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P38859

- DNA2_YEAST

UniProt

P38859 - DNA2_YEAST

Protein

DNA replication ATP-dependent helicase/nuclease DNA2

Gene

DNA2

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    Key enzyme involved in DNA replication and DNA repair. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair by mediating the cleavage of 5'-ssDNA. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is atypical: it cannot load onto its tracking strand internally and has an absolute free 5'-end requirement. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function.6 Publications

    Catalytic activityi

    ATP + H2O = ADP + phosphate.

    Cofactori

    Binds 1 4Fe-4S cluster.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi519 – 5191Iron-sulfur (4Fe-4S)
    Metal bindingi768 – 7681Iron-sulfur (4Fe-4S)
    Metal bindingi771 – 7711Iron-sulfur (4Fe-4S)
    Metal bindingi777 – 7771Iron-sulfur (4Fe-4S)

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1074 – 10818ATPBy similarity

    GO - Molecular functioni

    1. 4 iron, 4 sulfur cluster binding Source: UniProtKB
    2. 5'-3' DNA helicase activity Source: UniProtKB
    3. 5'-flap endonuclease activity Source: SGD
    4. ATP binding Source: UniProtKB-KW
    5. ATP-dependent DNA helicase activity Source: SGD
    6. DNA binding Source: UniProtKB-KW
    7. metal ion binding Source: UniProtKB-KW
    8. nuclease activity Source: UniProtKB
    9. protein binding Source: UniProtKB
    10. single-stranded DNA-dependent ATPase activity Source: UniProtKB
    11. single-stranded DNA endodeoxyribonuclease activity Source: SGD

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. cellular response to DNA damage stimulus Source: UniProtKB
    3. DNA catabolic process, endonucleolytic Source: GOC
    4. DNA-dependent DNA replication Source: SGD
    5. DNA double-strand break processing Source: UniProtKB
    6. DNA duplex unwinding Source: GOC
    7. DNA repair Source: SGD
    8. DNA replication, Okazaki fragment processing Source: InterPro
    9. DNA strand renaturation Source: SGD
    10. lagging strand elongation Source: SGD
    11. meiotic DNA double-strand break processing Source: SGD
    12. replicative cell aging Source: SGD
    13. telomere maintenance Source: SGD

    Keywords - Molecular functioni

    Helicase, Hydrolase, Nuclease

    Keywords - Biological processi

    DNA damage, DNA repair, DNA replication

    Keywords - Ligandi

    4Fe-4S, ATP-binding, DNA-binding, Iron, Iron-sulfur, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciYEAST:G3O-31198-MONOMER.
    ReactomeiREACT_188901. Cytosolic iron-sulfur cluster assembly.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA replication ATP-dependent helicase/nuclease DNA2
    Including the following 2 domains:
    DNA replication nuclease DNA2 (EC:3.1.-.-)
    DNA replication ATP-dependent helicase DNA2 (EC:3.6.4.12)
    Gene namesi
    Name:DNA2
    Ordered Locus Names:YHR164C
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311: Chromosome VIII

    Organism-specific databases

    CYGDiYHR164c.
    SGDiS000001207. DNA2.

    Subcellular locationi

    Nucleus. Chromosome
    Note: Recruited to double-strand. break (DSB) sites following phosphorylation at Ser-17 and Ser-237.

    GO - Cellular componenti

    1. cytoplasm Source: SGD
    2. cytosol Source: Reactome
    3. nuclear chromosome, telomeric region Source: SGD
    4. nucleus Source: UniProtKB
    5. site of double-strand break Source: UniProtKB

