DPOLA_RAT
ID DPOLA_RAT Reviewed; 1451 AA.
AC O89042;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=DNA polymerase alpha catalytic subunit;
DE EC=2.7.7.7 {ECO:0000269|PubMed:10541966};
DE AltName: Full=DNA polymerase alpha catalytic subunit p180;
DE Flags: Fragment;
GN Name=Pola1; Synonyms=Pola;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=10541966; DOI=10.1007/s004320050322;
RA Popanda O., Flohr T., Fox G., Thielmann H.W.;
RT "A mutation detected in DNA polymerase delta cDNA from Novikoff hepatoma
RT cells correlates with abnormal catalytic properties of the enzyme.";
RL J. Cancer Res. Clin. Oncol. 125:598-608(1999).
CC -!- FUNCTION: Catalytic subunit of the DNA polymerase alpha complex (also
CC known as the alpha DNA polymerase-primase complex) which plays an
CC essential role in the initiation of DNA synthesis (PubMed:10541966).
CC During the S phase of the cell cycle, the DNA polymerase alpha complex
CC (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and
CC two primase subunits PRIM1 and PRIM2) is recruited to DNA at the
CC replicative forks via direct interactions with MCM10 and WDHD1. The
CC primase subunit of the polymerase alpha complex initiates DNA synthesis
CC by oligomerising short RNA primers on both leading and lagging strands.
CC These primers are initially extended by the polymerase alpha catalytic
CC subunit and subsequently transferred to polymerase delta and polymerase
CC epsilon for processive synthesis on the lagging and leading strand,
CC respectively. The reason this transfer occurs is because the polymerase
CC alpha has limited processivity and lacks intrinsic 3' exonuclease
CC activity for proofreading error, and therefore is not well suited for
CC replicating long complexes. In the cytosol, responsible for a
CC substantial proportion of the physiological concentration of cytosolic
CC RNA:DNA hybrids, which are necessary to prevent spontaneous activation
CC of type I interferon responses (By similarity) (PubMed:10541966).
CC {ECO:0000250|UniProtKB:P09884, ECO:0000269|PubMed:10541966}.
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:10541966};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22509;
CC Evidence={ECO:0000269|PubMed:10541966};
CC -!- SUBUNIT: Component of the alpha DNA polymerase complex (also known as
CC the alpha DNA polymerase-primase complex) consisting of four subunits:
CC the catalytic subunit POLA1, the regulatory subunit POLA2, and the
CC primase complex subunits PRIM1 and PRIM2 respectively. Interacts with
CC PARP1; this interaction functions as part of the control of replication
CC fork progression. Interacts with MCM10 and WDHD1; these interactions
CC recruit the polymerase alpha complex to the pre-replicative complex
CC bound to DNA. Interacts with RPA1; this interaction stabilizes the
CC replicative complex and reduces the misincorporation rate of DNA
CC polymerase alpha by acting as a fidelity clamp (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P09884}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09884}. Note=In the cytosol,
CC colocalizes with RNA:DNA hybrids with a speckled pattern.
CC {ECO:0000250|UniProtKB:P09884}.
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; AJ011605; CAA09720.1; -; mRNA.
DR RefSeq; NP_445931.1; NM_053479.1.
DR AlphaFoldDB; O89042; -.
DR SMR; O89042; -.
DR ComplexPortal; CPX-2089; DNA polymerase alpha:primase complex.
DR STRING; 10116.ENSRNOP00000018147; -.
DR iPTMnet; O89042; -.
DR PhosphoSitePlus; O89042; -.
DR jPOST; O89042; -.
DR PaxDb; O89042; -.
DR PRIDE; O89042; -.
DR GeneID; 85241; -.
DR KEGG; rno:85241; -.
DR CTD; 5422; -.
DR RGD; 621816; Pola1.
DR eggNOG; KOG0970; Eukaryota.
DR InParanoid; O89042; -.
DR OrthoDB; 293315at2759; -.
DR PhylomeDB; O89042; -.
DR Reactome; R-RNO-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR Reactome; R-RNO-174411; Polymerase switching on the C-strand of the telomere.
DR Reactome; R-RNO-174430; Telomere C-strand synthesis initiation.
DR Reactome; R-RNO-68952; DNA replication initiation.
DR Reactome; R-RNO-68962; Activation of the pre-replicative complex.
DR Reactome; R-RNO-69091; Polymerase switching.
DR Reactome; R-RNO-69166; Removal of the Flap Intermediate.
DR Reactome; R-RNO-69183; Processive synthesis on the lagging strand.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005658; C:alpha DNA polymerase:primase complex; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003688; F:DNA replication origin binding; IBA:GO_Central.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0000166; F:nucleotide binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0017076; F:purine nucleotide binding; IMP:RGD.
DR GO; GO:0019103; F:pyrimidine nucleotide binding; IMP:RGD.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071897; P:DNA biosynthetic process; IMP:RGD.
DR GO; GO:0006281; P:DNA repair; ISO:RGD.
DR GO; GO:0006260; P:DNA replication; IMP:RGD.
DR GO; GO:0006270; P:DNA replication initiation; ISS:UniProtKB.
DR GO; GO:0006269; P:DNA replication, synthesis of RNA primer; ISS:UniProtKB.
DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; ISS:UniProtKB.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:RGD.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0006273; P:lagging strand elongation; ISS:UniProtKB.
DR GO; GO:0006272; P:leading strand elongation; ISS:UniProtKB.
