{PDOC00658}
{PS00841; XPG_1}
{PS00842; XPG_2}
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* XPG 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 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.

-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.

-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.

-Expert(s) to contact by email:
           Clarkson S.G.; clarkson@medecine.unige.ch

-Last update: April 2006 / Patterns revised.

[ 1] Tanaka K., Wood R.D.
     "Xeroderma pigmentosum and nucleotide excision repair of DNA."
     Trends Biochem. Sci. 19:83-86(1994).
     PubMed=8160271
[ 2] Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., Clarkson S.G.
     "Complementation of the DNA repair defect in xeroderma pigmentosum
     group G cells by a human cDNA related to yeast RAD2."
     Nature 363:182-185(1993).
     PubMed=8483504; DOI=10.1038/363182a0
[ 3] Carr A.M., Sheldrick K.S., Murray J.M., al-Harithy R., Watts F.Z.,
     Lehmann A.R.
     "Evolutionary conservation of excision repair in Schizosaccharomyces
     pombe: evidence for a family of sequences related to the Saccharomyces
     cerevisiae RAD2 gene."
     Nucleic Acids Res. 21:1345-1349(1993).
     PubMed=8464724
[ 4] Murray J.M., Tavassoli M., al-Harithy R., Sheldrick K.S.,
     Lehmann A.R., Carr A.M., Watts F.Z.
     "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."
     Mol. Cell. Biol. 14:4878-4888(1994).
     PubMed=8007985
[ 5] Harrington J.J., Lieber M.R.
     "Functional domains within FEN-1 and RAD2 define a family of
     structure-specific endonucleases: implications for nucleotide excision
     repair."
     Genes Dev. 8:1344-1355(1994).
     PubMed=7926735
[ 6] Szankasi P., Smith G.R.
     "A role for exonuclease I from S. pombe in mutation avoidance and
     mismatch correction."
     Science 267:1166-1169(1995).
     PubMed=7855597
[ 7] Habraken Y., Sung P., Prakash L., Prakash S.
     "Yeast excision repair gene RAD2 encodes a single-stranded DNA
     endonuclease."
     Nature 366:365-368(1993).
     PubMed=8247134; DOI=10.1038/366365a0
[ 8] O'Donovan A., Scherly D., Clarkson S.G., Wood R.D.
     J. Biol. Chem. 269:15965-15968(1994).
[ 9] O'Donovan A., Davies A.A., Moggs J.G., West S.C., Wood R.D.
     Nature 371:432-435(1994).

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