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P54098 (DPOG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA polymerase subunit gamma-1

EC=2.7.7.7
Alternative name(s):
Mitochondrial DNA polymerase catalytic subunit
PolG-alpha
Gene names
Name:POLG
Synonyms:MDP1, POLG1, POLGA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1239 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Cofactor

Magnesium.

Subunit structure

Heterotrimer composed of a catalytic subunit and a homodimer of accessory subunits.

Subcellular location

Mitochondrion. Mitochondrion matrixmitochondrion nucleoid Ref.6.

Polymorphism

The poly-Gln region seems to be polymorphic.

Involvement in disease

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1 (PEOA1) [MIM:157640]: A disorder 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.19 Ref.20 Ref.34 Ref.35

Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB) [MIM:258450]: A severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the autosomal dominant forms.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]: A systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss. An atypical form of the disease is characterized by headaches and/or seizures manifesting in childhood or adolescence, followed by development of cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus in early adulthood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.21 Ref.22 Ref.23 Ref.26 Ref.27 Ref.30 Ref.31 Ref.33

Mitochondrial DNA depletion syndrome 4A (MTDPS4A) [MIM:203700]: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease 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 are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.24 Ref.25 Ref.30 Ref.31 Ref.36

Mitochondrial DNA depletion syndrome 4B (MTDPS4B) [MIM:613662]: An autosomal recessive progressive multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.37

Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36

Sequence similarities

Belongs to the DNA polymerase type-A family.

Ontologies

Keywords
   Biological processDNA replication
   Cellular componentMitochondrion
Mitochondrion nucleoid
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Leigh syndrome
Neurodegeneration
Neuropathy
Progressive external ophthalmoplegia
   LigandDNA-binding
Magnesium
   Molecular functionDNA-directed DNA polymerase
Nucleotidyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA metabolic process

Traceable author statement Ref.1. Source: ProtInc

DNA-dependent DNA replication

Traceable author statement PubMed 3619920. Source: ProtInc

aging

Inferred from electronic annotation. Source: Ensembl

base-excision repair, gap-filling

Inferred from direct assay PubMed 15177179. Source: MGI

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial DNA replication

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentgamma DNA polymerase complex

Inferred from electronic annotation. Source: Ensembl

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial nucleoid

Inferred from direct assay Ref.6. Source: BHF-UCL

mitochondrion

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA-directed DNA polymerase activity

Inferred from direct assay PubMed 15164064PubMed 15177179. Source: MGI

chromatin binding

Inferred from direct assay Ref.6. Source: UniProtKB

exonuclease activity

Inferred from electronic annotation. Source: Ensembl

protease binding

Inferred from physical interaction PubMed 14739292. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16263719PubMed 17762861PubMed 19837034. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

POLG2Q9UHN19EBI-852624,EBI-852642

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12391239DNA polymerase subunit gamma-1
PRO_0000101270

