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Protein

DNA polymerase nu

Gene

POLN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA polymerase with very low fidelity that catalyzes considerable misincorporation by inserting dTTP opposite a G template, and dGTP opposite a T template (PubMed:16787914, PubMed:17118716). Is the least accurate of the DNA polymerase A family (i.e. POLG, POLN and POLQ) (PubMed:17118716). Can perform accurate translesion DNA synthesis (TLS) past a 5S-thymine glycol. Can perform efficient strand displacement past a nick or a gap and gives rise to an amount of product similar to that on non-damaged template. Has no exonuclease activity (PubMed:16787914). Error-prone DNA polymerase that preferentially misincorporates dT regardless of template sequence (PubMed:25775266). May play a role in TLS during interstrand cross-link (ICL) repair (PubMed:19908865). May be involved in TLS when genomic replication is blocked by extremely large major groove DNA lesions. May function in the bypass of some DNA-protein and DNA-DNA cross-links. May have a role in cellular tolerance to DNA cross-linking agents (PubMed:20102227). Involved in the repair of DNA cross-links and double-strand break (DSB) resistance. Participates in FANCD2-mediated repair. Forms a complex with HELQ helicase that participates in homologous recombination (HR) repair and is essential for cellular protection against DNA cross-links (PubMed:19995904).6 Publications

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).2 Publications

Enzyme regulationi

Inhibited by ddTTP.1 Publication

Kineticsi

  1. KM=7.0 µM for dATP:T1 Publication
  2. KM=8.2 µM for dCTP:G1 Publication
  3. KM=7.7 µM for dGTP:C1 Publication
  4. KM=7.3 µM for dTTP:A1 Publication

    pH dependencei

    Optimum pH is 8.8.1 Publication

    GO - Molecular functioni

    • cyclin binding Source: UniProtKB
    • DNA binding Source: UniProtKB-KW
    • DNA-directed DNA polymerase activity Source: UniProtKB

    GO - Biological processi

    • DNA-dependent DNA replication Source: GO_Central
    • double-strand break repair via homologous recombination Source: UniProtKB
    • interstrand cross-link repair Source: UniProtKB
    • translesion synthesis Source: UniProtKB

    Keywordsi

    Molecular functionDNA-binding, DNA-directed DNA polymerase, Nucleotidyltransferase, Transferase
    Biological processDNA damage, DNA repair, DNA replication

    Enzyme and pathway databases

    ReactomeiR-HSA-6783310. Fanconi Anemia Pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA polymerase nu (EC:2.7.7.72 Publications)
    Gene namesi
    Name:POLN
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:18870. POLN.

    Subcellular locationi

    • Nucleus 1 Publication

    GO - Cellular componenti

    • cytoplasm Source: GO_Central
    • nucleoplasm Source: HPA
    • nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi623D → A: Abolishes catalytic activity. 2 Publications1
    Mutagenesisi675E → R: Reduces polymerase activity. No effect on accuracy. 1 Publication1
    Mutagenesisi679K → A: No effect on polymerase activity. Increases accuracy by ten-fold. 1 Publication1

    Organism-specific databases

    DisGeNETi353497.
    OpenTargetsiENSG00000130997.
    PharmGKBiPA134979866.

    Chemistry databases

    ChEMBLiCHEMBL2010628.

    Polymorphism and mutation databases

    BioMutaiPOLN.
    DMDMi90101282.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002279381 – 900DNA polymerase nuAdd BLAST900

    Proteomic databases

    EPDiQ7Z5Q5.
    PaxDbiQ7Z5Q5.
    PeptideAtlasiQ7Z5Q5.
    PRIDEiQ7Z5Q5.

    PTM databases

    iPTMnetiQ7Z5Q5.
    PhosphoSitePlusiQ7Z5Q5.

    Expressioni

    Tissue specificityi

    Highly expressed in testis and heart. Weakly expressed in skeletal muscle.1 Publication

    Gene expression databases

    BgeeiENSG00000130997.
    CleanExiHS_POLN.
    ExpressionAtlasiQ7Z5Q5. baseline and differential.
    GenevisibleiQ7Z5Q5. HS.

    Organism-specific databases

    HPAiHPA035939.
    HPA035940.

    Interactioni

    Subunit structurei

    Interacts with FANCD2, FANCI, PCNA, RAD51 and HELQ.1 Publication

    GO - Molecular functioni

    • cyclin binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi131695. 10 interactors.
    STRINGi9606.ENSP00000372316.

    Chemistry databases

    BindingDBiQ7Z5Q5.

