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P38859 (DNA2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA replication ATP-dependent helicase/nuclease DNA2

Including the following 2 domains:

  1. DNA replication nuclease DNA2
    EC=3.1.-.-
  2. DNA replication ATP-dependent helicase DNA2
    EC=3.6.4.12
Gene names
Name:DNA2
Ordered Locus Names:YHR164C
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length1522 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10

Catalytic activity

ATP + H2O = ADP + phosphate.

Cofactor

Binds 1 4Fe-4S cluster. Ref.11

Subcellular location

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

Post-translational modification

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. Ref.10

Sequence similarities

Belongs to the DNA2/NAM7 helicase family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
DNA replication
   Cellular componentChromosome
Nucleus
   Ligand4Fe-4S
ATP-binding
DNA-binding
Iron
Iron-sulfur
Metal-binding
Nucleotide-binding
   Molecular functionHelicase
Hydrolase
Nuclease
   PTMPhosphoprotein
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay Ref.11. Source: GOC

DNA catabolic process, endonucleolytic

Inferred from direct assay Ref.5PubMed 23671118Ref.4. Source: GOC

DNA double-strand break processing

Inferred from mutant phenotype Ref.10. Source: UniProtKB

DNA duplex unwinding

Inferred from direct assay Ref.8Ref.3. Source: GOC

DNA repair

Inferred from mutant phenotype PubMed 10101169. Source: SGD

DNA replication, Okazaki fragment processing

Inferred from electronic annotation. Source: InterPro

DNA strand renaturation

Inferred from direct assay PubMed 17032657. Source: SGD

DNA-dependent DNA replication

Inferred from direct assay PubMed 9710536. Source: SGD

cellular response to DNA damage stimulus

Inferred from direct assay Ref.10. Source: UniProtKB

lagging strand elongation

Inferred from mutant phenotype PubMed 10101169PubMed 10330154. Source: SGD

meiotic DNA double-strand break processing

Inferred from genetic interaction PubMed 20150422. Source: SGD

replicative cell aging

Inferred from mutant phenotype PubMed 12024027. Source: SGD

telomere maintenance

Inferred from mutant phenotype PubMed 12024033. Source: SGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19520826. Source: SGD

cytosol

Traceable author statement. Source: Reactome

nuclear chromosome, telomeric region

Inferred from direct assay PubMed 12024033. Source: SGD

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

site of double-strand break

Inferred from direct assay Ref.10. Source: UniProtKB

   Molecular_function4 iron, 4 sulfur cluster binding

Inferred from direct assay Ref.11. Source: UniProtKB

5'-3' DNA helicase activity

Inferred from direct assay Ref.8. Source: UniProtKB

5'-flap endonuclease activity

Inferred from direct assay Ref.5. Source: SGD

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent DNA helicase activity

Inferred from direct assay Ref.3. Source: SGD

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nuclease activity

Inferred from direct assay Ref.11. Source: UniProtKB

single-stranded DNA endodeoxyribonuclease activity

Inferred from direct assay PubMed 23671118Ref.4. Source: SGD

single-stranded DNA-dependent ATPase activity

Inferred from direct assay Ref.11. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAD27P267933EBI-5973,EBI-14693

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15221522DNA replication ATP-dependent helicase/nuclease DNA2
PRO_0000080711

Regions

Nucleotide binding1074 – 10818ATP By similarity
Region450 – 900451Nuclease activity
Region901 – 1522622Helicase activity

Sites

Metal binding5191Iron-sulfur (4Fe-4S)
Metal binding7681Iron-sulfur (4Fe-4S)
Metal binding7711Iron-sulfur (4Fe-4S)
Metal binding7771Iron-sulfur (4Fe-4S)

Amino acid modifications

Modified residue41Phosphothreonine Ref.10
Modified residue171Phosphoserine; by CDK1 Ref.10
Modified residue2371Phosphoserine; by CDK1 Ref.10
Modified residue9621Phosphothreonine Ref.7

