POLH_HUMAN
ID POLH_HUMAN Reviewed; 713 AA.
AC Q9Y253; Q7L8E3; Q96BC4; Q9BX13;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=DNA polymerase eta;
DE EC=2.7.7.7 {ECO:0000269|PubMed:27284197};
DE AltName: Full=RAD30 homolog A;
DE AltName: Full=Xeroderma pigmentosum variant type protein;
GN Name=POLH; Synonyms=RAD30, RAD30A, XPV;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 132-163;
RP 395-404; 429-450 AND 495-511, FUNCTION, INVOLVEMENT IN XPV, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Cervix carcinoma;
RX PubMed=10385124; DOI=10.1038/21447;
RA Masutani C., Kusumoto R., Yamada A., Dohmae N., Yokoi M., Yuasa M.,
RA Araki M., Iwai S., Takio K., Hanaoka F.;
RT "The XPV (Xeroderma pigmentosum variant) gene encodes human DNA polymerase
RT eta.";
RL Nature 399:700-704(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT XPV LEU-75 DEL.
RX PubMed=10398605; DOI=10.1126/science.285.5425.263;
RA Johnson R.E., Kondratick C.M., Prakash S., Prakash L.;
RT "hRAD30 mutations in the variant form of xeroderma pigmentosum.";
RL Science 285:263-265(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN XPV.
RX PubMed=11032022; DOI=10.1038/sj.onc.1203842;
RA Yuasa M., Masutani C., Eki T., Hanaoka F.;
RT "Genomic structure, chromosomal localization and identification of
RT mutations in the xeroderma pigmentosum variant (XPV) gene.";
RL Oncogene 19:4721-4728(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-209; TRP-334; MET-478;
RP PRO-584; VAL-595 AND LEU-647.
RG NIEHS SNPs program;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF SER-62 AND ALA-68.
RX PubMed=11743006; DOI=10.1093/emboj/20.24.7303;
RA Glick E., Vigna K.L., Loeb L.A.;
RT "Mutations in human DNA polymerase eta motif II alter bypass of DNA
RT lesions.";
RL EMBO J. 20:7303-7312(2001).
RN [8]
RP FUNCTION.
RX PubMed=11376341; DOI=10.1038/88740;
RA Zeng X., Winter D.B., Kasmer C., Kraemer K.H., Lehmann A.R., Gearhart P.J.;
RT "DNA polymerase eta is an A-T mutator in somatic hypermutation of
RT immunoglobulin variable genes.";
RL Nat. Immunol. 2:537-541(2001).
RN [9]
RP FUNCTION, INTERACTION WITH POLI, AND SUBCELLULAR LOCATION.
RX PubMed=12606586; DOI=10.1093/emboj/cdf618;
RA Kannouche P.L., Fernandez de Henestrosa A.R., Coull B., Vidal A.E.,
RA Gray C., Zicha D., Woodgate R., Lehmann A.R.;
RT "Localization of DNA polymerases eta and iota to the replication machinery
RT is tightly co-ordinated in human cells.";
RL EMBO J. 22:1223-1233(2003).
RN [10]
RP FUNCTION, AND SCHIFF BASE FORMATION.
RX PubMed=14630940; DOI=10.1101/gad.1146103;
RA Haracska L., Prakash L., Prakash S.;
RT "A mechanism for the exclusion of low-fidelity human Y-family DNA
RT polymerases from base excision repair.";
RL Genes Dev. 17:2777-2785(2003).
RN [11]
RP MUTAGENESIS OF TYR-52.
RX PubMed=12644469; DOI=10.1074/jbc.m300686200;
RA Glick E., Chau J.S., Vigna K.L., McCulloch S.D., Adman E.T., Kunkel T.A.,
RA Loeb L.A.;
RT "Amino acid substitutions at conserved tyrosine 52 alter fidelity and
RT bypass efficiency of human DNA polymerase eta.";
RL J. Biol. Chem. 278:19341-19346(2003).
RN [12]
RP FUNCTION.
RX PubMed=14734526; DOI=10.1084/jem.20031831;
RA Faili A., Aoufouchi S., Weller S., Vuillier F., Stary A., Sarasin A.,
RA Reynaud C.-A., Weill J.-C.;
RT "DNA polymerase eta is involved in hypermutation occurring during
RT immunoglobulin class switch recombination.";
RL J. Exp. Med. 199:265-270(2004).
RN [13]
RP INTERACTION WITH MONOUBIQUITINATED PCNA, MOTIF, AND MUTAGENESIS OF
RP 324-ASN--PRO-326 AND 705-GLU--HIS-713.
RX PubMed=15149598; DOI=10.1016/s1097-2765(04)00259-x;
RA Kannouche P.L., Wing J., Lehmann A.R.;
RT "Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a
RT possible mechanism for the polymerase switch in response to DNA damage.";
RL Mol. Cell 14:491-500(2004).
RN [14]
RP FUNCTION, INTERACTION WITH UBIQUITIN, SUBCELLULAR LOCATION, UBIQUITINATION,
RP MOTIF, AND MUTAGENESIS OF CYS-638; ASP-652 AND 705-GLU--HIS-713.
RX PubMed=16357261; DOI=10.1126/science.1120615;
RA Bienko M., Green C.M., Crosetto N., Rudolf F., Zapart G., Coull B.,
RA Kannouche P., Wider G., Peter M., Lehmann A.R., Hofmann K., Dikic I.;
RT "Ubiquitin-binding domains in Y-family polymerases regulate translesion
RT synthesis.";
RL Science 310:1821-1824(2005).
RN [15]
RP INTERACTION WITH POLDIP2.
RX PubMed=20554254; DOI=10.1016/j.dnarep.2010.04.010;
RA Tissier A., Janel-Bintz R., Coulon S., Klaile E., Kannouche P., Fuchs R.P.,
RA Cordonnier A.M.;
RT "Crosstalk between replicative and translesional DNA polymerases: PDIP38
RT interacts directly with Poleta.";
RL DNA Repair 9:922-928(2010).
RN [16]
RP UBIQUITINATION AT LYS-682; LYS-686; LYS-694 AND LYS-709.
RX PubMed=20159558; DOI=10.1016/j.molcel.2009.12.039;
RA Bienko M., Green C.M., Sabbioneda S., Crosetto N., Matic I., Hibbert R.G.,
RA Begovic T., Niimi A., Mann M., Lehmann A.R., Dikic I.;
RT "Regulation of translesion synthesis DNA polymerase eta by
RT monoubiquitination.";
RL Mol. Cell 37:396-407(2010).
RN [17]
RP UBIQUITINATION BY RCHY1/PIRH2.