Regions

Compositional bias43 – 6018Poly-Gln
Compositional bias535 – 5384Poly-Glu

Natural variations

Natural variant31R → P in PEOB. Ref.7 Ref.16
VAR_012153
Natural variant181P → S.
Corresponds to variant rs3087373 [ dbSNP | Ensembl ].
VAR_014904
Natural variant551Q → QQ. Ref.3 Ref.4
VAR_019265
Natural variant551Q → QQQ. Ref.3 Ref.4
VAR_019266
Natural variant1931R → Q. Ref.4
Corresponds to variant rs3176162 [ dbSNP | Ensembl ].
VAR_019267
Natural variant2271R → W in PEOB and MTDPS4B. Ref.14 Ref.18 Ref.37
VAR_023663
Natural variant2321R → G in MTDPS4A. Ref.25
VAR_058870
Natural variant2321R → H in LS. Ref.36
VAR_058871
Natural variant2441L → P in MTDPS4A. Ref.25
VAR_058872
Natural variant2511T → I in PEOB, MTDPS4A and MTDPS4B. Ref.8 Ref.11 Ref.13 Ref.14 Ref.18 Ref.25 Ref.36
Corresponds to variant rs113994094 [ dbSNP | Ensembl ].
VAR_023664
Natural variant2681G → A in PEOB; sporadic case. Ref.13
Corresponds to variant rs61752784 [ dbSNP | Ensembl ].
VAR_058873
Natural variant3041L → R in PEOB; also found in SANDO. Ref.7 Ref.16 Ref.31
VAR_012154
Natural variant3041L → SANDO in PEOB.
VAR_058874
Natural variant3081Q → H in PEOB; sporadic case. Ref.30
VAR_058875
Natural variant3091R → L in PEOB. Ref.8 Ref.18
VAR_023665
Natural variant3121W → R in PEOB; sporadic case. Ref.13 Ref.14
VAR_023666
Natural variant3241P → S.
Corresponds to variant rs2307437 [ dbSNP | Ensembl ].
VAR_014905
Natural variant3801G → D in PEOB. Ref.31
VAR_058876
Natural variant4311G → V in PEOB; sporadic case. Ref.14
VAR_023667
Natural variant4631L → F. Ref.34
VAR_058877
Natural variant4671A → T in PEOB, SANDO and MTDPS4A; results in clearly decreased activity, DNA binding and processivity of the polymerase. Ref.7 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.22 Ref.25 Ref.26 Ref.27 Ref.31 Ref.36
Corresponds to variant rs113994095 [ dbSNP | Ensembl ].
VAR_012155
Natural variant4681N → D in PEOB. Ref.20
Corresponds to variant rs145843073 [ dbSNP | Ensembl ].
VAR_023668
Natural variant4971Q → H in SANDO; atypical form with spinocerebellar ataxia and epilepsy. Ref.27
VAR_023669
Natural variant5111S → N in PEOA1. Ref.34
VAR_058878
Natural variant5171G → V in SANDO. Ref.30
Corresponds to variant rs61752783 [ dbSNP | Ensembl ].
VAR_058879
Natural variant5461R → C. Ref.4
Corresponds to variant rs2307447 [ dbSNP | Ensembl ].
VAR_014906
Natural variant5621R → Q in PEOB; sporadic case. Ref.13
VAR_058880
Natural variant5741R → W in PEOB; sporadic case. Ref.30
VAR_058881
Natural variant5791R → W in PEOB; autosomal recessive. Ref.10
VAR_023670
Natural variant5871P → L in PEOB, MTDPS4A and MTDPS4B. Ref.10 Ref.11 Ref.13 Ref.18 Ref.25 Ref.36
Corresponds to variant rs113994096 [ dbSNP | Ensembl ].
VAR_023671
Natural variant6031M → L in PEOB. Ref.29
VAR_058882
Natural variant6271R → Q in SANDO; shows DNA binding affinity and processivities similar to the controls. Ref.26
VAR_058883
Natural variant6271R → W in SANDO; sporadic case. Ref.16
VAR_023672
Natural variant6481P → R in PEOB; sporadic case; also in SANDO. Ref.30 Ref.33
VAR_058884
Natural variant6621E → K. Ref.4
Corresponds to variant rs2307450 [ dbSNP | Ensembl ].
VAR_014907
