Q9UHN1 (DPOG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase subunit gamma-2, mitochondrial
EC=2.7.7.7

Alternative name(s):
DNA polymerase gamma accessory 55 kDa subunit
Short name=p55
Mitochondrial DNA polymerase accessory subunit
MtPolB
PolG-beta

Gene names

Name:	POLG2
Synonyms:	MTPOLB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	485 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mitochondrial polymerase processivity subunit. Stimulates the polymerase and exonuclease activities, and increases the processivity of the enzyme. Binds to ss-DNA.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Subunit structure	Heterotrimer composed of a catalytic subunit and an homodimer of accessory subunits.
Subcellular location	Mitochondrion.
Involvement in disease	Defects in POLG2 are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 4 (PEOA4) [MIM:610131]. 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. Ref.7

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Mitochondrion
Disease	Disease mutation Progressive external ophthalmoplegia
Domain	Transit peptide
Ligand	DNA-binding
Molecular function	DNA-directed DNA polymerase Nucleotidyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Non-traceable author statement Ref.1. Source: UniProtKB DNA-dependent DNA replication Traceable author statement. Source: ProtInc glycyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrial chromosome Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro DNA-directed DNA polymerase activity Non-traceable author statement. Source: UniProtKB glycine-tRNA ligase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct single-stranded DNA binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
POLG	P54098	8	EBI-852642,EBI-852624

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 485

DNA polymerase subunit gamma-2, mitochondrial

PRO_0000007314

Amino acid modifications

Modified residue

288

1

N6-acetyllysine Ref.6

Natural variations

Natural variant

169

1

A → T. Ref.2 Ref.4
Corresponds to variant rs1427463 [ dbSNP | Ensembl ].

VAR_032028

Natural variant

416

1

G → A There is no functional deficit. Ref.4 Ref.8
Corresponds to variant rs17850455 [ dbSNP | Ensembl ].

VAR_032029

Natural variant

451

1

G → E in PEOA4; affects stimulation of the catalytic subunit. Ref.7

VAR_029364

Experimental info

Sequence conflict

114 – 124

11

WWTSVVVFREQ → MVDLGGGVHGA in AAC51321. Ref.5

Sequence conflict

122

1

R → T in AAD56542. Ref.3

Sequence conflict

136

1

G → S in AAD56542. Ref.3

Sequence conflict

136

1

G → S in AAC51321. Ref.5

Sequence conflict

287 – 292

6

NKLYYN → TNFTTI in AAC51321. Ref.5

Secondary structure

1

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485

Helix Strand Turn

Details...