    Keywords - Cellular componenti

    Chromosome, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi4 – 41T → A: Abolishes phosphorylation by CDK1, leading to a poor recruitment at double-strand. break (DSB) sites following DNA damage; when associated with A-17 and A-237. 1 Publication
    Mutagenesisi17 – 171S → A: Abolishes phosphorylation by CDK1, leading to a poor recruitment at double-strand. break (DSB) sites following DNA damage; when associated with A-4 and A-237. 1 Publication
    Mutagenesisi17 – 171S → D: Mimics phosphorylation; restores nuclear localization and recruitment at double-strand. break (DSB) sites following DNA damage; when associated with D-237. 1 Publication
    Mutagenesisi237 – 2371S → A: Abolishes phosphorylation by CDK1, leading to a poor recruitment at double-strand. break (DSB) sites following DNA damage; when associated with A-4 and A-17. 1 Publication
    Mutagenesisi237 – 2371S → D: Mimics phosphorylation; restores nuclear localization and recruitment at double-strand. break (DSB) sites following DNA damage; when associated with D-17. 1 Publication
    Mutagenesisi504 – 5041P → S in dna2-1; temperature-sensitive mutant unable to grow at 37 degrees Celsius, probably due to abolition of iron-sulfur-binding. 1 Publication
    Mutagenesisi519 – 5191C → A: Abolishes iron-sulfur-binding; when associated with A-768; A-771 and A-777. Impaired nuclease and ATPase activities; when associated with A-768. 1 Publication
    Mutagenesisi675 – 6751E → A: Nuclease dead mutant. No helicase activity when the 5'-end of the substrate is blocked. 1 Publication
    Mutagenesisi677 – 6771K → R: Nuclease dead mutant. No helicase activity when the 5'-end of the substrate is blocked. 1 Publication
    Mutagenesisi768 – 7681C → A: Abolishes iron-sulfur-binding; when associated with A-519; A-771 and A-777. Impaired nuclease and ATPase activities; when associated with A-519. 1 Publication
    Mutagenesisi771 – 7711C → A: Abolishes iron-sulfur-binding; when associated with A-519; A-768 and A-777. Impaired nuclease and ATPase activities; when associated with A-777. 1 Publication
    Mutagenesisi777 – 7771C → A: Abolishes iron-sulfur-binding; when associated with A-519; A-768 and A-771. Impaired nuclease and ATPase activities; when associated with A-771. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 15221522DNA replication ATP-dependent helicase/nuclease DNA2PRO_0000080711Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei4 – 41Phosphothreonine1 Publication
    Modified residuei17 – 171Phosphoserine; by CDK11 Publication
    Modified residuei237 – 2371Phosphoserine; by CDK11 Publication
    Modified residuei962 – 9621Phosphothreonine1 Publication

    Post-translational modificationi

    Phosphorylated at Ser-17 and Ser-237 by CDK1 in response to DNA damage, leading to promote recruitment to double-strand break (DSB) sites and DNA resection.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP38859.
    PaxDbiP38859.

    Expressioni

    Gene expression databases

    GenevestigatoriP38859.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RAD27P267933EBI-5973,EBI-14693

    Protein-protein interaction databases

    BioGridi36598. 76 interactions.
    DIPiDIP-2324N.
    IntActiP38859. 8 interactions.
    MINTiMINT-620090.
    STRINGi4932.YHR164C.

    Structurei

    3D structure databases

    ProteinModelPortaliP38859.
    SMRiP38859. Positions 1049-1466.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni450 – 900451Nuclease activityAdd
    BLAST
    Regioni901 – 1522622Helicase activityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the DNA2/NAM7 helicase family.Curated

    Phylogenomic databases

    eggNOGiCOG1112.
    GeneTreeiENSGT00550000074852.
    HOGENOMiHOG000112234.
    KOiK10742.
    OMAiMTLYRAQ.
    OrthoDBiEOG7FZ06K.

    Family and domain databases

    Gene3Di3.40.50.300. 2 hits.
    InterProiIPR026851. Dna2.
    IPR014808. DNA_replication_fac_Dna2_N.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR10887:SF14. PTHR10887:SF14. 1 hit.
    PfamiPF08696. Dna2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 2 hits.

    Sequencei

    Sequence statusi: Complete.