Natural variant7371G → R in PEOB; with absence of progressive external ophthalmoplegia. Ref.28
Corresponds to variant rs121918054 [ dbSNP | Ensembl ].
VAR_058885
Natural variant7481W → S in SANDO and MTDPS4A; some patients manifest an atypical SANDO form with spinocerebellar ataxia and epilepsy. Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.31 Ref.36
VAR_023673
Natural variant7671A → D in MTDPS4A. Ref.30
VAR_058886
Natural variant8071R → C in SANDO. Ref.33
VAR_058887
Natural variant8071R → P in PEOB; sporadic case. Ref.13
VAR_058888
Natural variant8311Y → C in PEOA1 and MTDPS4A. Ref.19 Ref.36
Corresponds to variant rs4154971 [ dbSNP | Ensembl ].
VAR_023674
Natural variant8481G → S in PEOB, MTDPS4A, MTDPS4B and LS. Ref.8 Ref.12 Ref.18 Ref.24 Ref.25 Ref.36 Ref.37
VAR_023675
Natural variant8531R → W in PEOB; with absence of progressive external ophthalmoplegia. Ref.28 Ref.29
VAR_058889
Natural variant8641N → S in MTDPS4B. Ref.11
VAR_023676
Natural variant8791Q → H in MTDPS4A. Ref.30
VAR_058890
Natural variant8851T → S in MTDPS4A. Ref.30
VAR_058891
Natural variant8891A → T in PEOB. Ref.10
VAR_023677
Natural variant9141T → P in MTDPS4A. Ref.30 Ref.31 Ref.36
VAR_058892
Natural variant9231G → D in PEOA1. Ref.8
VAR_023678
Natural variant9321H → Y in SANDO and PEOB; sporadic case. Ref.13 Ref.21
VAR_023679
Natural variant9431R → H in PEOA1. Ref.8
VAR_023680
Natural variant9531R → C in PEOA1. Ref.20
Corresponds to variant rs11546842 [ dbSNP | Ensembl ].
VAR_023681
Natural variant9551Y → C in PEOA1; can underlie parkinsonism; 45-fold decrease in apparent binding affinity for the incoming nucleoside triphosphate; 2-fold less accurate for basepair substitutions than wild-type. Ref.7 Ref.8 Ref.9 Ref.16 Ref.20
VAR_012156
Natural variant9571A → P in MTDPS4A. Ref.25
VAR_058893
Natural variant9571A → S in PEOA1. Ref.8
VAR_023682
Natural variant10471R → Q in PEOB; sporadic case. Ref.14
VAR_023683
Natural variant10511G → R in SANDO. Ref.21
VAR_023684
Natural variant10761G → V in PEOB. Ref.10
VAR_023685
Natural variant10961R → C in PEOB; sporadic case. Ref.14
VAR_023686
Natural variant10961R → H in MTDPS4A. Ref.30
VAR_058894
Natural variant11041S → C in PEOB; sporadic case. Ref.14
VAR_023687
Natural variant11051A → T in PEOB. Ref.20
VAR_023688
Natural variant11061V → I in PEOB. Ref.18
VAR_023689
Natural variant11101H → Y in MTDPS4A. Ref.36
VAR_058895
Natural variant11341H → R in MTDPS4A. Ref.36
VAR_058896
Natural variant11361E → K in MTDPS4A. Ref.36
VAR_065092
Natural variant11421R → W. Ref.4
Corresponds to variant rs2307442 [ dbSNP | Ensembl ].
VAR_014908
Natural variant11431E → G. Ref.4 Ref.13 Ref.22 Ref.23 Ref.25 Ref.31 Ref.36
Corresponds to variant rs2307441 [ dbSNP | Ensembl ].
VAR_014909
Natural variant11461R → C in PEOB. Ref.4 Ref.29
Corresponds to variant rs2307440 [ dbSNP | Ensembl ].
VAR_014910
Natural variant11761S → L in PEOA1. Ref.8 Ref.18
VAR_023690
Natural variant11841D → N in PEOB. Ref.29
VAR_058897
Natural variant11861D → H in PEOA1. Ref.35
VAR_065119
Natural variant11911K → N in MTDPS4A. Ref.30
VAR_058898
Natural variant12361Q → H. Ref.4 Ref.10 Ref.13 Ref.26 Ref.31 Ref.36
Corresponds to variant rs3087374 [ dbSNP | Ensembl ].
VAR_014911