Helix

69 – 75

7

Beta strand

83 – 86

4

Helix

88 – 92

5

Helix

101 – 118

18

Turn

119 – 122

4

Beta strand

125 – 127

3

Beta strand

132 – 134

3

Beta strand

146 – 149

4

Helix

150 – 153

4

Helix

154 – 156

3

Beta strand

157 – 159

3

Turn

161 – 165

5

Helix

166 – 168

3

Helix

171 – 177

7

Beta strand

179 – 181

3

Helix

186 – 190

5

Helix

193 – 198

6

Turn

199 – 202

4

Beta strand

207 – 217

11

Beta strand

231 – 243

13

Helix

245 – 264

20

Helix

270 – 272

3

Beta strand

273 – 276

4

Beta strand

281 – 284

4

Beta strand

288 – 293

6

Beta strand

296 – 305

10

Helix

309 – 314

6

Helix

319 – 321

3

Beta strand

324 – 331

8

Beta strand

334 – 341

8

Helix

342 – 352

11

Turn

376 – 378

3

Beta strand

382 – 387

6

Helix

395 – 397

3

Helix

398 – 407

10

Turn

408 – 410

3

Beta strand

413 – 415

3

Beta strand

419 – 421

3

Helix

426 – 434

9

Beta strand

438 – 443

6

Helix

445 – 448

4

Beta strand

456 – 460

5

Helix

472 – 484

13

Sequences

	Sequence		Length	Mass (Da)
	Q9UHN1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B99734BFEA249192	FASTA	485	54,911
	10 20 30 40 50 60 MRSRVAVRAC HKVCRCLLSG FGGRVDAGQP ELLTERSSPK GGHVKSHAEL EGNGEHPEAP 70 80 90 100 110 120 GSGEGSEALL EICQRRHFLS GSKQQLSRDS LLSGCHPGFG PLGVELRKNL AAEWWTSVVV 130 140 150 160 170 180 FREQVFPVDA LHHKPGPLLP GDSAFRLVSA ETLREILQDK ELSKEQLVAF LENVLKTSGK 190 200 210 220 230 240 LRENLLHGAL EHYVNCLDLV NKRLPYGLAQ IGVCFHPVFD TKQIRNGVKS IGEKTEASLV 250 260 270 280 290 300 WFTPPRTSNQ WLDFWLRHRL QWWRKFAMSP SNFSSSDCQD EEGRKGNKLY YNFPWGKELI 310 320 330 340 350 360 ETLWNLGDHE LLHMYPGNVS KLHGRDGRKN VVPCVLSVNG DLDRGMLAYL YDSFQLTENS 370 380 390 400 410 420 FTRKKNLHRK VLKLHPCLAP IKVALDVGRG PTLELRQVCQ GLFNELLENG ISVWPGYLET 430 440 450 460 470 480 MQSSLEQLYS KYDEMSILFT VLVTETTLEN GLIHLRSRDT TMKEMMHISK LKDFLIKYIS SAKNV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mitochondrial p55 accessory subunit of human DNA polymerase gamma enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance." Lim S.E., Longley M.J., Copeland W.C. J. Biol. Chem. 274:38197-38203(1999) [PubMed: 10608893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum.
[2]	"Protein sequences conserved in prokaryotic aminoacyl-tRNA synthetases are important for the activity of the processivity factor of human mitochondrial DNA polymerase." Carrodeguas J.A., Bogenhagen D.F. Nucleic Acids Res. 28:1237-1244(2000) [PubMed: 10666468] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-169.
[3]	"Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization." Johnson A.A., Tsai Y.-C., Graves S.W., Johnson K.A. Biochemistry 39:1702-1708(2000) [PubMed: 10677218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-169 AND ALA-416. Tissue: Cervix and Ovary.
[5]	"Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos. Cloning, molecular analysis, and association in the native enzyme." Wang Y., Farr C.L., Kaguni L.S. J. Biol. Chem. 272:13640-13646(1997) [PubMed: 9153213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-485.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288, MASS SPECTROMETRY.
[7]	"Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia." Longley M.J., Clark S., Man C.Y.W., Hudson G., Durham S.E., Taylor R.W., Nightingale S., Turnbull D.M., Copeland W.C., Chinnery P.F. Am. J. Hum. Genet. 78:1026-1034(2006) [PubMed: 16685652] [Abstract] Cited for: VARIANT PEOA4 GLU-451, CHARACTERIZATION OF VARIANT PEOA4 GLU-451.
[8]	"Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1." Ferraris S., Clark S., Garelli E., Davidzon G., Moore S.A., Kardon R.H., Bienstock R.J., Longley M.J., Mancuso M., Gutierrez Rios P., Hirano M., Copeland W.C., DiMauro S. Arch. Neurol. 65:125-131(2008) [PubMed: 18195150] [Abstract] Cited for: VARIANT ALA-416, CHARACTERIZATION OF VARIANT ALA-416.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF142992 mRNA. Translation: AAD50382.1.
AF177201 mRNA. Translation: AAD56640.1.
AF184344 mRNA. Translation: AAD56542.1.
BC000913 mRNA. Translation: AAH00913.2.
BC009194 mRNA. Translation: AAH09194.1.
U94703 mRNA. Translation: AAC51321.1.

IPI

IPI00033486.

RefSeq

NP_009146.2. NM_007215.3.

UniGene

Hs.437009.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2G4C	X-ray	3.15	A/B/C/D	26-485	[»]
3IKL	X-ray	3.10	A/B	1-485	[»]
3IKM	X-ray	3.24	B/C/E/F	59-485	[»]

ProteinModelPortal

Q9UHN1.

SMR

Q9UHN1. Positions 67-485.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UHN1. 3 interactions.

STRING

Q9UHN1.

PTM databases

PhosphoSite

Q9UHN1.

Polymorphism databases

DMDM

17367139.

Proteomic databases

PRIDE

Q9UHN1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000322670; ENSP00000317618; ENSG00000136480.

GeneID

11232.

KEGG

hsa:11232.

UCSC

uc002jei.1. human.

Organism-specific databases

CTD

11232.

GeneCards

GC17M062473.

H-InvDB

HIX0014107.

HGNC

HGNC:9180. POLG2.

HPA

CAB017030.
HPA023202.

MIM

604983. gene.
610131. phenotype.

neXtProt

NX_Q9UHN1.

Orphanet

254892. Autosomal dominant progressive external ophthalmoplegia.

PharmGKB

PA33501.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07350.

GeneTree

ENSGT00390000000244.

HOGENOM

HBG446594.

HOVERGEN

HBG051401.

InParanoid

Q9UHN1.

OMA

PGYLETM.

OrthoDB

EOG4KD6M0.

PhylomeDB

Q9UHN1.

Gene expression databases

ArrayExpress

Q9UHN1.

Bgee

Q9UHN1.

CleanEx

HS_POLG2.

Genevestigator

Q9UHN1.

GermOnline

ENSG00000136480. Homo sapiens.

Family and domain databases

InterPro

IPR004154. Anticodon-bd.
IPR002315. tRNA-synt_gly.
[Graphical view]

Gene3D

G3DSA:3.40.50.800. Anticodon_bd. 1 hit.

KO

K02333.

PANTHER

PTHR10745. tRNA-synt_gly. 1 hit.

Pfam

PF03129. HGTP_anticodon. 1 hit.
[Graphical view]

SUPFAM

SSF52954. Anticodon_bd. 1 hit.

ProtoNet

Search...

Other

NextBio

42746.

SOURCE

Search...

Entry information

Entry name

DPOG2_HUMAN

Accession

Primary (citable) accession number: Q9UHN1
Secondary accession number(s): O00419 , Q0IJ81, Q96GW2, Q9UK35, Q9UK94

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 99 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.