InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Xpc

Summary

InnateDB Protein

IDBP-170260.6

Last Modified

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

Gene Symbol

Xpc

Protein Name

xeroderma pigmentosum, complementation group C

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000032182

InnateDB Gene

IDBG-170258 (Xpc)

Protein Structure

UniProt Annotation

Function

Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by Rad23b and Rad23a. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA- binding activity.The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, Xpa, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the Xpc:Rad23b dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. Xpc:Rad23b induces a bend in DNA upon binding. Xpc:Rad23b stimulates the activity of DNA glycosylases Tdg and Smug1 (By similarity). {ECO:0000250}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Omnipresent in the nucleus and consistently associates with and dissociates from DNA in the absence of DNA damage. Continuously shuttles between the cytoplasm and the nucleus, which is impeded by the presence of NER lesions (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 35 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	35 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003684	damaged DNA binding
GO:0003697	single-stranded DNA binding
GO:0005515	protein binding

Biological Process

GO:0000715	nucleotide-excision repair, DNA damage recognition
GO:0006281	DNA repair
GO:0006289	nucleotide-excision repair
GO:0006974	cellular response to DNA damage stimulus
GO:0010224	response to UV-B
GO:0031573	intra-S DNA damage checkpoint
GO:0042493	response to drug
GO:1901990	regulation of mitotic cell cycle phase transition

Cellular Component

GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0070062	extracellular vesicular exosome
GO:0071942	XPC complex

Protein Structure and Domains

PDB ID

MGI:103557

InterPro

IPR018026 DNA repair protein Rad4, subgroup
IPR018325 Rad4/PNGase transglutaminase-like fold
IPR018326 Rad4 beta-hairpin domain 1
IPR018327 Rad4 beta-hairpin domain 2
IPR018328 Rad4 beta-hairpin domain 3

PFAM

PF03835
PF10403
PF10404
PF10405

PRINTS

PIRSF

SMART

SM01030
SM01031
SM01032

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P51612