RX PubMed=21791603; DOI=10.1128/mcb.05808-11;
RA Jung Y.S., Hakem A., Hakem R., Chen X.;
RT "Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress
RT translesion DNA synthesis.";
RL Mol. Cell. Biol. 31:3997-4006(2011).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=22801543; DOI=10.4161/cc.21280;
RA Chea J., Zhang S., Zhao H., Zhang Z., Lee E.Y., Darzynkiewicz Z., Lee M.Y.;
RT "Spatiotemporal recruitment of human DNA polymerase delta to sites of UV
RT damage.";
RL Cell Cycle 11:2885-2895(2012).
RN [19]
RP FUNCTION, INTERACTION WITH TRAIP, SUBCELLULAR LOCATION, AND UBIQUITINATION
RP BY TRAIP.
RX PubMed=24553286; DOI=10.1242/dev.101196;
RA Wallace H.A., Merkle J.A., Yu M.C., Berg T.G., Lee E., Bosco G., Lee L.A.;
RT "TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase
RT eta.";
RL Development 141:1332-1341(2014).
RN [20]
RP INTERACTION WITH PALB2 AND BRCA2.
RX PubMed=24485656; DOI=10.1016/j.celrep.2014.01.009;
RA Buisson R., Niraj J., Pauty J., Maity R., Zhao W., Coulombe Y., Sung P.,
RA Masson J.Y.;
RT "Breast cancer proteins PALB2 and BRCA2 stimulate polymerase eta in
RT recombination-associated DNA synthesis at blocked replication forks.";
RL Cell Rep. 6:553-564(2014).
RN [21]
RP FUNCTION.
RX PubMed=24449906; DOI=10.1073/pnas.1324001111;
RA Lee Y.S., Gregory M.T., Yang W.;
RT "Human Pol zeta purified with accessory subunits is active in translesion
RT DNA synthesis and complements Pol eta in cisplatin bypass.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2954-2959(2014).
RN [22] {ECO:0007744|PDB:3WUP}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 630-665 IN COMPLEX WITH ZINC.
RX PubMed=27062441; DOI=10.1111/febs.13734;
RA Suzuki N., Rohaim A., Kato R., Dikic I., Wakatsuki S., Kawasaki M.;
RT "A novel mode of ubiquitin recognition by the ubiquitin-binding zinc finger
RT domain of WRNIP1.";
RL FEBS J. 283:2004-2017(2016).
RN [23] {ECO:0007744|PDB:5KFA, ECO:0007744|PDB:5KFB, ECO:0007744|PDB:5KFC, ECO:0007744|PDB:5KFD, ECO:0007744|PDB:5KFE, ECO:0007744|PDB:5KFF}
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 1-432 IN COMPLEX WITH DNA;
RP NUCLEOTIDE; MAGNESIUM AND MANGANESE, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, DOMAIN, AND MUTAGENESIS OF ARG-61.
RX PubMed=27284197; DOI=10.1126/science.aad9633;
RA Gao Y., Yang W.;
RT "Capture of a third Mg is essential for catalyzing DNA synthesis.";
RL Science 352:1334-1337(2016).
RN [24]
RP VARIANTS XPV GLU-535 AND THR-589.
RX PubMed=11121129; DOI=10.1046/j.1523-1747.2000.00154.x;
RA Itoh T., Linn S., Kamide R., Tokushige H., Katori N., Hosaka Y.,
RA Yamaizumi M.;
RT "Xeroderma pigmentosum variant heterozygotes show reduced levels of
RT recovery of replicative DNA synthesis in the presence of caffeine after
RT ultraviolet irradiation.";
RL J. Invest. Dermatol. 115:981-985(2000).
RN [25]
RP VARIANTS XPV LEU-75 DEL; HIS-111 PRO-122; VAL-263 AND SER-361.
RX PubMed=11773631; DOI=10.1073/pnas.022473899;
RA Broughton B.C., Cordonnier A., Kleijer W.J., Jaspers N.G., Fawcett H.,
RA Raams A., Garritsen V.H., Stary A., Avril M.-F., Boudsocq F., Masutani C.,
RA Hanaoka F., Fuchs R.P.P., Sarasin A., Lehmann A.R.;
RT "Molecular analysis of mutations in DNA polymerase eta in xeroderma
RT pigmentosum variant patients.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:815-820(2002).
RN [26]
RP VARIANTS XPV VAL-37 DEL; PRO-93; ASP-266; ARG-295 AND ALA-692.
RX PubMed=24130121; DOI=10.1002/humu.22462;
RA Opletalova K., Bourillon A., Yang W., Pouvelle C., Armier J., Despras E.,
RA Ludovic M., Mateus C., Robert C., Kannouche P., Soufir N., Sarasin A.;
RT "Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-
RT variant patients reveals 12 new disease-causing POLH mutations.";
RL Hum. Mutat. 35:117-128(2014).
RN [27]
RP VARIANT [LARGE SCALE ANALYSIS] ASP-153.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: DNA polymerase specifically involved in the DNA repair by
CC translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006,
CC PubMed:24449906, PubMed:24553286, PubMed:16357261). Due to low
CC processivity on both damaged and normal DNA, cooperates with the
CC heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for
CC complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite
CC the lesion, the primer is further extended by the tetrameric POLZ
CC complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link,
CC inserts dCTP opposite the 3' guanine (PubMed:24449906). Particularly
CC important for the repair of UV-induced pyrimidine dimers
CC (PubMed:10385124, PubMed:11743006). Although inserts the correct base,
CC may cause base transitions and transversions depending upon the
CC context. May play a role in hypermutation at immunoglobulin genes
CC (PubMed:11376341, PubMed:14734526). Forms a Schiff base with 5'-
CC deoxyribose phosphate at abasic sites, but does not have any lyase
CC activity, preventing the release of the 5'-deoxyribose phosphate (5'-
CC dRP) residue. This covalent trapping of the enzyme by the 5'-dRP
CC residue inhibits its DNA synthetic activity during base excision
CC repair, thereby avoiding high incidence of mutagenesis
CC (PubMed:14630940). Targets POLI to replication foci (PubMed:12606586).
CC {ECO:0000269|PubMed:10385124, ECO:0000269|PubMed:11376341,
CC ECO:0000269|PubMed:11743006, ECO:0000269|PubMed:12606586,
CC ECO:0000269|PubMed:14630940, ECO:0000269|PubMed:14734526,
CC ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:24449906,
CC ECO:0000269|PubMed:24553286}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7;
CC Evidence={ECO:0000269|PubMed:27284197};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27284197};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27284197};
CC Note=Binds 2 Mg(2+) (PubMed:27284197). Prefers Mg(2+), but can also use
CC Mn(2+) (PubMed:27284197). In vitro, can also utilize other divalent
CC cations such as Ca(2+) (PubMed:27284197).