    Structurei

    Secondary structure

    1900
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi196 – 199Combined sources4
    Helixi200 – 202Combined sources3
    Helixi205 – 217Combined sources13
    Beta strandi219 – 227Combined sources9
    Turni233 – 235Combined sources3
    Beta strandi244 – 253Combined sources10
    Beta strandi273 – 275Combined sources3
    Beta strandi280 – 284Combined sources5
    Helixi293 – 311Combined sources19
    Beta strandi316 – 320Combined sources5
    Helixi321 – 332Combined sources12
    Helixi333 – 335Combined sources3
    Helixi338 – 340Combined sources3
    Helixi349 – 356Combined sources8
    Beta strandi358 – 360Combined sources3
    Helixi365 – 372Combined sources8
    Helixi390 – 417Combined sources28
    Helixi421 – 426Combined sources6
    Turni427 – 430Combined sources4
    Helixi431 – 440Combined sources10
    Beta strandi443 – 445Combined sources3
    Helixi447 – 472Combined sources26
    Helixi481 – 488Combined sources8
    Turni489 – 491Combined sources3
    Helixi494 – 497Combined sources4
    Beta strandi500 – 506Combined sources7
    Beta strandi508 – 511Combined sources4
    Helixi516 – 521Combined sources6
    Turni522 – 525Combined sources4
    Helixi528 – 545Combined sources18
    Helixi547 – 550Combined sources4
    Beta strandi561 – 566Combined sources6
    Beta strandi568 – 570Combined sources3
    Beta strandi573 – 577Combined sources5
    Turni579 – 581Combined sources3
    Beta strandi587 – 590Combined sources4
    Beta strandi602 – 605Combined sources4
    Helixi607 – 610Combined sources4
    Beta strandi618 – 624Combined sources7
    Helixi627 – 636Combined sources10
    Helixi639 – 643Combined sources5
    Helixi654 – 662Combined sources9
    Helixi666 – 668Combined sources3
    Helixi671 – 685Combined sources15
    Helixi690 – 696Combined sources7
    Helixi701 – 714Combined sources14
    Helixi717 – 732Combined sources16
    Beta strandi733 – 736Combined sources4
    Beta strandi738 – 740Combined sources3
    Beta strandi742 – 744Combined sources3
    Helixi746 – 749Combined sources4
    Helixi753 – 788Combined sources36
    Beta strandi796 – 801Combined sources6
    Beta strandi804 – 809Combined sources6
    Helixi811 – 813Combined sources3
    Helixi814 – 826Combined sources13
    Helixi827 – 829Combined sources3
    Beta strandi832 – 834Combined sources3
    Beta strandi844 – 853Combined sources10

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4XVIX-ray3.10A194-859[»]
    4XVKX-ray2.95A194-859[»]
    4XVLX-ray3.30A194-859[»]
    4XVMX-ray3.20A194-859[»]
    ProteinModelPortaliQ7Z5Q5.
    SMRiQ7Z5Q5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the DNA polymerase type-A family.Curated

    Phylogenomic databases

    eggNOGiENOG410IPH2. Eukaryota.
    COG0749. LUCA.
    GeneTreeiENSGT00640000091272.
    HOGENOMiHOG000230904.
    HOVERGENiHBG079981.
    InParanoidiQ7Z5Q5.
    KOiK16618.
    OMAiVHKIKST.
    OrthoDBiEOG091G07H6.
    PhylomeDBiQ7Z5Q5.
    TreeFamiTF337202.

