POLI_HUMAN
ID POLI_HUMAN Reviewed; 740 AA.
AC Q9UNA4; Q8N590; Q9H0S1; Q9NYH6;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=DNA polymerase iota;
DE EC=2.7.7.7 {ECO:0000269|PubMed:11013228, ECO:0000269|PubMed:11387224, ECO:0000269|PubMed:27555320};
DE AltName: Full=Eta2;
DE AltName: Full=RAD30 homolog B;
GN Name=POLI; Synonyms=RAD30B;
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 [GENOMIC DNA], AND VARIANTS GLY-96; MET-261; LYS-276;
RP ARG-474; SER-532 AND ARG-560.
RG NIEHS SNPs program;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-740, VARIANT THR-731, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=10458907; DOI=10.1006/geno.1999.5906;
RA McDonald J.P., Rapic-Otrin V., Epstein J.A., Broughton B.C., Wang X.,
RA Lehmann A.R., Wolgemuth D.J., Woodgate R.;
RT "Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase
RT eta.";
RL Genomics 60:20-30(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-740, AND VARIANT SER-532.
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-740.
RC TISSUE=Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-740, AND VARIANT THR-731.
RA Poltoratsky V.P., Scharff M.D.;
RT "Human eta2 gene homologous to bacterial UmuC and Rev1 genes.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11013228; DOI=10.1093/emboj/19.19.5259;
RA Tissier A., Frank E.G., McDonald J.P., Iwai S., Hanaoka F., Woodgate R.;
RT "Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase
RT iota.";
RL EMBO J. 19:5259-5266(2000).
RN [8]
RP FUNCTION, AND SCHIFF BASE FORMATION.
RX PubMed=11251121; DOI=10.1126/science.1058386;
RA Bebenek K., Tissier A., Frank E.G., McDonald J.P., Prasad R., Wilson S.H.,
RA Woodgate R., Kunkel T.A.;
RT "5'-deoxyribose phosphate lyase activity of human DNA polymerase iota in
RT vitro.";
RL Science 291:2156-2159(2001).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11387224; DOI=10.1093/emboj/20.11.2914;
RA Frank E.G., Tissier A., McDonald J.P., Rapic-Otrin V., Zeng X.,
RA Gearhart P.J., Woodgate R.;
RT "Altered nucleotide misinsertion fidelity associated with poliota-dependent
RT replication at the end of a DNA template.";
RL EMBO J. 20:2914-2922(2001).
RN [10]
RP FUNCTION.
RX PubMed=12410315; DOI=10.1038/nature01117;
RA Faili A., Aoufouchi S., Flatter E., Gueranger Q., Reynaud C.-A.,
RA Weill J.-C.;
RT "Induction of somatic hypermutation in immunoglobulin genes is dependent on
RT DNA polymerase iota.";
RL Nature 419:944-947(2002).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH POLH.
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 [12]
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 [13]
RP FUNCTION.
RX PubMed=15199127; DOI=10.1128/mcb.24.13.5687-5693.2004;
RA Washington M.T., Minko I.G., Johnson R.E., Wolfle W.T., Harris T.M.,
RA Lloyd R.S., Prakash S., Prakash L.;
RT "Efficient and error-free replication past a minor-groove DNA adduct by the
RT sequential action of human DNA polymerases iota and kappa.";
RL Mol. Cell. Biol. 24:5687-5693(2004).
RN [14] {ECO:0007744|PDB:1T3N}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 52-439 IN COMPLEX WITH DNA;
RP NUCLEOTIDE AND MAGNESIUM, FUNCTION, AND DOMAIN.
RX PubMed=15254543; DOI=10.1038/nature02692;
RA Nair D.T., Johnson R.E., Prakash S., Prakash L., Aggarwal A.K.;
RT "Replication by human DNA polymerase-iota occurs by Hoogsteen base-
RT pairing.";
RL Nature 430:377-380(2004).
RN [15] {ECO:0007744|PDB:5KT2, ECO:0007744|PDB:5KT3, ECO:0007744|PDB:5KT4, ECO:0007744|PDB:5KT5, ECO:0007744|PDB:5KT6, ECO:0007744|PDB:5KT7}
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 26-445 IN COMPLEXES WITH DNA;
RP MAGNESIUM AND MANGANESE, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, MUTAGENESIS
RP OF 1-MET--ALA-25, AND VARIANT GLY-96.