CC {ECO:0000269|PubMed:27284197};
CC -!- ACTIVITY REGULATION: The enzyme in complex with the DNA substrate binds
CC a third divalent metal cation (PubMed:27284197). The binding of this
CC third divalent cation, which is coordinated by water molecules and two
CC oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA
CC synthesis (PubMed:27284197). {ECO:0000269|PubMed:27284197}.
CC -!- SUBUNIT: Interacts with REV1 (By similarity). Interacts with
CC monoubiquitinated PCNA, but not unmodified PCNA (PubMed:15149598).
CC Interacts with POLI; this interaction targets POLI to the replication
CC machinery (PubMed:12606586). Interacts with PALB2 and BRCA2; the
CC interactions are direct and are required to sustain the recruitment of
CC POLH at blocked replication forks and to stimulate POLH-dependent DNA
CC synthesis on D loop substrates (PubMed:24485656). Interacts (via C-
CC terminus) with TRAIP (PubMed:24553286). Interacts with ubiquitin
CC (PubMed:16357261). Interacts with POLDIP2 (PubMed:20554254).
CC {ECO:0000250|UniProtKB:Q9JJN0, ECO:0000269|PubMed:12606586,
CC ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:16357261,
CC ECO:0000269|PubMed:20554254, ECO:0000269|PubMed:24485656,
CC ECO:0000269|PubMed:24553286}.
CC -!- INTERACTION:
CC Q9Y253; P51587: BRCA2; NbExp=6; IntAct=EBI-2827270, EBI-79792;
CC Q9Y253; Q86YC2: PALB2; NbExp=7; IntAct=EBI-2827270, EBI-1222653;
CC Q9Y253; Q6FI35: PCNA; NbExp=3; IntAct=EBI-2827270, EBI-8469539;
CC Q9Y253; P0CG48: UBC; NbExp=4; IntAct=EBI-2827270, EBI-3390054;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12606586,
CC ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:22801543,
CC ECO:0000269|PubMed:24553286}. Note=Binding to ubiquitinated PCNA
CC mediates colocalization to replication foci during DNA replication and
CC persists at sites of stalled replication forks following UV irradiation
CC (PubMed:12606586, PubMed:16357261, PubMed:24553286). After UV
CC irradiation, recruited to DNA damage sites within 1 hour, to a maximum
CC of about 80%; this recruitment may not be not restricted to cells
CC active in DNA replication (PubMed:22801543). Colocalizes with TRAIP to
CC nuclear foci (PubMed:24553286). {ECO:0000269|PubMed:12606586,
CC ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:22801543,
CC ECO:0000269|PubMed:24553286}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y253-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y253-2; Sequence=VSP_012799;
CC -!- DOMAIN: The catalytic core consists of fingers, palm and thumb
CC subdomains, but the fingers and thumb subdomains are much smaller than
CC in high-fidelity polymerases; residues from five sequence motifs of the
CC Y-family cluster around an active site cleft that can accommodate DNA
CC and nucleotide substrates with relaxed geometric constraints, with
CC consequently higher rates of misincorporation and low processivity.
CC {ECO:0000269|PubMed:27284197}.
CC -!- DOMAIN: The UBZ3-type zinc finger domain and the PIP-box mediate the
CC interaction with ubiquitinated PCNA and are both necessary for the
CC enzymatic activity in translesion synthesis.
CC {ECO:0000269|PubMed:15149598, ECO:0000269|PubMed:16357261}.
CC -!- PTM: Monoubiquitinated by RCHY1/PIRH2 (PubMed:20159558,
CC PubMed:21791603). Ubiquitination depends on integrity of the UBZ3-type
CC zinc finger domain and is enhanced by TRAIP (PubMed:24553286,
CC PubMed:16357261). Ubiquitination inhibits the ability of PolH to
CC interact with PCNA and to bypass UV-induced lesions (PubMed:20159558,
CC PubMed:21791603, PubMed:24553286). {ECO:0000269|PubMed:16357261,
CC ECO:0000269|PubMed:20159558, ECO:0000269|PubMed:21791603,
CC ECO:0000269|PubMed:24553286}.
CC -!- DISEASE: Xeroderma pigmentosum variant type (XPV) [MIM:278750]: An
CC autosomal recessive pigmentary skin disorder characterized by solar
CC hypersensitivity of the skin, high predisposition for developing
CC cancers on areas exposed to sunlight and, in some cases, neurological
CC abnormalities. XPV shows normal nucleotide excision repair, but an
CC exaggerated delay in recovery of replicative DNA synthesis. Most
CC patients with the variant type of xeroderma pigmentosum do not develop
CC clinical symptoms and skin neoplasias until a later age. Clinical
CC manifestations are limited to photo-induced deterioration of the skin
CC and eyes. {ECO:0000269|PubMed:10385124, ECO:0000269|PubMed:10398605,
CC ECO:0000269|PubMed:11032022, ECO:0000269|PubMed:11121129,
CC ECO:0000269|PubMed:11773631, ECO:0000269|PubMed:24130121}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-Y family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPVID303.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/polh/";
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DR EMBL; AB024313; BAA81666.1; -; mRNA.
DR EMBL; AF158185; AAD43810.1; -; mRNA.
DR EMBL; AB038008; BAB18601.1; -; Genomic_DNA.
DR EMBL; AY388614; AAQ81300.1; -; Genomic_DNA.
DR EMBL; AL353602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015742; AAH15742.1; -; mRNA.
DR CCDS; CCDS4902.1; -. [Q9Y253-1]
DR CCDS; CCDS78147.1; -. [Q9Y253-2]
DR RefSeq; NP_001278899.1; NM_001291970.1. [Q9Y253-2]
DR RefSeq; NP_006493.1; NM_006502.2. [Q9Y253-1]
DR PDB; 2I5O; NMR; -; A=628-662.
DR PDB; 2LSK; NMR; -; B=524-539.
DR PDB; 3JAA; EM; 22.00 A; A=1-432.
DR PDB; 3MR2; X-ray; 1.83 A; A=1-432.
DR PDB; 3MR3; X-ray; 1.75 A; A=1-432.
DR PDB; 3MR5; X-ray; 1.80 A; A=1-432.
DR PDB; 3MR6; X-ray; 1.90 A; A=1-432.
DR PDB; 3SI8; X-ray; 2.15 A; A=1-432.
DR PDB; 3TQ1; X-ray; 2.56 A; A=1-432.
DR PDB; 3WUP; X-ray; 1.60 A; A=630-665.
