POLH_MOUSE
ID POLH_MOUSE Reviewed; 694 AA.
AC Q9JJN0; Q9JJJ2;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=DNA polymerase eta;
DE EC=2.7.7.7 {ECO:0000250|UniProtKB:Q9Y253};
DE AltName: Full=RAD30 homolog A;
DE AltName: Full=Xeroderma pigmentosum variant type protein homolog;
GN Name=Polh; Synonyms=Rad30a, Xpv;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv; TISSUE=Embryo;
RX PubMed=10871396; DOI=10.1093/nar/28.13.2473;
RA Yamada A., Masutani C., Iwai S., Hanaoka F.;
RT "Complementation of defective translesion synthesis and UV light-
RT sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA
RT polymerase eta.";
RL Nucleic Acids Res. 28:2473-2480(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP INTERACTION WITH REV1.
RX PubMed=14657033; DOI=10.1093/emboj/cdg626;
RA Guo C., Fischhaber P.L., Luk-Paszyc M.J., Masuda Y., Zhou J., Kamiya K.,
RA Kisker C., Friedberg E.C.;
RT "Mouse Rev1 protein interacts with multiple DNA polymerases involved in
RT translesion DNA synthesis.";
RL EMBO J. 22:6621-6630(2003).
CC -!- FUNCTION: DNA polymerase specifically involved in the DNA repair by
CC translesion synthesis (TLS) (PubMed:10871396). Due to low processivity
CC on both damaged and normal DNA, cooperates with the heterotetrameric
CC (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA
CC lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer
CC is further extended by the tetrameric POLZ complex. In the case of 1,2-
CC intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3'
CC guanine (By similarity). Particularly important for the repair of UV-
CC induced pyrimidine dimers (PubMed:10871396). Although inserts the
CC correct base, may cause base transitions and transversions depending
CC upon the context. May play a role in hypermutation at immunoglobulin
CC genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic
CC sites, but does not have any lyase activity, preventing the release of
CC the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping
CC of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity
CC during base excision repair, thereby avoiding high incidence of
CC mutagenesis. Targets POLI to replication foci (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y253, ECO:0000269|PubMed:10871396}.
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:0000250|UniProtKB:Q9Y253};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9Y253};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9Y253};
CC Note=Binds 2 Mg(2+). Prefers Mg(2+), but can also use Mn(2+). In vitro,
CC can also utilize other divalent cations such as Ca(2+).
CC {ECO:0000250|UniProtKB:Q9Y253};
CC -!- ACTIVITY REGULATION: The enzyme in complex with the DNA substrate binds
CC a third divalent metal cation. The binding of this third divalent
CC cation, which is coordinated by water molecules and two oxygen atoms
CC from DNA and dNTP, is essential for catalyzing the DNA synthesis.
CC {ECO:0000250|UniProtKB:Q9Y253}.
CC -!- SUBUNIT: Interacts with REV1 (PubMed:14657033). Interacts with
CC monoubiquitinated PCNA, but not unmodified PCNA (By similarity).
CC Interacts with POLI; this interaction targets POLI to the replication
CC machinery (By similarity). 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 (By similarity). Interacts (via C-
CC terminus) with TRAIP. Interacts with ubiquitin (By similarity).
CC Interacts with POLDIP2. {ECO:0000250|UniProtKB:Q9Y253,
CC ECO:0000269|PubMed:14657033}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y253}.
CC Note=Binding to ubiquitinated PCNA mediates colocalization to
CC replication foci during DNA replication and persists at sites of
CC stalled replication forks following UV irradiation. 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. Colocalizes with TRAIP to nuclear foci.
CC {ECO:0000250|UniProtKB:Q9Y253}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10871396}.
CC -!- INDUCTION: Up-regulated in proliferating cultured fibroblasts.
CC {ECO:0000269|PubMed:10871396}.
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:0000250|UniProtKB:Q9Y253}.
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:0000250|UniProtKB:Q9Y253}.
CC -!- PTM: Monoubiquitinated by RCHY1/PIRH2. Ubiquitination depends on
CC integrity of the UBZ3-type zinc finger domain and is enhanced by TRAIP.
CC Ubiquitination inhibits the ability of PolH to interact with PCNA and
CC to bypass UV-induced lesions. {ECO:0000250|UniProtKB:Q9Y253}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-Y family. {ECO:0000305}.
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DR EMBL; AB027128; BAA97570.1; -; mRNA.
DR EMBL; AB037184; BAA97585.1; -; mRNA.
DR EMBL; AK036296; BAC29375.1; -; mRNA.
DR CCDS; CCDS28822.1; -.
DR RefSeq; NP_109640.1; NM_030715.3.
DR AlphaFoldDB; Q9JJN0; -.
DR SMR; Q9JJN0; -.
DR BioGRID; 219842; 8.
DR IntAct; Q9JJN0; 1.
DR STRING; 10090.ENSMUSP00000024749; -.
DR iPTMnet; Q9JJN0; -.
DR PhosphoSitePlus; Q9JJN0; -.
