Homo sapiens Protein: XPC | |||||||||||||||||||||||
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Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-19994.6 | ||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||
Gene Symbol | XPC | ||||||||||||||||||||||
Protein Name | xeroderma pigmentosum, complementation group C | ||||||||||||||||||||||
Synonyms | p125; RAD4; XP3; XPCC; | ||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||
Ensembl Protein | ENSP00000285021 | ||||||||||||||||||||||
InnateDB Gene | IDBG-19992 (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. | ||||||||||||||||||||||
Subcellular Localization | Nucleus. Cytoplasm. 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. | ||||||||||||||||||||||
Disease Associations | Xeroderma pigmentosum complementation group C (XP-C) [MIM:278720]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. {ECO:0000269PubMed:10766188, ECO:0000269PubMed:8298653}. 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 65 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||
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 |
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PFAM |
PF03835
PF10403 PF10404 PF10405 |
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PRINTS | |||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||
SMART |
SM01030
SM01031 SM01032 |
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TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | Q01831 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-Q01831 | ||||||||||||||||||||||
TrEMBL | X5DRB1 | ||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 7508 | ||||||||||||||||||||||
UniGene | Hs.475538 | ||||||||||||||||||||||
RefSeq | NP_004619 | ||||||||||||||||||||||
HUGO | HGNC:12816 | ||||||||||||||||||||||
OMIM | 613208 | ||||||||||||||||||||||
CCDS | CCDS46763 | ||||||||||||||||||||||
HPRD | 02046 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AC093495 AF261892 AF261893 AF261894 AF261895 AF261896 AF261897 AF261898 AF261899 AF261900 AF261901 AK222844 AK295711 AY131066 BC016620 D21089 EU530520 EU530521 EU530523 EU530528 EU530530 EU530531 FJ695191 FJ695192 KJ534962 X65024 | ||||||||||||||||||||||
GenPept | AAF87574 AAH16620 AAM77801 ACD74564 ACD74570 ACE74247 ACE74250 ACE74251 ACE74253 ACE74254 AHW56602 BAA04651 BAD96564 BAG58555 CAA46158 | ||||||||||||||||||||||