DR GO; GO:1902975; P:mitotic DNA replication initiation; IBA:GO_Central.
DR GO; GO:0032479; P:regulation of type I interferon production; ISS:UniProtKB.
DR CDD; cd05532; POLBc_alpha; 1.
DR Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 1.10.3200.20; -; 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; IPR024647; DNA_pol_a_cat_su_N.
DR InterPro; IPR042087; DNA_pol_B_thumb.
DR InterPro; IPR023211; DNA_pol_palm_dom_sf.
DR InterPro; IPR038256; Pol_alpha_znc_sf.
DR InterPro; IPR045846; POLBc_alpha.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR015088; Znf_DNA-dir_DNA_pol_B_alpha.
DR Pfam; PF12254; DNA_pol_alpha_N; 1.
DR Pfam; PF00136; DNA_pol_B; 1.
DR Pfam; PF03104; DNA_pol_B_exo1; 1.
DR Pfam; PF08996; zf-DNA_Pol; 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 Acetylation; Cytoplasm; DNA replication; DNA-binding;
KW DNA-directed DNA polymerase; Metal-binding; Nucleotidyltransferase;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..>1451
FT /note="DNA polymerase alpha catalytic subunit"
FT /id="PRO_0000046430"
FT ZN_FING 1290..1320
FT /note="CysA-type"
FT REGION 105..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..722
FT /note="DNA-binding"
FT /evidence="ECO:0000255"
FT REGION 816..836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1252..1383
FT /note="DNA-binding"
FT /evidence="ECO:0000255"
FT MOTIF 1355..1381
FT /note="CysB motif"
FT COMPBIAS 113..134
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..836
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1355
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P33609"
FT MOD_RES 413
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT MOD_RES 977
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P33609"
FT NON_TER 1451
SQ SEQUENCE 1451 AA; 165306 MW; F0E1B16F8B8D5CD2 CRC64;
MAPVHGDDCK LETSAVSDSG SFVASRARRE KKSKKGRQEA LERLKKAKAG EKYKYEVEDL
TSVYEEVDEE QYSKLVQARQ DDDWIVDDDG IGYVEDGREI FDDDLEDDAL DTCGEGSDGK
AHRKDRKDVK KPSVTKPNNI KAMFIASAGK KTTDKTVDLS KDDLLGDILQ DLNTETPQIA
PPPVLIPKKK RSTGASPNPF SVHTATAVPS GKIASPVSRK EPPLTPVPLK RAEFAGDLAQ
PECPEDEQES GVIEFEDGDF DEPMDTEEVD EEEPVTAKIW DQESEPVEGV KHEADPETGT
TSFLDSFLPD VSCWDIDQKD ENSFLLQEVQ VDSNHLPLVK GADDEQVFQF YWLDAYEDPY
NQPGVVFLFG KVWVESAKTH VSCCVMVKNI ERTLYFLPRE MKIDLNTGKE TATPITMKDV
YEEFDSKISA KYKIMKFKSK IVEKNYAFEI PDVPEKSEYL EVRYSAEVPQ LPQNLKGETF
SHVFGTNTSS LELFLMNRKI KGPCWLEVKN PQLLNQPISW CKFEAMALKP DLVNVIKDVS
PPPLVVMSFS MKTMQNVQNH QHEIIAMAAL VHHNFPLDKA PPKPPFQTHF CVVSKPKDCI
FPCAFKEVIK KKNMEVEVAA TERTLLGFFL AKVHKLDPDI LVGHNICGFE LEVLLQRINE
CKVPFWSKIG RLRRSNMPKL GSRSGFGERN ATCGRMICDV EISVKELIHC KSYHLSELVQ
QILKTERIVI PTENIRNMYS EPSHLLYLLE HIWKDARFIL QIMCELNVLP LALQITNIAG
NIMSRTLMGG RSERNEFLLL HAFYENNYIV PDKQIFRKPQ QKPGDEDEEI DGDTNKYKKG
RKKAAYAGGL VLDPKVGFYD KFILLLDFNS LYPSIIQEFN ICFTTVQRVA SETLKATEDE
EQEQIPELPD PNLDMGILPR EIRKLVERRK QVKQLMKQQD LNPDLVLQYD IRQKALKLTA
NSMYGCLGFS YSRFYAKPLA ALVTYKGREI LMHTKEMVQK MNLEVIYGDT DSIMINTNST
NLEEVFKLGN KVKNEVNKLY KLLEIDIDGV FKSLLLLKKK KYAALVVEPT SDGNYITKQE
LKGLDIVRRD WCDLAKDTGN FVIGQILSDQ SRDTIVENIQ KRLIEIGENV LNGSVPVSQF
EINKALTKDP QDYPDKKSLP HVHVALWINS QGGRKVKAGD TVSYVICQDG SNLPATQRAY
APEQLQKQDN LAIDTQYYLA QQIHPVVARI CEPIDGIDAV LIALWLGLDS TQFRVHQYHK
DEENDALLGG PAQLTDEEKY KDCEKFKCLC PSCGTENIYD NVFEGSGMDM EPSLNRCSNI
DCKASPATFM VQLSNKLIMD IRRCIKKYYD GWLICEEPTC RNRIRRLPLH FSRNGPLCPA
CMKAVLRPEY SDKSLYTQLC FYRYIFDADC ALEKLPEHEK DKLKKQFFTP RVLQDYRKVK
NIAEHFLSWS G