RX PubMed=27555320; DOI=10.1074/jbc.m116.748285;
RA Choi J.Y., Patra A., Yeom M., Lee Y.S., Zhang Q., Egli M., Guengerich F.P.;
RT "Kinetic and Structural Impact of Metal Ions and Genetic Variations on
RT Human DNA Polymerase iota.";
RL J. Biol. Chem. 291:21063-21073(2016).
CC -!- FUNCTION: Error-prone DNA polymerase specifically involved in DNA
CC repair (PubMed:11013228, PubMed:11387224). Plays an important role in
CC translesion synthesis, where the normal high-fidelity DNA polymerases
CC cannot proceed and DNA synthesis stalls (PubMed:11013228,
CC PubMed:11387224, PubMed:14630940, PubMed:15199127). Favors Hoogsteen
CC base-pairing in the active site (PubMed:15254543). Inserts the correct
CC base with high-fidelity opposite an adenosine template
CC (PubMed:15254543). Exhibits low fidelity and efficiency opposite a
CC thymidine template, where it will preferentially insert guanosine
CC (PubMed:11013228). May play a role in hypermutation of immunoglobulin
CC genes (PubMed:12410315). Forms a Schiff base with 5'-deoxyribose
CC phosphate at abasic sites, but may not have lyase activity
CC (PubMed:11251121, PubMed:14630940). {ECO:0000269|PubMed:11013228,
CC ECO:0000269|PubMed:11251121, ECO:0000269|PubMed:11387224,
CC ECO:0000269|PubMed:12410315, ECO:0000269|PubMed:14630940,
CC ECO:0000269|PubMed:15199127, ECO:0000269|PubMed:15254543}.
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:11013228, ECO:0000269|PubMed:11387224,
CC ECO:0000269|PubMed:27555320};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27555320};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27555320};
CC Note=Binds nucleotide much more tightly and catalyzes nucleotide
CC insertion much more efficiently in the presence of Mg(2+) than in the
CC presence of Mn(2+). {ECO:0000269|PubMed:27555320};
CC -!- SUBUNIT: Interacts with POLH (PubMed:12606586). Interacts with REV1 (By
CC similarity). Interacts with ubiquitin (By similarity).
CC {ECO:0000250|UniProtKB:Q6R3M4, ECO:0000269|PubMed:12606586}.
CC -!- INTERACTION:
CC Q9UNA4; Q15038: DAZAP2; NbExp=3; IntAct=EBI-741774, EBI-724310;
CC Q9UNA4; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-741774, EBI-748420;
CC Q9UNA4; Q92993: KAT5; NbExp=3; IntAct=EBI-741774, EBI-399080;
CC Q9UNA4; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-741774, EBI-11742507;
CC Q9UNA4; Q15843: NEDD8; NbExp=2; IntAct=EBI-741774, EBI-716247;
CC Q9UNA4; Q6FI35: PCNA; NbExp=2; IntAct=EBI-741774, EBI-8469539;
CC Q9UNA4; P17252: PRKCA; NbExp=3; IntAct=EBI-741774, EBI-1383528;
CC Q9UNA4; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-741774, EBI-9090795;
CC Q9UNA4; Q8WW34: TMEM239; NbExp=3; IntAct=EBI-741774, EBI-9675724;
CC Q9UNA4; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-741774, EBI-359276;
CC Q9UNA4; Q9HCM9: TRIM39; NbExp=4; IntAct=EBI-741774, EBI-739510;
CC Q9UNA4; P0CG48: UBC; NbExp=4; IntAct=EBI-741774, EBI-3390054;
CC Q9UNA4; P18887: XRCC1; NbExp=2; IntAct=EBI-741774, EBI-947466;
CC Q9UNA4; P61981: YWHAG; NbExp=3; IntAct=EBI-741774, EBI-359832;
CC Q9UNA4; Q8NCP5: ZBTB44; NbExp=3; IntAct=EBI-741774, EBI-5658292;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12606586}.
CC Note=Binding to ubiquitin mediates localization to replication forks
CC after UV-induced DNA damage. {ECO:0000250|UniProtKB:Q6R3M4}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in testis.
CC {ECO:0000269|PubMed:10458907, ECO:0000269|PubMed:11387224}.
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:15254543, ECO:0000269|PubMed:27555320}.
