Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA replication ATP-dependent helicase/nuclease DNA2

Gene

Dna2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. 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: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. 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 subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi137Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi394Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi397Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi403Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi649 – 656ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, 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

ReactomeiR-MMU-174437. Removal of the Flap Intermediate from the C-strand.
R-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
R-MMU-69166. Removal of the Flap Intermediate.
R-MMU-69473. G2/M DNA damage checkpoint.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication ATP-dependent helicase/nuclease DNA2
Alternative name(s):
DNA replication ATP-dependent helicase-like homolog
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
Synonyms:Dna2l, Kiaa0083
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2443732. Dna2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002636041 – 1062DNA replication ATP-dependent helicase/nuclease DNA2Add BLAST1062

Post-translational modificationi

Acetylated by EP300, leading to stimulate the 5'-3' endonuclease, the 5'-3' helicase and DNA-dependent ATPase activities, possibly by increasing DNA substrate affinity.By similarity

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ6ZQJ5.
PaxDbiQ6ZQJ5.
PeptideAtlasiQ6ZQJ5.
PRIDEiQ6ZQJ5.

PTM databases

iPTMnetiQ6ZQJ5.
PhosphoSitePlusiQ6ZQJ5.

Expressioni

Gene expression databases

BgeeiENSMUSG00000036875.
CleanExiMM_DNA2.
GenevisibleiQ6ZQJ5. MM.

Interactioni

Subunit structurei

Interacts with BLM and WDHD1.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Terf1P703714EBI-6919222,EBI-6919183
Terf2O351444EBI-6919222,EBI-6919263

Protein-protein interaction databases

IntActiQ6ZQJ5. 2 interactors.
STRINGi10090.ENSMUSP00000115750.

Structurei

Secondary structure

11062
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 9Combined sources6
Helixi23 – 34Combined sources12
Helixi43 – 45Combined sources3
Beta strandi47 – 57Combined sources11
Beta strandi59 – 74Combined sources16
Beta strandi79 – 83Combined sources5
Helixi85 – 89Combined sources5
Beta strandi97 – 102Combined sources6
Beta strandi106 – 111Combined sources6
Beta strandi113 – 115Combined sources3
Beta strandi117 – 121Combined sources5
Helixi128 – 133Combined sources6
Turni134 – 136Combined sources3
Helixi138 – 146Combined sources9
Helixi148 – 150Combined sources3
Helixi155 – 172Combined sources18
Helixi177 – 188Combined sources12
Helixi191 – 200Combined sources10
Helixi204 – 225Combined sources22
Helixi231 – 233Combined sources3
Beta strandi252 – 268Combined sources17
Turni269 – 272Combined sources4
Beta strandi273 – 287Combined sources15
Beta strandi290 – 301Combined sources12
Helixi309 – 322Combined sources14
Turni323 – 325Combined sources3
Beta strandi330 – 336Combined sources7
Turni337 – 339Combined sources3
Beta strandi342 – 346Combined sources5
Helixi349 – 367Combined sources19
Beta strandi370 – 374Combined sources5
Beta strandi379 – 381Combined sources3
Helixi391 – 395Combined sources5
Helixi400 – 409Combined sources10
Helixi421 – 431Combined sources11
Helixi436 – 453Combined sources18
Helixi456 – 458Combined sources3
Helixi463 – 466Combined sources4
Helixi470 – 474Combined sources5
Beta strandi475 – 484Combined sources10
Beta strandi490 – 493Combined sources4
Beta strandi496 – 502Combined sources7
Beta strandi504 – 506Combined sources3
Beta strandi518 – 525Combined sources8
Helixi526 – 528Combined sources3
Beta strandi532 – 539Combined sources8
Beta strandi541 – 550Combined sources10
Beta strandi561 – 565Combined sources5
Helixi570 – 572Combined sources3
Helixi573 – 582Combined sources10
Beta strandi584 – 586Combined sources3
Helixi587 – 596Combined sources10
Helixi609 – 611Combined sources3
Helixi614 – 616Combined sources3
Helixi617 – 625Combined sources9
Helixi629 – 640Combined sources12
Beta strandi641 – 649Combined sources9
Helixi655 – 668Combined sources14
Beta strandi673 – 679Combined sources7
Helixi680 – 692Combined sources13
Helixi703 – 705Combined sources3
Turni708 – 710Combined sources3
Helixi711 – 713Combined sources3
Helixi715 – 721Combined sources7
Helixi727 – 734Combined sources8
Beta strandi738 – 743Combined sources6
Helixi744 – 746Combined sources3
Helixi750 – 753Combined sources4
Beta strandi757 – 762Combined sources6
Helixi765 – 767Combined sources3
Helixi770 – 773Combined sources4
Helixi775 – 779Combined sources5
Beta strandi780 – 787Combined sources8
Helixi799 – 803Combined sources5
Turni804 – 807Combined sources4
Helixi810 – 814Combined sources5
Helixi818 – 820Combined sources3
Beta strandi821 – 824Combined sources4
Beta strandi826 – 830Combined sources5
Helixi832 – 841Combined sources10
Beta strandi848 – 851Combined sources4
Helixi852 – 856Combined sources5
Helixi864 – 871Combined sources8
Turni872 – 874Combined sources3
Helixi881 – 887Combined sources7
Beta strandi893 – 897Combined sources5
Beta strandi899 – 901Combined sources3
Beta strandi906 – 908Combined sources3
Beta strandi911 – 913Combined sources3
Helixi915 – 930Combined sources16
Helixi935 – 937Combined sources3
Beta strandi938 – 941Combined sources4
Helixi945 – 957Combined sources13
Beta strandi963 – 966Combined sources4
Helixi968 – 971Combined sources4
Beta strandi976 – 982Combined sources7
Beta strandi988 – 990Combined sources3
Helixi995 – 997Combined sources3
Helixi999 – 1006Combined sources8
Beta strandi1008 – 1017Combined sources10
Helixi1019 – 1022Combined sources4
Helixi1026 – 1036Combined sources11
Turni1037 – 1039Combined sources3
Beta strandi1041 – 1043Combined sources3
Helixi1050 – 1053Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EANX-ray2.36A1-1056[»]
5EAWX-ray3.00A/B1-1056[»]
5EAXX-ray3.05A/B1-1056[»]
ProteinModelPortaliQ6ZQJ5.
SMRiQ6ZQJ5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni82 – 520Nuclease activityBy similarityAdd BLAST439
Regioni521 – 1062Helicase activityBy similarityAdd BLAST542