Secondary structure

......................................................................................................................................................... 1239
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P54098 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 2D9ECCD75AD6E01E

FASTA1,239139,562
        10         20         30         40         50         60 
MSRLLWRKVA GATVGPGPVP APGRWVSSSV PASDPSDGQR RRQQQQQQQQ QQQQQPQQPQ 

        70         80         90        100        110        120 
VLSSEGGQLR HNPLDIQMLS RGLHEQIFGQ GGEMPGEAAV RRSVEHLQKH GLWGQPAVPL 

       130        140        150        160        170        180 
PDVELRLPPL YGDNLDQHFR LLAQKQSLPY LEAANLLLQA QLPPKPPAWA WAEGWTRYGP 

       190        200        210        220        230        240 
EGEAVPVAIP EERALVFDVE VCLAEGTCPT LAVAISPSAW YSWCSQRLVE ERYSWTSQLS 

       250        260        270        280        290        300 
PADLIPLEVP TGASSPTQRD WQEQLVVGHN VSFDRAHIRE QYLIQGSRMR FLDTMSMHMA 

       310        320        330        340        350        360 
ISGLSSFQRS LWIAAKQGKH KVQPPTKQGQ KSQRKARRGP AISSWDWLDI SSVNSLAEVH 

       370        380        390        400        410        420 
RLYVGGPPLE KEPRELFVKG TMKDIRENFQ DLMQYCAQDV WATHEVFQQQ LPLFLERCPH 

       430        440        450        460        470        480 
PVTLAGMLEM GVSYLPVNQN WERYLAEAQG TYEELQREMK KSLMDLANDA CQLLSGERYK 

       490        500        510        520        530        540 
EDPWLWDLEW DLQEFKQKKA KKVKKEPATA SKLPIEGAGA PGDPMDQEDL GPCSEEEEFQ 

       550        560        570        580        590        600 
QDVMARACLQ KLKGTTELLP KRPQHLPGHP GWYRKLCPRL DDPAWTPGPS LLSLQMRVTP 

       610        620        630        640        650        660 
KLMALTWDGF PLHYSERHGW GYLVPGRRDN LAKLPTGTTL ESAGVVCPYR AIESLYRKHC 

       670        680        690        700        710        720 
LEQGKQQLMP QEAGLAEEFL LTDNSAIWQT VEELDYLEVE AEAKMENLRA AVPGQPLALT 

       730        740        750        760        770        780 
ARGGPKDTQP SYHHGNGPYN DVDIPGCWFF KLPHKDGNSC NVGSPFAKDF LPKMEDGTLQ 

       790        800        810        820        830        840 
AGPGGASGPR ALEINKMISF WRNAHKRISS QMVVWLPRSA LPRAVIRHPD YDEEGLYGAI 

       850        860        870        880        890        900 
LPQVVTAGTI TRRAVEPTWL TASNARPDRV GSELKAMVQA PPGYTLVGAD VDSQELWIAA 

       910        920        930        940        950        960 
VLGDAHFAGM HGCTAFGWMT LQGRKSRGTD LHSKTATTVG ISREHAKIFN YGRIYGAGQP 

       970        980        990       1000       1010       1020 
FAERLLMQFN HRLTQQEAAE KAQQMYAATK GLRWYRLSDE GEWLVRELNL PVDRTEGGWI 

      1030       1040       1050       1060       1070       1080 
SLQDLRKVQR ETARKSQWKK WEVVAERAWK GGTESEMFNK LESIATSDIP RTPVLGCCIS 

      1090       1100       1110       1120       1130       1140 
RALEPSAVQE EFMTSRVNWV VQSSAVDYLH LMLVAMKWLF EEFAIDGRFC ISIHDEVRYL 

      1150       1160       1170       1180       1190       1200 
VREEDRYRAA LALQITNLLT RCMFAYKLGL NDLPQSVAFF SAVDIDRCLR KEVTMDCKTP 