    Family and domain databases

    InterProiView protein in InterPro
    IPR001098. DNA-dir_DNA_pol_A_palm_dom.
    IPR002298. DNA_polymerase_A.
    PfamiView protein in Pfam
    PF00476. DNA_pol_A. 1 hit.
    PRINTSiPR00868. DNAPOLI.
    SMARTiView protein in SMART
    SM00482. POLAc. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q7Z5Q5-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MENYEALVGF DLCNTPLSSV AQKIMSAMHS GDLVDSKTWG KSTETMEVIN
    60 70 80 90 100
    KSSVKYSVQL EDRKTQSPEK KDLKSLRSQT SRGSAKLSPQ SFSVRLTDQL
    110 120 130 140 150
    SADQKQKSIS SLTLSSCLIP QYNQEASVLQ KKGHKRKHFL MENINNENKG
    160 170 180 190 200
    SINLKRKHIT YNNLSEKTSK QMALEEDTDD AEGYLNSGNS GALKKHFCDI
    210 220 230 240 250
    RHLDDWAKSQ LIEMLKQAAA LVITVMYTDG STQLGADQTP VSSVRGIVVL
    260 270 280 290 300
    VKRQAEGGHG CPDAPACGPV LEGFVSDDPC IYIQIEHSAI WDQEQEAHQQ
    310 320 330 340 350
    FARNVLFQTM KCKCPVICFN AKDFVRIVLQ FFGNDGSWKH VADFIGLDPR
    360 370 380 390 400
    IAAWLIDPSD ATPSFEDLVE KYCEKSITVK VNSTYGNSSR NIVNQNVREN
    410 420 430 440 450
    LKTLYRLTMD LCSKLKDYGL WQLFRTLELP LIPILAVMES HAIQVNKEEM
    460 470 480 490 500
    EKTSALLGAR LKELEQEAHF VAGERFLITS NNQLREILFG KLKLHLLSQR
    510 520 530 540 550
    NSLPRTGLQK YPSTSEAVLN ALRDLHPLPK IILEYRQVHK IKSTFVDGLL
    560 570 580 590 600
    ACMKKGSISS TWNQTGTVTG RLSAKHPNIQ GISKHPIQIT TPKNFKGKED
    610 620 630 640 650
    KILTISPRAM FVSSKGHTFL AADFSQIELR ILTHLSGDPE LLKLFQESER
    660 670 680 690 700
    DDVFSTLTSQ WKDVPVEQVT HADREQTKKV VYAVVYGAGK ERLAACLGVP
    710 720 730 740 750
    IQEAAQFLES FLQKYKKIKD FARAAIAQCH QTGCVVSIMG RRRPLPRIHA
    760 770 780 790 800
    HDQQLRAQAE RQAVNFVVQG SAADLCKLAM IHVFTAVAAS HTLTARLVAQ
    810 820 830 840 850
    IHDELLFEVE DPQIPECAAL VRRTMESLEQ VQALELQLQV PLKVSLSAGR
    860 870 880 890 900
    SWGHLVPLQE AWGPPPGPCR TESPSNSLAA PGSPASTQPP PLHFSPSFCL
    Length:900
    Mass (Da):100,307
    Last modified:March 21, 2006 - v2
    Checksum:iD44758D71BCD3F02
    GO
    Isoform 2 (identifier: Q7Z5Q5-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         578-610: NIQGISKHPIQITTPKNFKGKEDKILTISPRAM → ICARQVASDFQKCVEVSDAMMNSSIFWWLLKLY
         611-899: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:611
    Mass (Da):68,690
    Checksum:iEB21C241912D8601
    GO

    Sequence cautioni

    The sequence BAD18421 differs from that shown. Probable cloning artifact.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti8V → A in BAG64670 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_025647121Q → H2 PublicationsCorresponds to variant dbSNP:rs2353552Ensembl.1
    Natural variantiVAR_025648201R → G1 PublicationCorresponds to variant dbSNP:rs35884361Ensembl.1
    Natural variantiVAR_025649310M → L1 PublicationCorresponds to variant dbSNP:rs10018786Ensembl.1
    Natural variantiVAR_025650315P → S1 PublicationCorresponds to variant dbSNP:rs11725880Ensembl.1
    Natural variantiVAR_025651336G → S1 PublicationCorresponds to variant dbSNP:rs10011549Ensembl.1
    Natural variantiVAR_025652425R → C2 PublicationsCorresponds to variant dbSNP:rs9328764Ensembl.1
    Natural variantiVAR_025653502S → G1 PublicationCorresponds to variant dbSNP:rs34574483Ensembl.1
    Natural variantiVAR_025654711F → L1 PublicationCorresponds to variant dbSNP:rs34554757Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_054402578 – 610NIQGI…SPRAM → ICARQVASDFQKCVEVSDAM MNSSIFWWLLKLY in isoform 2. 1 PublicationAdd BLAST33
    Alternative sequenceiVSP_054403611 – 899Missing in isoform 2. 1 PublicationAdd BLAST289

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY136549 mRNA. Translation: AAN52116.1.
    AK131239 mRNA. Translation: BAD18421.1. Sequence problems.
    AK303673 mRNA. Translation: BAG64670.1.
    DQ060036 Genomic DNA. Translation: AAY43130.1.
    AL136360, AL158068 Genomic DNA. Translation: CAM16854.1.
    AL158068, AL136360 Genomic DNA. Translation: CAM20461.1.
    CH471131 Genomic DNA. Translation: EAW82539.1.
    CCDSiCCDS3360.1. [Q7Z5Q5-1]
    RefSeqiNP_861524.2. NM_181808.3. [Q7Z5Q5-1]
    UniGeneiHs.368454.

    Genome annotation databases

    EnsembliENST00000382865; ENSP00000372316; ENSG00000130997. [Q7Z5Q5-1]
    ENST00000511885; ENSP00000435506; ENSG00000130997. [Q7Z5Q5-1]
    GeneIDi353497.
    KEGGihsa:353497.
    UCSCiuc003ger.3. human. [Q7Z5Q5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    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.

    Entry informationi

    Entry nameiDPOLN_HUMAN
    AccessioniPrimary (citable) accession number: Q7Z5Q5
    Secondary accession number(s): A2A336
    , B4E158, Q4TTW4, Q6ZNF4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
    Last sequence update: March 21, 2006
    Last modified: June 7, 2017
    This is version 121 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families