DR PDB; 4DL2; X-ray; 2.15 A; A=1-432.
DR PDB; 4DL3; X-ray; 2.10 A; A=1-432.
DR PDB; 4DL4; X-ray; 2.00 A; A=1-432.
DR PDB; 4DL5; X-ray; 2.92 A; A=1-432.
DR PDB; 4DL6; X-ray; 2.50 A; A=1-432.
DR PDB; 4DL7; X-ray; 1.97 A; A=1-432.
DR PDB; 4ECQ; X-ray; 1.50 A; A=1-432.
DR PDB; 4ECR; X-ray; 1.89 A; A=1-432.
DR PDB; 4ECS; X-ray; 1.95 A; A=1-432.
DR PDB; 4ECT; X-ray; 1.80 A; A=1-432.
DR PDB; 4ECU; X-ray; 1.95 A; A=1-432.
DR PDB; 4ECV; X-ray; 1.52 A; A=1-432.
DR PDB; 4ECW; X-ray; 1.90 A; A=1-432.
DR PDB; 4ECX; X-ray; 1.74 A; A=1-432.
DR PDB; 4ECY; X-ray; 1.94 A; A=1-432.
DR PDB; 4ECZ; X-ray; 1.83 A; A=1-432.
DR PDB; 4ED0; X-ray; 1.65 A; A=1-432.
DR PDB; 4ED1; X-ray; 1.81 A; A=1-432.
DR PDB; 4ED2; X-ray; 1.71 A; A=1-432.
DR PDB; 4ED3; X-ray; 1.79 A; A=1-432.
DR PDB; 4ED6; X-ray; 2.21 A; A=1-432.
DR PDB; 4ED7; X-ray; 1.72 A; A=1-432.
DR PDB; 4ED8; X-ray; 1.52 A; A=1-432.
DR PDB; 4EEY; X-ray; 2.32 A; A=1-432.
DR PDB; 4J9K; X-ray; 2.03 A; A=1-432.
DR PDB; 4J9L; X-ray; 1.85 A; A=1-432.
DR PDB; 4J9M; X-ray; 2.25 A; A=1-432.
DR PDB; 4J9N; X-ray; 1.96 A; A=1-432.
DR PDB; 4J9O; X-ray; 2.60 A; A=1-432.
DR PDB; 4J9P; X-ray; 2.30 A; A=1-432.
DR PDB; 4J9Q; X-ray; 1.96 A; A=1-432.
DR PDB; 4J9R; X-ray; 2.35 A; A=1-432.
DR PDB; 4J9S; X-ray; 1.95 A; A=1-432.
DR PDB; 4O3N; X-ray; 1.58 A; A=1-432.
DR PDB; 4O3O; X-ray; 1.70 A; A=1-432.
DR PDB; 4O3P; X-ray; 1.72 A; A=1-432.
DR PDB; 4O3Q; X-ray; 1.72 A; A=1-432.
DR PDB; 4O3R; X-ray; 1.62 A; A=1-432.
DR PDB; 4O3S; X-ray; 1.72 A; A=1-432.
DR PDB; 4Q8E; X-ray; 1.55 A; A=1-432.
DR PDB; 4Q8F; X-ray; 2.80 A; A=1-432.
DR PDB; 4RNM; X-ray; 2.14 A; A=1-432.
DR PDB; 4RNN; X-ray; 1.81 A; A=1-432.
DR PDB; 4RNO; X-ray; 2.82 A; A=1-432.
DR PDB; 4RU9; X-ray; 2.65 A; A=1-432.
DR PDB; 4YP3; X-ray; 1.89 A; A=1-432.
DR PDB; 4YQW; X-ray; 2.06 A; A=1-432.
DR PDB; 4YR0; X-ray; 1.78 A; A=1-432.
DR PDB; 4YR2; X-ray; 1.95 A; A=1-432.
DR PDB; 4YR3; X-ray; 2.00 A; A=1-432.
DR PDB; 5DG7; X-ray; 2.26 A; A=1-432.
DR PDB; 5DG8; X-ray; 2.12 A; A=1-432.
DR PDB; 5DG9; X-ray; 2.15 A; A=1-432.
DR PDB; 5DGA; X-ray; 2.30 A; A=1-432.
DR PDB; 5DGB; X-ray; 1.79 A; A=1-432.
DR PDB; 5DLF; X-ray; 1.97 A; A=1-432.
DR PDB; 5DLG; X-ray; 2.35 A; A=1-432.
DR PDB; 5DQG; X-ray; 2.29 A; A=1-432.
DR PDB; 5DQH; X-ray; 1.99 A; A=1-432.
DR PDB; 5DQI; X-ray; 2.30 A; A=1-432.
DR PDB; 5EWE; X-ray; 1.66 A; A=1-432.
DR PDB; 5EWF; X-ray; 1.78 A; A=1-432.
DR PDB; 5EWG; X-ray; 1.75 A; A=1-432.
DR PDB; 5F9L; X-ray; 2.59 A; A=1-432.
DR PDB; 5F9N; X-ray; 2.23 A; A=1-432.
DR PDB; 5JUM; X-ray; 2.60 A; A=1-432.
DR PDB; 5KFA; X-ray; 1.51 A; A=1-432.
DR PDB; 5KFB; X-ray; 1.55 A; A=1-432.
DR PDB; 5KFC; X-ray; 1.50 A; A=1-432.
DR PDB; 5KFD; X-ray; 1.65 A; A=1-432.
DR PDB; 5KFE; X-ray; 1.55 A; A=1-432.
DR PDB; 5KFF; X-ray; 1.70 A; A=1-432.
DR PDB; 5KFG; X-ray; 1.55 A; A=1-432.
DR PDB; 5KFH; X-ray; 1.72 A; A=1-432.
DR PDB; 5KFI; X-ray; 1.65 A; A=1-432.
DR PDB; 5KFJ; X-ray; 1.70 A; A=1-432.
DR PDB; 5KFK; X-ray; 1.70 A; A=1-432.
DR PDB; 5KFL; X-ray; 1.65 A; A=1-432.
DR PDB; 5KFM; X-ray; 1.60 A; A=1-432.
DR PDB; 5KFN; X-ray; 1.45 A; A=1-432.
DR PDB; 5KFO; X-ray; 1.52 A; A=1-432.
DR PDB; 5KFP; X-ray; 1.70 A; A=1-432.
DR PDB; 5KFQ; X-ray; 1.55 A; A=1-432.
DR PDB; 5KFR; X-ray; 1.75 A; A=1-432.
DR PDB; 5KFS; X-ray; 1.46 A; A=1-432.