      1210       1220       1230 
SNPTGMERRY GIPQGEALDI YQIIELTKGS LEKRSQPGP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma."
Ropp P.A., Copeland W.C.
Genomics 36:449-458(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Mitochondrial DNA polymerases from yeast to man: a new family of polymerases."
Lecrenier N.L., van der Bruggen P., Foury F.
Gene 185:147-152(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Watanabe T.K., Shimizu F., Nishino N., Fujiwara T., Kanemoto N., Suzuki M., Nakamura Y., Hirai Y., Maekawa H., Takahashi E.
Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-GLN-55 INS.
Tissue: Brain.
[4]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-55 INS; GLN-193; CYS-546; LYS-662; TRP-1142; GLY-1143; CYS-1146 AND HIS-1236.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph and Testis.
[6]"The layered structure of human mitochondrial DNA nucleoids."
Bogenhagen D.F., Rousseau D., Burke S.
J. Biol. Chem. 283:3665-3675(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH MITOCHONDRIAL DNA, IDENTIFICATION BY MASS SPECTROMETRY.
[7]"Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions."
Van Goethem G., Dermaut B., Loefgren A., Martin J.-J., Van Broeckhoven C.
Nat. Genet. 28:211-212(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB PRO-3; ARG-304; THR-467 AND CYS-955.
[8]"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 G.P., Zeviani M.
Ann. Neurol. 52:211-219(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOA1 ASP-923; HIS-943; CYS-955; SER-957 AND LEU-1176, VARIANTS PEO ILE-251; LEU-309 AND SER-848.
[9]"Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis."
Ponamarev M.V., Longley M.J., Nguyen D., Kunkel T.A., Copeland W.C.
J. Biol. Chem. 277:15225-15228(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PEOA1 CYS-955.
[10]"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. 60:1279-1284(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB TRP-579; LEU-587; THR-889 AND VAL-1076, VARIANT HIS-1236.
[11]"Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy."
Van Goethem G., Schwartz M., Loefgren A., Dermaut B., Van Broeckhoven C., Vissing J.
Eur. J. Hum. Genet. 11:547-549(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTDPS4B ILE-251; LEU-587 AND SER-864.
[12]"Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle."
Van Goethem G., Loefgren A., Dermaut B., Ceuterick C., Martin J.-J., Van Broeckhoven C.
Hum. Mutat. 22:175-176(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOB SER-848.
[13]"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 G.P.
Hum. Mutat. 22:498-499(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB ILE-251; ALA-268; ARG-312; THR-467; GLN-562; LEU-587; PRO-807 AND TYR-932, VARIANTS GLY-1143 AND HIS-1236.
[14]"Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)."
Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F., Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M.
Neurology 60:1354-1356(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB TRP-227; ILE-251; ARG-312; VAL-431; THR-467; GLN-1047; CYS-1096 AND CYS-1104.
[15]"Patient homozygous for a recessive POLG mutation presents with features of MERRF."
Van Goethem G., Mercelis R., Loefgren A., Seneca S., Ceuterick C., Martin J.-J., Van Broeckhoven C.
Neurology 61:1811-1813(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MERRF THR-467.
[16]"Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia."
Van Goethem G., Martin J.-J., Dermaut B., Loefgren A., Wibail A., Ververken D., Tack P., Dehaene I., Van Zandijcke M., Moonen M., Ceuterick C., De Jonghe P., Van Broeckhoven C.
Neuromuscul. Disord. 13:133-142(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB PRO-3; ARG-304; THR-467 AND CYS-955, VARIANT SANDO TRP-627.
[17]"POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion."
Naviaux R.K., Nguyen K.V.
Ann. Neurol. 55:706-712(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTDPS4A THR-467.
[18]"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. 56:454-455(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB TRP-227; ILE-251 LEU-309; LEU-587; SER-848 ILE-1106 AND LEU-1176.
[19]"A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and parkinsonism."
Mancuso M., Filosto M., Oh S.J., DiMauro S.
Arch. Neurol. 61:1777-1779(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOA1 CYS-831.
[20]"Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study."
Luoma P., Melberg A., Rinne J.O., Kaukonen J.A., Nupponen N.N., Chalmers R.M., Oldfors A., Rautakorpi I., Peltonen L., Majamaa K., Somer H., Suomalainen A.
Lancet 364:875-882(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOA1 CYS-953 AND CYS-955, VARIANTS PEOB ASP-468 AND THR-1105.
[21]"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 62:316-318(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SANDO TYR-932 AND ARG-1051.
[22]"POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement."
Van Goethem G., Luoma P., Rantamaeki M., Al-Memar A., Kaakkola S., Hackman P., Krahe R., Loefgren A., Martin J.-J., De Jonghe P., Suomalainen A., Udd B., Van Broeckhoven C.
Neurology 63:1251-1257(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOB THR-467, VARIANT SANDO SER-748, VARIANT GLY-1143.
[23]"Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin."
