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Protein

DNA polymerase alpha catalytic subunit

Gene

Pola1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).By similarity

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1287ZincBy similarity1
Metal bindingi1290ZincBy similarity1
Metal bindingi1314ZincBy similarity1
Metal bindingi1319ZincBy similarity1
Metal bindingi1352Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1357Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1375Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1378Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1287 – 1317CysA-typeAdd BLAST31

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

DNA-directed DNA polymerase, Nucleotidyltransferase, Transferase

Keywords - Biological processi

DNA replication

Keywords - Ligandi

4Fe-4S, DNA-binding, Iron, Iron-sulfur, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-113501. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
R-MMU-113510. E2F mediated regulation of DNA replication.
R-MMU-174411. Polymerase switching on the C-strand of the telomere.
R-MMU-174430. Telomere C-strand synthesis initiation.
R-MMU-68952. DNA replication initiation.
R-MMU-68962. Activation of the pre-replicative complex.
R-MMU-69091. Polymerase switching.
R-MMU-69166. Removal of the Flap Intermediate.
R-MMU-69183. Processive synthesis on the lagging strand.
R-MMU-69205. G1/S-Specific Transcription.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase alpha catalytic subunit (EC:2.7.7.7)
Alternative name(s):
DNA polymerase alpha catalytic subunit p180
Gene namesi
Name:Pola1
Synonyms:Pola
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:99660. Pola1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2797.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000464291 – 1465DNA polymerase alpha catalytic subunitAdd BLAST1465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei180PhosphothreonineBy similarity1
Modified residuei192PhosphoserineBy similarity1
Modified residuei215PhosphoserineCombined sources1
Modified residuei230N6-acetyllysineCombined sources1
Modified residuei974N6-succinyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP33609.
MaxQBiP33609.
PaxDbiP33609.
PeptideAtlasiP33609.
PRIDEiP33609.

PTM databases

iPTMnetiP33609.
PhosphoSitePlusiP33609.

Expressioni

Gene expression databases

BgeeiENSMUSG00000006678.
CleanExiMM_POLA1.
GenevisibleiP33609. MM.

Interactioni

Subunit structurei

The DNA polymerase alpha complex is composed of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1 and PRIM2 respectively. Interacts with PARP1; this interaction functions as part of the control of replication fork progression. Interacts with MCM10 and WDHD1; these interactions recruit the polymerase alpha complex to the pre-replicative complex bound to DNA. Interacts with RPA1; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Pola2P336115EBI-688051,EBI-848759
Prim1P206644EBI-688051,EBI-848742

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi202287. 1 interactor.
IntActiP33609. 4 interactors.
MINTiMINT-1727003.
STRINGi10090.ENSMUSP00000006856.

Structurei

3D structure databases

ProteinModelPortaliP33609.
SMRiP33609.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni654 – 719DNA-binding regionSequence analysisAdd BLAST66
Regioni1249 – 1380DNA-binding regionSequence analysisAdd BLAST132

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1352 – 1378CysB motifAdd BLAST27

Domaini

The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.By similarity

Sequence similaritiesi

Belongs to the DNA polymerase type-B family.Curated
Contains 1 CysA-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1287 – 1317CysA-typeAdd BLAST31