DR PDB; 5KFT; X-ray; 1.52 A; A=1-432.
DR PDB; 5KFU; X-ray; 1.55 A; A=1-432.
DR PDB; 5KFV; X-ray; 1.60 A; A=1-432.
DR PDB; 5KFW; X-ray; 1.62 A; A=1-432.
DR PDB; 5KFX; X-ray; 1.52 A; A=1-432.
DR PDB; 5KFY; X-ray; 1.70 A; A=1-432.
DR PDB; 5KFZ; X-ray; 1.44 A; A=1-432.
DR PDB; 5KG0; X-ray; 1.60 A; A=1-432.
DR PDB; 5KG1; X-ray; 1.62 A; A=1-432.
DR PDB; 5KG2; X-ray; 1.60 A; A=1-432.
DR PDB; 5KG3; X-ray; 1.70 A; A=1-432.
DR PDB; 5KG4; X-ray; 1.60 A; A=1-432.
DR PDB; 5KG5; X-ray; 1.60 A; A=1-432.
DR PDB; 5KG6; X-ray; 1.55 A; A=1-432.
DR PDB; 5KG7; X-ray; 1.75 A; A=1-432.
DR PDB; 5L1I; X-ray; 2.78 A; A=1-432.
DR PDB; 5L1J; X-ray; 1.94 A; A=1-432.
DR PDB; 5L1K; X-ray; 1.82 A; A=1-432.
DR PDB; 5L1L; X-ray; 1.62 A; A=1-432.
DR PDB; 5L9X; X-ray; 1.90 A; A=1-432.
DR PDB; 6D0M; X-ray; 1.83 A; A=1-432.
DR PDB; 6D0Z; X-ray; 1.75 A; A=1-432.
DR PDB; 6M7O; X-ray; 3.00 A; A=1-432.
DR PDB; 6M7P; X-ray; 1.75 A; A=1-432.
DR PDB; 6M7T; X-ray; 2.80 A; A=1-432.
DR PDB; 6M7U; X-ray; 3.40 A; A=1-432.
DR PDB; 6M7V; X-ray; 3.06 A; A=1-432.
DR PDB; 6MP3; X-ray; 1.91 A; A=1-432.
DR PDB; 6MQ8; X-ray; 1.97 A; A=3-432.
DR PDB; 6MXO; X-ray; 2.04 A; A=3-435.
DR PDB; 6PL7; X-ray; 2.50 A; A=1-432.
DR PDB; 6PL8; X-ray; 2.17 A; A=1-432.
DR PDB; 6PLC; X-ray; 2.50 A; A=1-432.
DR PDB; 6PZ3; X-ray; 2.40 A; A=1-432.
DR PDB; 6Q02; X-ray; 2.09 A; A=1-432.
DR PDB; 6UI2; X-ray; 2.35 A; A=1-432.
DR PDB; 6UQI; X-ray; 2.50 A; A=1-432.
DR PDB; 6V5K; X-ray; 2.69 A; A=1-432.
DR PDB; 6W5X; X-ray; 2.59 A; A=1-432.
DR PDB; 6WK6; X-ray; 2.35 A; A=1-432.
DR PDB; 7L69; X-ray; 1.91 A; A=1-432.
DR PDB; 7LCD; X-ray; 1.98 A; A=1-432.
DR PDB; 7M7L; X-ray; 1.58 A; A=1-432.
DR PDB; 7M7M; X-ray; 1.46 A; A=1-432.
DR PDB; 7M7N; X-ray; 1.31 A; A=1-432.
DR PDB; 7M7O; X-ray; 1.80 A; A=1-432.
DR PDB; 7M7P; X-ray; 1.80 A; A=1-432.
DR PDB; 7M7Q; X-ray; 2.27 A; A=1-432.
DR PDB; 7M7R; X-ray; 1.81 A; A=1-432.
DR PDB; 7M7S; X-ray; 1.85 A; A=1-432.
DR PDB; 7M7T; X-ray; 1.46 A; A=1-432.
DR PDB; 7M7U; X-ray; 1.94 A; A=1-432.
DR PDB; 7M7Y; X-ray; 1.80 A; A=1-432.
DR PDB; 7M7Z; X-ray; 1.82 A; A=1-432.
DR PDB; 7M80; X-ray; 1.98 A; A=1-432.
DR PDB; 7M81; X-ray; 2.05 A; A=1-432.
DR PDB; 7M82; X-ray; 2.07 A; A=1-432.
DR PDB; 7M83; X-ray; 1.55 A; A=1-432.
DR PDB; 7M84; X-ray; 1.47 A; A=1-432.
DR PDB; 7M85; X-ray; 1.75 A; A=1-432.
DR PDB; 7M86; X-ray; 1.55 A; A=1-432.
DR PDB; 7M87; X-ray; 1.85 A; A=1-432.
DR PDB; 7M88; X-ray; 1.66 A; A=1-432.
DR PDB; 7M89; X-ray; 1.83 A; A=1-432.
DR PDB; 7M8A; X-ray; 1.91 A; A=1-432.
DR PDB; 7M8B; X-ray; 1.85 A; A=1-432.
DR PDB; 7M8C; X-ray; 1.85 A; A=1-432.
DR PDB; 7M8D; X-ray; 1.92 A; A=1-432.
DR PDBsum; 2I5O; -.
DR PDBsum; 2LSK; -.
DR PDBsum; 3JAA; -.
DR PDBsum; 3MR2; -.
DR PDBsum; 3MR3; -.
DR PDBsum; 3MR5; -.
DR PDBsum; 3MR6; -.
DR PDBsum; 3SI8; -.
DR PDBsum; 3TQ1; -.
DR PDBsum; 3WUP; -.
DR PDBsum; 4DL2; -.
DR PDBsum; 4DL3; -.
DR PDBsum; 4DL4; -.
DR PDBsum; 4DL5; -.
DR PDBsum; 4DL6; -.
DR PDBsum; 4DL7; -.
DR PDBsum; 4ECQ; -.
DR PDBsum; 4ECR; -.
DR PDBsum; 4ECS; -.
DR PDBsum; 4ECT; -.
DR PDBsum; 4ECU; -.
DR PDBsum; 4ECV; -.
DR PDBsum; 4ECW; -.
DR PDBsum; 4ECX; -.
DR PDBsum; 4ECY; -.
DR PDBsum; 4ECZ; -.
DR PDBsum; 4ED0; -.
DR PDBsum; 4ED1; -.
DR PDBsum; 4ED2; -.
DR PDBsum; 4ED3; -.
DR PDBsum; 4ED6; -.
DR PDBsum; 4ED7; -.
DR PDBsum; 4ED8; -.
