PROSITE documentation PDOC00658

XPG protein signatures

Description

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)
Consensus pattern: [VILT]-[KREIT]-[PV]-x-[FYIL]-[VI]-[FW]-D-G-x(2)-[PILHSTF]-x-[LVCQMFAKS]-K
Sequences known to belong to this class detected by the pattern: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00841
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00841
• Scan Swiss-Prot/TrEMBL entries against PS00841
• view ligand binding statistics
Matching PDB structures: 1B43 1MC8 1RXV 1RXW ... [ALL]
XPG_2, PS00842; XPG protein signature 2  (PATTERN)
Consensus pattern: [GSN]-[LIVM]-[PERD]-[FYSCV]-[LIVM]-x-A-P-x-E-A-[DE]-[PAS]-[QSE]-[CLM]
Sequences known to belong to this class detected by the pattern: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00842
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00842
• Scan Swiss-Prot/TrEMBL entries against PS00842
• view ligand binding statistics
Matching PDB structures: 1UL1 3Q8K 3Q8L 3Q8M ... [ALL]

References

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).

Copyright

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.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)