ID POLI_MOUSE Reviewed; 717 AA.
AC Q6R3M4; Q641P1; Q6R3M3; Q9R1A6;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 08-NOV-2023, entry version 147.
DE RecName: Full=DNA polymerase iota;
DE EC=2.7.7.7 {ECO:0000269|PubMed:15026325};
DE AltName: Full=Rad30 homolog B;
GN Name=Poli; Synonyms=Rad30b;
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] (ISOFORM 1), VARIANTS SER-4; ARG-7 AND SER-518,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP VARIANTS SER-4; ARG-7; LYS-334; ALA-378; SER-518; TYR-524; GLU-569;
RP ASP-574; ARG-606 AND ILE-643, AND ALTERNATIVE SPLICING.
RC STRAIN=A/J, and BALB/cJ;
RX PubMed=15026325; DOI=10.1158/0008-5472.can-03-3080;
RA Wang M., Devereux T.R., Vikis H.G., McCulloch S.D., Holliday W., Anna C.,
RA Wang Y., Bebenek K., Kunkel T.A., Guan K., You M.;
RT "Pol iota is a candidate for the mouse pulmonary adenoma resistance 2
RT locus, a major modifier of chemically induced lung neoplasia.";
RL Cancer Res. 64:1924-1931(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT SER-518.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [4]
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).
RN [5]
RP FUNCTION, INTERACTION WITH UBIQUITIN, SUBCELLULAR LOCATION, UBIQUITINATION,
RP MOTIF, AND MUTAGENESIS OF LEU-508; PRO-509; LEU-693; PRO-694;
RP 496-LEU--ASN-524 AND 681-PHE--GLY-709.
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).
CC -!- FUNCTION: Error-prone DNA polymerase specifically involved in DNA
CC repair (PubMed:15026325, PubMed:16357261). Plays an important role in
CC translesion synthesis, where the normal high-fidelity DNA polymerases
CC cannot proceed and DNA synthesis stalls (PubMed:15026325,
CC PubMed:16357261). Favors Hoogsteen base-pairing in the active site.
CC Inserts the correct base with high-fidelity opposite an adenosine
CC template (By similarity). Exhibits low fidelity and efficiency opposite
CC a thymidine template, where it will preferentially insert guanosine (By
CC similarity). May play a role in hypermutation of immunoglobulin genes
CC (By similarity). Forms a Schiff base with 5'-deoxyribose phosphate at
CC abasic sites, but may not have lyase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9UNA4, ECO:0000269|PubMed:15026325,
CC ECO:0000269|PubMed:16357261}.
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:15026325};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UNA4};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9UNA4};
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:0000250|UniProtKB:Q9UNA4};
CC -!- SUBUNIT: Interacts with POLH (By similarity). Interacts with REV1
CC (PubMed:14657033). Interacts with ubiquitin (PubMed:16357261).
CC {ECO:0000250|UniProtKB:Q9UNA4, ECO:0000269|PubMed:14657033,
CC ECO:0000269|PubMed:16357261}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Binding to ubiquitin
CC mediates localization to replication forks after UV-induced DNA damage.
CC {ECO:0000269|PubMed:16357261}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6R3M4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6R3M4-2; Sequence=VSP_012800;
CC -!- TISSUE SPECIFICITY: Detected in testis, and at very low levels in
CC spleen, lung and brain. Detected in round spermatids, but not in
CC prophase spermatocytes. {ECO:0000269|PubMed:10458907}.
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:Q9UNA4}.
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:0000269|PubMed:16357261}.
CC -!- PTM: Monoubiquitinated (PubMed:16357261). Protein monoubiquitination
CC prevents POLI binding to ubiquitin via the ubiquitin-binding motif 1
CC and ubiquitin-binding motif 2 (PubMed:16357261).
CC {ECO:0000269|PubMed:16357261}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-Y family. {ECO:0000305}.
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DR EMBL; AF151691; AAD50424.1; -; mRNA.
DR EMBL; AY515316; AAS75834.1; -; mRNA.
DR EMBL; AY515317; AAS75835.1; -; mRNA.
DR EMBL; BC082278; AAH82278.1; -; mRNA.
DR CCDS; CCDS50317.1; -. [Q6R3M4-2]
DR RefSeq; NP_001129562.1; NM_001136090.2.
DR RefSeq; NP_001276444.1; NM_001289515.1.
DR RefSeq; NP_001276445.1; NM_001289516.1.