CC -!- DOMAIN: Ubiquitin-binding motif 1 and ubiquitin-binding motif 2
CC regulate POLI protein monoubiquitination and localization to nuclear
CC foci after UV-induced DNA damage. {ECO:0000250|UniProtKB:Q6R3M4}.
CC -!- PTM: Monoubiquitinated. Protein monoubiquitination prevents POLI
CC binding to ubiquitin via the ubiquitin-binding motif 1 and ubiquitin-
CC binding motif 2. {ECO:0000250|UniProtKB:Q6R3M4}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-Y family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD50381.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF63383.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH32662.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAM11872.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB66605.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/poli/";
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DR EMBL; AY094607; AAM11872.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC093462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF140501; AAD50381.1; ALT_INIT; mRNA.
DR EMBL; AL136670; CAB66605.1; ALT_INIT; mRNA.
DR EMBL; BC032662; AAH32662.1; ALT_INIT; mRNA.
DR EMBL; AF245438; AAF63383.1; ALT_INIT; mRNA.
DR CCDS; CCDS11954.2; -.
DR RefSeq; NP_009126.2; NM_007195.2.
DR PDB; 1T3N; X-ray; 2.30 A; A/B=52-439.
DR PDB; 1ZET; X-ray; 2.30 A; A=52-439.
DR PDB; 2ALZ; X-ray; 2.50 A; A=50-439.
DR PDB; 2DPI; X-ray; 2.30 A; A=26-445.
DR PDB; 2DPJ; X-ray; 2.30 A; A=26-445.
DR PDB; 2FLL; X-ray; 2.60 A; A=26-445.
DR PDB; 2FLN; X-ray; 2.50 A; A=26-445.
DR PDB; 2FLP; X-ray; 2.40 A; A=26-445.
DR PDB; 2KHU; NMR; -; A=697-740.
DR PDB; 2KHW; NMR; -; A=697-740.
DR PDB; 2KTF; NMR; -; B=704-730.
DR PDB; 2L0F; NMR; -; B=699-740.
DR PDB; 2L0G; NMR; -; A=704-730.
DR PDB; 2MBB; NMR; -; A=516-555.
DR PDB; 3EPG; X-ray; 2.50 A; A=26-445.
DR PDB; 3EPI; X-ray; 2.90 A; A=26-445.
DR PDB; 3G6V; X-ray; 2.20 A; A=26-445.
DR PDB; 3G6X; X-ray; 2.08 A; A=26-445.
DR PDB; 3G6Y; X-ray; 2.10 A; A=26-445.
DR PDB; 3GV5; X-ray; 2.00 A; B/D=26-445.
DR PDB; 3GV7; X-ray; 2.20 A; B=26-445.
DR PDB; 3GV8; X-ray; 2.00 A; B=26-445.
DR PDB; 3H40; X-ray; 2.30 A; A=51-439.
DR PDB; 3H4B; X-ray; 2.85 A; A=50-439.
DR PDB; 3H4D; X-ray; 2.20 A; A=50-439.
DR PDB; 3NGD; X-ray; 2.80 A; A=26-445.
DR PDB; 3OSN; X-ray; 1.90 A; A=26-445.
DR PDB; 3Q8P; X-ray; 1.95 A; B=26-445.
DR PDB; 3Q8Q; X-ray; 2.03 A; B=26-445.
DR PDB; 3Q8R; X-ray; 2.45 A; B=26-445.
DR PDB; 3Q8S; X-ray; 2.09 A; B=26-445.
DR PDB; 4EBC; X-ray; 2.90 A; A=26-445.
DR PDB; 4EBD; X-ray; 2.57 A; A=26-445.
DR PDB; 4EBE; X-ray; 2.10 A; A=26-445.
DR PDB; 4EYH; X-ray; 2.90 A; B=26-445.
DR PDB; 4EYI; X-ray; 2.90 A; B=26-445.
DR PDB; 4FS1; X-ray; 2.50 A; A=26-445.
DR PDB; 4FS2; X-ray; 2.05 A; A=26-445.
DR PDB; 5KT2; X-ray; 2.49 A; A=26-445.
DR PDB; 5KT3; X-ray; 2.64 A; A=26-445.
DR PDB; 5KT4; X-ray; 2.78 A; A=1-445.
DR PDB; 5KT5; X-ray; 2.80 A; A=1-445.
