DNA damage repair protein page: XPA (RAD14)

(Last Update: 04/20/00 )

The XPA protein is part of the nucleotide excision repair mechanism. It seems to serve as the primary recognition mechanism for the neucleotide-excision reapir mechanism. It binds damaged DNA after XPC or RNA pol II. (Obviously, a more detailed paragraph is needed here, but I don't want to violate someone's copyright.)

SwissProt sequence XPA_HUMAN is used as the master sequence for the alignments on this page.

Domains and features (from SwissProt)

26..47
Nuclear localization signal
No significant similarities to sequences other than XPA are found for this signal.
78..84
Poly-GLU (7 Es)
105..129
Zinc finger
The zinc finger appears to have the CXXC X17 CXXC pattern of the GATA zinc fingers, which usually appear in pairs in transcription factors that bind to (A/T)GATA(A/G), and of Prokaryotic dksA/traR C4-type zinc finger. The GATA finger also appears unpaired in various transcriptional activators. The detailed patterns in PROSITE are too specific to match the zinc finger in XPA. The closest BLAST matches are to C2H2 fingers, but the zinc finger in XPA clearly uses 4 CYS residues to coordinate the zinc. None of the standard zinc fingers is a good match.

Variants associated with mutations are not presented in this section, but in the mutation table.

Protein sequences (names from NCBI's non-redundant data base):

gi|139816|sp|P23025|XPA_HUMAN
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS (XERODERMA PIGMENTOSUM" (Homo sapiens)
gi|4507937|ref|NP_000371.1||
"xeroderma pigmentosum, complementation group A." (Homo sapiens)
gi|139817|sp|P27088|XPA_XENLA
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS HOMOLOG (XERODERMA" (Xenopus laevis)
gi|505150|dbj|BAA06693.1|
"xpacxe2 protein." (Xenopus laevis)
gi|2501672|sp|Q64267|XPA_MOUSE
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS HOMOLOG (XERODERMA" (Mus musculus)
gi|4185895|emb|CAA21834|
"EG:EG0007.8." (Drosophila melanogaster)
gi|2507539|sp|P28518|XPA_DROME
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS HOMOLOG (XERODERMA" (Drosophila melanogaster)
gi|85191|pir||JQ1325
"DNA excision repair protein XPAC - fruit fly (Drosophila" (Drosophila melanogaster)
gi|139814|sp|P27089|XPA_CHICK
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS HOMOLOG (XERODERMA" (Gallus gallus)
gi|501115
"XPAC." (Homo sapiens)
gi|6323857|ref|NP_013928.1|RAD14|
"human xeroderma pigmentosum group A DNA repair gene homolog;" (Saccharomyces cerevisiae)
gi|4265|emb|CAA45420|
"hydrophilic protein." (Saccharomyces cerevisiae)
gi|3136025|emb|CAA19045.1|
"putative dna repair protein with XPA domain; yeast rad14 homolog." (Schizosaccharomyces pombe)
gi|3878401|emb|CAA95829.1|
"Similarity to Xenopus DNA-repair protein complementing XP-A cells" (Caenorhabditis elegans)
gi|5822443|pdb|1XPA|
"Solution Structure Of The Dna- And Rpa-Binding Domain Of The Human" (Homo sapiens)
gi|5453692|ref|NP_006336.1||
"expressed in human eonic lung." (Homo sapiens)
gi|6435647|pdb|1D4U|A
"Chain A, Interactions Of Human Nucleotide Excision Repair Protein" (Homo sapiens)
gi|3915301|sp|Q64029|XPA_CRIGR
"DNA-REPAIR PROTEIN COMPLEMENTING XP-A CELLS HOMOLOG (XERODERMA" (Cricetulus griseus)
gi|1709994|sp|P53709|RA14_CANAL
"DNA REPAIR PROTEIN RAD14." (Candida albicans)
gi|595929
"excision repair-controlling." (Homo sapiens)

The Swissprot entry for yeast is disguised in the above list as gi|6323857|ref|NP_013928.1|RAD14| : RA14_YEAST ra14_yeast in Entrez Proteome YPD report ;

Structures in PDB:

1xpa; pdbsum entry
residues 99-219 of xpa_human
1d4uA; pdbsum entry
residues 99-209 of xpa_human

Multiple alignment (using SAM-T99 method)

pretty-printed (human-readable)
gzipped A2M format (machine-readable)

Predicted secondary structure

CASP format
FASTA format
RDB format

True secondary structure from PDB.

Potential Archea matches

Organism Score file Most likely homolog Alignment
Aeropyrum pernix aero.dist
no likely homologs
Archaeoglobus fulgidus aful.dist
no likely homologs
Methanobacterium thermoautotrophicum thermo.dist
no likely homologs
Methanococcus jannaschii jann.dist no likely homologs
Pyrococcus abyssi pabyssi.dist
no likely homologs
Pyrococcus horikoshii pyrohori.dist
no likely homologs

Mutation table from Summary of Mutations in UV-Sensitive Disorders

Mutations in human XPA gene Repair
nucleotide
change
aa/splice RFLP number of alleles severity site references
del(C349-T353) fs 3(het) exon 3 [Satokata et al., 1992b; States et al. 1998]
...
How should references be handled? MEDLINE pointers?

Predicted alignments to PDB files

see actual structures.

Predicted tertiary structure.

None yet---should there be links to sites like Swiss-Prot, or should we just do our own modeling?

What other information should be included in this?


This is a draft page with information about DNA-repair proteins. There is a lot more work to be done on these pages.
(icon needed) UCSC Center for Biomolecular Engineering slug icon to go to School of Engineering home page UCSC Engineering (icon needed) DNA repair main page
       

The Bioinformatics group at UCSC is supported in part by NSF grant BIR-9408579, NSF grant MIP-9488395, DOE grant DE-FG03-95ER62112, LACOR grant 4158U0015-3A-01, and by GANN and NSF graduate fellowships.

The DNA-repair pages are not currently funded, so development of them is very slow.

Questions about page content should be directed to

Kevin Karplus
Computer Engineering
University of California, Santa Cruz
Santa Cruz, CA 95064
USA
karplus@soe.ucsc.edu
(831) 459-4250