P54098 (DPOG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1239 AA.
Sequence status	Complete.
Protein existence	Evidence 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 matrix › mitochondrion 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 process	DNA replication
Cellular component	Mitochondrion Mitochondrion nucleoid
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leigh syndrome Neurodegeneration Neuropathy Progressive external ophthalmoplegia
Ligand	DNA-binding Magnesium
Molecular function	DNA-directed DNA polymerase Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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_component	gamma 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
Molecular_function	DNA 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
POLG2	Q9UHN1	9	EBI-852624,EBI-852642

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1239

1239

DNA polymerase subunit gamma-1

PRO_0000101270

Regions

Compositional bias

43 – 60

18

Poly-Gln

Compositional bias

535 – 538

4

Poly-Glu

Natural variations

Natural variant

3

1

R → P in PEOB. Ref.7 Ref.16

VAR_012153

Natural variant

18

1

P → S.
Corresponds to variant rs3087373 [ dbSNP | Ensembl ].

VAR_014904

Natural variant

55

1

Q → QQ. Ref.3 Ref.4

VAR_019265

Natural variant

55

1

Q → QQQ. Ref.3 Ref.4

VAR_019266

Natural variant

193

1

R → Q. Ref.4
Corresponds to variant rs3176162 [ dbSNP | Ensembl ].

VAR_019267

Natural variant

227

1

R → W in PEOB and MTDPS4B. Ref.14 Ref.18 Ref.37

VAR_023663

Natural variant

232

1

R → G in MTDPS4A. Ref.25

VAR_058870

Natural variant

232

1

R → H in LS. Ref.36

VAR_058871

Natural variant

244

1

L → P in MTDPS4A. Ref.25

VAR_058872

Natural variant

251

1

T → 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 variant

268

1

G → A in PEOB; sporadic case. Ref.13
Corresponds to variant rs61752784 [ dbSNP | Ensembl ].

VAR_058873

Natural variant

304

1

L → R in PEOB; also found in SANDO. Ref.7 Ref.16 Ref.31

VAR_012154

Natural variant

304

1

L → SANDO in PEOB.

VAR_058874

Natural variant

308

1

Q → H in PEOB; sporadic case. Ref.30

VAR_058875

Natural variant

309

1

R → L in PEOB. Ref.8 Ref.18

VAR_023665

Natural variant

312

1

W → R in PEOB; sporadic case. Ref.13 Ref.14

VAR_023666

Natural variant

324

1

P → S.
Corresponds to variant rs2307437 [ dbSNP | Ensembl ].

VAR_014905

Natural variant

380

1

G → D in PEOB. Ref.31

VAR_058876

Natural variant

431

1

G → V in PEOB; sporadic case. Ref.14

VAR_023667

Natural variant

463

1

L → F. Ref.34

VAR_058877

Natural variant

467

1

A → 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 variant

468

1

N → D in PEOB. Ref.20
Corresponds to variant rs145843073 [ dbSNP | Ensembl ].

VAR_023668

Natural variant

497

1

Q → H in SANDO; atypical form with spinocerebellar ataxia and epilepsy. Ref.27

VAR_023669

Natural variant

511

1

S → N in PEOA1. Ref.34

VAR_058878

Natural variant

517

1

G → V in SANDO. Ref.30
Corresponds to variant rs61752783 [ dbSNP | Ensembl ].

VAR_058879

Natural variant

546

1

R → C. Ref.4
Corresponds to variant rs2307447 [ dbSNP | Ensembl ].

VAR_014906

Natural variant

562

1

R → Q in PEOB; sporadic case. Ref.13

VAR_058880

Natural variant

574

1

R → W in PEOB; sporadic case. Ref.30

VAR_058881

Natural variant

579

1

R → W in PEOB; autosomal recessive. Ref.10

VAR_023670

Natural variant

587

1

P → 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 variant

603

1

M → L in PEOB. Ref.29

VAR_058882

Natural variant

627

1

R → Q in SANDO; shows DNA binding affinitiy and processivities similar to the controls. Ref.26

VAR_058883

Natural variant

627

1

R → W in SANDO; sporadic case. Ref.16

VAR_023672

Natural variant

648

1

P → R in PEOB; sporadic case; also in SANDO. Ref.30 Ref.33

VAR_058884

Natural variant

662

1

E → K. Ref.4
Corresponds to variant rs2307450 [ dbSNP | Ensembl ].

VAR_014907

Natural variant

737

1

G → R in PEOB; with absence of progressive external ophthalmoplegia. Ref.28
Corresponds to variant rs121918054 [ dbSNP | Ensembl ].

VAR_058885

Natural variant

748

1

W → 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 variant

767

1

A → D in MTDPS4A. Ref.30

VAR_058886

Natural variant

807

1

R → C in SANDO. Ref.33

VAR_058887

Natural variant

807

1

R → P in PEOB; sporadic case. Ref.13

VAR_058888

Natural variant

831

1

Y → C in PEOA1 and MTDPS4A. Ref.19 Ref.36
Corresponds to variant rs4154971 [ dbSNP | Ensembl ].