Hakonen A.H., Heiskanen S., Juvonen V., Lappalainen I., Luoma P.T., Rantamaeki M., Van Goethem G., Loefgren A., Hackman P., Paetau A., Kaakkola S., Majamaa K., Varilo T., Udd B., Kaeaeriaeinen H., Bindoff L.A., Suomalainen A.
Am. J. Hum. Genet. 77:430-441(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SANDO SER-748, VARIANT GLY-1143.
[24]"POLG mutations and Alpers syndrome."
Davidzon G., Mancuso M., Ferraris S., Quinzii C., Hirano M., Peters H.L., Kirby D., Thorburn D.R., DiMauro S.
Ann. Neurol. 57:921-923(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTDPS4A SER-748 AND SER-848.
[25]"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 128:723-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTDPS4A GLY-232; PRO-244; ILE-251 THR-467; LEU-587; SER-748 SER-848 AND PRO-957, VARIANT GLY-1143.
[26]"Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome."
Luoma P.T., Luo N., Loescher W.N., Farr C.L., Horvath R., Wanschitz J., Kiechl S., Kaguni L.S., Suomalainen A.
Hum. Mol. Genet. 14:1907-1920(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOB THR-467, VARIANT SANDO GLN-627, VARIANT HIS-1236, CHARACTERIZATION OF VARIANT PEOB THR-467, CHARACTERIZATION OF VARIANT SANDO GLN-627.
[27]"Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations."
Winterthun S., Ferrari G., He L., Taylor R.W., Zeviani M., Turnbull D.M., Engelsen B.A., Moen G., Bindoff L.A.
Neurology 64:1204-1208(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SANDO THR-467; HIS-497 AND SER-748.
[28]"Early-onset familial parkinsonism due to POLG mutations."
Davidzon G., Greene P., Mancuso M., Klos K.J., Ahlskog J.E., Hirano M., DiMauro S.
Ann. Neurol. 59:859-862(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB ARG-737 AND TRP-853.
[29]"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 M.A., Garesse R., Arenas J., Martin M.A.
Arch. Neurol. 63:107-111(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB LEU-603; TRP-853; CYS-1146 AND ASN-1184.
[30]"Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene."
Horvath R., Hudson G., Ferrari G., Fuetterer N., Ahola S., Lamantea E., Prokisch H., Lochmueller H., McFarland R., Ramesh V., Klopstock T., Freisinger P., Salvi F., Mayr J.A., Santer R., Tesarova M., Zeman J., Udd B. expand/collapse author list , Taylor R.W., Turnbull D., Hanna M., Fialho D., Suomalainen A., Zeviani M., Chinnery P.F.
Brain 129:1674-1684(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB HIS-308; TRP-574 AND ARG-648, VARIANT SANDO VAL-517, VARIANTS MTDPS4A ASP-767; HIS-879; SER-885; PRO-914; HIS-1096 AND ASN-1191.
[31]"Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay."
Naiemi M., Bannwarth S., Procaccio V., Pouget J., Desnuelle C., Pellissier J.-F., Roetig A., Munnich A., Calvas P., Richelme C., Jonveaux P., Castelnovo G., Simon M., Clanet M., Wallace D., Paquis-Flucklinger V.
Eur. J. Hum. Genet. 14:917-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PEOB ARG-304; ASP-380 AND THR-467, VARIANT SANDO SER-748, VARIANT MTDPS4A PRO-914, VARIANTS GLY-1143 AND HIS-1236.
[32]Erratum
Naiemi M., Bannwarth S., Procaccio V., Pouget J., Desnuelle C., Pellissier J.-F., Roetig A., Munnich A., Calvas P., Richelme C., Jonveaux P., Castelnovo G., Simon M., Clanet M., Wallace D., Paquis-Flucklinger V.
Eur. J. Hum. Genet. 15:607-607(2006)
[33]"SANDO: two novel mutations in POLG1 gene."
Gago M.F., Rosas M.J., Guimaraes J., Ferreira M., Vilarinho L., Castro L., Carpenter S.
Neuromuscul. Disord. 16:507-509(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SANDO ARG-648 AND CYS-807.
[34]"Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism."
Hudson G., Schaefer A.M., Taylor R.W., Tiangyou W., Gibson A., Venables G., Griffiths P., Burn D.J., Turnbull D.M., Chinnery P.F.
Arch. Neurol. 64:553-557(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOA1 ASN-511, VARIANT PHE-463.
[35]"Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia."
Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F., Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S., Papadimitriou A., Bresolin N., Comi G.P.
J. Neurol. 255:1384-1391(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PEOA1 HIS-1186.
[36]"Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion."
Taanman J.-W., Rahman S., Pagnamenta A.T., Morris A.A.M., Bitner-Glindzicz M., Wolf N.I., Leonard J.V., Clayton P.T., Schapira A.H.V.
Hum. Mutat. 30:248-254(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LS HIS-232 AND SER-848, VARIANTS MTDPS4A ILE-251; THR-467; LEU-587; SER-748; CYS-831; SER-848; PRO-914; TYR-1110; ARG-1134 AND LYS-1136, VARIANTS GLY-1143 AND HIS-1236.
[37]"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 R.W., d'Amati G.
Neurology 72:1103-1105(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTDPS4B TRP-227 AND SER-848.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U60325 mRNA. Translation: AAC50712.1.
X98093 mRNA. Translation: CAA66719.1.
D84103 mRNA. Translation: BAA12223.1.
AF497906 Genomic DNA. Translation: AAM77583.1.
BC042571 mRNA. Translation: AAH42571.1.
BC050559 mRNA. Translation: AAH50559.1.
CCDSCCDS10350.1.
PIRG02750.
RefSeqNP_001119603.1. NM_001126131.1.
NP_002684.1. NM_002693.2.
UniGeneHs.706868.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3IKMX-ray3.24A/D70-1239[»]
ProteinModelPortalP54098.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111424. 2 interactions.
IntActP54098. 5 interactions.
MINTMINT-4531455.
STRING9606.ENSP00000268124.