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0970. Eukaryota.
COG0417. LUCA.
GeneTreeiENSGT00550000074891.
HOGENOMiHOG000163524.
HOVERGENiHBG080008.
InParanoidiP33609.
KOiK02320.
OMAiHFVGRMV.
OrthoDBiEOG091G00RR.
PhylomeDBiP33609.
TreeFamiTF103001.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProiIPR006172. DNA-dir_DNA_pol_B.
IPR017964. DNA-dir_DNA_pol_B_CS.
IPR006133. DNA-dir_DNA_pol_B_exonuc.
IPR006134. DNA-dir_DNA_pol_B_multi_dom.
IPR024647. DNA_pol_a_cat_su_N.
IPR023211. DNA_pol_palm_dom.
IPR029702. POLA/Pol1.
IPR012337. RNaseH-like_dom.
IPR015088. Znf_DNA-dir_DNA_pol_B_alpha.
[Graphical view]
PANTHERiPTHR10322:SF21. PTHR10322:SF21. 4 hits.
PfamiPF12254. DNA_pol_alpha_N. 1 hit.
PF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF08996. zf-DNA_Pol. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P33609-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPMHEEDCK LEASAVSDSG SFAASRARRE KKSKKGRQEA LERLKKAKAG
60 70 80 90 100
EKYKYEVEDL TSVYEEVDEE QYSKLVQARQ DDDWIVDDDG IGYVEDGREI
110 120 130 140 150
FDDDLEDDAL DTCGKGSDGK AHRKDRKDVK KPSVTKPNNI KAMFIASAGK
160 170 180 190 200
KTTDKAVDLS KDDLLGDILQ DLNTETAQIT PPPVLIPKKK RSTGALLNPF
210 220 230 240 250
SVHTPKAIPS GKPASPVLRN EPLLTPIPLK RAELAGELAQ PECPEDEQEL
260 270 280 290 300
GVMEFEDGDF DESMDTEKVD EKPVTAKTWD QETEPVERVE HEADPERGTT
310 320 330 340 350
SYLENFLPDV SCWDIDQDDE SIPQEVQVDS SNLPLVKGAD DEQVFQFYWL
360 370 380 390 400
DAYEDPYNQP GVVFLFGKVW IESVKTHVSC CVMVKNIERT LYFLPREMKF
410 420 430 440 450
DLNTGKETAI PVTMKDVYEE FDSKISAKYK IMKFKSKIVE KNYAFEIPDV
460 470 480 490 500
PEKSEYLEVR YSAEVPQLPQ NLKGETFSHV FGTNTSSLEL FLMNRKIKGP
510 520 530 540 550
CWLEVKNPQL LNQPISWCKF EVMALKPDLV NVIKDVSPPP LVVMSFSMKT
560 570 580 590 600
MQNVQNHQHE IIAMAALVHH SFALDKAPPE PPFQTHFCVV SKPKDCIFPC
610 620 630 640 650
DFKEVISKKN MKVEIAATER TLIGFFLAKV HKIDPDILVG HNICSFELEV
660 670 680 690 700
LLQRINECKV PYWSKIGRLR RSNMPKLGSR SGFGERNATC GRMICDVEIS
710 720 730 740 750
AKELIHCKSY HLSELVQQIL KTERIVIPTE NIRNMYSESS YLLYLLEHIW
760 770 780 790 800
KDARFILQIM CELNVLPLAL QITNIAGNIM SRTLMGGRSE RNEFLLLHAF
810 820 830 840 850
YENNYIVPDK QIFRKPQQKL GDEDEEIDGD TNKYKKGRKK ATYAGGLVLD
860 870 880 890 900
PKVGFYDKFI LLLDFNSLYP SIIQEFNICF TTVQRVTSEV QKATEDEEQE
910 920 930 940 950
QIPELPDPNL EMGILPREIR KLVERRKQVK QLMKQQDLNP DLVLQYDIRQ
960 970 980 990 1000
KALKLTANSM YGCLGFSYSR FYAKPLAALV TYKGREILMH TKDMVQKMNL
1010 1020 1030 1040 1050
EVIYGDTDSI MINTNSTNLE EVFKLGNKVK SEVNKLYKLL EIDIDAVFKS
1060 1070 1080 1090 1100
LLLLKKKKYA ALVVEPTSDG NYITKQELKG LDIVRRDWCD LAKDTGNFVI
1110 1120 1130 1140 1150
GQILSDQSRD TIVENIQKRL IEIGENVLNG SVPVSQFEIN KALTKDPQDY
1160 1170 1180 1190 1200
PDRKSLPHVH VALWINSQGG RKVKAGDTVS YVICQDGSNL TATQRAYAPE
1210 1220 1230 1240 1250
QLQKLDNLAI DTQYYLAQQI HPVVARICEP IDGIDAVLIA LWLGLDSTQF
1260 1270 1280 1290 1300
RVHQYHKDEE NDALLGGPAQ LTDEEKYKDC EKFKCLCPSC GTENIYDNVF
1310 1320 1330 1340 1350
EGSGLDMEPS LYRCSNVDCK VSPLTFMVQL SNKLIMDIRR CIKKYYDGWL
1360 1370 1380 1390 1400
ICEEPTCCSR LRRLPLHFSR NGPLCPVCMK AVLRPEYSDK SLYTQLCFYR
1410 1420 1430 1440 1450
YIFDADCALE KLTEHEKDKL KKQFFPLRVL QDYRKVKNIA EQFLSWSGYS
1460
EVNLSKLFAN YAGKS
Length:1,465
Mass (Da):167,340
Last modified:June 1, 1994 - v2
Checksum:i46D1A9818A7944A3
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti1180S → F in temperature-sensitive FT20 cell line; defective activity. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13543 mRNA. Translation: BAA40003.1.
D17384 mRNA. Translation: BAA04202.1.
CCDSiCCDS30272.1.
PIRiS45628.
RefSeqiNP_032918.1. NM_008892.2.
UniGeneiMm.1923.