VAR_023674

Natural variant

848

1

G → S in PEOB, MTDPS4A, MTDPS4B and LS. Ref.8 Ref.12 Ref.18 Ref.24 Ref.25 Ref.36 Ref.37

VAR_023675

Natural variant

853

1

R → W in PEOB; with absence of progressive external ophthalmoplegia. Ref.28 Ref.29

VAR_058889

Natural variant

864

1

N → S in MTDPS4B. Ref.11

VAR_023676

Natural variant

879

1

Q → H in MTDPS4A. Ref.30

VAR_058890

Natural variant

885

1

T → S in MTDPS4A. Ref.30

VAR_058891

Natural variant

889

1

A → T in PEOB. Ref.10

VAR_023677

Natural variant

914

1

T → P in MTDPS4A. Ref.30 Ref.31 Ref.36

VAR_058892

Natural variant

923

1

G → D in PEOA1. Ref.8

VAR_023678

Natural variant

932

1

H → Y in SANDO and PEOB; sporadic case. Ref.13 Ref.21

VAR_023679

Natural variant

943

1

R → H in PEOA1. Ref.8

VAR_023680

Natural variant

953

1

R → C in PEOA1. Ref.20
Corresponds to variant rs11546842 [ dbSNP | Ensembl ].

VAR_023681

Natural variant

955

1

Y → 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 variant

957

1

A → P in MTDPS4A. Ref.25

VAR_058893

Natural variant

957

1

A → S in PEOA1. Ref.8

VAR_023682

Natural variant

1047

1

R → Q in PEOB; sporadic case. Ref.14

VAR_023683

Natural variant

1051

1

G → R in SANDO. Ref.21

VAR_023684

Natural variant

1076

1

G → V in PEOB. Ref.10

VAR_023685

Natural variant

1096

1

R → C in PEOB; sporadic case. Ref.14

VAR_023686

Natural variant

1096

1

R → H in MTDPS4A. Ref.30

VAR_058894

Natural variant

1104

1

S → C in PEOB; sporadic case. Ref.14

VAR_023687

Natural variant

1105

1

A → T in PEOB. Ref.20

VAR_023688

Natural variant

1106

1

V → I in PEOB. Ref.18

VAR_023689

Natural variant

1110

1

H → Y in MTDPS4A. Ref.36

VAR_058895

Natural variant

1134

1

H → R in MTDPS4A. Ref.36

VAR_058896

Natural variant

1136

1

E → K in MTDPS4A. Ref.36

VAR_065092

Natural variant

1142

1

R → W. Ref.4
Corresponds to variant rs2307442 [ dbSNP | Ensembl ].

VAR_014908

Natural variant

1143

1

E → G. Ref.4 Ref.13 Ref.22 Ref.23 Ref.25 Ref.31 Ref.36
Corresponds to variant rs2307441 [ dbSNP | Ensembl ].

VAR_014909

Natural variant

1146

1

R → C in PEOB. Ref.4 Ref.29
Corresponds to variant rs2307440 [ dbSNP | Ensembl ].

VAR_014910

Natural variant

1176

1

S → L in PEOA1. Ref.8 Ref.18

VAR_023690

Natural variant

1184

1

D → N in PEOB. Ref.29

VAR_058897

Natural variant

1186

1

D → H in PEOA1. Ref.35

VAR_065119

Natural variant

1191

1

K → N in MTDPS4A. Ref.30

VAR_058898

Natural variant

1236

1

Q → H. Ref.4 Ref.10 Ref.13 Ref.26 Ref.31 Ref.36
Corresponds to variant rs3087374 [ dbSNP | Ensembl ].

VAR_014911

Secondary structure

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1239

Helix Strand Turn

Details...

