Chem May 3, 2002
Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M Ann Neurol Aug. 1, 2002
Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Van Goethem G, Martin JJ, Dermaut B, Lofgren A, Wibail A, Ververken D, Tack P, Dehaene I, Van Zandijcke M, Moonen M, Ceuterick C, De Jonghe P, Van Broeckhoven C Neuromuscul Disord Jan. 1, 2003
Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M Neurology April 22, 2003
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Van Goethem G, Schwartz M, Lofgren A, Dermaut B, Van Broeckhoven C, Vissing J Eur J Hum Genet July 1, 2003
Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle. Van Goethem G, Lofgren A, Dermaut B, Ceuterick C, Martin JJ, Van Broeckhoven C Hum Mutat Aug. 1, 2003
Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. Filosto M, Mancuso M, Nishigaki Y, Pancrudo J, Harati Y, Gooch C, Mankodi A, Bayne L, Bonilla E, Shanske S, Hirano M, DiMauro S Arch Neurol Sept. 1, 2003
POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions. Di Fonzo A, Bordoni A, Crimi M, Sara G, Del Bo R, Bresolin N, Comi GP Hum Mutat Dec. 1, 2003
Patient homozygous for a recessive POLG mutation presents with features of MERRF. Van Goethem G, Mercelis R, Lofgren A, Seneca S, Ceuterick C, Martin JJ, Van Broeckhoven C Neurology Dec. 23, 2003
Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Luoma P, Melberg A, Rinne JO, Kaukonen JA, Nupponen NN, Chalmers RM, Oldfors A, Rautakorpi I, Peltonen L, Majamaa K, Somer H, Suomalainen A Lancet Jan. 1, 2004
POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness. Mancuso M, Filosto M, Bellan M, Liguori R, Montagna P, Baruzzi A, DiMauro S, Carelli V Neurology Feb. 27, 2004
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Naviaux RK, Nguyen KV Ann Neurol May 1, 2004
Sequence analysis of familial PEO shows additional mutations associated with the 752C-->T and 3527C-->T changes in the POLG1 gene. Lamantea E, Zeviani M Ann Neurol Sept. 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Van Goethem G, Luoma P, Rantamaki M, Al Memar A, Kaakkola S, Hackman P, Krahe R, Lofgren A, Martin JJ, De Jonghe P, Suomalainen A, Udd B, Van Broeckhoven C Neurology Oct. 12, 2004
A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism. Mancuso M, Filosto M, Oh SJ, DiMauro S Arch Neurol Nov. 1, 2004
Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA. Ferrari G, Lamantea E, Donati A, Filosto M, Briem E, Carrara F, Parini R, Simonati A, Santer R, Zeviani M Brain April 1, 2005
Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM, Engelsen BA, Moen G, Bindoff LA Neurology April 12, 2005
POLG mutations and Alpers syndrome. Davidzon G, Mancuso M, Ferraris S, Quinzii C, Hirano M, Peters HL, Kirby D, Thorburn DR, DiMauro S Ann Neurol June 1, 2005
Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome. Luoma PT, Luo N, Loscher WN, Farr CL, Horvath R, Wanschitz J, Kiechl S, Kaguni LS, Suomalainen A Hum Mol Genet July 15, 2005
Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma PT, Rantamaki M, Goethem GV, Lofgren A, Hackman P, Paetau A, Kaakkola S, Majamaa K, Varilo T, Udd B, Kaariainen H, Bindoff LA, Suomalainen A Am J Hum Genet Sept. 1, 2005
Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. Gonzalez-Vioque E, Blazquez A, Fernandez-Moreira D, Bornstein B, Bautista J, Arpa J, Navarro C, Campos Y, Fernandez-Moreno MA, Garesse R, Arenas J, Martin MA Arch Neurol Feb. 1, 2006
Early-onset familial parkinsonism due to POLG mutations. Davidzon G, Greene P, Mancuso M, Klos KJ, Ahlskog JE, Hirano M, DiMauro S Ann Neurol May 1, 2006
Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Horvath R, Hudson G, Ferrari G, Futterer N, Ahola S, Lamantea E, Prokisch H, Lochmuller H, McFarland R, Ramesh V, Klopstock T, Freisinger P, Salvi F, Mayr JA, Santer R, Tesarova M, Zeman J, Udd B, Taylor RW, Turnbull D, Hanna M, Fialho D, Suomalainen A, Zeviani M, Chinnery PF Brain July 1, 2006
Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. Naimi M, Bannwarth S, Procaccio V, Pouget J, Desnuelle C, Pellissier JF, Rotig A, Munnich A, Calvas P, Richelme C, Jonveaux P, Castelnovo G, Simon M, Clanet M, Wallace D, Paquis-Flucklinger V Eur J Hum Genet Aug. 1, 2006
SANDO: two novel mutations in POLG1 gene. Gago MF, Rosas MJ, Guimaraes J, Ferreira M, Vilarinho L, Castro L, Carpenter S Neuromuscul Disord Aug. 1, 2006
Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism. Hudson G, Schaefer AM, Taylor RW, Tiangyou W, Gibson A, Venables G, Griffiths P, Burn DJ, Turnbull DM, Chinnery PF Arch Neurol April 1, 2007
Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. Taanman JW, Rahman S, Pagnamenta AT, Morris AA, Bitner-Glindzicz M, Wolf NI, Leonard JV, Clayton PT, Schapira AH Hum Mutat Jan. 1, 2009
Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations. Giordano C, Powell H, Leopizzi M, De Curtis M, Travaglini C, Sebastiani M, Gallo P, Taylor RW, d'Amati G Neurology March 24, 2009


Last modification of this entry: Oct. 15, 2010.

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