DR EPD; Q9JJN0; -.
DR MaxQB; Q9JJN0; -.
DR PaxDb; Q9JJN0; -.
DR PRIDE; Q9JJN0; -.
DR ProteomicsDB; 289780; -.
DR Antibodypedia; 1879; 208 antibodies from 30 providers.
DR DNASU; 80905; -.
DR Ensembl; ENSMUST00000024749; ENSMUSP00000024749; ENSMUSG00000023953.
DR GeneID; 80905; -.
DR KEGG; mmu:80905; -.
DR UCSC; uc008crx.1; mouse.
DR CTD; 5429; -.
DR MGI; MGI:1891457; Polh.
DR VEuPathDB; HostDB:ENSMUSG00000023953; -.
DR eggNOG; KOG2095; Eukaryota.
DR GeneTree; ENSGT00940000157048; -.
DR HOGENOM; CLU_012348_7_2_1; -.
DR InParanoid; Q9JJN0; -.
DR OMA; CALARYE; -.
DR OrthoDB; 1593931at2759; -.
DR PhylomeDB; Q9JJN0; -.
DR TreeFam; TF103010; -.
DR Reactome; R-MMU-110320; Translesion Synthesis by POLH.
DR Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR BioGRID-ORCS; 80905; 5 hits in 107 CRISPR screens.
DR ChiTaRS; Polh; mouse.
DR PRO; PR:Q9JJN0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9JJN0; protein.
DR Bgee; ENSMUSG00000023953; Expressed in endothelial cell of lymphatic vessel and 219 other tissues.
DR ExpressionAtlas; Q9JJN0; baseline and differential.
DR Genevisible; Q9JJN0; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IEA:InterPro.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071494; P:cellular response to UV-C; IMP:MGI.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:MGI.
DR GO; GO:0042276; P:error-prone translesion synthesis; IBA:GO_Central.
DR GO; GO:0006301; P:postreplication repair; IDA:MGI.
DR GO; GO:0006290; P:pyrimidine dimer repair; IDA:MGI.
DR GO; GO:0009314; P:response to radiation; IBA:GO_Central.
DR GO; GO:0010225; P:response to UV-C; ISO:MGI.
DR Gene3D; 3.30.1490.100; -; 1.
DR Gene3D; 3.30.70.270; -; 2.
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 DNA damage; DNA repair; DNA replication; DNA synthesis; DNA-binding;
KW DNA-directed DNA polymerase; Isopeptide bond; Magnesium; Manganese;
KW Metal-binding; Mutator protein; Nucleotidyltransferase; Nucleus;
KW Reference proteome; Schiff base; Transferase; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..694
FT /note="DNA polymerase eta"
FT /id="PRO_0000173987"
FT DOMAIN 9..258
FT /note="UmuC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT ZN_FING 609..643
FT /note="UBZ3-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT REGION 565..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 682..689
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT COMPBIAS 579..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 663..680
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 116
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT BINDING 13
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 13
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 13
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 13
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 14
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 14
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 61
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 115
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 115
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 116
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT BINDING 616
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT BINDING 619
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT BINDING 631
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT BINDING 635
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01255"
FT CROSSLNK 663
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT CROSSLNK 667
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT CROSSLNK 675
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
FT CROSSLNK 690
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y253"
SQ SEQUENCE 694 AA; 76167 MW; 727895AB5DB84BC8 CRC64;
MAPGQNRVVA LVDMDCFFVQ VEQRQNPHLR NKPCAVVQYK SWKGGGIIAV SYEARAFGVT
RNMWADDAKK LCPDLLLAQV RESRGKANLT KYREASVEVM EIMSYFAVIE RASIDEAYID
LTSAVQERLQ KLQGQPISAD LLPSTYIEGL PRGPTVEETV QKEAIRKQGL LQWLDSLQSD
DPTSPDLRLT VGAMIVEEMR AAIESKTGFQ CSAGISHNKV LAKLACGLNK PNRQTLVSHG
SVPQLFSQMP IRKIRSLGGK LGASVIEVLG IEYMGDLTQF TESQLQSHFG EKNGSWLYAM
CRGIEHDPVK PRQLPKTIGC SKNFPGKTAL ATREQVQWWL LQLALELEER LTKDRNDNDR
VATQLVVSIR FQGDRRLSSL RRCCALPRYD AHKMSQDAFA AIRNCNTSGI QTEWSPPLTM
LFLCATKFSA AAPPACTDIT AFLSSDSSCQ PKVPIASSET RTQGSGPAVP TSKEAATSLA
SFFQKAAKKQ RMKETSFVPL NTATEKLSSK PSLVFQSSQT TGSQSFFKQK SLLLQHTQLS
NSAAPDPPQA SPAAQPSCLP AECVDSGPDD GAVKPVSSKA VSTEMNVAGD SPNVLDSPAY
NSQEVTQRAT EDQVLCEKCD SLVPVWDMPE HTDYHFALEL QKSFLQPCTS KPQAIPAVSP
QGKRNPKSPS ASSSKRLRPH GMQTLESFFK PLTH
