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XPA xeroderma pigmentosum, complementation group A)

Written2001-02Anne Stary, Alain Sarasin
Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesxeroderma pigmentosum
Alias_symbol (synonym)XPAC
XP1
HGNC (Hugo) XPA
LocusID (NCBI) 7507
Atlas_Id 104
Location 9q22.33  [Link to chromosome band 9q22]
Location_base_pair Starts at 100437191 and ends at 100459691 bp from pter ( according to hg19-Feb_2009)  [Mapping XPA.png]
Fusion genes
(updated 2016)
TEX10 (9q31.1) / XPA (9q22.33)

DNA/RNA

Description human xeroderma pigmentosum group A 25kbp, six exons, 2 polyadenylation signals
Transcription 1377 b mRNA; suggestion of 1 major transcript; promoter G+C rich (73%); one CAAT box and no TATA box.

Protein

Description 273 amino acids, 31 kDa. DNA excision repair protein. The functional domain for damaged DNA recognition contains a zinc-finger motif with 4 cysteine residues : Cys-X2-Cys-X17-Cys-X2-Cys motif and a glutamic acid cluster encoded by Exon 2. The nuclear localization signal is located in Exon 1.
Expression ubiquitous
Localisation nuclear
Function Initiates DNA repair by binding to damaged sites with various affinities, depending upon the chemical structure of the lesion
Two proteins have been identified and implicated in (one of) the first steps of Nucleotide Excision Repair (NER), i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product. Cells from XPA patients are extremely sensitive to UV and have very low nucleotide excision repair activity. In vitro the XPA protein binds preferentially to damaged DNA compared to nondamaged DNA. The XPA protein binds to replication protein A (RPA) which enhances the affinity of XPA for damaged DNA and is essential for NER. The XPA protein has been shown to bind to ERCC1 and TFIIH. It is possible that the complex XPA/RPA may tell to the repair machinery which strand contained the damage and therefore should be eliminated.
Homology Xpac (FlyBase ID) ; Xpa (MGI)

Mutations

Germinal 13 nucleotide substitutions and 5 small insertion/deletion in patients

Implicated in

Note
Entity xeroderma pigmentosum XPA
Disease predisposition to skin cancer: early skin tumours ( basal cell carcinoma, squamous cell carcinoma and melanoma); early internal tumours
  

Bibliography

Mammalian DNA nucleotide excision repair reconstituted with purified protein components.
Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Protić M, Hübscher U, Egly JM, Wood RD
Cell. 1995 ; 80 (6) : 859-868.
PMID 7697716
 
Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.
Araújo SJ, Tirode F, Coin F, Pospiech H, Syväoja JE, Stucki M, Hübscher U, Egly JM, Wood RD
Genes & development. 2000 ; 14 (3) : 349-359.
PMID 10673506
 
The XPA protein is a zinc metalloprotein with an ability to recognize various kinds of DNA damage.
Asahina H, Kuraoka I, Shirakawa M, Morita EH, Miura N, Miyamoto I, Ohtsuka E, Okada Y, Tanaka K
Mutation research. 1994 ; 315 (3) : 229-237.
PMID 7526200
 
Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites.
Batty D, Rapic'-Otrin V, Levine AS, Wood RD
Journal of molecular biology. 2000 ; 300 (2) : 275-290.
PMID 10873465
 
Damage recognition in nucleotide excision repair of DNA.
Batty DP, Wood RD
Gene. 2000 ; 241 (2) : 193-204.
PMID 10675030
 
Relative susceptibilities of XPA knockout mice and their heterozygous and wild-type littermates to UVB-induced skin cancer.
Berg RJ, de Vries A, van Steeg H, de Gruijl FR
Cancer research. 1997 ; 57 (4) : 581-584.
PMID 9044829
 
Human nucleotide excision repair protein XPA: 1H NMR and CD solution studies of a synthetic peptide fragment corresponding to the zinc-binding domain (101-141).
Buchko GW, Kennedy MA
Journal of biomolecular structure & dynamics. 1997 ; 14 (6) : 677-690.
PMID 9195337
 