    P38859-1 [UniParc]FASTAAdd to Basket

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    MPGTPQKNKR SASISVSPAK KTEEKEIIQN DSKAILSKQT KRKKKYAFAP     50
    INNLNGKNTK VSNASVLKSI AVSQVRNTSR TKDINKAVSK SVKQLPNSQV 100
    KPKREMSNLS RHHDFTQDED GPMEEVIWKY SPLQRDMSDK TTSAAEYSDD 150
    YEDVQNPSST PIVPNRLKTV LSFTNIQVPN ADVNQLIQEN GNEQVRPKPA 200
    EISTRESLRN IDDILDDIEG DLTIKPTITK FSDLPSSPIK APNVEKKAEV 250
    NAEEVDKMDS TGDSNDGDDS LIDILTQKYV EKRKSESQIT IQGNTNQKSG 300
    AQESCGKNDN TKSRGEIEDH ENVDNQAKTG NAFYENEEDS NCQRIKKNEK 350
    IEYNSSDEFS DDSLIELLNE TQTQVEPNTI EQDLDKVEKM VSDDLRIATD 400
    STLSAYALRA KSGAPRDGVV RLVIVSLRSV ELPKIGTQKI LECIDGKGEQ 450
    SSVVVRHPWV YLEFEVGDVI HIIEGKNIEN KRLLSDDKNP KTQLANDNLL 500
    VLNPDVLFSA TSVGSSVGCL RRSILQMQFQ DPRGEPSLVM TLGNIVHELL 550
    QDSIKYKLSH NKISMEIIIQ KLDSLLETYS FSIIICNEEI QYVKELVMKE 600
    HAENILYFVN KFVSKSNYGC YTSISGTRRT QPISISNVID IEENIWSPIY 650
    GLKGFLDATV EANVENNKKH IVPLEVKTGK SRSVSYEVQG LIYTLLLNDR 700
    YEIPIEFFLL YFTRDKNMTK FPSVLHSIKH ILMSRNRMSM NFKHQLQEVF 750
    GQAQSRFELP PLLRDSSCDS CFIKESCMVL NKLLEDGTPE ESGLVEGEFE 800
    ILTNHLSQNL ANYKEFFTKY NDLITKEESS ITCVNKELFL LDGSTRESRS 850
    GRCLSGLVVS EVVEHEKTEG AYIYCFSRRR NDNNSQSMLS SQIAANDFVI 900
    ISDEEGHFCL CQGRVQFINP AKIGISVKRK LLNNRLLDKE KGVTTIQSVV 950
    ESELEQSSLI ATQNLVTYRI DKNDIQQSLS LARFNLLSLF LPAVSPGVDI 1000
    VDERSKLCRK TKRSDGGNEI LRSLLVDNRA PKFRDANDDP VIPYKLSKDT 1050
    TLNLNQKEAI DKVMRAEDYA LILGMPGTGK TTVIAEIIKI LVSEGKRVLL 1100
    TSYTHSAVDN ILIKLRNTNI SIMRLGMKHK VHPDTQKYVP NYASVKSYND 1150
    YLSKINSTSV VATTCLGIND ILFTLNEKDF DYVILDEASQ ISMPVALGPL 1200
    RYGNRFIMVG DHYQLPPLVK NDAARLGGLE ESLFKTFCEK HPESVAELTL 1250
    QYRMCGDIVT LSNFLIYDNK LKCGNNEVFA QSLELPMPEA LSRYRNESAN 1300
    SKQWLEDILE PTRKVVFLNY DNCPDIIEQS EKDNITNHGE AELTLQCVEG 1350
    MLLSGVPCED IGVMTLYRAQ LRLLKKIFNK NVYDGLEILT ADQFQGRDKK 1400
    CIIISMVRRN SQLNGGALLK ELRRVNVAMT RAKSKLIIIG SKSTIGSVPE 1450
    IKSFVNLLEE RNWVYTMCKD ALYKYKFPDR SNAIDEARKG CGKRTGAKPI 1500
    TSKSKFVSDK PIIKEILQEY ES 1522
    Length:1,522
    Mass (Da):171,694
    Last modified:February 1, 1995 - v1
    Checksum:i213A0458A6C69D78
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U00027 Genomic DNA. Translation: AAB68010.1.
    BK006934 Genomic DNA. Translation: DAA06857.1.
    PIRiS48904.
    RefSeqiNP_012034.1. NM_001179295.1.