Experimental info

Mutagenesis41T → 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. Ref.10
Mutagenesis171S → 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. Ref.10
Mutagenesis171S → D: Mimics phosphorylation; restores nuclear localization and recruitment at double-strand. break (DSB) sites following DNA damage; when associated with D-237. Ref.10
Mutagenesis2371S → 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. Ref.10
Mutagenesis2371S → D: Mimics phosphorylation; restores nuclear localization and recruitment at double-strand. break (DSB) sites following DNA damage; when associated with D-17. Ref.10
Mutagenesis5041P → S in dna2-1; temperature-sensitive mutant unable to grow at 37 degrees Celsius, probably due to abolition of iron-sulfur-binding. Ref.11
Mutagenesis5191C → 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. Ref.11
Mutagenesis6751E → A: Nuclease dead mutant. No helicase activity when the 5'-end of the substrate is blocked. Ref.8
Mutagenesis6771K → R: Nuclease dead mutant. No helicase activity when the 5'-end of the substrate is blocked. Ref.8
Mutagenesis7681C → 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. Ref.11
Mutagenesis7711C → 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. Ref.11
Mutagenesis7771C → 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. Ref.11

Sequences

Sequence LengthMass (Da)Tools
P38859 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 213A0458A6C69D78

FASTA1,522171,694
        10         20         30         40         50         60 
MPGTPQKNKR SASISVSPAK KTEEKEIIQN DSKAILSKQT KRKKKYAFAP INNLNGKNTK 

        70         80         90        100        110        120 
VSNASVLKSI AVSQVRNTSR TKDINKAVSK SVKQLPNSQV KPKREMSNLS RHHDFTQDED 

       130        140        150        160        170        180 
GPMEEVIWKY SPLQRDMSDK TTSAAEYSDD YEDVQNPSST PIVPNRLKTV LSFTNIQVPN 

       190        200        210        220        230        240 
ADVNQLIQEN GNEQVRPKPA EISTRESLRN IDDILDDIEG DLTIKPTITK FSDLPSSPIK 

       250        260        270        280        290        300 
APNVEKKAEV NAEEVDKMDS TGDSNDGDDS LIDILTQKYV EKRKSESQIT IQGNTNQKSG 

       310        320        330        340        350        360 
AQESCGKNDN TKSRGEIEDH ENVDNQAKTG NAFYENEEDS NCQRIKKNEK IEYNSSDEFS 

       370        380        390        400        410        420 
DDSLIELLNE TQTQVEPNTI EQDLDKVEKM VSDDLRIATD STLSAYALRA KSGAPRDGVV 

       430        440        450        460        470        480 
RLVIVSLRSV ELPKIGTQKI LECIDGKGEQ SSVVVRHPWV YLEFEVGDVI HIIEGKNIEN 

       490        500        510        520        530        540 
KRLLSDDKNP KTQLANDNLL VLNPDVLFSA TSVGSSVGCL RRSILQMQFQ DPRGEPSLVM 

       550        560        570        580        590        600 
TLGNIVHELL QDSIKYKLSH NKISMEIIIQ KLDSLLETYS FSIIICNEEI QYVKELVMKE 

       610        620        630        640        650        660 
HAENILYFVN KFVSKSNYGC YTSISGTRRT QPISISNVID IEENIWSPIY GLKGFLDATV 

       670        680        690        700        710        720 
EANVENNKKH IVPLEVKTGK SRSVSYEVQG LIYTLLLNDR YEIPIEFFLL YFTRDKNMTK 

       730        740        750        760        770        780 
FPSVLHSIKH ILMSRNRMSM NFKHQLQEVF GQAQSRFELP PLLRDSSCDS CFIKESCMVL 

       790        800        810        820        830        840 
NKLLEDGTPE ESGLVEGEFE ILTNHLSQNL ANYKEFFTKY NDLITKEESS ITCVNKELFL 

       850        860        870        880        890        900 
LDGSTRESRS GRCLSGLVVS EVVEHEKTEG AYIYCFSRRR NDNNSQSMLS SQIAANDFVI 

