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P33609

- DPOLA_MOUSE

UniProt

P33609 - DPOLA_MOUSE

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
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 2 (01 Jun 1994)
      Previous versions | rss
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    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 binding Source: IntAct
    11. 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. mitotic S phase Source: UniProtKB
    9. nucleic acid phosphodiester bond hydrolysis Source: GOC
    10. translesion synthesis Source: RefGenome

    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

    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

    ArrayExpressiP33609.
    BgeeiP33609.
    CleanExiMM_POLA1.
    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.
    IPR012337. RNaseH-like_dom.
    IPR015088. Znf_DNA-dir_DNA_pol_B_alpha.
    [Graphical view]
    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

    MAPMHEEDCK LEASAVSDSG SFAASRARRE KKSKKGRQEA LERLKKAKAG     50
    EKYKYEVEDL TSVYEEVDEE QYSKLVQARQ DDDWIVDDDG IGYVEDGREI 100
    FDDDLEDDAL DTCGKGSDGK AHRKDRKDVK KPSVTKPNNI KAMFIASAGK 150
    KTTDKAVDLS KDDLLGDILQ DLNTETAQIT PPPVLIPKKK RSTGALLNPF 200
    SVHTPKAIPS GKPASPVLRN EPLLTPIPLK RAELAGELAQ PECPEDEQEL 250
    GVMEFEDGDF DESMDTEKVD EKPVTAKTWD QETEPVERVE HEADPERGTT 300
    SYLENFLPDV SCWDIDQDDE SIPQEVQVDS SNLPLVKGAD DEQVFQFYWL 350
    DAYEDPYNQP GVVFLFGKVW IESVKTHVSC CVMVKNIERT LYFLPREMKF 400
    DLNTGKETAI PVTMKDVYEE FDSKISAKYK IMKFKSKIVE KNYAFEIPDV 450
    PEKSEYLEVR YSAEVPQLPQ NLKGETFSHV FGTNTSSLEL FLMNRKIKGP 500
    CWLEVKNPQL LNQPISWCKF EVMALKPDLV NVIKDVSPPP LVVMSFSMKT 550
    MQNVQNHQHE IIAMAALVHH SFALDKAPPE PPFQTHFCVV SKPKDCIFPC 600
    DFKEVISKKN MKVEIAATER TLIGFFLAKV HKIDPDILVG HNICSFELEV 650
    LLQRINECKV PYWSKIGRLR RSNMPKLGSR SGFGERNATC GRMICDVEIS 700
    AKELIHCKSY HLSELVQQIL KTERIVIPTE NIRNMYSESS YLLYLLEHIW 750
    KDARFILQIM CELNVLPLAL QITNIAGNIM SRTLMGGRSE RNEFLLLHAF 800
    YENNYIVPDK QIFRKPQQKL GDEDEEIDGD TNKYKKGRKK ATYAGGLVLD 850
    PKVGFYDKFI LLLDFNSLYP SIIQEFNICF TTVQRVTSEV QKATEDEEQE 900
    QIPELPDPNL EMGILPREIR KLVERRKQVK QLMKQQDLNP DLVLQYDIRQ 950
    KALKLTANSM YGCLGFSYSR FYAKPLAALV TYKGREILMH TKDMVQKMNL 1000
    EVIYGDTDSI MINTNSTNLE EVFKLGNKVK SEVNKLYKLL EIDIDAVFKS 1050
    LLLLKKKKYA ALVVEPTSDG NYITKQELKG LDIVRRDWCD LAKDTGNFVI 1100
    GQILSDQSRD TIVENIQKRL IEIGENVLNG SVPVSQFEIN KALTKDPQDY 1150
    PDRKSLPHVH VALWINSQGG RKVKAGDTVS YVICQDGSNL TATQRAYAPE 1200
    QLQKLDNLAI DTQYYLAQQI HPVVARICEP IDGIDAVLIA LWLGLDSTQF 1250
    RVHQYHKDEE NDALLGGPAQ LTDEEKYKDC EKFKCLCPSC GTENIYDNVF 1300
    EGSGLDMEPS LYRCSNVDCK VSPLTFMVQL SNKLIMDIRR CIKKYYDGWL 1350
    ICEEPTCCSR LRRLPLHFSR NGPLCPVCMK AVLRPEYSDK SLYTQLCFYR 1400
    YIFDADCALE KLTEHEKDKL KKQFFPLRVL QDYRKVKNIA EQFLSWSGYS 1450
    EVNLSKLFAN YAGKS 1465
    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

    ArrayExpressi P33609.
    Bgeei P33609.
    CleanExi MM_POLA1.
    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.
    IPR012337. RNaseH-like_dom.
    IPR015088. Znf_DNA-dir_DNA_pol_B_alpha.
    [Graphical view ]
    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

    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 1, 2014
    This is version 125 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