Genome annotation databases

EnsembliENSMUST00000006856; ENSMUSP00000006856; ENSMUSG00000006678.
GeneIDi18968.
KEGGimmu:18968.
UCSCiuc009tss.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13543 mRNA. Translation: BAA40003.1.
D17384 mRNA. Translation: BAA04202.1.
CCDSiCCDS30272.1.
PIRiS45628.
RefSeqiNP_032918.1. NM_008892.2.
UniGeneiMm.1923.

3D structure databases

ProteinModelPortaliP33609.
SMRiP33609.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202287. 1 interactor.
IntActiP33609. 4 interactors.
MINTiMINT-1727003.
STRINGi10090.ENSMUSP00000006856.

Chemistry databases

ChEMBLiCHEMBL2797.

PTM databases

iPTMnetiP33609.
PhosphoSitePlusiP33609.

Proteomic databases

EPDiP33609.
MaxQBiP33609.
PaxDbiP33609.
PeptideAtlasiP33609.
PRIDEiP33609.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006856; ENSMUSP00000006856; ENSMUSG00000006678.
GeneIDi18968.
KEGGimmu:18968.
UCSCiuc009tss.2. mouse.

Organism-specific databases

CTDi5422.
MGIiMGI:99660. Pola1.

Phylogenomic databases

eggNOGiKOG0970. Eukaryota.
COG0417. LUCA.
GeneTreeiENSGT00550000074891.
HOGENOMiHOG000163524.
HOVERGENiHBG080008.
InParanoidiP33609.
KOiK02320.
OMAiHFVGRMV.
OrthoDBiEOG091G00RR.
PhylomeDBiP33609.
TreeFamiTF103001.

Enzyme and pathway databases

ReactomeiR-MMU-113501. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
R-MMU-113510. E2F mediated regulation of DNA replication.
R-MMU-174411. Polymerase switching on the C-strand of the telomere.
R-MMU-174430. Telomere C-strand synthesis initiation.
R-MMU-68952. DNA replication initiation.
R-MMU-68962. Activation of the pre-replicative complex.
R-MMU-69091. Polymerase switching.
R-MMU-69166. Removal of the Flap Intermediate.
R-MMU-69183. Processive synthesis on the lagging strand.
R-MMU-69205. G1/S-Specific Transcription.

Miscellaneous databases

PROiP33609.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006678.
CleanExiMM_POLA1.
GenevisibleiP33609. MM.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProiIPR006172. DNA-dir_DNA_pol_B.
IPR017964. DNA-dir_DNA_pol_B_CS.
IPR006133. DNA-dir_DNA_pol_B_exonuc.
IPR006134. DNA-dir_DNA_pol_B_multi_dom.
IPR024647. DNA_pol_a_cat_su_N.
IPR023211. DNA_pol_palm_dom.
IPR029702. POLA/Pol1.
IPR012337. RNaseH-like_dom.
IPR015088. Znf_DNA-dir_DNA_pol_B_alpha.
[Graphical view]
PANTHERiPTHR10322:SF21. PTHR10322:SF21. 4 hits.
PfamiPF12254. DNA_pol_alpha_N. 1 hit.
PF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF08996. zf-DNA_Pol. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPOLA_MOUSE
AccessioniPrimary (citable) accession number: P33609
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
Conserved regions II, IV, III and I are thought to be involved in substrate recognition, binding or PP(i) hydrolysis.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.