ID:POLH_HUMAN DESCRIPTION: RecName: Full=DNA polymerase eta; EC=2.7.7.7; AltName: Full=RAD30 homolog A; AltName: Full=Xeroderma pigmentosum variant type protein; FUNCTION: DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci. CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). COFACTOR: Divalent metal cations. Prefers magnesium, but can also use manganese. SUBUNIT: Interacts with REV1 (By similarity). Interacts with monoubiquitinated PCNA, but not unmodified PCNA. Interacts with POLI. SUBCELLULAR LOCATION: Nucleus. Note=Accumulates at replication forks after DNA damage. DOMAIN: The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. PTM: Monoubiquitinated by RCHY1/PIRH2; ubiquitination inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions. DISEASE: Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:278750]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes. SIMILARITY: Belongs to the DNA polymerase type-Y family. SIMILARITY: Contains 1 umuC domain. WEB RESOURCE: Name=Allelic variations of the XP genes; URL="http://www.xpmutations.org/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/XPVID303.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/POLH"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/polh/";
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 Q9Y253
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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.
AK023893 - Homo sapiens cDNA FLJ13831 fis, clone THYRO1000662, highly similar to DNA polymerase eta (EC 2.7.7.7). AK307660 - Homo sapiens cDNA, FLJ97608. AK294430 - Homo sapiens cDNA FLJ52108 complete cds, highly similar to DNA polymerase eta (EC 2.7.7.7). AK316151 - Homo sapiens cDNA, FLJ79050 complete cds, highly similar to DNA polymerase eta (EC 2.7.7.7). AB024313 - Homo sapiens XPV mRNA for DNA polymerase eta, complete cds. AF158185 - Homo sapiens xeroderma pigmentosum variant RAD30 (RAD30) mRNA, complete cds. BC015742 - Homo sapiens polymerase (DNA directed), eta, mRNA (cDNA clone MGC:23030 IMAGE:4872554), complete cds. JD464647 - Sequence 445671 from Patent EP1572962. JD041196 - Sequence 22220 from Patent EP1572962. CU677415 - Synthetic construct Homo sapiens gateway clone IMAGE:100017645 5' read POLH mRNA. KJ901649 - Synthetic construct Homo sapiens clone ccsbBroadEn_11043 POLH gene, encodes complete protein. AK122807 - Homo sapiens cDNA FLJ16395 fis, clone TRACH2024139, highly similar to DNA polymerase eta (EC 2.7.7.7). AK025631 - Homo sapiens cDNA: FLJ21978 fis, clone HEP06046, highly similar to AF158185 Homo sapiens xeroderma pigmentosum variant RAD30 (RAD30) mRNA. AJ420484 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1855121. JD357287 - Sequence 338311 from Patent EP1572962. JD192324 - Sequence 173348 from Patent EP1572962. JD087234 - Sequence 68258 from Patent EP1572962. JD499138 - Sequence 480162 from Patent EP1572962. JD240435 - Sequence 221459 from Patent EP1572962. JD238710 - Sequence 219734 from Patent EP1572962. JD114088 - Sequence 95112 from Patent EP1572962. JD445734 - Sequence 426758 from Patent EP1572962. JD504536 - Sequence 485560 from Patent EP1572962. JD212740 - Sequence 193764 from Patent EP1572962. JD198131 - Sequence 179155 from Patent EP1572962. JD413435 - Sequence 394459 from Patent EP1572962. JD413436 - Sequence 394460 from Patent EP1572962. JD247003 - Sequence 228027 from Patent EP1572962. JD247004 - Sequence 228028 from Patent EP1572962. JD561353 - Sequence 542377 from Patent EP1572962. JD179710 - Sequence 160734 from Patent EP1572962. JD127892 - Sequence 108916 from Patent EP1572962. JD303084 - Sequence 284108 from Patent EP1572962. JD136707 - Sequence 117731 from Patent