Human nucleotide excision repair protein XPA: expression and NMR backbone assignments of the 14.7 kDa minimal damaged DNA binding domain (Met98-Phe219).
Buchko GW, Ni S, Thrall BD, Kennedy MA
Journal of biomolecular NMR. 1997 ; 10 (3) : 313-314.
PMID 9390412
 
Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population.
Butkiewicz D, Rusin M, Harris CC, Chorazy M
Human mutation. 2000 ; 15 (6) : 577-578.
PMID 10862089
 
Development of a new easy complementation assay for DNA repair deficient human syndromes using cloned repair genes.
Carreau M, Eveno E, Quilliet X, Chevalier-Lagente O, Benoit A, Tanganelli B, Stefanini M, Vermeulen W, Hoeijmakers JH, Sarasin A
Carcinogenesis. 1995 ; 16 (5) : 1003-1009.
PMID 7767957
 
A novel function of emodin: enhancement of the nucleotide excision repair of UV- and cisplatin-induced DNA damage in human cells.
Chang LC, Sheu HM, Huang YS, Tsai TR, Kuo KW
Biochemical pharmacology. 1999 ; 58 (1) : 49-57.
PMID 10403518
 
A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.
Cleaver JE, Thompson LH, Richardson AS, States JC
Human mutation. 1999 ; 14 (1) : 9-22.
PMID 10447254
 
Loss of the xeroderma pigmentosum group A gene (XPA) enhances apoptosis of cultured cerebellar neurons induced by UV but not by low-K+ medium.
Enokido Y, Inamura N, Araki T, Satoh T, Nakane H, Yoshino M, Nakatsu Y, Tanaka K, Hatanaka H
Journal of neurochemistry. 1997 ; 69 (1) : 246-251.
PMID 9202316
 
Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA.
Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, Tanaka K, Shirakawa M
Nature structural biology. 1998 ; 5 (8) : 701-706.
PMID 9699634
 
Neurodegeneration in hereditary nucleotide repair disorders.
Itoh M, Hayashi M, Shioda K, Minagawa M, Isa F, Tamagawa K, Morimatsu Y, Oda M
Brain & development. 1999 ; 21 (5) : 326-333.
PMID 10413020
 
Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair.
Kobayashi T, Takeuchi S, Saijo M, Nakatsu Y, Morioka H, Otsuka E, Wakasugi M, Nikaido O, Tanaka K
Nucleic acids research. 1998 ; 26 (20) : 4662-4668.
PMID 9753735
 
Siblings with xeroderma pigmentosum complementation group A with different skin cancer development: importance of sun protection at an early age.
Kondoh M, Ueda M, Nakagawa K, Ichihashi M
Journal of the American Academy of Dermatology. 1994 ; 31 (6) : 993-996.
PMID 7962783
 
Identification of a damaged-DNA binding domain of the XPA protein.
Kuraoka I, Morita EH, Saijo M, Matsuda T, Morikawa K, Shirakawa M, Tanaka K
Mutation research. 1996 ; 362 (1) : 87-95.
PMID 8538652
 
Quantification of XPA gene expression levels in human and mouse cell lines by competitive RT-PCR.
Layher SK, Cleaver JE
Mutation research. 1997 ; 383 (1) : 9-19.
PMID 9042415
 
Functional studies on the interaction between human replication protein A and Xeroderma pigmentosum group A complementing protein (XPA).
Lee BE, Sung JW, Kim DK, Lee JR, Kim ND, Kang SW, Kim DK
Molecules and cells. 1999 ; 9 (2) : 185-190.
PMID 10340474
 
Expression of a transfected DNA repair gene (XPA) in xeroderma pigmentosum group A cells restores normal DNA repair and mutagenesis of UV-treated plasmids.
Levy DD, Saijo M, Tanaka K, Kraemer KH
Carcinogenesis. 1995 ; 16 (7) : 1557-1563.
PMID 7614689
 
Interactions of the transcription/DNA repair factor TFIIH and XP repair proteins with DNA lesions in a cell-free repair assay.
Li RY, Calsou P, Jones CJ, Salles B
Journal of molecular biology. 1998 ; 281 (2) : 211-218.
PMID 9698541
 
