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P33609

- DPOLA_MOUSE

UniProt

P33609 - DPOLA_MOUSE

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Protein

DNA polymerase alpha catalytic subunit

Gene

Pola1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Binds 1 4Fe-4S cluster.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi1287 – 12871ZincBy similarity
Metal bindingi1290 – 12901ZincBy similarity
Metal bindingi1314 – 13141ZincBy similarity
Metal bindingi1319 – 13191ZincBy similarity
Metal bindingi1352 – 13521Iron-sulfur (4Fe-4S)By similarity
Metal bindingi1357 – 13571Iron-sulfur (4Fe-4S)By similarity
Metal bindingi1375 – 13751Iron-sulfur (4Fe-4S)By similarity
Metal bindingi1378 – 13781Iron-sulfur (4Fe-4S)By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1287 – 131731CysA-typeAdd
BLAST

GO - Molecular functioni

  1. 3'-5' exonuclease activity Source: RefGenome
  2. 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  3. chromatin binding Source: UniProtKB
  4. DNA binding Source: UniProtKB
  5. DNA-directed DNA polymerase activity Source: UniProtKB
  6. DNA primase activity Source: Ensembl
  7. metal ion binding Source: UniProtKB-KW
  8. nucleoside binding Source: InterPro
  9. nucleotide binding Source: UniProtKB
  10. protein heterodimerization activity Source: MGI

GO - Biological processi

  1. cell proliferation Source: UniProtKB
  2. DNA replication Source: UniProtKB
  3. DNA replication initiation Source: UniProtKB
  4. DNA strand elongation involved in DNA replication Source: UniProtKB
  5. double-strand break repair via nonhomologous end joining Source: UniProtKB
  6. lagging strand elongation Source: UniProtKB
  7. leading strand elongation Source: UniProtKB
  8. nucleic acid phosphodiester bond hydrolysis Source: GOC
  9. translesion synthesis Source: RefGenome
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

ReactomeiREACT_198608. G1/S-Specific Transcription.
REACT_206830. E2F mediated regulation of DNA replication.
REACT_208887. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_224446. Telomere C-strand synthesis initiation.
REACT_225604. Polymerase switching on the C-strand of the telomere.

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
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:99660. Pola1.

Subcellular locationi

GO - Cellular componenti

  1. alpha DNA polymerase:primase complex Source: UniProtKB
  2. chromatin Source: Ensembl
  3. cytoplasm Source: Ensembl
  4. nuclear envelope Source: UniProtKB
  5. nuclear matrix Source: UniProtKB
  6. nucleolus Source: UniProtKB
  7. nucleoplasm Source: UniProtKB
  8. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14651465DNA polymerase alpha catalytic subunitPRO_0000046429Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801PhosphothreonineBy similarity
Modified residuei192 – 1921PhosphoserineBy similarity
Modified residuei215 – 2151PhosphoserineBy similarity
Modified residuei230 – 2301N6-acetyllysine1 Publication
Modified residuei974 – 9741N6-succinyllysine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP33609.
PaxDbiP33609.
PRIDEiP33609.

PTM databases

PhosphoSiteiP33609.

Expressioni

Gene expression databases

BgeeiP33609.
CleanExiMM_POLA1.
ExpressionAtlasiP33609. baseline and differential.
GenevestigatoriP33609.

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

Protein-protein interaction databases

BioGridi202287. 1 interaction.
IntActiP33609. 4 interactions.
MINTiMINT-1727003.

Structurei

3D structure databases

ProteinModelPortaliP33609.
SMRiP33609. Positions 345-1244, 1273-1426.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni654 – 71966DNA-binding regionSequence AnalysisAdd
BLAST
Regioni1249 – 1380132DNA-binding regionSequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1352 – 137827CysB motifAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1287 – 131731CysA-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG0417.
GeneTreeiENSGT00550000074891.
HOGENOMiHOG000163524.
HOVERGENiHBG080008.
InParanoidiP33609.
KOiK02320.
OMAiEKYRDCE.
OrthoDBiEOG7CNZDZ.
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:SF18. PTHR10322:SF18. 1 hit.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1180 – 11801S → F in temperature-sensitive FT20 cell line; defective activity. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
D13543 mRNA. Translation: BAA40003.1 .
D17384 mRNA. Translation: BAA04202.1 .
CCDSi CCDS30272.1.
PIRi S45628.
RefSeqi NP_032918.1. NM_008892.2.
UniGenei Mm.1923.

3D structure databases

ProteinModelPortali P33609.
SMRi P33609. Positions 345-1244, 1273-1426.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 202287. 1 interaction.
IntActi P33609. 4 interactions.
MINTi MINT-1727003.

Chemistry

BindingDBi P33609.

PTM databases

PhosphoSitei P33609.

Proteomic databases

MaxQBi P33609.
PaxDbi P33609.
PRIDEi P33609.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000006856 ; ENSMUSP00000006856 ; ENSMUSG00000006678 .
GeneIDi 18968.
KEGGi mmu:18968.
UCSCi uc009tss.2. mouse.

Organism-specific databases

CTDi 5422.
MGIi MGI:99660. Pola1.

Phylogenomic databases

eggNOGi COG0417.
GeneTreei ENSGT00550000074891.
HOGENOMi HOG000163524.
HOVERGENi HBG080008.
InParanoidi P33609.
KOi K02320.
OMAi EKYRDCE.
OrthoDBi EOG7CNZDZ.
PhylomeDBi P33609.
TreeFami TF103001.

Enzyme and pathway databases

Reactomei REACT_198608. G1/S-Specific Transcription.
REACT_206830. E2F mediated regulation of DNA replication.
REACT_208887. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_224446. Telomere C-strand synthesis initiation.
REACT_225604. Polymerase switching on the C-strand of the telomere.

Miscellaneous databases

NextBioi 295308.
PROi P33609.
SOURCEi Search...

Gene expression databases

Bgeei P33609.
CleanExi MM_POLA1.
ExpressionAtlasi P33609. baseline and differential.
Genevestigatori P33609.

Family and domain databases

Gene3Di 3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProi IPR006172. 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 ]
PANTHERi PTHR10322:SF18. PTHR10322:SF18. 1 hit.
Pfami PF12254. 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 ]
PRINTSi PR00106. DNAPOLB.
SMARTi SM00486. POLBc. 1 hit.
[Graphical view ]
SUPFAMi SSF53098. SSF53098. 1 hit.
PROSITEi PS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase alpha-primase complex and their gene expression during cell proliferation and the cell cycle."
    Miyazawa H., Izumi M., Tada S., Takada R., Masutani M., Ui M., Hanaoka F.
    J. Biol. Chem. 268:8111-8122(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 454-472 AND 1438-1455.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-230, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-974, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.
  4. "Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase alpha from a temperature-sensitive mouse FM3A cell line."
    Izumi M., Miyazawa H., Harakawa S., Yatagai F., Hanaoka F.
    J. Biol. Chem. 269:7639-7644(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PHE-1180.

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: October 29, 2014
This is version 126 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

External Data

Dasty 3