Description: Homo sapiens polymerase (DNA directed), beta (POLB), mRNA. RefSeq Summary (NM_002690): The protein encoded by this gene is a DNA polymerase involved in base excision and repair, also called gap-filling DNA synthesis. The encoded protein, acting as a monomer, is normally found in the cytoplasm, but it translocates to the nucleus upon DNA damage. Several transcript variants of this gene exist, but the full-length nature of only one has been described to date. [provided by RefSeq, Sep 2011]. Transcript (Including UTRs) Position: hg19 chr8:42,195,973-42,229,331 Size: 33,359 Total Exon Count: 14 Strand: + Coding Region Position: hg19 chr8:42,196,143-42,229,175 Size: 33,033 Coding Exon Count: 14
ID:DPOLB_HUMAN DESCRIPTION: RecName: Full=DNA polymerase beta; EC=2.7.7.7; EC=4.2.99.-; 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 (By similarity). SUBUNIT: Monomer. Interacts with APEX1, HUWE1/ARF-BP1, STUB1/CHIP and USP47. INTERACTION: Q9H5J8:TAF1D; NbExp=4; IntAct=EBI-713836, EBI-716128; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cytoplasmic in normal conditions. Translocates to the nucleus following DNA damage. DOMAIN: Residues 239-252 form a flexible loop which appears to affect the polymerase fidelity (By similarity). PTM: Methylation by PRMT6 stimulates the polymerase activity by enhancing DNA binding and processivity. PTM: 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. SIMILARITY: Belongs to the DNA polymerase type-X family. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/polb/";
breast cancer Sliwinski, T. et al. 2006, Polymorphisms of the DNA polymerase beta gene in breast cancer, Breast Cancer Res Treat 2006.
[PubMed 17131038]
Polbeta may play a role in the breast carcinogenesis and the Lys289Met polymorphism of the polbeta gene may be considered as an independent, early, molecular diagnostic marker in breast cancer.
Cholesterol Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903299]
Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
Cholesterol Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903299]
Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P06746
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006260 DNA replication GO:0006261 DNA-dependent DNA replication GO:0006281 DNA repair GO:0006284 base-excision repair GO:0006286 base-excision repair, base-free sugar-phosphate removal GO:0006287 base-excision repair, gap-filling GO:0006288 base-excision repair, DNA ligation GO:0006290 pyrimidine dimer repair GO:0006915 apoptotic process GO:0006954 inflammatory response GO:0006974 cellular response to DNA damage stimulus GO:0007435 salivary gland morphogenesis GO:0007568 aging GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0010332 response to gamma radiation GO:0016445 somatic diversification of immunoglobulins GO:0016446 somatic hypermutation of immunoglobulin genes GO:0016579 protein deubiquitination GO:0045471 response to ethanol GO:0048535 lymph node development GO:0048536 spleen development GO:0048872 homeostasis of number of cells GO:0051402 neuron apoptotic process GO:0055093 response to hyperoxia GO:0071707 immunoglobulin heavy chain V-D-J recombination GO:0071897 DNA biosynthetic process GO:0006297 nucleotide-excision repair, DNA gap filling