DR RefSeq; XP_006526009.1; XM_006525946.3.
DR PDB; 2KWU; NMR; -; A=673-717.
DR PDB; 2KWV; NMR; -; A=487-532.
DR PDB; 3AI4; X-ray; 1.60 A; A=668-717.
DR PDBsum; 2KWU; -.
DR PDBsum; 2KWV; -.
DR PDBsum; 3AI4; -.
DR AlphaFoldDB; Q6R3M4; -.
DR BMRB; Q6R3M4; -.
DR SMR; Q6R3M4; -.
DR BioGRID; 204998; 6.
DR IntAct; Q6R3M4; 1.
DR STRING; 10090.ENSMUSP00000112563; -.
DR BindingDB; Q6R3M4; -.
DR ChEMBL; CHEMBL5159; -.
DR iPTMnet; Q6R3M4; -.
DR PhosphoSitePlus; Q6R3M4; -.
DR MaxQB; Q6R3M4; -.
DR PaxDb; 10090-ENSMUSP00000112563; -.
DR ProteomicsDB; 289945; -. [Q6R3M4-1]
DR ProteomicsDB; 289946; -. [Q6R3M4-2]
DR GeneID; 26447; -.
DR KEGG; mmu:26447; -.
DR AGR; MGI:1347081; -.
DR CTD; 11201; -.
DR MGI; MGI:1347081; Poli.
DR eggNOG; KOG2095; Eukaryota.
DR InParanoid; Q6R3M4; -.
DR OrthoDB; 2918002at2759; -.
DR PhylomeDB; Q6R3M4; -.
DR Reactome; R-MMU-5656121; Translesion synthesis by POLI.
DR Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR BioGRID-ORCS; 26447; 1 hit in 113 CRISPR screens.
DR PRO; PR:Q6R3M4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q6R3M4; Protein.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
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:0019985; P:translesion synthesis; IMP:MGI.
DR CDD; cd01703; PolY_Pol_iota; 1.
DR Gene3D; 3.30.70.270; -; 1.
DR Gene3D; 3.40.1170.60; -; 1.
DR Gene3D; 6.10.250.1630; -; 2.
DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR Gene3D; 3.30.1490.100; DNA polymerase, Y-family, little finger domain; 1.
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; IPR024728; PolY_HhH_motif.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR001126; UmuC.
DR PANTHER; PTHR46404; DNA POLYMERASE IOTA; 1.
DR PANTHER; PTHR46404:SF1; DNA POLYMERASE IOTA; 1.
DR Pfam; PF00817; IMS; 1.
DR Pfam; PF11799; IMS_C; 1.
DR Pfam; PF11798; IMS_HHH; 1.
DR PIRSF; PIRSF036603; DPol_eta; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF100879; Lesion bypass DNA polymerase (Y-family), little finger domain; 1.
DR PROSITE; PS50173; UMUC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; DNA damage; DNA repair;
KW DNA replication; DNA synthesis; DNA-binding; DNA-directed DNA polymerase;
KW Magnesium; Manganese; Metal-binding; Mutator protein;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Schiff base;
KW Transferase; Ubl conjugation.
