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P23025 (XPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA repair protein complementing XP-A cells
Alternative name(s):
Xeroderma pigmentosum group A-complementing protein
Gene names
Name:XPA
Synonyms:XPAC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length273 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation. Ref.16

Subunit structure

Interacts with GPN1. Interacts with RPA1 and RPA2; the interaction is direct and associates XPA with the RPA complex. Interacts (via N-terminus) with CEP164 upon UV irradiation. Interacts with HERC2. Ref.8 Ref.16 Ref.17 Ref.19 Ref.20

Subcellular location

Nucleus Ref.10 Ref.16 Ref.17.

Tissue specificity

Expressed in various cell lines and in skin fibroblasts. Ref.9 Ref.10

Post-translational modification

ATR-dependent phosphorylation of XPA at Ser-196 is important for cell survival in response to UV damage.

Ubiquitinated by HERC2 leading to degradation by the proteasome. Ref.17

Involvement in disease

Xeroderma pigmentosum complementation group A (XP-A) [MIM:278700]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-A patients show the most severe skin symptoms and progressive neurological disorders.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.22 Ref.23

Sequence similarities

Belongs to the XPA family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Xeroderma pigmentosum
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

nucleotide-excision repair

Traceable author statement. Source: Reactome

nucleotide-excision repair, DNA damage removal

Traceable author statement. Source: Reactome

response to UV

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

intercellular bridge

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functiondamaged DNA binding

Inferred from direct assay Ref.8. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 10944529Ref.17Ref.8PubMed 8197175PubMed 8999876PubMed 9013642. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 17720715. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 8197175. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 273272DNA repair protein complementing XP-A cells
PRO_0000208648

Regions

Zinc finger105 – 12925
Region4 – 9794Interaction with CEP164 and required for UV resistance
Motif26 – 4722Nuclear localization signal Potential
Compositional bias78 – 847Poly-Glu

Amino acid modifications

Modified residue21N-acetylalanine Ref.15 Ref.18
Modified residue1961Phosphoserine Ref.14

Natural variations

Natural variant781Missing. Ref.3
VAR_014203
Natural variant941P → L in XP-A.
VAR_007727
Natural variant971V → I.
Corresponds to variant rs10983315 [ dbSNP | Ensembl ].
VAR_037907
Natural variant1081C → F in XP-A; severe form. Ref.21 Ref.23
VAR_007728
Natural variant1301R → K in XP-A.
VAR_007729
Natural variant1851Q → H in XP-A.
VAR_007730
Natural variant2281R → Q.
Corresponds to variant rs1805160 [ dbSNP | Ensembl ].
VAR_014799
Natural variant2341V → L.
Corresponds to variant rs3176749 [ dbSNP | Ensembl ].
VAR_029325
Natural variant2441H → R in XP-A; mild form. Ref.22
VAR_007731
Natural variant2521L → V.
Corresponds to variant rs3176750 [ dbSNP | Ensembl ].
VAR_020324
Natural variant2561M → V.
Corresponds to variant rs57519506 [ dbSNP | Ensembl ].
VAR_061987

Secondary structure

............................... 273
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23025 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: F89F735219A8494B

FASTA27331,368
        10         20         30         40         50         60 
MAAADGALPE AAALEQPAEL PASVRASIER KRQRALMLRQ ARLAARPYSA TAAAATGGMA 

        70         80         90        100        110        120 
NVKAAPKIID TGGGFILEEE EEEEQKIGKV VHQPGPVMEF DYVICEECGK EFMDSYLMNH 

       130        140        150        160        170        180 
FDLPTCDNCR DADDKHKLIT KTEAKQEYLL KDCDLEKREP PLKFIVKKNP HHSQWGDMKL 

       190        200        210        220        230        240 
YLKLQIVKRS LEVWGSQEAL EEAKEVRQEN REKMKQKKFD KKVKELRRAV RSSVWKRETI 

       250        260        270 
VHQHEYGPEE NLEDDMYRKT CTMCGHELTY EKM 

« Hide

References

« Hide 'large scale' references
[1]"Analysis of a human DNA excision repair gene involved in group A Xeroderma pigmentosum and containing a zinc-finger domain."
Tanaka K., Miura N., Satokata I., Miyamoto I., Yoshida M.C., Satoh Y., Kondo S., Yasui A., Okayama H., Okada Y.
Nature 348:73-76(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fibroblast.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-78 DEL.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: B-cell.
[7]"Genomic characterization of the human DNA excision repair-controlling gene XPAC."
Satokata I., Iwai K., Matsuda T., Okada Y., Tanaka K.
Gene 136:345-348(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-57.
Tissue: Spermatocyte.
[8]"RPA involvement in the damage-recognition and incision steps of nucleotide excision repair."
He Z., Henricksen L.A., Wold M.S., Ingles C.J.
Nature 374:566-569(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RPA1 AND RPA2.
[9]"Characterization of the human XPA promoter."
Topping R.S., Myrand S.P., Williams B.L., Albert J.C., States J.C.
Gene 166:341-342(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-273, TISSUE SPECIFICITY.
Tissue: Placenta.
[10]"Identification and characterization of xpac protein, the gene product of the human XPAC (Xeroderma pigmentosum group A complementing) gene."
Miura N., Miyamoto I., Asahina H., Satokata I., Tanaka K., Okada Y.
J. Biol. Chem. 266:19786-19789(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"Mutational analysis of the structure and function of the Xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair."
Miyamoto I., Miura N., Niwa H., Miyazaki J., Tanaka K.
J. Biol. Chem. 267:12182-12187(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[12]"Molecular analysis of Xeroderma pigmentosum group A gene."
Tanaka K.
Jpn. J. Hum. Genet. 38:1-14(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS XP-A.
[13]"A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy."
Cleaver J.E., Thompson L.H., Richardson A.S., States J.C.
Hum. Mutat. 14:9-22(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS XP-A.
[14]"Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation."
Wu X., Shell S.M., Yang Z., Zou Y.
Cancer Res. 66:2997-3005(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-196.
[15]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[16]"UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity."
Pan Y.R., Lee E.Y.
Cell Cycle 8:655-664(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CEP164, SUBCELLULAR LOCATION.
[17]"Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase."
Kang T.H., Lindsey-Boltz L.A., Reardon J.T., Sancar A.
Proc. Natl. Acad. Sci. U.S.A. 107:4890-4895(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, SUBCELLULAR LOCATION, INTERACTION WITH HERC2.
Tissue: Embryonic kidney and Lung adenocarcinoma.
[18]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"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.
Nat. Struct. Biol. 5:701-706(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 98-219, DNA-BINDING, INTERACTION WITH RPA1.
[20]"Interactions of human nucleotide excision repair protein XPA with DNA and RPA70 Delta C327: chemical shift mapping and 15N NMR relaxation studies."
Buchko G.W., Daughdrill G.W., de Lorimier R., Sudha Rao B.K., Isern N.G., Lingbeck J.M., Taylor J.-S., Wold M.S., Gochin M., Spicer L.D., Lowry D.F., Kennedy M.A.
Biochemistry 38:15116-15128(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 98-208, DNA-BINDING, INTERACTION WITH RPA1.
[21]"Molecular basis of group A Xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene."
Satokata I., Tanaka K., Okada Y.
Hum. Genet. 88:603-607(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XP-A PHE-108.
[22]"Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A Xeroderma pigmentosum."
Satokata I., Tanaka K., Yuba S., Okada Y.
Mutat. Res. 273:203-212(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XP-A ARG-244.
[23]"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 J.C., McDuffie E.R., Myrand S.P., McDowell M., Cleaver J.E.
Hum. Mutat. 12:103-113(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XP-A PHE-108.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D14533 mRNA. Translation: BAA03403.1.
BT019518 mRNA. Translation: AAV38325.1.
AF503166 Genomic DNA. Translation: AAM18969.1.
AL445531 Genomic DNA. Translation: CAI15428.1.
CH471105 Genomic DNA. Translation: EAW58855.1.
BC014965 mRNA. Translation: AAH14965.1.
U16815 Genomic DNA. Translation: AAB60404.1.
U10347 expand/collapse EMBL AC list , U10343, U10344, U10345, U10346 Genomic DNA. Translation: AAA92883.1.
CCDSCCDS6729.1.
PIRI38886.
JG0190.
RefSeqNP_000371.1. NM_000380.3.
UniGeneHs.654364.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1D4UNMR-A98-208[»]
1XPANMR-A98-219[»]
2JNWNMR-B67-80[»]
DisProtDP00243.
ProteinModelPortalP23025.
SMRP23025. Positions 98-210.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113344. 23 interactions.
DIPDIP-24191N.
IntActP23025. 8 interactions.
MINTMINT-192332.
STRING9606.ENSP00000364270.

PTM databases

PhosphoSiteP23025.

Polymorphism databases

DMDM139816.

Proteomic databases

MaxQBP23025.
PaxDbP23025.
PRIDEP23025.

Protocols and materials databases

DNASU7507.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375128; ENSP00000364270; ENSG00000136936.
GeneID7507.
KEGGhsa:7507.
UCSCuc004axr.4. human.

Organism-specific databases

CTD7507.
GeneCardsGC09M100437.
GeneReviewsXPA.
HGNCHGNC:12814. XPA.
HPACAB000155.
HPA030997.
HPA056856.
MIM278700. phenotype.
611153. gene.
neXtProtNX_P23025.
Orphanet276249. Xeroderma pigmentosum complementation group A.
PharmGKBPA368.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5145.
HOGENOMHOG000045820.
HOVERGENHBG009053.
InParanoidP23025.
KOK10847.
OMAVAHQHEY.
PhylomeDBP23025.
TreeFamTF101241.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressP23025.
BgeeP23025.
CleanExHS_XPA.
GenevestigatorP23025.

Family and domain databases

Gene3D3.90.530.10. 1 hit.
InterProIPR009061. DNA-bd_dom_put.
IPR000465. XPA.
IPR022656. XPA_C.
IPR022658. XPA_CS.
IPR022652. Znf_XPA_CS.
[Graphical view]
PANTHERPTHR10142. PTHR10142. 1 hit.
PfamPF05181. XPA_C. 1 hit.
PF01286. XPA_N. 1 hit.
[Graphical view]
SUPFAMSSF46955. SSF46955. 1 hit.
TIGRFAMsTIGR00598. rad14. 1 hit.
PROSITEPS00752. XPA_1. 1 hit.
PS00753. XPA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23025.
GeneWikiXPA.
GenomeRNAi7507.
NextBio29387.
PROP23025.
SOURCESearch...

Entry information

Entry nameXPA_HUMAN
AccessionPrimary (citable) accession number: P23025
Secondary accession number(s): Q5T1U9, Q6LCW7, Q6LD02
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 9, 2014
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM