DPOLA_XENLA
ID DPOLA_XENLA Reviewed; 1458 AA.
AC Q9DE46;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=DNA polymerase alpha catalytic subunit;
DE EC=2.7.7.7;
DE AltName: Full=DNA polymerase alpha catalytic subunit p180;
GN Name=pola1; Synonyms=pola;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Oocyte;
RX PubMed=10886370; DOI=10.1046/j.1365-2443.2000.00340.x;
RA Mimura S., Masuda T., Matsui T., Takisawa H.;
RT "Central role for cdc45 in establishing an initiation complex of DNA
RT replication in Xenopus egg extracts.";
RL Genes Cells 5:439-452(2000).
CC -!- FUNCTION: Plays an essential role in the initiation of DNA replication.
CC During the S phase of the cell cycle, the DNA polymerase alpha complex
CC (composed of a catalytic subunit POLA1/p180, a regulatory subunit
CC POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is
CC recruited to DNA at the replicative forks via direct interactions with
CC MCM10 and WDHD1. The primase subunit of the polymerase alpha complex
CC initiates DNA synthesis by oligomerising short RNA primers on both
CC leading and lagging strands. These primers are initially extended by
CC the polymerase alpha catalytic subunit and subsequently transferred to
CC polymerase delta and polymerase epsilon for processive synthesis on the
CC lagging and leading strand, respectively. The reason this transfer
CC occurs is because the polymerase alpha has limited processivity and
CC lacks intrinsic 3' exonuclease activity for proofreading error, and
CC therefore is not well suited for replicating long complexes (By
CC similarity). {ECO:0000250}.
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 -!- SUBUNIT: The DNA polymerase alpha complex is composed of four subunits:
CC the catalytic subunit POLA1, the regulatory subunit POLA2, and the
CC small and the large primase subunits PRIM1 and PRIM2 respectively.
CC Interacts with PARP1; this interaction functions as part of the control
CC of replication fork progression. Interacts with MCM10 and WDHD1; these
CC interactions recruit the polymerase alpha complex to the pre-
CC replicative complex bound to DNA. Interacts with RPA1; this interaction
CC stabilizes the replicative complex and reduces the misincorporation
CC rate of DNA polymerase alpha by acting as a fidelity clamp (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9DE46; Q0IHI4: tipin; NbExp=3; IntAct=EBI-3645423, EBI-7570880;
CC Q9DE46; O13046: wdhd1; NbExp=2; IntAct=EBI-3645423, EBI-3510652;
CC -!- SUBCELLULAR LOCATION: Nucleus.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF202992; AAG35630.1; -; mRNA.
DR RefSeq; NP_001082055.1; NM_001088586.1.
DR AlphaFoldDB; Q9DE46; -.
DR SMR; Q9DE46; -.
DR BioGRID; 99535; 1.
DR IntAct; Q9DE46; 3.
DR MINT; Q9DE46; -.
DR PRIDE; Q9DE46; -.
DR GeneID; 398200; -.
DR KEGG; xla:398200; -.
DR CTD; 398200; -.
DR Xenbase; XB-GENE-1000552; pola1.S.
DR OrthoDB; 293315at2759; -.
DR Proteomes; UP000186698; Chromosome 2S.
DR Bgee; 398200; Expressed in egg cell and 19 other tissues.
DR GO; GO:0005658; C:alpha DNA polymerase:primase complex; 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:0003887; F:DNA-directed DNA polymerase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; ISS:UniProtKB.
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: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; IEA:InterPro.
