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POLH |
Protein FULL name:
DNA polymerase eta [Homo sapiens].
POLH (Homo sapiens) is product of expression of POLH gene.
Human diseases related to this protein:
POLH is involved in:
BER in Homo sapiens
Keywords:
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: Binds REV1L (By similarity). Binds monoubiquitinated PCNA, but not unmodified PCNA. Binds 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.
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; [LINK]
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]
WEB RESOURCE: Name=GeneReviews; [LINK]
WEB RESOURCE: Name=NIEHS-SNPs; [LINK]
| NCBI GenPept GI number(s): |
5729982 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | Q9Y253 |
Q9Y253 |
| PFAM: | - |
Q9Y253 (Link - using uniprot id) |
| InterPro: | - |
Q9Y253 (Link - using uniprot id) |
| CATH: | None | |
| SCOP: | None | |
| PDB: | - | - |
Protein sequence:
|
MATGQDRVVALVDMDCFFVQVEQRQNPHLRNKPCAVVQYKSWKGGGIIAV SYEARAFGVTRSMWADDAKKLCPDLLLAQVRESRGKANLTKYREASVEVM EIMSRFAVIERASIDEAYVDLTSAVQERLQKLQGQPISADLLPSTYIEGL PQGPTTAEETVQKEGMRKQGLFQWLDSLQIDNLTSPDLQLTVGAVIVEEM RAAIERETGFQCSAGISHNKVLAKLACGLNKPNRQTLVSHGSVPQLFSQM PIRKIRSLGGKLGASVIEILGIEYMGELTQFTESQLQSHFGEKNGSWLYA MCRGIEHDPVKPRQLPKTIGCSKNFPGKTALATREQVQWWLLQLAQELEE RLTKDRNDNDRVATQLVVSIRVQGDKRLSSLRRCCALTRYDAHKMSHDAF TVIKNCNTSGIQTEWSPPLTMLFLCATKFSASAPSSSTDITSFLSSDPSS LPKVPVTSSEAKTQGSGPAVTATKKATTSLESFFQKAAERQKVKEASLSS LTAPTQAPMSNSPSKPSLPFQTSQSTGTEPFFKQKSLLLKQKQLNNSSVS SPQQNPWSNCKALPNSLPTEYPGCVPVCEGVSKLEESSKATPAEMDLAHN SQSMHASSASKSVLEVTQKATPNPSLLAAEDQVPCEKCGSLVPVWDMPEH MDYHFALELQKSFLQPHSSNPQVVSAVSHQGKRNPKSPLACTNKRPRPEG MQTLESFFKPLTH |
POLH (Homo sapiens) is able to recognize following damages:
POLH (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. | Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F | Nature June 17, 1999 |
| hRAD30 mutations in the variant form of xeroderma pigmentosum. | Johnson RE, Kondratick CM, Prakash S, Prakash L | Science July 9, 1999 |
| Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene. | Yuasa M, Masutani C, Eki T, Hanaoka F | Oncogene Sept. 28, 2000 |
| Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation. | Itoh T, Linn S, Kamide R, Tokushige H, Katori N, Hosaka Y, Yamaizumi M | J Invest Dermatol Dec. 1, 2000 |
| DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. | Zeng X, Winter DB, Kasmer C, Kraemer KH, Lehmann AR, Gearhart PJ | Nat Immunol June 1, 2001 |
| Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions. | Glick E, Vigna KL, Loeb LA | EMBO J Dec. 17, 2001 |
| Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients. | Broughton BC, Cordonnier A, Kleijer WJ, Jaspers NG, Fawcett H, Raams A, Garritsen VH, Stary A, Avril MF, Boudsocq F, Masutani C, Hanaoka F, Fuchs RP, Sarasin A, Lehmann AR | Proc Natl Acad Sci U S A Feb. 22, 2002 |
| Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells. | Kannouche P, Fernandez de Henestrosa AR, Coull B, Vidal AE, Gray C, Zicha D, Woodgate R, Lehmann AR | EMBO J March 3, 2003 |
| Amino acid substitutions at conserved tyrosine 52 alter fidelity and bypass efficiency of human DNA polymerase eta. | Glick E, Chau JS, Vigna KL, McCulloch SD, Adman ET, Kunkel TA, Loeb LA | J Biol Chem May 23, 2003 |
| The DNA sequence and analysis of human chromosome 6. | Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S | Nature Oct. 23, 2003 |
| A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. | Haracska L, Prakash L, Prakash S | Genes Dev Nov. 15, 2003 |
| DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination. | Faili A, Aoufouchi S, Weller S, Vuillier F, Stary A, Sarasin A, Reynaud CA, Weill JC | J Exp Med Feb. 19, 2004 |
| Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. | Kannouche PL, Wing J, Lehmann AR | Mol Cell May 21, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| The consensus coding sequences of human breast and colorectal cancers. | Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE | Science Oct. 13, 2006 |
| Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. | Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | Cell Nov. 3, 2006 |
| Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. | Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD | J Proteome Res Nov. 1, 2007 |
| A quantitative atlas of mitotic phosphorylation. | Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP | Proc Natl Acad Sci U S A Aug. 5, 2008 |
Last modification of this entry: Oct. 15, 2010.
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