DR PDB; 5KT6; X-ray; 3.54 A; A=1-445.
DR PDB; 5KT7; X-ray; 3.15 A; A=1-445.
DR PDB; 5ULW; X-ray; 2.62 A; A=26-445.
DR PDB; 5ULX; X-ray; 1.96 A; A=26-445.
DR PDBsum; 1T3N; -.
DR PDBsum; 1ZET; -.
DR PDBsum; 2ALZ; -.
DR PDBsum; 2DPI; -.
DR PDBsum; 2DPJ; -.
DR PDBsum; 2FLL; -.
DR PDBsum; 2FLN; -.
DR PDBsum; 2FLP; -.
DR PDBsum; 2KHU; -.
DR PDBsum; 2KHW; -.
DR PDBsum; 2KTF; -.
DR PDBsum; 2L0F; -.
DR PDBsum; 2L0G; -.
DR PDBsum; 2MBB; -.
DR PDBsum; 3EPG; -.
DR PDBsum; 3EPI; -.
DR PDBsum; 3G6V; -.
DR PDBsum; 3G6X; -.
DR PDBsum; 3G6Y; -.
DR PDBsum; 3GV5; -.
DR PDBsum; 3GV7; -.
DR PDBsum; 3GV8; -.
DR PDBsum; 3H40; -.
DR PDBsum; 3H4B; -.
DR PDBsum; 3H4D; -.
DR PDBsum; 3NGD; -.
DR PDBsum; 3OSN; -.
DR PDBsum; 3Q8P; -.
DR PDBsum; 3Q8Q; -.
DR PDBsum; 3Q8R; -.
DR PDBsum; 3Q8S; -.
DR PDBsum; 4EBC; -.
DR PDBsum; 4EBD; -.
DR PDBsum; 4EBE; -.
DR PDBsum; 4EYH; -.
DR PDBsum; 4EYI; -.
DR PDBsum; 4FS1; -.
DR PDBsum; 4FS2; -.
DR PDBsum; 5KT2; -.
DR PDBsum; 5KT3; -.
DR PDBsum; 5KT4; -.
DR PDBsum; 5KT5; -.
DR PDBsum; 5KT6; -.
DR PDBsum; 5KT7; -.
DR PDBsum; 5ULW; -.
DR PDBsum; 5ULX; -.
DR AlphaFoldDB; Q9UNA4; -.
DR SMR; Q9UNA4; -.
DR BioGRID; 116370; 28.
DR IntAct; Q9UNA4; 25.
DR MINT; Q9UNA4; -.
DR STRING; 9606.ENSP00000462664; -.
DR BindingDB; Q9UNA4; -.
DR ChEMBL; CHEMBL5391; -.
DR GlyGen; Q9UNA4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UNA4; -.
DR PhosphoSitePlus; Q9UNA4; -.
DR BioMuta; POLI; -.
DR DMDM; 327478565; -.
DR EPD; Q9UNA4; -.
DR jPOST; Q9UNA4; -.
DR MassIVE; Q9UNA4; -.
DR MaxQB; Q9UNA4; -.
DR PaxDb; Q9UNA4; -.
DR PeptideAtlas; Q9UNA4; -.
DR PRIDE; Q9UNA4; -.
DR ProteomicsDB; 85277; -.
DR Antibodypedia; 1864; 490 antibodies from 31 providers.
DR DNASU; 11201; -.
DR Ensembl; ENST00000579534.6; ENSP00000462664.1; ENSG00000101751.11.
DR GeneID; 11201; -.
DR KEGG; hsa:11201; -.
DR MANE-Select; ENST00000579534.6; ENSP00000462664.1; NM_007195.3; NP_009126.2.
DR UCSC; uc002lfj.5; human.
DR CTD; 11201; -.
DR DisGeNET; 11201; -.
DR GeneCards; POLI; -.
DR HGNC; HGNC:9182; POLI.
DR HPA; ENSG00000101751; Low tissue specificity.
DR MIM; 605252; gene.
DR neXtProt; NX_Q9UNA4; -.
DR OpenTargets; ENSG00000101751; -.
DR PharmGKB; PA33502; -.
DR VEuPathDB; HostDB:ENSG00000101751; -.
DR eggNOG; KOG2095; Eukaryota.
DR GeneTree; ENSGT00940000159487; -.
DR HOGENOM; CLU_012348_9_0_1; -.