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 DNA replication; DNA-binding; DNA-directed DNA polymerase; Metal-binding;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..1458
FT /note="DNA polymerase alpha catalytic subunit"
FT /id="PRO_0000046431"
FT ZN_FING 1280..1310
FT /note="CysA-type"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 650..715
FT /note="DNA-binding"
FT /evidence="ECO:0000255"
FT REGION 1241..1373
FT /note="DNA-binding"
FT /evidence="ECO:0000255"
FT MOTIF 1345..1371
FT /note="CysB motif"
FT COMPBIAS 9..25
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1368
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
FT BINDING 1371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P09884"
SQ SEQUENCE 1458 AA; 165061 MW; 25C29BAC5CC6B9E8 CRC64;
MSDSGSFAAS RSRREKTEKS GRKEALERLK RAKAGEKVKY EVEQVSSIYE EVDEAEYSKL
VRDRQDDDWI VDDDGTGYVE DGREIFDDDL EDNALADSGK GAKGAPKDKT NVKKSSVSKP
NNIKSMFMAS AVKKTTDKAV DLSKDDLLGD LLQDLKSQAV PITPPPVITL KKKKLAGSPL
NPFSVPPTAP KVLPTSVKRL PAVTKPGHPA AQSKASVPRQ IKKEPKAELI SSAVGPLKVE
AQVKEEDSGM VEFDDGDFDE PMEEDVEITP VDSSTIKTQA QSIKCVKEEN IKEEKSSFIT
SATLNESCWD QIDEAEPMTT EIQVDSSHLP LVTGADGSQV FRFYWLDAYE DQYSQPGVVY
LFGKVWIESA DAYVSCCVSV KNIERTVYLL PRENRVQLST GKDTGAPVSM MHVYQEFNEA
VAEKYKIMKF KSKKVDKDYA FEIPDVPASS EYLEVRYSAD SPQLPQDLKG ETFSHVFGTN
TSSLELFLLS RKIKGPSWLE IKSPQLSSQP MSWCKVEAVV TRPDQVSVVK DLAPPPVVVL
SLSMKTVQNA KTHQNEIVAI AALVHHTFPL DKAPPQPPFQ THFCVLSKLN DCIFPYDYNE
AVKQKNANIE IALTERTLLG FFLAKIHKID PDVIVGHDIY GFDLEVLLQR INSCKVPFWS
KIGRLRRSVM PKLGGRSGFA ERNAACGRII CDIEISAKEL IRCKSYHLSE LVHQILKAER
VVIPPENIRN AYNDSVHLLY MLENTWIDAK FILQIMCELN VLPLALQITN IAGNVMSRTL
MGGRSERNEY LLLHAFTENN FIVPDKPVFK KMQQTTVEDN DDMGTDQNKN KSRKKAAYAG
GLVLEPKVGF YDKFILLLDF NSLYPSIIQE YNICFTTVHR EAPSTQKGED QDEIPELPHS
DLEMGILPRE IRKLVERRRH VKQLMKQPDL NPDLYLQYDI RQKALKLTAN SMYGCLGFSY
SRFYAKPLAA LVTHQGREIL LHTKEMVQKM NLEVIYGDTD SIMINTNCNN LEEVFKLGNR
VKSEINKSYK LLEIDIDGIF KSLLLLKKKK YAALTVEPTG DGKYVTKQEL KGLDIVRRDW
CELAKQAGNY VISQILSDQP RDSIVENIQK KLTEIGENVT NGTVPITQYE INKALTKDPQ
DYPDKKSLPH VHVALWINSQ GGRKVKAGDT ISYVICQDGS NLSASQRAYA QEQLQKQENL
SIDTQYYLSQ QVHPVVARIC EPIDGIDSAL IAMWLGLDPS QFRAHRHYQQ DEENDALLGG
PSQLTDEEKY RDCERFKFFC PKCGTENIYD NVFDGSGLQI EPGLKRCSKP ECDASPLDYV
IQVHNKLLLD IRRYIKKYYS GWLVCEEKTC QNRTRRLPLS FSRNGPICQA CSKATLRSEY
PEKALYTQLC FYRFIFDWDY ALEKVVSEQE RGHLKKKLFQ ESENQYKKLK STVDQVLSRS
GYSEVNLSKL FQTLNTIK