Sequence similaritiesi

Belongs to the DNA2/NAM7 helicase family.Curated

Phylogenomic databases

eggNOGiKOG1805. Eukaryota.
COG1112. LUCA.
GeneTreeiENSGT00780000122010.
HOGENOMiHOG000168456.
HOVERGENiHBG081456.
InParanoidiQ6ZQJ5.
KOiK10742.
OMAiHWCGLLA.
OrthoDBiEOG091G01N1.
PhylomeDBiQ6ZQJ5.
TreeFamiTF314903.

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. 2 hits.
PfamiPF08696. Dna2. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6ZQJ5-1) [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
MEPLDELDLL LLEEDGGAEA VPRVELLRKK ADALFPETVL SRGVDNRYLV
60 70 80 90 100
LAVETSQNER GAEEKRLHVT ASQDREHEVL CILRNGWSSV PVEPGDIVHL
110 120 130 140 150
EGDCTSEPWI IDDDFGYFIL YPDMMISGTS VASSIRCLRR AVLSETFRGS
160 170 180 190 200
DPATRQMLIG TILHEVFQKA ISESFAPERL QELALQTLRE VRHLKEMYRL
210 220 230 240 250
NLSQDEILCE VEEYLPSFSK WAEDFMRKGP SSEFPQMQLS LPSDGSNRSS
260 270 280 290 300
PCNIEVVKSL DIEESIWSPR FGLKGKIDVT VGVKIHRDCK MKYKVMPLEL
310 320 330 340 350
KTGKESNSIE HRSQVVLYTL LSQERREDPE AGWLLYLKTG QMYPVPANHL
360 370 380 390 400
DKRELLKLRN WLAASLLHRV SRAAPGEEAR LSALPQIIEE EKTCKYCSQI
410 420 430 440 450
GNCALYSRAV EEQGDDASIP EAMLSKIQEE TRHLQLAHLK YFSLWCLMLT
460 470 480 490 500
LESQSKDNRK THQSIWLTPA SELEESGNCV GNLVRTEPVS RVCDGQYLHN
510 520 530 540 550
FQRKNGPMPA TNLMAGDRII LSGEERKLFA LSKGYVKKMN KAAVTCLLDR
560 570 580 590 600
NLSTLPATTV FRLDREERHG DISTPLGNLS KLMESTDPSK RLRELIIDFR
610 620 630 640 650
EPQFIAYLSS VLPHDAKDTV ANILKGLNKP QRQAMKRVLL SKDYTLIVGM
660 670 680 690 700
PGTGKTTTIC ALVRILSACG FSVLLTSYTH SAVDNILLKL AKFKVGFLRL
710 720 730 740 750
GQSHKVHPDI QKFTEEEICR SRSIASLAHL EELYNSHPIV ATTCMGINHP
760 770 780 790 800
IFSRKTFDFC IVDEASQISQ PVCLGPLFFS RRFVLVGDHQ QLPPLVVNRE
810 820 830 840 850
ARALGMSESL FKRLERNESA VVQLTVQYRM NRKIMSLSNK LTYAGKLECG
860 870 880 890 900
SDRVANAVLA LPNLKDARLS LQLYADYSDS PWLAGVLEPD NPVCFLNTDK
910 920 930 940 950
VPAPEQVENG GVSNVTEARL IVFLTSTFIK AGCSPSDIGV IAPYRQQLRI
960 970 980 990 1000
ISDLLARSSV GMVEVNTVDK YQGRDKSLIL VSFVRSNEDG TLGELLKDWR
1010 1020 1030 1040 1050
RLNVALTRAK HKLILLGSVS SLKRFPPLGT LFDHLNAEQL ILDLPSREHE
1060
SLSHILGDCQ RD
Length:1,062
Mass (Da):119,447
Last modified:December 12, 2006 - v2
Checksum:iCD009CB89ACA775C
GO
Isoform 2 (identifier: Q6ZQJ5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     932-966: GCSPSDIGVIAPYRQQLRIISDLLARSSVGMVEVN → AAPQTLASSPRTDSSCGSSATYWPGLLLGWLRLTQ
     967-1062: Missing.