DR InParanoid; Q9UNA4; -.
DR OMA; EKHYSRE; -.
DR OrthoDB; 1593931at2759; -.
DR PhylomeDB; Q9UNA4; -.
DR TreeFam; TF324222; -.
DR BRENDA; 2.7.7.7; 2681.
DR PathwayCommons; Q9UNA4; -.
DR Reactome; R-HSA-5656121; Translesion synthesis by POLI.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR SignaLink; Q9UNA4; -.
DR BioGRID-ORCS; 11201; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; POLI; human.
DR EvolutionaryTrace; Q9UNA4; -.
DR GeneWiki; POLI; -.
DR GenomeRNAi; 11201; -.
DR Pharos; Q9UNA4; Tchem.
DR PRO; PR:Q9UNA4; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9UNA4; protein.
DR Bgee; ENSG00000101751; Expressed in calcaneal tendon and 189 other tissues.
DR ExpressionAtlas; Q9UNA4; baseline and differential.
DR Genevisible; Q9UNA4; HS.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
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:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0042276; P:error-prone translesion synthesis; TAS:Reactome.
DR GO; GO:0019985; P:translesion synthesis; IBA:GO_Central.
DR Gene3D; 3.30.1490.100; -; 1.
DR Gene3D; 3.30.70.270; -; 1.
DR IDEAL; IID00106; -.
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; IPR001126; UmuC.
DR Pfam; PF00817; IMS; 1.
DR Pfam; PF11799; IMS_C; 1.
DR SUPFAM; SSF100879; SSF100879; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50173; UMUC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; DNA replication; DNA synthesis;
KW DNA-binding; DNA-directed DNA polymerase; Magnesium; Manganese;
KW Metal-binding; Mutator protein; Nucleotidyltransferase; Nucleus;
KW Reference proteome; Schiff base; Transferase; Ubl conjugation.
FT CHAIN 1..740
FT /note="DNA polymerase iota"
FT /id="PRO_0000173988"
FT DOMAIN 55..268
FT /note="UmuC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..314
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0000269|PubMed:27555320, ECO:0007744|PDB:1T3N,
FT ECO:0007744|PDB:5KT2, ECO:0007744|PDB:5KT4,
FT ECO:0007744|PDB:5KT6"
FT REGION 325..439
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0000269|PubMed:27555320, ECO:0007744|PDB:1T3N,
FT ECO:0007744|PDB:5KT2, ECO:0007744|PDB:5KT4,
FT ECO:0007744|PDB:5KT6"
FT REGION 581..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 527..544
FT /note="Ubiquitin-binding 1 (UBM1)"
FT /evidence="ECO:0000250|UniProtKB:Q6R3M4"
FT MOTIF 708..725
FT /note="Ubiquitin-binding 2 (UBM2)"
FT /evidence="ECO:0000250|UniProtKB:Q6R3M4"
FT COMPBIAS 583..615
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 677..703
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 152
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT BINDING 59
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0000269|PubMed:27555320, ECO:0007744|PDB:1T3N,
FT ECO:0007744|PDB:5KT4"
FT BINDING 59
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:27555320,
FT ECO:0007744|PDB:5KT5"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0000269|PubMed:27555320, ECO:0007744|PDB:1T3N,
FT ECO:0007744|PDB:5KT4"
FT BINDING 60
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:27555320,
FT ECO:0007744|PDB:5KT5"
FT BINDING 64
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0007744|PDB:1T3N"
FT BINDING 96
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0007744|PDB:1T3N"
FT BINDING 151
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15254543,
FT ECO:0000269|PubMed:27555320, ECO:0007744|PDB:1T3N,
FT ECO:0007744|PDB:5KT4"
FT BINDING 151
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:27555320,
FT ECO:0007744|PDB:5KT5"
FT VARIANT 96
FT /note="R -> G (large decrease in catalytic activity
FT efficiency which is partially rescued by the presence of
FT Mn(2+) instead Mg(2+); dbSNP:rs3218778)"
FT /evidence="ECO:0000269|PubMed:27555320, ECO:0000269|Ref.1"
FT /id="VAR_021239"
FT VARIANT 261
FT /note="I -> M (in dbSNP:rs3218784)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_021240"
FT VARIANT 276
FT /note="E -> K (in dbSNP:rs3218783)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_021241"
FT VARIANT 474
FT /note="H -> R (in dbSNP:rs3730823)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_021242"
FT VARIANT 532
FT /note="F -> S (in dbSNP:rs3218786)"
FT /evidence="ECO:0000269|PubMed:11230166, ECO:0000269|Ref.1"
FT /id="VAR_021243"
FT VARIANT 560
FT /note="C -> R (in dbSNP:rs3218787)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_021244"
FT VARIANT 731
FT /note="A -> T (in dbSNP:rs8305)"
FT /evidence="ECO:0000269|PubMed:10458907, ECO:0000269|Ref.6"
FT /id="VAR_021245"
FT MUTAGEN 1..25
FT /note="Missing: Small decrease in catalytic activity
FT efficiency which is partially rescued by the presence of
FT Mn(2+) instead Mg(2+)."