DR PDBsum; 4EEY; -.
DR PDBsum; 4J9K; -.
DR PDBsum; 4J9L; -.
DR PDBsum; 4J9M; -.
DR PDBsum; 4J9N; -.
DR PDBsum; 4J9O; -.
DR PDBsum; 4J9P; -.
DR PDBsum; 4J9Q; -.
DR PDBsum; 4J9R; -.
DR PDBsum; 4J9S; -.
DR PDBsum; 4O3N; -.
DR PDBsum; 4O3O; -.
DR PDBsum; 4O3P; -.
DR PDBsum; 4O3Q; -.
DR PDBsum; 4O3R; -.
DR PDBsum; 4O3S; -.
DR PDBsum; 4Q8E; -.
DR PDBsum; 4Q8F; -.
DR PDBsum; 4RNM; -.
DR PDBsum; 4RNN; -.
DR PDBsum; 4RNO; -.
DR PDBsum; 4RU9; -.
DR PDBsum; 4YP3; -.
DR PDBsum; 4YQW; -.
DR PDBsum; 4YR0; -.
DR PDBsum; 4YR2; -.
DR PDBsum; 4YR3; -.
DR PDBsum; 5DG7; -.
DR PDBsum; 5DG8; -.
DR PDBsum; 5DG9; -.
DR PDBsum; 5DGA; -.
DR PDBsum; 5DGB; -.
DR PDBsum; 5DLF; -.
DR PDBsum; 5DLG; -.
DR PDBsum; 5DQG; -.
DR PDBsum; 5DQH; -.
DR PDBsum; 5DQI; -.
DR PDBsum; 5EWE; -.
DR PDBsum; 5EWF; -.
DR PDBsum; 5EWG; -.
DR PDBsum; 5F9L; -.
DR PDBsum; 5F9N; -.
DR PDBsum; 5JUM; -.
DR PDBsum; 5KFA; -.
DR PDBsum; 5KFB; -.
DR PDBsum; 5KFC; -.
DR PDBsum; 5KFD; -.
DR PDBsum; 5KFE; -.
DR PDBsum; 5KFF; -.
DR PDBsum; 5KFG; -.
DR PDBsum; 5KFH; -.
DR PDBsum; 5KFI; -.
DR PDBsum; 5KFJ; -.
DR PDBsum; 5KFK; -.
DR PDBsum; 5KFL; -.
DR PDBsum; 5KFM; -.
DR PDBsum; 5KFN; -.
DR PDBsum; 5KFO; -.
DR PDBsum; 5KFP; -.
DR PDBsum; 5KFQ; -.
DR PDBsum; 5KFR; -.
DR PDBsum; 5KFS; -.
DR PDBsum; 5KFT; -.
DR PDBsum; 5KFU; -.
DR PDBsum; 5KFV; -.
DR PDBsum; 5KFW; -.
DR PDBsum; 5KFX; -.
DR PDBsum; 5KFY; -.
DR PDBsum; 5KFZ; -.
DR PDBsum; 5KG0; -.
DR PDBsum; 5KG1; -.
DR PDBsum; 5KG2; -.
DR PDBsum; 5KG3; -.
DR PDBsum; 5KG4; -.
DR PDBsum; 5KG5; -.
DR PDBsum; 5KG6; -.
DR PDBsum; 5KG7; -.
DR PDBsum; 5L1I; -.
DR PDBsum; 5L1J; -.
DR PDBsum; 5L1K; -.
DR PDBsum; 5L1L; -.
DR PDBsum; 5L9X; -.
DR PDBsum; 6D0M; -.
DR PDBsum; 6D0Z; -.
DR PDBsum; 6M7O; -.
DR PDBsum; 6M7P; -.
DR PDBsum; 6M7T; -.
DR PDBsum; 6M7U; -.
DR PDBsum; 6M7V; -.
DR PDBsum; 6MP3; -.
DR PDBsum; 6MQ8; -.
DR PDBsum; 6MXO; -.
DR PDBsum; 6PL7; -.
DR PDBsum; 6PL8; -.
DR PDBsum; 6PLC; -.
DR PDBsum; 6PZ3; -.
DR PDBsum; 6Q02; -.
DR PDBsum; 6UI2; -.
DR PDBsum; 6UQI; -.
DR PDBsum; 6V5K; -.
DR PDBsum; 6W5X; -.
DR PDBsum; 6WK6; -.
DR PDBsum; 7L69; -.
DR PDBsum; 7LCD; -.
DR PDBsum; 7M7L; -.
DR PDBsum; 7M7M; -.
DR PDBsum; 7M7N; -.
DR PDBsum; 7M7O; -.
DR PDBsum; 7M7P; -.
DR PDBsum; 7M7Q; -.
DR PDBsum; 7M7R; -.
DR PDBsum; 7M7S; -.
DR PDBsum; 7M7T; -.
DR PDBsum; 7M7U; -.
DR PDBsum; 7M7Y; -.
DR PDBsum; 7M7Z; -.
DR PDBsum; 7M80; -.
DR PDBsum; 7M81; -.
DR PDBsum; 7M82; -.
DR PDBsum; 7M83; -.
DR PDBsum; 7M84; -.
DR PDBsum; 7M85; -.
DR PDBsum; 7M86; -.
DR PDBsum; 7M87; -.
DR PDBsum; 7M88; -.
DR PDBsum; 7M89; -.
DR PDBsum; 7M8A; -.
DR PDBsum; 7M8B; -.
DR PDBsum; 7M8C; -.
DR PDBsum; 7M8D; -.
DR AlphaFoldDB; Q9Y253; -.
DR BMRB; Q9Y253; -.
DR SMR; Q9Y253; -.
DR BioGRID; 111425; 55.
DR CORUM; Q9Y253; -.
DR IntAct; Q9Y253; 28.
DR MINT; Q9Y253; -.
DR STRING; 9606.ENSP00000361310; -.
DR BindingDB; Q9Y253; -.
DR ChEMBL; CHEMBL5542; -.
DR GlyGen; Q9Y253; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y253; -.
DR PhosphoSitePlus; Q9Y253; -.
DR BioMuta; POLH; -.
DR DMDM; 59798441; -.
DR EPD; Q9Y253; -.
DR jPOST; Q9Y253; -.
DR MassIVE; Q9Y253; -.
DR MaxQB; Q9Y253; -.
DR PaxDb; Q9Y253; -.
DR PeptideAtlas; Q9Y253; -.
DR PRIDE; Q9Y253; -.
DR ProteomicsDB; 85655; -. [Q9Y253-1]
DR ProteomicsDB; 85656; -. [Q9Y253-2]
DR Antibodypedia; 1879; 208 antibodies from 30 providers.
