InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DNA2

Summary

InnateDB Protein

IDBP-76118.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DNA2

Protein Name

DNA replication helicase 2 homolog (yeast)

Synonyms

DNA2L; hDNA2;

Species

Homo sapiens

Ensembl Protein

ENSP00000351185

InnateDB Gene

IDBG-76116 (DNA2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:16595799, ECO:0000269PubMed:16595800, ECO:0000269PubMed:18995831, ECO:0000269PubMed:19487465, ECO:0000269PubMed:21325134, ECO:0000269PubMed:21572043, ECO:0000269PubMed:22570407, ECO:0000269PubMed:22570476}.

Subcellular Localization

Nucleus. Mitochondrion. Note=Was initially reported to be exclusively mitochondrial (PubMed:18995831). However, it was later shown to localize both in mitochondrion and nucleus (PubMed:19487465). {ECO:0000269PubMed:18995831, ECO:0000269PubMed:19487465}.

Disease Associations

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6 (PEOA6) [MIM:615156]: A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression. {ECO:0000269PubMed:23352259}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003678	DNA helicase activity
GO:0004386	helicase activity
GO:0004518	nuclease activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016887	ATPase activity
GO:0016890	site-specific endodeoxyribonuclease activity, specific for altered base
GO:0017108	5'-flap endonuclease activity
GO:0043139	5'-3' DNA helicase activity
GO:0043142	single-stranded DNA-dependent ATPase activity
GO:0046872	metal ion binding
GO:0051539	4 iron, 4 sulfur cluster binding

Biological Process

GO:0000076	DNA replication checkpoint
GO:0000278	mitotic cell cycle
GO:0000722	telomere maintenance via recombination
GO:0000723	telomere maintenance
GO:0000729	DNA double-strand break processing
GO:0000737	DNA catabolic process, endonucleolytic
GO:0006200	ATP catabolic process
GO:0006260	DNA replication
GO:0006264	mitochondrial DNA replication
GO:0006271	DNA strand elongation involved in DNA replication
GO:0006284	base-excision repair
GO:0032201	telomere maintenance via semi-conservative replication
GO:0032508	DNA duplex unwinding
GO:0033567	DNA replication, Okazaki fragment processing
GO:0043137	DNA replication, removal of RNA primer
GO:0043504	mitochondrial DNA repair
GO:0045740	positive regulation of DNA replication