Conserved Site

XPG conserved site (IPR019974)

Short name: XPG_CS

Description

Xeroderma pigmentosum (XP) [PMID: 8160271] is a human autosomal recessive disease, characterised by a high incidence of sunlight-induced skin cancer. People's skin cells with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-G is one of the most rare and phenotypically heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA excision repair [PMID: 8464724, PMID: 8206890]. XP-G can be corrected by a 133 Kd nuclear protein, XPGC [PMID: 8160271]. XPGC is an acidic protein that confers normal UV resistance in expressing cells [PMID: 8206890]. It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms [PMID: 8206890, PMID: 8090225]. XPGC cleaves one strand of the duplex at the border with the single-stranded region [PMID: 8090225].

XPG belongs to a family of proteins that includes RAD2 from Saccharomyces cerevisiae (Baker's yeast) and rad13 from Schizosaccharomyces pombe (Fission yeast), which are single-stranded DNA endonucleases [PMID: 8090225, PMID: 8247134]; mouse and human FEN-1, a structure-specific endonuclease; RAD2 from fission yeast and RAD27 from budding yeast; fission yeast exo1, a 5'-3' double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, and yeast DIN7. Sequence alignment of this family of proteins reveals that similarities are largely confined to two regions. The first is located at the N-terminal extremity (N-region) and corresponds to the first 95 to 105 amino acids. The second region is internal (I-region) and found towards the C terminus; it spans about 140 residues and contains a highly conserved core of 27 amino acids that includes a conserved pentapeptide (E-A-[DE]-A-[QS]). It is possible that the conserved acidic residues are involved in the catalytic mechanism of DNA excision repair in XPG. The amino acids linking the N- and I-regions are not conserved.

The first pattern, PS00841, corresponds to the central part of the N-region, the second pattern, PS00842, is part of the I-region and includes the putative catalytic core pentapeptide.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0016788 hydrolase activity, acting on ester bonds

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE patterns