DR DNASU; 5429; -.
DR Ensembl; ENST00000372226.1; ENSP00000361300.1; ENSG00000170734.12. [Q9Y253-2]
DR Ensembl; ENST00000372236.9; ENSP00000361310.4; ENSG00000170734.12. [Q9Y253-1]
DR GeneID; 5429; -.
DR KEGG; hsa:5429; -.
DR MANE-Select; ENST00000372236.9; ENSP00000361310.4; NM_006502.3; NP_006493.1.
DR UCSC; uc003ovq.5; human. [Q9Y253-1]
DR CTD; 5429; -.
DR DisGeNET; 5429; -.
DR GeneCards; POLH; -.
DR GeneReviews; POLH; -.
DR HGNC; HGNC:9181; POLH.
DR HPA; ENSG00000170734; Low tissue specificity.
DR MalaCards; POLH; -.
DR MIM; 278750; phenotype.
DR MIM; 603968; gene.
DR neXtProt; NX_Q9Y253; -.
DR OpenTargets; ENSG00000170734; -.
DR Orphanet; 90342; Xeroderma pigmentosum variant.
DR PharmGKB; PA279; -.
DR VEuPathDB; HostDB:ENSG00000170734; -.
DR eggNOG; KOG2095; Eukaryota.
DR GeneTree; ENSGT00940000157048; -.
DR HOGENOM; CLU_012348_7_2_1; -.
DR InParanoid; Q9Y253; -.
DR OMA; CALARYE; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; Q9Y253; -.
DR TreeFam; TF103010; -.
DR BRENDA; 2.7.7.7; 2681.
DR PathwayCommons; Q9Y253; -.
DR Reactome; R-HSA-110320; Translesion Synthesis by POLH.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR SABIO-RK; Q9Y253; -.
DR SignaLink; Q9Y253; -.
DR SIGNOR; Q9Y253; -.
DR BioGRID-ORCS; 5429; 19 hits in 1081 CRISPR screens.
DR ChiTaRS; POLH; human.
DR EvolutionaryTrace; Q9Y253; -.
DR GeneWiki; DNA_polymerase_eta; -.
DR GenomeRNAi; 5429; -.
DR Pharos; Q9Y253; Tchem.
DR PRO; PR:Q9Y253; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y253; protein.
DR Bgee; ENSG00000170734; Expressed in buccal mucosa cell and 200 other tissues.
DR ExpressionAtlas; Q9Y253; baseline and differential.
DR Genevisible; Q9Y253; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005657; C:replication fork; IBA:GO_Central.
DR GO; GO:0035861; C:site of double-strand break; IBA:GO_Central.
DR GO; GO:0003684; F:damaged DNA binding; TAS:ProtInc.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071494; P:cellular response to UV-C; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IDA:UniProtKB.
DR GO; GO:0070987; P:error-free translesion synthesis; TAS:Reactome.
DR GO; GO:0042276; P:error-prone translesion synthesis; IBA:GO_Central.
DR GO; GO:0006290; P:pyrimidine dimer repair; IEA:Ensembl.
DR GO; GO:0006282; P:regulation of DNA repair; TAS:ProtInc.
DR GO; GO:0009314; P:response to radiation; IBA:GO_Central.
DR GO; GO:0010225; P:response to UV-C; IDA:UniProtKB.
DR Gene3D; 3.30.1490.100; -; 1.
DR Gene3D; 3.30.70.270; -; 2.
DR IDEAL; IID00108; -.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR036775; DNA_pol_Y-fam_lit_finger_sf.
DR InterPro; IPR017961; DNA_pol_Y-fam_little_finger.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR041298; UBZ3.
DR InterPro; IPR001126; UmuC.
DR Pfam; PF00817; IMS; 1.
DR Pfam; PF11799; IMS_C; 1.
DR Pfam; PF18439; zf_UBZ; 1.
DR SUPFAM; SSF100879; SSF100879; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50173; UMUC; 1.
DR PROSITE; PS51907; ZF_UBZ3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; DNA damage; DNA repair; DNA replication; DNA synthesis;
KW DNA-binding; DNA-directed DNA polymerase; Isopeptide bond; Magnesium;
KW Metal-binding; Mutator protein; Nucleotidyltransferase; Nucleus;
KW Reference proteome; Schiff base; Transferase; Ubl conjugation;
KW Xeroderma pigmentosum; Zinc; Zinc-finger.
FT CHAIN 1..713
FT /note="DNA polymerase eta"
FT /id="PRO_0000173986"
FT DOMAIN 9..259
FT /note="UmuC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT ZN_FING 628..662
FT /note="UBZ3-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT REGION 441..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 677..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 701..708
FT /note="PIP-box"
FT /evidence="ECO:0000269|PubMed:15149598,
FT ECO:0000269|PubMed:16357261"
FT BINDING 13
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 13
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 13
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 13
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 14
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 14
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 61
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000269|PubMed:27284197"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 115
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 115
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 116
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFN, ECO:0007744|PDB:5KFP"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27284197,
FT ECO:0007744|PDB:5KFO"
FT BINDING 635
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3WUP"
FT BINDING 638
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3WUP"
FT BINDING 650
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3WUP"
FT BINDING 654
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255,
FT ECO:0000269|PubMed:27062441, ECO:0007744|PDB:3WUP"
FT CROSSLNK 682
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20159558"
FT CROSSLNK 686
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20159558"
FT CROSSLNK 694
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20159558"
FT CROSSLNK 709
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20159558"
FT VAR_SEQ 415..713
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012799"
FT VARIANT 37
FT /note="Missing (in XPV)"
FT /evidence="ECO:0000269|PubMed:24130121"
FT /id="VAR_070835"
FT VARIANT 75
FT /note="Missing (in XPV; impairs translesion synthesis)"
FT /evidence="ECO:0000269|PubMed:10398605,
FT ECO:0000269|PubMed:11773631"
FT /id="VAR_021226"
FT VARIANT 93
FT /note="R -> P (in XPV; dbSNP:rs756931657)"
FT /evidence="ECO:0000269|PubMed:24130121"
FT /id="VAR_070836"
FT VARIANT 111
FT /note="R -> H (in XPV; dbSNP:rs758423288)"
FT /id="VAR_021227"
FT VARIANT 122
FT /note="T -> P (in XPV; dbSNP:rs1561900151)"
FT /evidence="ECO:0000269|PubMed:11773631"
FT /id="VAR_021228"
FT VARIANT 153
FT /note="G -> D (in a breast cancer sample; somatic mutation;
FT dbSNP:rs367709714)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036220"
FT VARIANT 209
FT /note="G -> V (in dbSNP:rs2307456)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021229"
FT VARIANT 263
FT /note="G -> V (in XPV; impairs translesion synthesis;
FT dbSNP:rs1413703153)"
FT /evidence="ECO:0000269|PubMed:11773631"
FT /id="VAR_021230"
FT VARIANT 266
FT /note="V -> D (in XPV)"
FT /evidence="ECO:0000269|PubMed:24130121"
FT /id="VAR_070837"
FT VARIANT 295
FT /note="G -> R (in XPV)"
FT /evidence="ECO:0000269|PubMed:24130121"
FT /id="VAR_070838"
FT VARIANT 334
FT /note="R -> W (in dbSNP:rs9333548)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021231"
FT VARIANT 361
FT /note="R -> S (in XPV)"
FT /evidence="ECO:0000269|PubMed:11773631"
FT /id="VAR_021232"
FT VARIANT 478
FT /note="T -> M (in dbSNP:rs9296419)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021233"
FT VARIANT 535
FT /note="K -> E (in XPV; dbSNP:rs56307355)"
FT /evidence="ECO:0000269|PubMed:11121129"
FT /id="VAR_021234"
FT VARIANT 584
FT /note="L -> P (in dbSNP:rs9333554)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021235"
FT VARIANT 589
FT /note="K -> T (in XPV; dbSNP:rs121908565)"
FT /evidence="ECO:0000269|PubMed:11121129"
FT /id="VAR_021236"
FT VARIANT 595
FT /note="M -> V (in dbSNP:rs9333555)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021237"
FT VARIANT 647
FT /note="M -> L (in dbSNP:rs6941583)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021238"
FT VARIANT 692
FT /note="T -> A (in XPV; dbSNP:rs199562456)"
FT /evidence="ECO:0000269|PubMed:24130121"
FT /id="VAR_070839"
FT MUTAGEN 52
FT /note="Y->A,F: Reduces DNA polymerase activity."