Note: No experimental confirmation available.
Show »
Length:966
Mass (Da):108,508
Checksum:iC3C38997DFB65AE9
GO

Sequence cautioni

The sequence BAC97861 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti285I → K in BAC25919 (PubMed:16141072).Curated1
Sequence conflicti375P → L in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti400I → M in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti486T → M in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti543A → V in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti881P → S in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti957R → Q in AAH25182 (PubMed:15489334).Curated1
Sequence conflicti1037A → T in AAH25182 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021872932 – 966GCSPS…MVEVN → AAPQTLASSPRTDSSCGSSA TYWPGLLLGWLRLTQ in isoform 2. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_021873967 – 1062Missing in isoform 2. 1 PublicationAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129051 mRNA. Translation: BAC97861.1. Different initiation.
AK028381 mRNA. Translation: BAC25919.1.
BC025182 mRNA. Translation: AAH25182.1.
BC115716 mRNA. Translation: AAI15717.1.
CCDSiCCDS35923.1. [Q6ZQJ5-1]
RefSeqiNP_796346.2. NM_177372.3. [Q6ZQJ5-1]
XP_017169460.1. XM_017313971.1. [Q6ZQJ5-2]
UniGeneiMm.21492.

Genome annotation databases

EnsembliENSMUST00000092462; ENSMUSP00000090119; ENSMUSG00000036875. [Q6ZQJ5-2]
ENSMUST00000131422; ENSMUSP00000115750; ENSMUSG00000036875. [Q6ZQJ5-1]
GeneIDi327762.
KEGGimmu:327762.
UCSCiuc007fji.2. mouse. [Q6ZQJ5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129051 mRNA. Translation: BAC97861.1. Different initiation.
AK028381 mRNA. Translation: BAC25919.1.
BC025182 mRNA. Translation: AAH25182.1.
BC115716 mRNA. Translation: AAI15717.1.
CCDSiCCDS35923.1. [Q6ZQJ5-1]
RefSeqiNP_796346.2. NM_177372.3. [Q6ZQJ5-1]
XP_017169460.1. XM_017313971.1. [Q6ZQJ5-2]
UniGeneiMm.21492.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EANX-ray2.36A1-1056[»]
5EAWX-ray3.00A/B1-1056[»]
5EAXX-ray3.05A/B1-1056[»]
ProteinModelPortaliQ6ZQJ5.
SMRiQ6ZQJ5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ6ZQJ5. 2 interactors.
STRINGi10090.ENSMUSP00000115750.

PTM databases

iPTMnetiQ6ZQJ5.
PhosphoSitePlusiQ6ZQJ5.

Proteomic databases

EPDiQ6ZQJ5.
PaxDbiQ6ZQJ5.
PeptideAtlasiQ6ZQJ5.
PRIDEiQ6ZQJ5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092462; ENSMUSP00000090119; ENSMUSG00000036875. [Q6ZQJ5-2]
ENSMUST00000131422; ENSMUSP00000115750; ENSMUSG00000036875. [Q6ZQJ5-1]
GeneIDi327762.
KEGGimmu:327762.
UCSCiuc007fji.2. mouse. [Q6ZQJ5-1]

Organism-specific databases

CTDi1763.
MGIiMGI:2443732. Dna2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1805. Eukaryota.
COG1112. LUCA.
GeneTreeiENSGT00780000122010.
HOGENOMiHOG000168456.
HOVERGENiHBG081456.
InParanoidiQ6ZQJ5.
KOiK10742.
OMAiHWCGLLA.
OrthoDBiEOG091G01N1.
PhylomeDBiQ6ZQJ5.
TreeFamiTF314903.

Enzyme and pathway databases

ReactomeiR-MMU-174437. Removal of the Flap Intermediate from the C-strand.
R-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
R-MMU-69166. Removal of the Flap Intermediate.
R-MMU-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

ChiTaRSiDna2. mouse.
PROiQ6ZQJ5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036875.
CleanExiMM_DNA2.
GenevisibleiQ6ZQJ5. MM.

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. 2 hits.
PfamiPF08696. Dna2. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiDNA2_MOUSE
AccessioniPrimary (citable) accession number: Q6ZQJ5
Secondary accession number(s): Q14BM9, Q8BSZ0, Q8R3J3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 12, 2006
Last modified: November 2, 2016
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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.