UniProt Accession

 DNA2_HUMAN; P51530; Q2NKM1; Q5TC49; Q5TC50; Q6P455; Q6PI80; Q7Z6H9; Q8N346 

Genbank Protein ID

 D42046; AL136233; AL136233; BC041115; BC053574; BC063664; BC111740; BC028188 

Genbank Nucleotide ID

 BAA07647.1; CAI17238.1; CAI17237.1; AAH41115.1; AAH53574.1; AAH63664.1; AAI11741.1; AAH28188.1 

Protein Name

 DNA replication ATP-dependent helicase/nuclease DNA2 

Protein Synonyms/Alias

 hDNA2; DNA replication ATP-dependent helicase-like homolog; DNA replication nuclease DNA2; DNA replication ATP-dependent helicase DNA2 

Gene Name

 DNA2 

Gene Synonyms/Alias

 DNA2L; KIAA0083 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
28	LPAELFQKKVVASFP	ubiquitination	[1, 2]
29	PAELFQKKVVASFPR	ubiquitination	[2]
58	AVNTVQNKEGNCEKR	ubiquitination	[2]
77	ASQSLENKELCILRN	ubiquitination	[2]
194	IQEIRHLKEMYRLNL	ubiquitination	[2]
227	WAGDFMHKNTSTDFP	ubiquitination	[2]
257	TCNIEVVKPMDIEES	ubiquitination	[2]
293	RGYKTKYKIMPLELK	ubiquitination	[2]
300	KIMPLELKTGKESNS	ubiquitination	[1, 2]
303	PLELKTGKESNSIEH	ubiquitination	[1]
351	VPANHLDKRELLKLR	ubiquitination	[1, 2]
377	SKSATRQKTQLASLP	ubiquitination	[1, 2]
391	PQIIEEEKTCKYCSQ	ubiquitination	[2]
394	IEEEKTCKYCSQIGN	ubiquitination	[2]
425	VPIVMLPKIEEETQH	ubiquitination	[2]
459	SQSKDNKKNHQNIWL	ubiquitination	[2]
474	MPASEMEKSGSCIGN	ubiquitination	[2]
489	LIRMEHVKIVCDGQY	ubiquitination	[2]
503	YLHNFQCKHGAIPVT	ubiquitination	[2]
536	ALSRGYVKEINMTTV	ubiquitination	[2]
567	FRLDQEEKNCDIDTP	ubiquitination	[2]
580	TPLGNLSKLMENTFV	ubiquitination	[2]
589	MENTFVSKKLRDLII	ubiquitination	[2]
590	ENTFVSKKLRDLIID	ubiquitination	[2]
624	DTVACILKGLNKPQR	ubiquitination	[2, 3, 4]
641	MKKVLLSKDYTLIVG	ubiquitination	[2]
693	LLKLAKFKIGFLRLG	ubiquitination	[2]
704	LRLGQIQKVHPAIQQ	ubiquitination	[2]
811	GMSESLFKRLEQNKS	ubiquitination	[1, 2]
832	VQYRMNSKIMSLSNK	ubiquitination	[2]
845	NKLTYEGKLECGSDK	ubiquitination	[2]
852	KLECGSDKVANAVIN	ubiquitination	[2]
908	PAPEQVEKGGVSNVT	ubiquitination	[1]
948	APYRQQLKIINDLLA	ubiquitination	[2]
968	VEVNTVDKYQGRDKS	ubiquitination	[1, 3, 4, 5]
995	GTVGELLKDWRRLNV	ubiquitination	[2]
1037	LNHLNSEKLIIDLPS	ubiquitination	[2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 

Functional Description

 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. 

Sequence Annotation

 NP_BIND 648 655 ATP (Potential).
 REGION 81 519 Nuclease activity (By similarity).
 REGION 520 1060 Helicase activity (By similarity).
 METAL 136 136 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 393 393 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 396 396 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 402 402 Iron-sulfur (4Fe-4S) (By similarity).  

Keyword

 4Fe-4S; Acetylation; Alternative splicing; ATP-binding; Complete proteome; DNA damage; DNA repair; DNA replication; DNA-binding; Endonuclease; Helicase; Hydrolase; Iron; Iron-sulfur; Metal-binding; Mitochondrion; Multifunctional enzyme; Nuclease; Nucleotide-binding; Nucleus; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1060 AA 

Protein Sequence

Gene Ontology

 GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
 GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB.
 GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0043142; F:single-stranded DNA-dependent ATPase activity; IDA:UniProtKB.
 GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; IDA:UniProtKB.
 GO:0006284; P:base-excision repair; IDA:UniProtKB.
 GO:0000729; P:DNA double-strand break processing; IDA:UniProtKB.
 GO:0000076; P:DNA replication checkpoint; IMP:UniProtKB.
 GO:0043137; P:DNA replication, removal of RNA primer; IDA:UniProtKB.
 GO:0043504; P:mitochondrial DNA repair; IDA:UniProtKB.
 GO:0006264; P:mitochondrial DNA replication; IDA:UniProtKB.
 GO:0000278; P:mitotic cell cycle; TAS:Reactome.
 GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB.
 GO:0000722; P:telomere maintenance via recombination; TAS:Reactome.
 GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. 

Interpro

 IPR026851; Dna2.
 IPR014808; DNA_replication_fac_Dna2_N.
 IPR027417; P-loop_NTPase. 

Pfam

 PF08696; Dna2 

SMART

  

PROSITE

  

PRINTS