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PDOC00658
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1995-07-26
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* XPGC protein signatures *
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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).