P06766 (DPOLB_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase beta
EC=2.7.7.7
EC=4.2.99.-

Gene names

Name:

Polb

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	335 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	Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Binds 2 magnesium ions per subunit.
Subunit structure	Interacts with APEX1, HUWE1/ARF-BP1, STUB1/CHIP and USP47 By similarity. Monomer.
Subcellular location	Nucleus. Cytoplasm By similarity. Note: Cytoplasmic in normal conditions. Translocates to the nucleus following DNA damage By similarity.
Domain	Residues 239-252 form a flexible loop which appears to affect the polymerase fidelity.
Post-translational modification	Methylation by PRMT6 stimulates the polymerase activity by enhancing DNA binding and processivity By similarity. Ubiquitinated at Lys-41, Lys-61 and Lys-81: monoubiquitinated by HUWE1/ARF-BP1. Monoubiquitinated protein is then the target of STUB1/CHIP, which catalyzes polyubiquitination from monoubiquitin, leading to degradation by the proteasome. USP47 mediates the deubiquitination of monoubiquitinated protein, preventing polyubiquitination by STUB1/CHIP and its subsequent degradation By similarity.
Sequence similarities	Belongs to the DNA polymerase type-X family.

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication DNA synthesis
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding Magnesium Metal-binding Sodium
Molecular function	DNA-directed DNA polymerase Lyase Nucleotidyltransferase Transferase
PTM	Isopeptide bond Methylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW base-excision repair Inferred from sequence or structural similarity. Source: UniProtKB cell death Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara pyrimidine dimer repair Inferred from direct assay PubMed 12388548. Source: RGD response to ethanol Inferred from expression pattern PubMed 18259862. Source: RGD
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay PubMed 967678. Source: RGD spindle microtubule Inferred from electronic annotation. Source: Compara
Molecular_function	DNA-directed DNA polymerase activity Inferred from sequence or structural similarity. Source: UniProtKB damaged DNA binding Inferred from direct assay PubMed 12388548. Source: RGD lyase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from direct assay Ref.13. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 335

334

DNA polymerase beta

PRO_0000218780

Regions

Region

183 – 192

10

DNA binding

Sites

Active site

72

1

Schiff-base intermediate with DNA By similarity

Metal binding

101

1

Sodium; via carbonyl oxygen

Metal binding

103

1

Sodium; via carbonyl oxygen

Metal binding

106

1

Sodium; via carbonyl oxygen

Metal binding

190

1

Magnesium 1

Metal binding

190

1

Magnesium 2

Metal binding

192

1

Magnesium 1

Metal binding

192

1

Magnesium 2

Metal binding

256

1

Magnesium 2

Amino acid modifications

Modified residue

83

1

Omega-N-methylarginine; by PRMT6 By similarity

Modified residue

152

1

Omega-N-methylarginine; by PRMT6 By similarity

Cross-link

41

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

61

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

81

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis

190

1

D → E or S: Loss of activity. Ref.7

Mutagenesis

191

1

M → I: No loss of activity.

Mutagenesis

191

1

M → T: 50% loss of activity.

Mutagenesis

192

1

D → E or S: Loss of activity. Ref.7

Mutagenesis

246

1

D → V: Misincorporates T nucleotide opposite G/C template. Ref.9

Sequence conflict

228

1

L → R in AAA41901. Ref.1

Sequence conflict

228

1

L → R in AAB00389. Ref.2

Sequence conflict

228

1

L → R in AAA41900. Ref.4

Secondary structure

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335

Helix Strand Turn

Details...