Beta strand

75 – 77

3

Helix

83 – 86

4

Helix

97 – 105

9

Turn

106 – 111

6

Beta strand

114 – 116

3

Helix

135 – 159

25

Beta strand

179 – 181

3

Beta strand

192 – 195

4

Beta strand

207 – 210

4

Helix

224 – 227

4

Beta strand

235 – 237

3

Beta strand

240 – 242

3

Turn

243 – 247

5

Helix

248 – 251

4

Beta strand

254 – 256

3

Beta strand

260 – 262

3

Beta strand

271 – 274

4

Helix

277 – 279

3

Helix

296 – 301

6

Helix

306 – 317

12

Helix

354 – 360

7

Beta strand

373 – 376

4

Turn

377 – 380

4

Helix

385 – 415

31

Helix

422 – 431

10

Helix

440 – 473

34

Helix

483 – 490

8

Beta strand

519 – 521

3

Beta strand

537 – 540

4

Helix

541 – 558

18

Beta strand

559 – 561

3

Beta strand

563 – 568

6

Beta strand

587 – 589

3

Turn

592 – 595

4

Turn

597 – 604

8

Beta strand

616 – 618

3

Beta strand

627 – 629

3

Helix

636 – 644

9

Helix

647 – 671

25

Helix

716 – 721

6

Turn

738 – 740

3

Turn

755 – 757

3

Helix

770 – 775

6

Beta strand

776 – 778

3

Beta strand

784 – 786

3

Helix

787 – 810

24

Beta strand

818 – 821

4

Turn

822 – 829

8

Beta strand

833 – 835

3

Turn

849 – 851

3

Helix

859 – 861

3

Helix

875 – 878

4

Beta strand

884 – 890

7

Helix

894 – 906

13

Beta strand

907 – 909

3

Turn

914 – 919

6

Turn

924 – 926

3

Helix

929 – 937

9

Helix

944 – 955

12

Helix

960 – 969

10

Helix

974 – 990

17

Beta strand

992 – 995

4

Beta strand

997 – 999

3

Helix

1001 – 1009

9

Beta strand

1010 – 1013

4

Helix

1027 – 1030

4

Beta strand

1033 – 1035

3

Helix

1037 – 1040

4

Turn

1041 – 1046

6

Helix

1047 – 1058

12

Beta strand

1061 – 1065

5

Beta strand

1068 – 1070

3

Helix

1093 – 1121

29

Beta strand

1122 – 1124

3

Beta strand

1136 – 1143

8

Helix

1146 – 1168

23

Helix

1175 – 1178

4

Beta strand

1184 – 1188

5

Helix

1193 – 1195

3

Beta strand

1200 – 1203

4

Beta strand

1207 – 1209

3

Helix

1220 – 1227

8

Beta strand

1232 – 1235

4

Sequences

	Sequence		Length	Mass (Da)
	P54098 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2D9ECCD75AD6E01E	FASTA	1,239	139,562
	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

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

NIEHS-SNPs

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.

IPI

IPI00004317.

PIR

G02750.

RefSeq

NP_001119603.1. NM_001126131.1.
NP_002684.1. NM_002693.2.

UniGene

Hs.706868.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IKM	X-ray	3.24	A/D	70-1239	[»]

ProteinModelPortal

P54098.

ModBase

Search...

Protein-protein interaction databases

IntAct

P54098. 5 interactions.

MINT

MINT-4531455.

STRING

9606.ENSP00000268124.

PTM databases

PhosphoSite

P54098.

Polymorphism databases

DMDM

1706507.

Proteomic databases

PaxDb

P54098.

PeptideAtlas

P54098.

PRIDE

P54098.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000268124; ENSP00000268124; ENSG00000140521.
ENST00000442287; ENSP00000399851; ENSG00000140521.

GeneID

5428.

KEGG

hsa:5428.

UCSC

uc002bnr.4. human.

Organism-specific databases

CTD

5428.

GeneCards

GC15M089859.

HGNC

HGNC:9179. POLG.

MIM

157640. phenotype.
174763. gene.
203700. phenotype.
256000. phenotype.
258450. phenotype.
607459. phenotype.
613662. phenotype.

neXtProt

NX_P54098.

Orphanet

726. Alpers syndrome.
254892. Autosomal dominant progressive external ophthalmoplegia.
254886. Autosomal recessive progressive external ophthalmoplegia.
298. Mitochondrial neurogastrointestinal encephalomyopathy.
94125. Recessive mitochondrial ataxic syndrome.
70595. Sensory ataxic neuropathy - dysarthria - ophthalmoparesis.
254881. Spinocerebellar ataxia with epilepsy.

PharmGKB

PA33500.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0749.

HOGENOM

HOG000176668.

HOVERGEN

HBG051400.

InParanoid

P54098.

KO

K02332.

OMA

DWSGQEI.

OrthoDB

EOG7T4MJC.

PhylomeDB

P54098.

Gene expression databases

ArrayExpress

P54098.

Bgee

P54098.

CleanEx

HS_POLG.

Genevestigator

P54098.

Family and domain databases

InterPro

IPR019760. 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]

PANTHER

PTHR10267. PTHR10267. 1 hit.

Pfam

PF00476. DNA_pol_A. 1 hit.
[Graphical view]

PIRSF

PIRSF000797. DNA_pol_mt. 1 hit.

PRINTS

PR00867. DNAPOLG.

SMART

SM00482. POLAc. 1 hit.
[Graphical view]

SUPFAM

SSF53098. SSF53098. 3 hits.

PROSITE

PS00447. DNA_POLYMERASE_A. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P54098.

ChEMBL

CHEMBL2732.

GeneWiki

POLG.

GenomeRNAi

5428.

NextBio

21001.

PRO

P54098.

SOURCE

Search...

Entry information

Entry name

DPOG1_HUMAN

Accession

Primary (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:	November 13, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.