InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SLX4

Summary

InnateDB Protein

IDBP-12163.5

Last Modified

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

Gene Symbol

SLX4

Protein Name

SLX4 structure-specific endonuclease subunit homolog (S. cerevisiae)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000294008

InnateDB Gene

IDBG-12161 (SLX4)

Protein Structure

UniProt Annotation

Function

Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure- specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81- EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269PubMed:19595721, ECO:0000269PubMed:19595722, ECO:0000269PubMed:19596235, ECO:0000269PubMed:19596236}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:19596235, ECO:0000269PubMed:19596236}. Note=Localizes to sites of DNA dammage.

Disease Associations

Fanconi anemia complementation group P (FANCP) [MIM:613951]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some individuals affected by Fanconi anemia of complementation group P have skeletal anomalies. {ECO:0000269PubMed:21240275, ECO:0000269PubMed:21240277}. 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 52 experimentally validated interaction(s) in this database.

Experimentally validated
Total	52 [view]
Protein-Protein	52 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008047	enzyme activator activity
GO:0008821	crossover junction endodeoxyribonuclease activity
GO:0017108	5'-flap endonuclease activity
GO:0048257	3'-flap endonuclease activity

Biological Process

GO:0000724	double-strand break repair via homologous recombination
GO:0000737	DNA catabolic process, endonucleolytic
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006289	nucleotide-excision repair
GO:0010792	DNA double-strand break processing involved in repair via single-strand annealing
GO:0043085	positive regulation of catalytic activity
GO:0045087	innate immune response (InnateDB)
GO:0072429	response to intra-S DNA damage checkpoint signaling

Cellular Component

GO:0000784	nuclear chromosome, telomeric region
GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0030054	cell junction
GO:0033557	Slx1-Slx4 complex
GO:0048476	Holliday junction resolvase complex
GO:0070522	ERCC4-ERCC1 complex