FT /evidence="ECO:0000269|PubMed:27555320"
FT CONFLICT 15
FT /note="Missing (in Ref. 3; AAD50381, 4; CAB66605 and 6;
FT AAF63383)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="S -> T (in Ref. 4; CAB66605)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="V -> A (in Ref. 6; AAF63383)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="D -> G (in Ref. 6; AAF63383)"
FT /evidence="ECO:0000305"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 63..71
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:3H40"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:3OSN"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:3H4D"
FT HELIX 106..112
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2FLN"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 125..141
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:3OSN"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 158..167
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 193..216
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 220..227
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:3EPG"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:3EPG"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 251..257
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 269..277
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 283..288
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 291..310
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 325..332
FT /evidence="ECO:0007829|PDB:3OSN"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:2ALZ"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 342..360
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 362..374
FT /evidence="ECO:0007829|PDB:3OSN"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:1ZET"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:3OSN"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:1ZET"
FT HELIX 401..404
FT /evidence="ECO:0007829|PDB:1T3N"
FT HELIX 405..419
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:3OSN"
FT STRAND 427..439
FT /evidence="ECO:0007829|PDB:3OSN"
FT HELIX 529..534
FT /evidence="ECO:0007829|PDB:2MBB"
FT HELIX 537..544
FT /evidence="ECO:0007829|PDB:2MBB"
FT STRAND 704..707
FT /evidence="ECO:0007829|PDB:2L0G"
FT HELIX 710..713
FT /evidence="ECO:0007829|PDB:2KHU"
FT HELIX 718..731
FT /evidence="ECO:0007829|PDB:2KHU"
SQ SEQUENCE 740 AA; 83006 MW; C1A5BF0894E91FDF CRC64;
MEKLGVEPEE EGGGDDDEED AEAWAMELAD VGAAASSQGV HDQVLPTPNA SSRVIVHVDL
DCFYAQVEMI SNPELKDKPL GVQQKYLVVT CNYEARKLGV KKLMNVRDAK EKCPQLVLVN
GEDLTRYREM SYKVTELLEE FSPVVERLGF DENFVDLTEM VEKRLQQLQS DELSAVTVSG
HVYNNQSINL LDVLHIRLLV GSQIAAEMRE AMYNQLGLTG CAGVASNKLL AKLVSGVFKP
NQQTVLLPES CQHLIHSLNH IKEIPGIGYK TAKCLEALGI NSVRDLQTFS PKILEKELGI
SVAQRIQKLS FGEDNSPVIL SGPPQSFSEE DSFKKCSSEV EAKNKIEELL ASLLNRVCQD
GRKPHTVRLI IRRYSSEKHY GRESRQCPIP SHVIQKLGTG NYDVMTPMVD ILMKLFRNMV
NVKMPFHLTL LSVCFCNLKA LNTAKKGLID YYLMPSLSTT SRSGKHSFKM KDTHMEDFPK
DKETNRDFLP SGRIESTRTR ESPLDTTNFS KEKDINEFPL CSLPEGVDQE VFKQLPVDIQ
EEILSGKSRE KFQGKGSVSC PLHASRGVLS FFSKKQMQDI PINPRDHLSS SKQVSSVSPC
EPGTSGFNSS SSSYMSSQKD YSYYLDNRLK DERISQGPKE PQGFHFTNSN PAVSAFHSFP
NLQSEQLFSR NHTTDSHKQT VATDSHEGLT ENREPDSVDE KITFPSDIDP QVFYELPEAV
QKELLAEWKR AGSDFHIGHK