       910        920        930        940        950        960 
ISDEEGHFCL CQGRVQFINP AKIGISVKRK LLNNRLLDKE KGVTTIQSVV ESELEQSSLI 

       970        980        990       1000       1010       1020 
ATQNLVTYRI DKNDIQQSLS LARFNLLSLF LPAVSPGVDI VDERSKLCRK TKRSDGGNEI 

      1030       1040       1050       1060       1070       1080 
LRSLLVDNRA PKFRDANDDP VIPYKLSKDT TLNLNQKEAI DKVMRAEDYA LILGMPGTGK 

      1090       1100       1110       1120       1130       1140 
TTVIAEIIKI LVSEGKRVLL TSYTHSAVDN ILIKLRNTNI SIMRLGMKHK VHPDTQKYVP 

      1150       1160       1170       1180       1190       1200 
NYASVKSYND YLSKINSTSV VATTCLGIND ILFTLNEKDF DYVILDEASQ ISMPVALGPL 

      1210       1220       1230       1240       1250       1260 
RYGNRFIMVG DHYQLPPLVK NDAARLGGLE ESLFKTFCEK HPESVAELTL QYRMCGDIVT 

      1270       1280       1290       1300       1310       1320 
LSNFLIYDNK LKCGNNEVFA QSLELPMPEA LSRYRNESAN SKQWLEDILE PTRKVVFLNY 

      1330       1340       1350       1360       1370       1380 
DNCPDIIEQS EKDNITNHGE AELTLQCVEG MLLSGVPCED IGVMTLYRAQ LRLLKKIFNK 

      1390       1400       1410       1420       1430       1440 
NVYDGLEILT ADQFQGRDKK CIIISMVRRN SQLNGGALLK ELRRVNVAMT RAKSKLIIIG 

      1450       1460       1470       1480       1490       1500 
SKSTIGSVPE IKSFVNLLEE RNWVYTMCKD ALYKYKFPDR SNAIDEARKG CGKRTGAKPI 

      1510       1520 
TSKSKFVSDK PIIKEILQEY ES 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII."
Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P. expand/collapse author list , Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., Vaudin M.
Science 265:2077-2082(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
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]"Dna2 exhibits a unique strand end-dependent helicase function."
Balakrishnan L., Polaczek P., Pokharel S., Campbell J.L., Bambara R.A.
J. Biol. Chem. 285:38861-38868(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U00027 Genomic DNA. Translation: AAB68010.1.
BK006934 Genomic DNA. Translation: DAA06857.1.
PIRS48904.
RefSeqNP_012034.1. NM_001179295.1.

3D structure databases

ProteinModelPortalP38859.
SMRP38859. Positions 445-474, 813-1470.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid36598. 76 interactions.
DIPDIP-2324N.
IntActP38859. 8 interactions.
MINTMINT-620090.
STRING4932.YHR164C.

Proteomic databases

PaxDbP38859.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYHR164C; YHR164C; YHR164C.
GeneID856569.
KEGGsce:YHR164C.

Organism-specific databases

CYGDYHR164c.
SGDS000001207. DNA2.

Phylogenomic databases

eggNOGCOG1112.
GeneTreeENSGT00550000074852.
HOGENOMHOG000112234.
KOK10742.
OMAMTLYRAQ.
OrthoDBEOG7FZ06K.

Enzyme and pathway databases

BioCycYEAST:G3O-31198-MONOMER.
ReactomeREACT_160098. Cytosolic Iron-sulfur Cluster Assembly (yeast).
REACT_191296. Metabolism.

Gene expression databases

GenevestigatorP38859.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR026851. Dna2.
IPR014808. DNA_replication_fac_Dna2_N.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10887:SF14. PTHR10887:SF14. 1 hit.
PfamPF08696. Dna2. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

NextBio982411.
PROP38859.

Entry information

Entry nameDNA2_YEAST
AccessionPrimary (citable) accession number: P38859
Secondary accession number(s): D3DLB3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome VIII

Yeast (Saccharomyces cerevisiae) chromosome VIII: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families