Helix

13 – 28

16

Beta strand

29 – 31

3

Helix

33 – 48

16

Helix

56 – 61

6

Beta strand

62 – 64

3

Helix

67 – 76

10

Beta strand

79 – 81

3

Helix

83 – 90

8

Helix

92 – 100

9

Turn

101 – 104

4

Helix

108 – 115

8

Turn

116 – 118

3

Helix

122 – 126

5

Helix

129 – 131

3

Helix

134 – 141

8

Turn

142 – 144

3

Helix

145 – 147

3

Helix

152 – 169

18

Beta strand

174 – 177

4

Helix

179 – 182

4

Beta strand

186 – 196

11

Turn

202 – 204

3

Helix

208 – 220

13

Beta strand

224 – 230

7

Beta strand

232 – 239

8

Beta strand

244 – 247

4

Beta strand

253 – 259

7

Helix

262 – 264

3

Helix

265 – 273

9

Helix

276 – 288

13

Beta strand

291 – 293

3

Beta strand

298 – 301

4

Beta strand

303 – 305

3

Helix

316 – 322

7

Helix

330 – 332

3

Sequences

	Sequence		Length	Mass (Da)
	P06766 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: BBF8498C0D3FBFC9	FASTA	335	38,327
	10 20 30 40 50 60 MSKRKAPQET LNGGITDMLV ELANFEKNVS QAIHKYNAYR KAASVIAKYP HKIKSGAEAK 70 80 90 100 110 120 KLPGVGTKIA EKIDEFLATG KLRKLEKIRQ DDTSSSINFL TRVTGIGPSA ARKLVDEGIK 130 140 150 160 170 180 TLEDLRKNED KLNHHQRIGL KYFEDFEKRI PREEMLQMQD IVLNEVKKLD PEYIATVCGS 190 200 210 220 230 240 FRRGAESSGD MDVLLTHPNF TSESSKQPKL LHRVVEQLQK VRFITDTLSK GETKFMGVCQ 250 260 270 280 290 300 LPSENDENEY PHRRIDIRLI PKDQYYCGVL YFTGSDIFNK NMRAHALEKG FTINEYTIRP 310 320 330 LGVTGVAGEP LPVDSEQDIF DYIQWRYREP KDRSE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homology between mammalian DNA polymerase beta and terminal deoxynucleotidyltransferase." Matsukage A., Nishikawa K., Ooi T., Seto Y., Yamaguchi M. J. Biol. Chem. 262:8960-8962(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Konopinski R., Nowak R., Siedlecki J.A. Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar.
[3]	"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: Thymus.
[4]	"Structure of rat DNA polymerase beta revealed by partial amino acid sequencing and cDNA cloning." Zmudzka B.Z., Sengupta D., Matsukage A., Cobianchi F., Kumar P., Wilson S.H. Proc. Natl. Acad. Sci. U.S.A. 83:5106-5110(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-335.
[5]	"Studies of the domain structure of mammalian DNA polymerase beta. Identification of a discrete template binding domain." Kumar P., Widen S.G., Williams K.R., Kedar P., Karpel R.L., Wilson S.H. J. Biol. Chem. 265:2124-2131(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, SEQUENCE REVISION TO 228.
[6]	"Site-directed mutagenesis of recombinant rat DNA polymerase beta: involvement of arginine-183 in primer recognition." Date T., Yamamoto S., Tanihara K., Nishimoto Y., Liu N., Matsukage A. Biochemistry 29:5027-5034(1990) [PubMed] [Europe PMC] [Abstract] Cited for: IMPORTANCE OF ARG-183 IN PRIMER BINDING.
[7]	"Aspartic acid residues at positions 190 and 192 of rat DNA polymerase beta are involved in primer binding." Date T., Yamamoto S., Tanihara K., Nishimoto Y., Matsukage A. Biochemistry 30:5286-5292(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-190 AND ASP-192, IMPORTANCE OF ASP-190 AND ASP-192 IN PRIMER BINDING.
[8]	"Mammalian DNA polymerase beta: characterization of a 16-kDa transdomain fragment containing the nucleic acid-binding activities of the native enzyme." Casas-Finet J.R., Kumar A., Karpel R.L., Wilson S.H. Biochemistry 31:10272-10280(1992) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING REGION.
[9]	"The D246V mutant of DNA polymerase beta misincorporates nucleotides: evidence for a role for the flexible loop in DNA positioning within the active site." Dalal S., Kosa J.L., Sweasy J.B. J. Biol. Chem. 279:577-584(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-246, IMPORTANCE OF ASP-246 IN FIDELITY.
[10]	"2.3-A crystal structure of the catalytic domain of DNA polymerase beta." Davies J.F. II, Almassy R.J., Hostomska Z., Ferre R.A., Hostomsky Z. Cell 76:1123-1133(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[11]	"Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism." Sawaya M.R., Pelletier H., Kumar A., Wilson S.H., Kraut J. Science 264:1930-1935(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[12]	"Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis." Pelletier H., Sawaya M.R. Biochemistry 35:12778-12787(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[13]	"Insight into the catalytic mechanism of DNA polymerase beta: structures of intermediate complexes." Arndt J.W., Gong W., Zhong X., Showalter A.K., Liu J., Dunlap C.A., Lin Z., Paxson C., Tsai M.-D., Chan M.K. Biochemistry 40:5368-5375(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[14]	"Three-dimensional solution structure of the N-terminal domain of DNA polymerase beta and mapping of the ssDNA interaction interface." Liu D., Prasad R., Wilson S.H., DeRose E.F., Mullen G.P. Biochemistry 35:6188-6200(1996) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-87.
[15]	"Backbone dynamics and refined solution structure of the N-terminal domain of DNA polymerase beta. Correlation with DNA binding and dRP lyase activity." Maciejewski M.W., Liu D., Prasad R., Wilson S.H., Mullen G.P. J. Mol. Biol. 296:229-253(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-87.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02776 mRNA. Translation: AAA41901.1.
U38801 mRNA. Translation: AAB00389.1.
BC098668 mRNA. Translation: AAH98668.1.
M13961 mRNA. Translation: AAA41900.1.

