home *** CD-ROM | disk | FTP | other *** search
- ***************************
- * XPGC 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 XPGC
- [2].
-
- The sequence of the XPGC protein from vertebrates is evolutionary related to
- that of two sets of DNA excision-repair proteins from fungi [3]:
-
- - RAD2 from budding yeast and rad13 from fission yeast. RAD2 is a single-
- stranded DNA endonuclease [4].
- - YKL113c (YKL510) from budding yeast and rad2 from fission yeast.
-
- 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 perfectly conserved hexapeptide (E-A-E-A-Q-C). It is
- possible that the conserved cysteine and the two adjacent glutamates be
- involved in the catalytic mechanism of DNA excision repair in XPGC. The amino
- acids linking the N- and I-regions are not conserved; indeed, they are largely
- absent from the rad2/YKL510 proteins.
-
- We have developed two signature patterns for XPGC 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 hexapeptide.
-
- -Consensus pattern: I-[KR]-P-x-[FY]-V-F-D-G-x(2)-P-x-L-K
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Consensus pattern: G-[LIVM]-P-[FY]-[LIVM]-x-A-P-x-E-A-E-A-Q-C
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Expert(s) to contact by email: Clarkson S.G.
- clarkson@cmu.unige.ch
-
- -Last update: June 1994 / Text revised.
-
- [ 1] Wood R.D., Coverley D.
- BioEssays 13:447-453(1991).
- [ 2] Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., Clarkson S.G.
- Nature 363:182-185(1993).
- [ 3] Carr A.M., Sheldrick K.S., Murray J.M., Al-Harithy R., Watts F.Z.,
- Lehmann A.R.
- Nucleic Acids Res. 21:1345-1349(1993).
- [ 4] Habraken Y., Sung P., Prakash L., Prakash S.
- Nature 366:365-368(1993).
-