    Genome annotation databases

    EnsemblFungiiYHR164C; YHR164C; YHR164C.
    GeneIDi856569.
    KEGGisce:YHR164C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U00027 Genomic DNA. Translation: AAB68010.1 .
    BK006934 Genomic DNA. Translation: DAA06857.1 .
    PIRi S48904.
    RefSeqi NP_012034.1. NM_001179295.1.

    3D structure databases

    ProteinModelPortali P38859.
    SMRi P38859. Positions 1049-1466.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 36598. 76 interactions.
    DIPi DIP-2324N.
    IntActi P38859. 8 interactions.
    MINTi MINT-620090.
    STRINGi 4932.YHR164C.

    Proteomic databases

    MaxQBi P38859.
    PaxDbi P38859.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YHR164C ; YHR164C ; YHR164C .
    GeneIDi 856569.
    KEGGi sce:YHR164C.

    Organism-specific databases

    CYGDi YHR164c.
    SGDi S000001207. DNA2.

    Phylogenomic databases

    eggNOGi COG1112.
    GeneTreei ENSGT00550000074852.
    HOGENOMi HOG000112234.
    KOi K10742.
    OMAi MTLYRAQ.
    OrthoDBi EOG7FZ06K.

    Enzyme and pathway databases

    BioCyci YEAST:G3O-31198-MONOMER.
    Reactomei REACT_188901. Cytosolic iron-sulfur cluster assembly.

    Miscellaneous databases

    NextBioi 982411.
    PROi P38859.

    Gene expression databases

    Genevestigatori P38859.

    Family and domain databases

    Gene3Di 3.40.50.300. 2 hits.
    InterProi IPR026851. Dna2.
    IPR014808. DNA_replication_fac_Dna2_N.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    PANTHERi PTHR10887:SF14. PTHR10887:SF14. 1 hit.
    Pfami PF08696. Dna2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 2 hits.
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    2. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    3. "A yeast gene required for DNA replication encodes a protein with homology to DNA helicases."
      Budd M.E., Campbell J.L.
      Proc. Natl. Acad. Sci. U.S.A. 92:7642-7646(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    4. "Dna2 of Saccharomyces cerevisiae possesses a single-stranded DNA-specific endonuclease activity that is able to act on double-stranded DNA in the presence of ATP."
      Bae S.H., Choi E., Lee K.H., Park J.S., Lee S.H., Seo Y.S.
      J. Biol. Chem. 273:26880-26890(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Dna2p helicase/nuclease is a tracking protein, like FEN1, for flap cleavage during Okazaki fragment maturation."
      Kao H.I., Campbell J.L., Bambara R.A.
      J. Biol. Chem. 279:50840-50849(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends."
      Zhu Z., Chung W.H., Shim E.Y., Lee S.E., Ira G.
      Cell 134:981-994(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
      Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
      Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-962, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. Cited for: FUNCTION, MUTAGENESIS OF GLU-675 AND LYS-677.
    9. "DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2."
      Cejka P., Cannavo E., Polaczek P., Masuda-Sasa T., Pokharel S., Campbell J.L., Kowalczykowski S.C.
      Nature 467:112-116(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation."
      Chen X., Niu H., Chung W.H., Zhu Z., Papusha A., Shim E.Y., Lee S.E., Sung P., Ira G.
      Nat. Struct. Mol. Biol. 18:1015-1019(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT THR-4; SER-17 AND SER-237, MUTAGENESIS OF THR-4; SER-17 AND SER-237.
    11. "Cross talk between the nuclease and helicase activities of Dna2: role of an essential iron-sulfur cluster domain."
      Pokharel S., Campbell J.L.
      Nucleic Acids Res. 40:7821-7830(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: COFACTOR, IRON-SULFUR-BINDING, MUTAGENESIS OF PRO-504; CYS-519; CYS-768; CYS-771 AND CYS-777.

    Entry informationi

    Entry nameiDNA2_YEAST
    AccessioniPrimary (citable) accession number: P38859
    Secondary accession number(s): D3DLB3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 126 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    3. Yeast chromosome VIII
      Yeast (Saccharomyces cerevisiae) chromosome VIII: entries and gene names

    External Data

    Dasty 3