DPOD1_DROME
ID DPOD1_DROME Reviewed; 1092 AA.
AC P54358; Q9VUW8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=DNA polymerase delta catalytic subunit {ECO:0000305};
DE EC=2.7.7.7 {ECO:0000269|PubMed:1360647, ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662};
DE AltName: Full=3'-5' exodeoxyribonuclease {ECO:0000305};
DE EC=3.1.11.- {ECO:0000269|PubMed:1360647, ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662};
GN Name=PolD1 {ECO:0000312|FlyBase:FBgn0263600};
GN Synonyms=DNApol-delta {ECO:0000303|PubMed:8543168}, DNApolD1 {ECO:0000305},
GN PolD {ECO:0000303|PubMed:31100062};
GN ORFNames=CG5949 {ECO:0000312|FlyBase:FBgn0263600};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8543168; DOI=10.1016/0378-1119(95)00567-6;
RA Chiang C.S., Lehman I.R.;
RT "Isolation and sequence determination of the cDNA encoding DNA polymerase
RT delta from Drosophila melanogaster.";
RL Gene 166:237-242(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=1360647; DOI=10.1093/nar/20.21.5779;
RA Peck V.M., Gerner E.W., Cress A.E.;
RT "Delta-type DNA polymerase characterized from Drosophila melanogaster
RT embryos.";
RL Nucleic Acids Res. 20:5779-5784(1992).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8415662; DOI=10.1073/pnas.90.19.9105;
RA Chiang C.S., Mitsis P.G., Lehman I.R.;
RT "DNA polymerase delta from embryos of Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9105-9109(1993).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=7907087; DOI=10.1016/s0021-9258(17)37567-1;
RA Aoyagi N., Matsuoka S., Furunobu A., Matsukage A., Sakaguchi K.;
RT "Drosophila DNA polymerase delta. Purification and characterization.";
RL J. Biol. Chem. 269:6045-6050(1994).
RN [8]
RP INTERACTION WITH PCNA AND PCNA2.
RX PubMed=17087725; DOI=10.1111/j.1742-4658.2006.05504.x;
RA Ruike T., Takeuchi R., Takata K., Oshige M., Kasai N., Shimanouchi K.,
RA Kanai Y., Nakamura R., Sugawara F., Sakaguchi K.;
RT "Characterization of a second proliferating cell nuclear antigen (PCNA2)
RT from Drosophila melanogaster.";
RL FEBS J. 273:5062-5073(2006).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE DNA POLYMERASE DELTA COMPLEX, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=31100062; DOI=10.1371/journal.pgen.1008169;
RA Ji J., Tang X., Hu W., Maggert K.A., Rong Y.S.;
RT "The processivity factor Pol32 mediates nuclear localization of DNA
RT polymerase delta and prevents chromosomal fragile site formation in
RT Drosophila development.";
RL PLoS Genet. 15:E1008169-E1008169(2019).
CC -!- FUNCTION: As the catalytic component of the DNA polymerase delta
CC complex, plays a crucial role in high fidelity genome replication,
CC including lagging strand synthesis, DNA recombination and repair (By
CC similarity). Exhibits both DNA polymerase and 3'- to 5'-exonuclease
CC activities (PubMed:7907087, PubMed:8415662, PubMed:1360647). Required
CC at the nucleus of rapidly dividing embryonic cells to activate genome
CC replication during the earliest cell cycles (PubMed:31100062). Likely
CC to require the presence of accessory proteins PolD2 and PolD3 for full
CC activity (PubMed:31100062). {ECO:0000250|UniProtKB:P28340,
CC ECO:0000269|PubMed:1360647, ECO:0000269|PubMed:31100062,
CC ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662}.
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; Evidence={ECO:0000269|PubMed:1360647,
CC ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P15436};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:P15436};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662};
CC -!- ACTIVITY REGULATION: Inhibited by KCL (PubMed:7907087, PubMed:1360647).
CC Also inhibited by carbonyldiphosphonate, aphidicolin and N-
CC ethylmaleimide (NEM) (PubMed:7907087, PubMed:8415662, PubMed:1360647).