AK223537 - Homo sapiens mRNA for polymerase (DNA directed), beta variant, clone: FCC125A07. BC100288 - Homo sapiens polymerase (DNA directed), beta, mRNA (cDNA clone MGC:117403 IMAGE:6151069), complete cds. AK314976 - Homo sapiens cDNA, FLJ95892, Homo sapiens polymerase (DNA directed), beta (POLB), mRNA. AK294025 - Homo sapiens cDNA FLJ57297 complete cds, highly similar to DNA polymerase beta (EC 2.7.7.7). D29013 - Homo sapiens mRNA for DNA polymerase beta, complete cds. M13140 - Human beta-polymerase mRNA, complete cds. BC106909 - Homo sapiens polymerase (DNA directed), beta, mRNA (cDNA clone MGC:125976 IMAGE:40031807), complete cds. KJ891840 - Synthetic construct Homo sapiens clone ccsbBroadEn_01234 POLB gene, encodes complete protein. KR711854 - Synthetic construct Homo sapiens clone CCSBHm_00031390 POLB (POLB) mRNA, encodes complete protein. KR711855 - Synthetic construct Homo sapiens clone CCSBHm_00031391 POLB (POLB) mRNA, encodes complete protein. AB464039 - Synthetic construct DNA, clone: pF1KB6406, Homo sapiens POLB gene for polymerase (DNA directed) beta, without stop codon, in Flexi system. CR541802 - Homo sapiens full open reading frame cDNA clone RZPDo834D1231D for gene POLB, polymerase (DNA directed), beta; complete cds, without stopcodon. CR536503 - Homo sapiens full open reading frame cDNA clone RZPDo834B0720D for gene POLB, polymerase (DNA directed), beta; complete cds, incl. stopcodon. JQ664683 - Homo sapiens mutant DNA polymerase beta mRNA, partial cds. JQ927442 - Homo sapiens DNA polymerase beta-like mRNA, complete sequence. L11607 - Homo sapiens beta-polymerase (POLB) mRNA, complete cds. S69873 - Homo sapiens mutant DNA polymerase beta mRNA, partial cds. JD268527 - Sequence 249551 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03410 - Base excision repair
Reactome (by CSHL, EBI, and GO)
Protein P06746 (Reactome details) participates in the following event(s):
R-HSA-110360 Recruitment of POLB to the AP site R-HSA-5649708 NEIL1,NEIL2 recruits POLB to incised AP site R-HSA-5649854 Recruitment of POLB to oxidatively damaged AP site R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1 R-HSA-110380 Dissociation of LIG3:XRCC1 complex from the BER site R-HSA-5649724 LIG3:XRCC1, POLB, NEIL1,NEIL2 and PNKP dissociate from the BER site R-HSA-5651792 LIG1 and POLB dissociate from repaired dsDNA R-HSA-110375 Excision of the abasic sugar phosphate (5'dRP) residue at the single strand break R-HSA-110376 Recruitment of LIG3:XRCC1 complex to the site of repair by POLB R-HSA-73931 LIG3-mediated DNA ligation via the single-nucleotide replacement pathway R-HSA-73932 Resynthesis of excised residue by POLB R-HSA-5649725 POLB excises the NEIL1,NEIL2-bound AP site (5'dRP) R-HSA-5649734 LIG3 ligates NEIL1,NEIL2-generated single strand break R-HSA-5649726 LIG3:XRCC1 and PNKP bind NEIL1,NEIL2:POLB:SSB(3'Pi)-gap-dsDNA R-HSA-5649723 POLB incorporates a single nucleotide in place of excised AP residue in NEIL1,NEIL2-mediated AP site resolution R-HSA-5649705 PNKP hydrolyzes the terminal 3'Pi at the NEIL1,NEIL2-generated single strand break (SSB) R-HSA-111253 POLB incorporates the first 3' dNMP and displaces 5'ddRP at SSB site R-HSA-5649883 POLB-mediated DNA strand displacement synthesis R-HSA-5649873 PARP1,PARP2 dimers and FEN1 bind POLB and displace APEX1 from damaged AP site R-HSA-5651723 PARP1,PARP2 dimers bound to FEN1 and POLB autoPARylate R-HSA-5651739 PAR-PARP1,PAR-PARP2 dissociate from FEN1 and POLB R-HSA-5651782 FEN1 bound to POLB cleaves displaced DNA strand (flap) R-HSA-5651773 LIG1 binds POLB at long-patch BER site R-HSA-5651789 LIG1 bound to POLB ligates SSB R-HSA-5696947 USP47 deubiquitinates POLB R-HSA-73930 Abasic sugar-phosphate removal via the single-nucleotide replacement pathway R-HSA-5649702 APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair R-HSA-110381 Resolution of AP sites via the single-nucleotide replacement pathway R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair R-HSA-5689880 Ub-specific processing proteases R-HSA-73933 Resolution of Abasic Sites (AP sites) R-HSA-5688426 Deubiquitination R-HSA-73884 Base Excision Repair R-HSA-597592 Post-translational protein modification R-HSA-73894 DNA Repair R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