IPI

IPI00389756.

PIR

A27112.

RefSeq

NP_058837.2. NM_017141.2.

UniGene

Rn.9346.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BNO	NMR	-	A	1-87	[»]
1BNP	NMR	-	A	1-87	[»]
1BPB	X-ray	2.30	A	88-335	[»]
1BPD	X-ray	3.60	A	1-335	[»]
1BPE	X-ray	2.90	A	1-335	[»]
1DK2	NMR	-	A	2-87	[»]
1DK3	NMR	-	A	1-87	[»]
1HUO	X-ray	2.60	A/B	1-335	[»]
1HUZ	X-ray	2.60	A/B	1-335	[»]
1JN3	X-ray	2.35	A	85-335	[»]
1NOM	X-ray	3.00	A	88-335	[»]
1RPL	X-ray	2.30	A	85-335	[»]
1ZQU	X-ray	2.60	A	88-335	[»]
1ZQV	X-ray	2.70	A	88-335	[»]
1ZQW	X-ray	2.30	A	88-335	[»]
1ZQX	X-ray	2.50	A	88-335	[»]
1ZQY	X-ray	2.30	A	88-335	[»]
1ZQZ	X-ray	2.70	A	88-335	[»]
2BPC	X-ray	2.80	A	88-335	[»]
2BPF	X-ray	2.90	A	2-334	[»]
2BPG	X-ray	3.60	A/B	1-335	[»]
2VAN	X-ray	2.10	A	91-335	[»]
3K75	X-ray	2.95	D/E	91-335	[»]
3LQC	X-ray	2.35	B	142-335	[»]
3UXN	X-ray	2.50	A/B	1-335	[»]
3UXO	X-ray	2.10	A/B	1-335	[»]
3UXP	X-ray	2.72	A/B	1-335	[»]
3V72	X-ray	2.49	A	1-335	[»]
3V7J	X-ray	2.25	A	4-335	[»]
3V7K	X-ray	2.27	A	4-335	[»]
3V7L	X-ray	2.66	A	4-335	[»]

ProteinModelPortal

P06766.

SMR

P06766. Positions 10-334.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44707N.

PTM databases

PhosphoSite

P06766.

Proteomic databases

PaxDb

P06766.

PRIDE

P06766.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000026039; ENSRNOP00000026039; ENSRNOG00000019150.

GeneID

29240.

KEGG

rno:29240.

UCSC

RGD:3363. rat.

Organism-specific databases

CTD

5423.

RGD

3363. Polb.

Phylogenomic databases

eggNOG

COG1796.

GeneTree

ENSGT00530000063002.

HOGENOM

HOG000007787.

HOVERGEN

HBG002359.

InParanoid

P06766.

KO

K02330.

OMA

GKEYPHR.

OrthoDB

EOG43FGX8.

Gene expression databases

ArrayExpress

P06766.

Genevestigator

P06766.

GermOnline

ENSRNOG00000019150. Rattus norvegicus.

Family and domain databases

InterPro

IPR002054. DNA-dir_DNA_pol_X.
IPR019843. DNA_pol-X_BS.
IPR010996. DNA_pol_b-like_N.
IPR018944. DNA_pol_lambd_fingers_domain.
IPR022312. DNA_pol_X.
IPR002008. DNA_pol_X_beta-like.
IPR003583. Hlx-hairpin-Hlx_DNA-bd_motif.
[Graphical view]

Pfam

PF10391. DNA_pol_lambd_f. 1 hit.
[Graphical view]

PRINTS

PR00869. DNAPOLX.
PR00870. DNAPOLXBETA.

SMART

SM00278. HhH1. 2 hits.
SM00483. POLXc. 1 hit.
[Graphical view]

SUPFAM

SSF81585. DNA_pol_lambd_fingers_domain. 1 hit.
SSF47802. DNApol_B_N_like. 1 hit.

PROSITE

PS00522. DNA_POLYMERASE_X. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P06766.

ChEMBL

CHEMBL4343.

EvolutionaryTrace

P06766.

NextBio

608510.

Entry information

Entry name

DPOLB_RAT

Accession

Primary (citable) accession number: P06766
Secondary accession number(s): Q4G081

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 139 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program