DNA repair protein XPA binds replication protein A (RPA).
Matsuda T, Saijo M, Kuraoka I, Kobayashi T, Nakatsu Y, Nagai A, Enjoji T, Masutani C, Sugasawa K, Hanaoka F
The Journal of biological chemistry. 1995 ; 270 (8) : 4152-4157.
PMID 7876167
 
Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA.
Morikawa K, Shirakawa M
Mutation research. 2000 ; 460 (3-4) : 257-275.
PMID 10946233
 
XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription.
Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K
The Journal of biological chemistry. 2000 ; 275 (45) : 34931-34937.
PMID 10944529
 
High prevalence of the point mutation in exon 6 of the xeroderma pigmentosum group A-complementing (XPAC) gene in xeroderma pigmentosum group A patients in Tunisia.
Nishigori C, Zghal M, Yagi T, Imamura S, Komoun MR, Takebe H
American journal of human genetics. 1993 ; 53 (5) : 1001-1006.
PMID 8105686
 
DNA damage recognition by XPA protein promotes efficient recruitment of transcription factor II H.
Nocentini S, Coin F, Saijo M, Tanaka K, Egly JM
The Journal of biological chemistry. 1997 ; 272 (37) : 22991-22994.
PMID 9287294
 
The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor.
Park CH, Mu D, Reardon JT, Sancar A
The Journal of biological chemistry. 1995 ; 270 (9) : 4896-4902.
PMID 7876263
 
Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.
Park CH, Sancar A
Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (11) : 5017-5021.
PMID 8197175
 
Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro.
Saijo M, Kuraoka I, Masutani C, Hanaoka F, Tanaka K
Nucleic acids research. 1996 ; 24 (23) : 4719-4724.
PMID 8972858
 
Two novel splicing mutations in the XPA gene in patients with group A xeroderma pigmentosum.
Satokata I, Uchiyama M, Tanaka K
Human molecular genetics. 1995 ; 4 (10) : 1993-1994.
PMID 8595429
 
Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein.
States JC, McDuffie ER, Myrand SP, McDowell M, Cleaver JE
Human mutation. 1998 ; 12 (2) : 103-113.
PMID 9671271
 
Strand specificity and absence of hot spots for p53 mutations in ultraviolet B-induced skin tumors of XPA-deficient mice.
Takeuchi S, Nakatsu Y, Nakane H, Murai H, Hirota S, Kitamura Y, Okuyama A, Tanaka K
Cancer research. 1998 ; 58 (4) : 641-646.
PMID 9485015
 
Order of assembly of human DNA repair excision nuclease.
Wakasugi M, Sancar A
The Journal of biological chemistry. 1999 ; 274 (26) : 18759-18768.
PMID 10373492
 
Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C.
Zeng L, Quilliet X, Chevallier-Lagente O, Eveno E, Sarasin A, Mezzina M
Gene therapy. 1997 ; 4 (10) : 1077-1084.
PMID 9415314
 
Retrovirus-mediated DNA repair gene transfer into xeroderma pigmentosum cells: perspectives for a gene therapy.
Zeng L, Sarasin A, Mezzina M
Cell biology and toxicology. 1998 ; 14 (2) : 105-110.
PMID 9553721
 
Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition.
de Boer J, van Steeg H, Berg RJ, Garssen J, de Wit J, van Oostrum CT, Beems RB, van der Horst GT, van Kreijl CF, de Gruijl FR, Bootsma D, Hoeijmakers JH, Weeda G
Cancer research. 1999 ; 59 (14) : 3489-3494.
PMID 10416615
 
Spontaneous liver tumors and benzo[a]pyrene-induced lymphomas in XPA-deficient mice.
de Vries A, van Oostrom CT, Dortant PM, Beems RB, van Kreijl CF, Capel PJ, van Steeg H
Molecular carcinogenesis. 1997 ; 19 (1) : 46-53.
PMID 9180928
 
Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice.
van Steeg H, Mullenders LH, Vijg J
Mutation research. 2000 ; 450 (1-2) : 167-180.
PMID 10838141
 