CC {ECO:0000269|PubMed:1360647, ECO:0000269|PubMed:7907087,
CC ECO:0000269|PubMed:8415662}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.2. {ECO:0000269|PubMed:7907087};
CC -!- SUBUNIT: Catalytic component of the DNA polymerase delta complex
CC consisting of three subunits: the catalytic subunit PolD1 and two
CC accessory subunits PolD2/Pol31 and PolD3/Pol32 (PubMed:31100062).
CC Within the delta complex, interacts with both PolD2 and PolD3, and is
CC able to interact with PolD2 in the absence of PolD3 (PubMed:31100062).
CC Interacts with PCNA AND PCNA2 (PubMed:17087725).
CC {ECO:0000269|PubMed:17087725, ECO:0000269|PubMed:31100062}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31100062}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:31100062}. Note=In embryos, accumulates
CC in the nucleus during interphase but disperses into the nucleoplasm at
CC the onset of mitosis. {ECO:0000269|PubMed:31100062}.
CC -!- TISSUE SPECIFICITY: Expressed in ovaries (at the protein level)
CC (PubMed:31100062). Expressed in embryos (at the protein level)
CC (PubMed:31100062, PubMed:7907087, PubMed:8415662, PubMed:1360647).
CC {ECO:0000269|PubMed:1360647, ECO:0000269|PubMed:31100062,
CC ECO:0000269|PubMed:7907087, ECO:0000269|PubMed:8415662}.
CC -!- DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the
CC formation of polymerase complexes. {ECO:0000250|UniProtKB:P15436}.
CC -!- MISCELLANEOUS: In eukaryotes there are five DNA polymerases: alpha,
CC beta, gamma, delta, and epsilon which are responsible for different
CC reactions of DNA synthesis.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-B family. {ECO:0000305}.
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DR EMBL; X88928; CAA61369.1; -; mRNA.
DR EMBL; AE014296; AAF49555.1; -; Genomic_DNA.
DR EMBL; AY113526; AAM29531.1; -; mRNA.
DR RefSeq; NP_524099.2; NM_079375.3.
DR AlphaFoldDB; P54358; -.
DR SMR; P54358; -.
DR BioGRID; 65057; 15.
DR DIP; DIP-22360N; -.
DR IntAct; P54358; 8.
DR STRING; 7227.FBpp0075277; -.
DR BindingDB; P54358; -.
DR ChEMBL; CHEMBL3124738; -.
DR PaxDb; P54358; -.
DR PRIDE; P54358; -.
DR EnsemblMetazoa; FBtr0075522; FBpp0075277; FBgn0263600.
DR GeneID; 39746; -.
DR KEGG; dme:Dmel_CG5949; -.
DR CTD; 39746; -.
DR FlyBase; FBgn0263600; PolD1.
DR VEuPathDB; VectorBase:FBgn0263600; -.
DR eggNOG; KOG0969; Eukaryota.
DR GeneTree; ENSGT00560000077365; -.
DR HOGENOM; CLU_000203_2_0_1; -.
DR InParanoid; P54358; -.
DR OMA; GNQKSPY; -.
DR OrthoDB; 20210at2759; -.
DR PhylomeDB; P54358; -.
DR Reactome; R-DME-69166; Removal of the Flap Intermediate.
DR Reactome; R-DME-69183; Processive synthesis on the lagging strand.
DR BioGRID-ORCS; 39746; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 39746; -.
DR PRO; PR:P54358; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0263600; Expressed in secondary oocyte and 47 other tissues.
DR Genevisible; P54358; DM.
DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IDA:FlyBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0006287; P:base-excision repair, gap-filling; IBA:GO_Central.
DR GO; GO:0045004; P:DNA replication proofreading; IDA:FlyBase.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:FlyBase.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IBA:GO_Central.
DR Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.90.1600.10; -; 1.
DR InterPro; IPR006172; DNA-dir_DNA_pol_B.
DR InterPro; IPR017964; DNA-dir_DNA_pol_B_CS.
DR InterPro; IPR006133; DNA-dir_DNA_pol_B_exonuc.
DR InterPro; IPR006134; DNA-dir_DNA_pol_B_multi_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR042087; DNA_pol_B_thumb.
DR InterPro; IPR023211; DNA_pol_palm_dom_sf.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR025687; Znf-C4pol.
DR Pfam; PF00136; DNA_pol_B; 1.
DR Pfam; PF03104; DNA_pol_B_exo1; 1.
DR Pfam; PF14260; zf-C4pol; 1.
DR PRINTS; PR00106; DNAPOLB.
DR SMART; SM00486; POLBc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS00116; DNA_POLYMERASE_B; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; DNA replication; DNA-binding; DNA-directed DNA polymerase;
KW Exonuclease; Hydrolase; Iron; Iron-sulfur; Metal-binding; Nuclease;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..1092
FT /note="DNA polymerase delta catalytic subunit"
FT /id="PRO_0000046447"
FT ZN_FING 997..1017
FT /note="CysA-type"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..19
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 1046..1064
FT /note="CysB motif"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 997
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1000
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1014
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1017
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1046
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1049
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1059
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 1064
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT CONFLICT 492
FT /note="L -> S (in Ref. 1; CAA61369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1092 AA; 124905 MW; 2FA380420298EA5C CRC64;
MDGKRKFNGT SNGHAKKPRN PDDDEEMGFE AELAAFENSE DMDQTLLMGD GPENQTTSER
WSRPPPPELD PSKHNLEFQQ LDVENYLGQP LPGMPGAQIG PVPVVRMFGV TMEGNSVCCH
VHGFCPYFYI EAPSQFEEHH CEKLQKALDQ KVIADIRNNK DNVQEAVLMV ELVEKLNIHG
YNGDKKQRYI KISVTLPRFV AAASRLLKKE VIMSEIDFQD CRAFENNIDF DIRFMVDTDV
VGCNWIELPM GHWRIRNSHS KPLPESRCQI EVDVAFDRFI SHEPEGEWSK VAPFRILSFD
IECAGRKGIF PEAKIDPVIQ IANMVIRQGE REPFIRNVFT LNECAPIIGS QVLCHDKETQ
MLDKWSAFVR EVDPDILTGY NINNFDFPYL LNRAAHLKVR NFEYLGRIKN IRSVIKEQML
QSKQMGRREN QYVNFEGRVP FDLLFVLLRD YKLRSYTLNA VSYHFLQEQK EDVHHSIITD
LQNGDEQTRR RLAMYCLKDA YLPLRLLEKL MAIVNYMEMA RVTGVPLESL LTRGQQIKVL
SQLLRKAKTK GFIMPSYTSQ GSDEQYEGAT VIEPKRGYYA DPISTLDFAS LYPSIMMAHN
LCYTTLVLGG TREKLRQQEN LQDDQVERTP ANNYFVKSEV RRGLLPEILE SLLAARKRAK
NDLKVETDPF KRKVLDGRQL ALKISANSVY GFTGAQVGKL PCLEISGSVT AYGRTMIEMT
KNEVESHYTQ ANGYENNAVV IYGDTDSVMV NFGVKTLERS MELGREAAEL VSSKFVHPIK
LEFEKVYYPY LLINKKRYAG LYFTRPDTYD KMDCKGIETV RRDNSPLVAN LMNSCLQKLL
IERDPDGAVA YVKQVIADLL CNRIDISHLV ITKELAKTDY AAKQAHVELA AKMKKRDPGT
APKLGDRVPY VICAAAKNTP AYQKAEDPLY VLENSVPIDA TYYLEQQLSK PLLRIFEPIL
GDNAESILLK GEHTRTRTVV TSKVGGLAGF MTKKTSCLGC KSLMPKGYEQ ACLCPHCEPR
MSELYQKEVG AKRELEETFS RLWTECQRCQ ESLHEEVICS NRDCPIFYMR QKVRMDLDNQ
EKRVLRFGLA EW
