PROSITE documentation PDOC00658
XPG protein signatures


Xeroderma pigmentosum (XP) [1] is a human autosomal recessive disease, characterized 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. The defect in XP-G can be corrected by a 133 Kd nuclear protein called XPG (or XPGC) [2].

XPG belongs to a family of proteins [2,3,4,5,6] that are composed of two main subsets:

  • Subset 1, to which belongs XPG, RAD2 from budding yeast and rad13 from fission yeast. RAD2 and XPG are single-stranded DNA endonucleases [7,8]. XPG makes the 3'incision in human DNA nucleotide excision repair [9].
  • Subset 2, to which belongs mouse and human FEN-1, rad2 from fission yeast, and RAD27 from budding yeast. FEN-1 is a structure-specific endonuclease.

In addition to the proteins listed in the above groups, this family also includes:

  • Fission yeast exo1, a 5'->3' double-stranded DNA exonuclease that could act in a pathway that corrects mismatched base pairs.
  • Yeast EXO1 (DHS1), a protein with probably the same function as exo1.
  • 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; indeed, they are largely absent from proteins belonging to the second subset.

We have developed two signature patterns for these proteins. The first corresponds to the central part of the N-region, the second to part of the I-region and includes the putative catalytic core pentapeptide.

Expert(s) to contact by email:

Clarkson S.G.

Last update:

April 2006 / Patterns revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

XPG_1, PS00841; XPG protein signature 1  (PATTERN)

XPG_2, PS00842; XPG protein signature 2  (PATTERN)


1AuthorsTanaka K. Wood R.D.
TitleXeroderma pigmentosum and nucleotide excision repair of DNA.
SourceTrends Biochem. Sci. 19:83-86(1994).
PubMed ID8160271

2AuthorsScherly D. Nouspikel T. Corlet J. Ucla C. Bairoch A. Clarkson S.G.
TitleComplementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2.
SourceNature 363:182-185(1993).
PubMed ID8483504

3AuthorsCarr A.M. Sheldrick K.S. Murray J.M. al-Harithy R. Watts F.Z. Lehmann A.R.
TitleEvolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene.
SourceNucleic Acids Res. 21:1345-1349(1993).
PubMed ID8464724

4AuthorsMurray J.M. Tavassoli M. al-Harithy R. Sheldrick K.S. Lehmann A.R. Carr A.M. Watts F.Z.
TitleStructural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage.
SourceMol. Cell. Biol. 14:4878-4888(1994).
PubMed ID8007985

5AuthorsHarrington J.J. Lieber M.R.
TitleFunctional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair.
SourceGenes Dev. 8:1344-1355(1994).
PubMed ID7926735

6AuthorsSzankasi P. Smith G.R.
TitleA role for exonuclease I from S. pombe in mutation avoidance and mismatch correction.
SourceScience 267:1166-1169(1995).
PubMed ID7855597

7AuthorsHabraken Y. Sung P. Prakash L. Prakash S.
TitleYeast excision repair gene RAD2 encodes a single-stranded DNA endonuclease.
SourceNature 366:365-368(1993).
PubMed ID8247134

8AuthorsO'Donovan A. Scherly D. Clarkson S.G. Wood R.D.
SourceJ. Biol. Chem. 269:15965-15968(1994).

9AuthorsO'Donovan A. Davies A.A. Moggs J.G. West S.C. Wood R.D.
SourceNature 371:432-435(1994).

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