 |
|
| PROSITE documentation PDOC00658 [for PROSITE entry PS00841] |
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: Last update:April 2006 / Patterns revised.
PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Tanaka K., Wood R.D. |
| Title | Xeroderma pigmentosum and nucleotide excision repair of DNA. | |
| Source | Trends Biochem. Sci. 19:83-86(1994). | |
| PubMed ID | 8160271 |
| 2 | Authors | Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., Clarkson S.G. |
| Title | Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. | |
| Source | Nature 363:182-185(1993). | |
| PubMed ID | 8483504 | |
| DOI | 10.1038/363182a0 |
| 3 | Authors | Carr A.M., Sheldrick K.S., Murray J.M., al-Harithy R., Watts F.Z., Lehmann A.R. |
| Title | Evolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene. | |
| Source | Nucleic Acids Res. 21:1345-1349(1993). | |
| PubMed ID | 8464724 |
| 4 | Authors | Murray J.M., Tavassoli M., al-Harithy R., Sheldrick K.S., Lehmann A.R., Carr A.M., Watts F.Z. |
| Title | Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage. | |
| Source | Mol. Cell. Biol. 14:4878-4888(1994). | |
| PubMed ID | 8007985 |
| 5 | Authors | Harrington J.J., Lieber M.R. |
| Title | Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair. | |
| Source | Genes Dev. 8:1344-1355(1994). | |
| PubMed ID | 7926735 |
| 6 | Authors | Szankasi P., Smith G.R. |
| Title | A role for exonuclease I from S. pombe in mutation avoidance and mismatch correction. | |
| Source | Science 267:1166-1169(1995). | |
| PubMed ID | 7855597 |
| 7 | Authors | Habraken Y., Sung P., Prakash L., Prakash S. |
| Title | Yeast excision repair gene RAD2 encodes a single-stranded DNA endonuclease. | |
| Source | Nature 366:365-368(1993). | |
| PubMed ID | 8247134 | |
| DOI | 10.1038/366365a0 |
| 8 | Authors | O'Donovan A., Scherly D., Clarkson S.G., Wood R.D. |
| Source | J. Biol. Chem. 269:15965-15968(1994). |
| 9 | Authors | O'Donovan A., Davies A.A., Moggs J.G., West S.C., Wood R.D. |
| Source | Nature 371:432-435(1994). |
PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to Prosite License or see: prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)