Citation

This paper should be referenced as such :
Stary, A ; Sarasin, A
XPA (xeroderma pigmentosum, complementation group A)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):100-102.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/XPAID104.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(1;2)(p36;p21) THADA/PRDM16
t(1;3)(p36;q21) RPN1/PRDM16


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Xeroderma pigmentosum


External links

Nomenclature
HGNC (Hugo)XPA   12814
LRG (Locus Reference Genomic)LRG_471
Cards
AtlasXPAID104
Entrez_Gene (NCBI)XPA  7507  xeroderma pigmentosum, complementation group A
AliasesXP1; XPAC
GeneCards (Weizmann)XPA
Ensembl hg19 (Hinxton)ENSG00000136936 [Gene_View]  chr9:100437191-100459691 [Contig_View]  XPA [Vega]
Ensembl hg38 (Hinxton)ENSG00000136936 [Gene_View]  chr9:100437191-100459691 [Contig_View]  XPA [Vega]
ICGC DataPortalENSG00000136936
TCGA cBioPortalXPA
AceView (NCBI)XPA
Genatlas (Paris)XPA
WikiGenes7507
SOURCE (Princeton)XPA
Genetics Home Reference (NIH)XPA
Genomic and cartography
GoldenPath hg19 (UCSC)XPA  -     chr9:100437191-100459691 -  9q22.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)XPA  -     9q22.3   [Description]    (hg38-Dec_2013)
EnsemblXPA - 9q22.3 [CytoView hg19]  XPA - 9q22.3 [CytoView hg38]
Mapping of homologs : NCBIXPA [Mapview hg19]  XPA [Mapview hg38]
OMIM278700   611153   
Gene and transcription
Genbank (Entrez)AI961077 AL531629 BC014965 BT019518 CB155090
RefSeq transcript (Entrez)NM_000380
RefSeq genomic (Entrez)NC_000009 NC_018920 NG_011642 NT_008470 NW_004929366
Consensus coding sequences : CCDS (NCBI)XPA
Cluster EST : UnigeneHs.654364 [ NCBI ]
CGAP (NCI)Hs.654364
Alternative Splicing GalleryENSG00000136936
Gene ExpressionXPA [ NCBI-GEO ]   XPA [ EBI - ARRAY_EXPRESS ]   XPA [ SEEK ]   XPA [ MEM ]
Gene Expression Viewer (FireBrowse)XPA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7507
GTEX Portal (Tissue expression)XPA
Protein : pattern, domain, 3D structure
UniProt/SwissProtP23025   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP23025  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP23025
Splice isoforms : SwissVarP23025
PhosPhoSitePlusP23025
Domaine pattern : Prosite (Expaxy)XPA_1 (PS00752)    XPA_2 (PS00753)   
Domains : Interpro (EBI)DNA-bd_dom_put    XPA    XPA_C    XPA_CS    Znf_XPA_CS   
Domain families : Pfam (Sanger)XPA_C (PF05181)    XPA_N (PF01286)   
Domain families : Pfam (NCBI)pfam05181    pfam01286   
Conserved Domain (NCBI)XPA
DMDM Disease mutations7507
Blocks (Seattle)XPA
PDB (SRS)1D4U    1XPA    2JNW   
PDB (PDBSum)1D4U    1XPA    2JNW   
PDB (IMB)1D4U    1XPA    2JNW   
PDB (RSDB)1D4U    1XPA    2JNW   
Structural Biology KnowledgeBase1D4U    1XPA    2JNW   
SCOP (Structural Classification of Proteins)1D4U    1XPA    2JNW   
CATH (Classification of proteins structures)1D4U    1XPA    2JNW   
SuperfamilyP23025
Human Protein AtlasENSG00000136936
Peptide AtlasP23025
HPRD02045
IPIIPI00009694   IPI00979716   
Protein Interaction databases
DIP (DOE-UCLA)P23025
IntAct (EBI)P23025
FunCoupENSG00000136936
BioGRIDXPA
STRING (EMBL)XPA
ZODIACXPA
Ontologies - Pathways
QuickGOP23025
Ontology : AmiGOnucleotide-excision repair factor 1 complex  nucleotide-excision repair, DNA damage recognition  nucleotide-excision repair, DNA duplex unwinding  damaged DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  DNA replication factor A complex  cytoplasm  Golgi apparatus  DNA repair  transcription-coupled nucleotide-excision repair  base-excision repair  nucleotide-excision repair, preincision complex stabilization  nucleotide-excision repair, preincision complex assembly  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  response to oxidative stress  intrinsic apoptotic signaling pathway in response to DNA damage  response to toxic substance  response to auditory stimulus  protein domain specific binding  nucleotide-excision repair, DNA incision  nucleotide-excision repair, DNA incision  multicellular organism growth  protein homodimerization activity  intercellular bridge  metal ion binding  global genome nucleotide-excision repair  UV-damage excision repair  nucleotide-excision repair involved in interstrand cross-link repair  
Ontology : EGO-EBInucleotide-excision repair factor 1 complex  nucleotide-excision repair, DNA damage recognition  nucleotide-excision repair, DNA duplex unwinding  damaged DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  DNA replication factor A complex  cytoplasm  Golgi apparatus  DNA repair  transcription-coupled nucleotide-excision repair  base-excision repair  nucleotide-excision repair, preincision complex stabilization  nucleotide-excision repair, preincision complex assembly  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  response to oxidative stress  intrinsic apoptotic signaling pathway in response to DNA damage  response to toxic substance  response to auditory stimulus  protein domain specific binding  nucleotide-excision repair, DNA incision  nucleotide-excision repair, DNA incision  multicellular organism growth  protein homodimerization activity  intercellular bridge  metal ion binding  global genome nucleotide-excision repair  UV-damage excision repair  nucleotide-excision repair involved in interstrand cross-link repair  
Pathways : KEGGNucleotide excision repair   
REACTOMEP23025 [protein]
REACTOME PathwaysR-HSA-73935 Formation of incision complex in GG-NER [pathway]
REACTOME PathwaysR-HSA-73941 Dual incision reaction in GG-NER [pathway]
NDEx NetworkXPA
Atlas of Cancer Signalling NetworkXPA
Wikipedia pathwaysXPA
Orthology - Evolution
OrthoDB7507
GeneTree (enSembl)ENSG00000136936
Phylogenetic Trees/Animal Genes : TreeFamXPA
HOVERGENP23025
HOGENOMP23025
Homologs : HomoloGeneXPA
Homology/Alignments : Family Browser (UCSC)XPA
Gene fusions - Rearrangements
Fusion : MitelmanTEX10/XPA [9q31.1/9q22.33]  [del(9)(q22)]  [del(9)(q22q31)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerXPA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)XPA
dbVarXPA
ClinVarXPA
1000_GenomesXPA 
Exome Variant ServerXPA
ExAC (Exome Aggregation Consortium)XPA (select the gene name)
Genetic variants : HAPMAP7507
Genomic Variants (DGV)XPA [DGVbeta]
DECIPHER (Syndromes)9:100437191-100459691  ENSG00000136936
CONAN: Copy Number AnalysisXPA 
Mutations
ICGC Data PortalXPA 
TCGA Data PortalXPA 
Broad Tumor PortalXPA
OASIS PortalXPA [ Somatic mutations - Copy number]
Cancer Gene: CensusXPA 
Somatic Mutations in Cancer : COSMICXPA  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDXPA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch XPA
DgiDB (Drug Gene Interaction Database)XPA
DoCM (Curated mutations)XPA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)XPA (select a term)
intoGenXPA
NCG5 (London)XPA
Cancer3DXPA(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM278700    611153   
Orphanet3253   
MedgenXPA
Genetic Testing Registry XPA
NextProtP23025 [Medical]
TSGene7507
GENETestsXPA
Huge Navigator XPA [HugePedia]
snp3D : Map Gene to Disease7507
BioCentury BCIQXPA
ClinGenXPA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7507
Chemical/Pharm GKB GenePA368
Clinical trialXPA
Miscellaneous
canSAR (ICR)XPA (select the gene name)
Probes
Litterature
PubMed196 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineXPA
EVEXXPA
GoPubMedXPA
iHOPXPA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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