FT /evidence="ECO:0000269|PubMed:12644469"
FT MUTAGEN 52
FT /note="Y->E: Reduces DNA polymerase activity. Increases
FT fidelity of replication and reduces translesion bypass."
FT /evidence="ECO:0000269|PubMed:12644469"
FT MUTAGEN 61
FT /note="R->A: Reduces enzymatic activity by two-thirds."
FT /evidence="ECO:0000269|PubMed:27284197"
FT MUTAGEN 62
FT /note="S->G: Increased DNA polymerase activity and
FT translesion bypass compared to wild-type."
FT /evidence="ECO:0000269|PubMed:11743006"
FT MUTAGEN 68
FT /note="A->S,V: Severe reduction in thymine dimer
FT translesion bypass."
FT /evidence="ECO:0000269|PubMed:11743006"
FT MUTAGEN 324..326
FT /note="NFP->AAA: Reduces binding to chromatin and to
FT monoubiquitinated PCNA. Abolishes binding to
FT monoubiquitinated PCNA; when associated with 705-E--H-713
FT Del."
FT /evidence="ECO:0000269|PubMed:15149598"
FT MUTAGEN 638
FT /note="C->A: Reduces cell resistance to UV-induced DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 652
FT /note="D->A: Abolishes ubiquitin binding and localization
FT to nuclear foci after UV-induced DNA damage but does not
FT affect catalytic activity."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 705..713
FT /note="Missing: Reduces cell resistance to UV-induced DNA
FT damage. Reduces binding to chromatin and to
FT monoubiquitinated PCNA. Abolishes binding to
FT monoubiquitinated PCNA; when associated with 324-A--A-326."
FT /evidence="ECO:0000269|PubMed:15149598,
FT ECO:0000269|PubMed:16357261"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:3MR5"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:5KFS"
FT HELIX 65..71
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:7M7R"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:7M7R"
FT HELIX 90..104
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 122..132
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:7M7P"
FT HELIX 163..176
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 186..208
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:4J9O"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:6UQI"
FT HELIX 261..270
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 275..280
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 292..301
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:5DG8"
FT STRAND 319..324
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 334..359
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 360..372
FT /evidence="ECO:0007829|PDB:7M7N"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:4YQW"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 392..403
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:7M7N"
FT STRAND 414..431
FT /evidence="ECO:0007829|PDB:7M7N"
FT HELIX 532..538
FT /evidence="ECO:0007829|PDB:2LSK"
FT STRAND 632..634
FT /evidence="ECO:0007829|PDB:3WUP"
FT TURN 636..638
FT /evidence="ECO:0007829|PDB:3WUP"
FT STRAND 641..643
FT /evidence="ECO:0007829|PDB:3WUP"
FT HELIX 644..646
FT /evidence="ECO:0007829|PDB:3WUP"
FT HELIX 647..659
FT /evidence="ECO:0007829|PDB:3WUP"
SQ SEQUENCE 713 AA; 78413 MW; 6D1D35A0F56ECE89 CRC64;
MATGQDRVVA LVDMDCFFVQ VEQRQNPHLR NKPCAVVQYK SWKGGGIIAV SYEARAFGVT
RSMWADDAKK LCPDLLLAQV RESRGKANLT KYREASVEVM EIMSRFAVIE RASIDEAYVD
LTSAVQERLQ KLQGQPISAD LLPSTYIEGL PQGPTTAEET VQKEGMRKQG LFQWLDSLQI
DNLTSPDLQL TVGAVIVEEM RAAIERETGF QCSAGISHNK VLAKLACGLN KPNRQTLVSH
GSVPQLFSQM PIRKIRSLGG KLGASVIEIL GIEYMGELTQ FTESQLQSHF GEKNGSWLYA
MCRGIEHDPV KPRQLPKTIG CSKNFPGKTA LATREQVQWW LLQLAQELEE RLTKDRNDND
RVATQLVVSI RVQGDKRLSS LRRCCALTRY DAHKMSHDAF TVIKNCNTSG IQTEWSPPLT
MLFLCATKFS ASAPSSSTDI TSFLSSDPSS LPKVPVTSSE AKTQGSGPAV TATKKATTSL
ESFFQKAAER QKVKEASLSS LTAPTQAPMS NSPSKPSLPF QTSQSTGTEP FFKQKSLLLK
QKQLNNSSVS SPQQNPWSNC KALPNSLPTE YPGCVPVCEG VSKLEESSKA TPAEMDLAHN
SQSMHASSAS KSVLEVTQKA TPNPSLLAAE DQVPCEKCGS LVPVWDMPEH MDYHFALELQ
KSFLQPHSSN PQVVSAVSHQ GKRNPKSPLA CTNKRPRPEG MQTLESFFKP LTH