FT CHAIN 1..717
FT /note="DNA polymerase iota"
FT /id="PRO_0000173989"
FT DOMAIN 30..243
FT /note="UmuC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..307
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT REGION 343..360
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT REGION 549..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 603..622
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 500..517
FT /note="Ubiquitin-binding 1 (UBM1)"
FT /evidence="ECO:0000269|PubMed:16357261"
FT MOTIF 685..702
FT /note="Ubiquitin-binding 2 (UBM2)"
FT /evidence="ECO:0000269|PubMed:16357261"
FT COMPBIAS 574..589
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 644..663
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..680
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 127
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00216"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT BINDING 35
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT BINDING 39
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT BINDING 71
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT BINDING 126
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9UNA4"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012800"
FT VARIANT 4
FT /note="L -> S (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:10458907,
FT ECO:0000269|PubMed:15026325"
FT VARIANT 7
FT /note="G -> R (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:10458907,
FT ECO:0000269|PubMed:15026325"
FT VARIANT 334
FT /note="Q -> K (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 378
FT /note="S -> A (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 518
FT /note="Y -> S (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:10458907,
FT ECO:0000269|PubMed:15026325, ECO:0000269|PubMed:15489334"
FT VARIANT 524
FT /note="N -> Y (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 569
FT /note="A -> E (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 574
FT /note="E -> D (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 606
FT /note="Q -> R (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT VARIANT 643
FT /note="T -> I (in strain: BALB/c)"
FT /evidence="ECO:0000269|PubMed:15026325"
FT MUTAGEN 496..524
FT /note="Missing: Abolishes ubiquitin binding and
FT localization to nuclear foci after UV-induced DNA damage."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 508
FT /note="L->A: Impairs ubiquitin binding and post-translation
FT modification via ubiquitination; when associated with A-
FT 509. Abolishes ubiquitin binding and localization to
FT nuclear foci after UV-induced DNA damage but does not
FT affect catalytic activity; when associated with A-508, A-
FT 693 and A-694."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 509
FT /note="P->A: Impairs ubiquitin binding and post-translation
FT modification via ubiquitination; when associated with A-
FT 508. Abolishes ubiquitin binding and localization to
FT nuclear foci after UV-induced DNA damage but does not
FT affect catalytic activity; when associated with A-509, A-
FT 693 and A-694."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 681..709
FT /note="Missing: Abolishes ubiquitin binding and
FT localization to nuclear foci after UV-induced DNA damage."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 693
FT /note="L->A: Impairs ubiquitin binding and post-translation
FT modification via ubiquitination; when associated with A-
FT 694. Abolishes ubiquitin binding and localization to
FT nuclear foci after UV-induced DNA damage but does not
FT affect catalytic activity; when associated with A-508, A-
FT 509 and A-694."
FT /evidence="ECO:0000269|PubMed:16357261"
FT MUTAGEN 694
FT /note="P->A: Impairs ubiquitin binding and post-translation
FT modification via ubiquitination; when associated with A-
FT 693. Abolishes ubiquitin binding and localization to
FT nuclear foci after UV-induced DNA damage but does not
FT affect catalytic activity; when associated with A-508, A-
FT 509 and A-693."
FT /evidence="ECO:0000269|PubMed:16357261"
FT CONFLICT 583
FT /note="G -> R (in Ref. 1; AAD50424)"
FT /evidence="ECO:0000305"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:2KWV"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:2KWV"
FT HELIX 510..516
FT /evidence="ECO:0007829|PDB:2KWV"
FT STRAND 682..684
FT /evidence="ECO:0007829|PDB:2KWU"
FT HELIX 687..690
FT /evidence="ECO:0007829|PDB:3AI4"
FT HELIX 695..700
FT /evidence="ECO:0007829|PDB:3AI4"
FT HELIX 701..705
FT /evidence="ECO:0007829|PDB:3AI4"
SQ SEQUENCE 717 AA; 79653 MW; 43E5D2D0ECB3AA85 CRC64;
MEPLHAGAAG SSRAVCSQGP PTQISSSRVI VHVDLDCFYA QVEMISNPEL KDRPLGVQQK
YLVVTCNYEA RKLGVRKLMN VRDAKEKCPQ LVLVNGEDLS RYREMSYKVT ELLEEFSPAV
ERLGFDENFV DLTEMVEKRL QQLPSEEVPS VTVFGHVYNN QSVNLHNIMH RRLVVGSQIA
AEMREAMYNQ LGLTGCAGVA PNKLLAKLVS GVFKPNQQTV LLPESCQHLI HSLNHIKEIP
GIGYKTAKRL EVLGINSVHD LQTFPIKTLE KELGIAIAQR IQQLSFGEDK SPVTPSGPPQ
SFSEEDTFKK CSSEVEAKAK IEELLSSLLT RVCQDGRKPH TVRLVIRRYS DKHCNRESRQ
CPIPSHVIQK LGTGNHDSMP PLIDILMKLF RNMVNVKMPF HLTLMSVCFC NLKALSSAKK
GPMDCYLTSL STPAYTDKRA FKVKDTHTED SHKEKEANWD CLPSRRIEST GTGESPLDAT
CFPKEKDTSD LPLQALPEGV DQEVFKQLPA DIQEEILYGK SRENLKGKGS LSCPLHASRG
VLSFFSTKQM QASRLSPRDT ALPSKRVSAA SPCEPGTSGL SPGSTSHPSC GKDCSYYIDS
QLKDEQTSQG PTESQGCQFS STNPAVSGFH SFPNLQTEQL FSTHRTVDSH KQTATASHQG
LESHQGLESR ELDSAEEKLP FPPDIDPQVF YELPEEVQKE LMAEWERAGA ARPSAHR
//