EP1572962. JD315282 - Sequence 296306 from Patent EP1572962. JD166285 - Sequence 147309 from Patent EP1572962. JD284446 - Sequence 265470 from Patent EP1572962. JD503754 - Sequence 484778 from Patent EP1572962. JD307317 - Sequence 288341 from Patent EP1572962. JD307318 - Sequence 288342 from Patent EP1572962. JD323591 - Sequence 304615 from Patent EP1572962. JD403234 - Sequence 384258 from Patent EP1572962. JD175750 - Sequence 156774 from Patent EP1572962. JD332056 - Sequence 313080 from Patent EP1572962. JD447740 - Sequence 428764 from Patent EP1572962. JD250009 - Sequence 231033 from Patent EP1572962. JD378365 - Sequence 359389 from Patent EP1572962. JD354539 - Sequence 335563 from Patent EP1572962. JD098852 - Sequence 79876 from Patent EP1572962. JD376062 - Sequence 357086 from Patent EP1572962. JD543097 - Sequence 524121 from Patent EP1572962. JD478433 - Sequence 459457 from Patent EP1572962. JD463661 - Sequence 444685 from Patent EP1572962. JD147998 - Sequence 129022 from Patent EP1572962. JD516231 - Sequence 497255 from Patent EP1572962. JD516232 - Sequence 497256 from Patent EP1572962. JD446403 - Sequence 427427 from Patent EP1572962. JD446404 - Sequence 427428 from Patent EP1572962. JD337828 - Sequence 318852 from Patent EP1572962. JD388705 - Sequence 369729 from Patent EP1572962. JD479128 - Sequence 460152 from Patent EP1572962. JD465169 - Sequence 446193 from Patent EP1572962. JD418160 - Sequence 399184 from Patent EP1572962. JD524462 - Sequence 505486 from Patent EP1572962. JD413189 - Sequence 394213 from Patent EP1572962. JD185143 - Sequence 166167 from Patent EP1572962. JD533846 - Sequence 514870 from Patent EP1572962. JD071958 - Sequence 52982 from Patent EP1572962. JD378294 - Sequence 359318 from Patent EP1572962. JD195171 - Sequence 176195 from Patent EP1572962. JD247081 - Sequence 228105 from Patent EP1572962. JD350811 - Sequence 331835 from Patent EP1572962. JD511937 - Sequence 492961 from Patent EP1572962. JD278369 - Sequence 259393 from Patent EP1572962. JD036338 - Sequence 17362 from Patent EP1572962. JD089579 - Sequence 70603 from Patent EP1572962. JD112482 - Sequence 93506 from Patent EP1572962. JD552353 - Sequence 533377 from Patent EP1572962. JD552352 - Sequence 533376 from Patent EP1572962. JD242669 - Sequence 223693 from Patent EP1572962. JD242668 - Sequence 223692 from Patent EP1572962. JD330871 - Sequence 311895 from Patent EP1572962. DQ595439 - Homo sapiens piRNA piR-61551, complete sequence.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9Y253 (Reactome details) participates in the following event(s):
R-HSA-110316 POLH binds monoUb:K164-PCNA at damaged TT-CPD-DNA template R-HSA-5655142 RCHY1 binds POLH R-HSA-5654989 SPRTN:VCP-mediated release of POLH from monoUb:K164-PCNA R-HSA-110317 Insertion of correct bases opposite the lesion by POLH R-HSA-110319 Elongation by POLH R-HSA-5654986 SPRTN binds monoUb:K164-PCNA associated with POLH R-HSA-5655170 RCHY1 monoubiquitinates POLH R-HSA-5653770 USP10 deubiquitinates monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-5654985 SPRTN recruits VCP to monoUb:K164-PCNA associated with POLH R-HSA-5653756 TRIM25 binds monoUb:164-PCNA R-HSA-5653766 USP10 binds monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-5653754 UBE2L6:TRIM25 ISGylates monoUb:K164-PCNA R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-110320 Translesion Synthesis by POLH R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-73893 DNA Damage Bypass R-HSA-73894 DNA Repair R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693538 Homology Directed Repair R-HSA-5693532 DNA Double-Strand Break Repair
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