Chemistry

BindingDBP54098.
ChEMBLCHEMBL2732.

PTM databases

PhosphoSiteP54098.

Polymorphism databases

DMDM1706507.

Proteomic databases

MaxQBP54098.
PaxDbP54098.
PeptideAtlasP54098.
PRIDEP54098.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268124; ENSP00000268124; ENSG00000140521.
ENST00000442287; ENSP00000399851; ENSG00000140521.
GeneID5428.
KEGGhsa:5428.
UCSCuc002bnr.4. human.

Organism-specific databases

CTD5428.
GeneCardsGC15M089859.
GeneReviewsPOLG.
HGNCHGNC:9179. POLG.
HPAHPA056821.
MIM157640. phenotype.
174763. gene.
203700. phenotype.
256000. phenotype.
258450. phenotype.
607459. phenotype.
613662. phenotype.
neXtProtNX_P54098.
Orphanet726. Alpers syndrome.
254892. Autosomal dominant progressive external ophthalmoplegia.
254886. Autosomal recessive progressive external ophthalmoplegia.
298. Mitochondrial neurogastrointestinal encephalomyopathy.
94125. Recessive mitochondrial ataxia syndrome.
70595. Sensory ataxic neuropathy - dysarthria - ophthalmoparesis.
254881. Spinocerebellar ataxia with epilepsy.
PharmGKBPA33500.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0749.
HOGENOMHOG000176668.
HOVERGENHBG051400.
InParanoidP54098.
KOK02332.
OMADWSGQEI.
OrthoDBEOG7T4MJC.
PhylomeDBP54098.

Gene expression databases

ArrayExpressP54098.
BgeeP54098.
CleanExHS_POLG.
GenevestigatorP54098.

Family and domain databases

Gene3D3.30.420.10. 2 hits.
InterProIPR019760. DNA-dir_DNA_pol_A_CS.
IPR002297. DNA-dir_DNA_pol_A_mt.
IPR016265. DNA-dir_DNA_pol_A_mt_sub.
IPR001098. DNA-dir_DNA_pol_A_palm_dom.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERPTHR10267. PTHR10267. 1 hit.
PfamPF00476. DNA_pol_A. 1 hit.
[Graphical view]
PIRSFPIRSF000797. DNA_pol_mt. 1 hit.
PRINTSPR00867. DNAPOLG.
SMARTSM00482. POLAc. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 3 hits.
PROSITEPS00447. DNA_POLYMERASE_A. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPOLG.
GenomeRNAi5428.
NextBio21001.
PROP54098.
SOURCESearch...

Entry information

Entry nameDPOG1_HUMAN
AccessionPrimary (citable) accession number: P54098
Secondary accession number(s): Q8NFM2, Q92515
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM