P23025 (XPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA repair protein complementing XP-A cells

Alternative name(s):
Xeroderma pigmentosum group A-complementing protein

Gene names

Name:	XPA
Synonyms:	XPAC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Protein existence	Evidence 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.13
Subunit structure	Interacts with GPN1 and RPA1. Interacts (via N-terminus) with CEP164 upon UV irradiation. Interacts with HERC2. Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Nucleus Ref.9 Ref.13 Ref.14.
Tissue specificity	Expressed in various cell lines and in skin fibroblasts. Ref.8 Ref.9
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ubiquitinated by HERC2 leading to degradation by the proteasome. Ref.14
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.17 Ref.18 Ref.19
Sequence similarities	Belongs to the XPA family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Xeroderma pigmentosum
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to DNA damage Inferred from electronic annotation. Source: Compara nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome response to UV Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	damaged DNA binding Traceable author statement PubMed 10946233. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RPA2	P15927	3	EBI-295222,EBI-621404
SIRT1	Q96EB6	8	EBI-295222,EBI-1802965
XAB2	Q9HCS7	2	EBI-295222,EBI-295232

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 273

273

DNA repair protein complementing XP-A cells

PRO_0000208648

Regions

Zinc finger

105 – 129

25

Region

4 – 97

94

Interaction with CEP164 and required for UV resistance

Motif

26 – 47

22

Nuclear localization signal Potential

Compositional bias

78 – 84

7

Poly-Glu

Natural variations

Natural variant

78

1

Missing. Ref.3

VAR_014203

Natural variant

94

1

P → L in XP-A.

VAR_007727

Natural variant

97

1

V → I.
Corresponds to variant rs10983315 [ dbSNP | Ensembl ].

VAR_037907

Natural variant

108

1

C → F in XP-A; severe form. Ref.17 Ref.19

VAR_007728

Natural variant

130

1

R → K in XP-A.

VAR_007729

Natural variant

185

1

Q → H in XP-A.

VAR_007730

Natural variant

228

1

R → Q.
Corresponds to variant rs1805160 [ dbSNP | Ensembl ].

VAR_014799

Natural variant

234

1

V → L.
Corresponds to variant rs3176749 [ dbSNP | Ensembl ].

VAR_029325

Natural variant

244

1

H → R in XP-A; mild form. Ref.18

VAR_007731

Natural variant

252

1

L → V.
Corresponds to variant rs3176750 [ dbSNP | Ensembl ].

VAR_020324

Natural variant

256

1

M → V.
Corresponds to variant rs57519506 [ dbSNP | Ensembl ].

VAR_061987

Secondary structure

1

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273

Helix Strand Turn

Details...

Beta strand

72 – 75

4

Turn

106 – 108

3

Beta strand

111 – 113

3

Beta strand

115 – 117

3

Turn

118 – 121

4

Turn

127 – 129

3

Beta strand

131 – 135

5

Helix

141 – 144

4

Turn

145 – 149

5

Beta strand

152 – 154

3

Turn

155 – 157

3

Beta strand

158 – 160

3

Beta strand

164 – 168

5

Beta strand

170 – 172

3

Beta strand

179 – 181

3

Helix

183 – 193

11

Helix

197 – 206

10

Sequences

	Sequence		Length	Mass (Da)
	P23025 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: F89F735219A8494B	FASTA	273	31,368
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.

Web resources

Allelic variations of the XP genes

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Protein Spotlight

Nature's flaws - Issue 142 of September 2012

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 , U10343, U10344, U10345, U10346 Genomic DNA. Translation: AAA92883.1.

IPI

IPI00009694.

PIR

I38886.
JG0190.

RefSeq

NP_000371.1. NM_000380.3.

UniGene

Hs.654364.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D4U	NMR	-	A	98-208	[»]
1XPA	NMR	-	A	98-219	[»]
2JNW	NMR	-	B	67-80	[»]

DisProt

DP00243.

ProteinModelPortal

P23025.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24191N.

IntAct

P23025. 8 interactions.

STRING

9606.ENSP00000364270.

PTM databases

PhosphoSite

P23025.

Polymorphism databases

DMDM

139816.

Proteomic databases

PaxDb

P23025.

PRIDE

P23025.

Protocols and materials databases

DNASU

7507.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375128; ENSP00000364270; ENSG00000136936.

GeneID

7507.

KEGG

hsa:7507.

UCSC

uc004axr.4. human.

Organism-specific databases

CTD

7507.

GeneCards

GC09M100437.

HGNC

HGNC:12814. XPA.

HPA

CAB000155.

MIM

278700. phenotype.
611153. gene.

neXtProt

NX_P23025.

Orphanet

276249. Xeroderma pigmentosum complementation group A.

PharmGKB

PA368.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5145.

HOGENOM

HOG000045820.

HOVERGEN

HBG009053.

InParanoid

P23025.

KO

K10847.

OMA

GFFLEEE.

OrthoDB

EOG4G7C06.

PhylomeDB

P23025.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P23025.

Bgee

P23025.

CleanEx

HS_XPA.

Genevestigator

P23025.

GermOnline

ENSG00000136936. Homo sapiens.

Family and domain databases

InterPro

IPR009061. DNA-bd_dom_put.
IPR000465. XPA.
IPR022656. XPA_C.
IPR022658. XPA_CS.
IPR022652. Znf_XPA_CS.
[Graphical view]

PANTHER

PTHR10142. PTHR10142. 1 hit.

Pfam

PF05181. XPA_C. 1 hit.
PF01286. XPA_N. 1 hit.
[Graphical view]

SUPFAM

SSF46955. Putativ_DNA_bind. 1 hit.

TIGRFAMs

TIGR00598. rad14. 1 hit.

PROSITE

PS00752. XPA_1. 1 hit.
PS00753. XPA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P23025.

GenomeRNAi

7507.

NextBio

29387.

SOURCE

Search...

Entry information

Entry name

XPA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 146 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.