Reviewed, UniProtKB/Swiss-Prot P23025 (XPA_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 CHK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation. Ref.14
Subunit structure	Interacts with XAB1 and RPA1. Interacts (via N-terminus) with CEP164 upon UV irradiation. Ref.14 Ref.15 Ref.16
Subcellular location	Nucleus. Ref.14 Ref.9
Tissue specificity	Expressed in various cell lines and in skin fibroblasts. Ref.9 Ref.8
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.13
Involvement in disease	Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:278700]; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders. 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
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	nucleotide-excision repair, DNA damage removal Inferred from Experiment. Source: Reactome
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	damaged DNA binding Traceable author statement. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro protein domain specific binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GPN1	Q9HCN4	2	EBI-295222,EBI-745137
XAB2	Q9HCS7	1	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

Amino acid modifications

Modified residue

196

1

Phosphoserine Ref.13

Natural variations

Natural variant

78

1

Missing

VAR_014203

Natural variant

94

1

P → L in XP-A.

VAR_007727

Natural variant

97

1

V → I: dbSNP rs10983315.

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: dbSNP rs1805160.

VAR_014799

Natural variant

234

1

V → L: dbSNP rs3176749.

VAR_029325

Natural variant

244

1

H → R in XP-A; mild form. Ref.18

VAR_007731

Natural variant

252

1

L → V: dbSNP rs3176750.

VAR_020324

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

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.

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.

.

.

.

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.

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.

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273

Helix Strand Turn

Details...

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

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)
	P23025-1 [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: 2234061] [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: 15164053] [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: 15489334] [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: 8294029] [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: 8543191] [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: 1918083] [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: 1601884] [Abstract] Cited for: MUTAGENESIS.
[11]	"Molecular analysis of Xeroderma pigmentosum group A gene." Tanaka K. Jpn. J. Hum. Genet. 38:1-14(1993) [PubMed: 8504220] [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: 10447254] [Abstract] Cited for: REVIEW ON VARIANTS XP-A.
[13]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196, MASS SPECTROMETRY.
[14]	"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: 19197159] [Abstract] Cited for: FUNCTION, INTERACTION WITH CEP164, SUBCELLULAR LOCATION.
[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: 9699634] [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: 10563794] [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: 1339397] [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: 1372103] [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: 9671271] [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

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.654364

3D structure databases

PDBPDBe

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

DisProt

DP00243.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24191N.

IntAct

P23025. 7 interactions.

STRING

P23025.

PTM databases

PhosphoSite

P23025.

Proteomic databases

PRIDE

P23025.

Genome annotation databases

Ensembl

ENST00000375128; ENSP00000364270; ENSG00000136936; Homo sapiens. [Genome view]

GeneID

7507.

KEGG

hsa:7507.

UCSC

uc004axr.2. human.

Organism-specific databases

CTD

7507.

GeneCards

GC09M099477.

H-InvDB

HIX0008216.

HGNC

HGNC:12814. XPA.

HPA

CAB000155.

MIM

278700. phenotype.
611153. gene.

Orphanet

910. Xeroderma pigmentosum.

PharmGKB

PA368.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P23025.

HOVERGEN

P23025.

OMA

VAHQHEY.

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

IPR000465. XPA.
[Graphical view]

PANTHER

PTHR10142. XPA. 1 hit.

Pfam

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

TIGRFAMs

TIGR00598. rad14. 1 hit.

PROSITE

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

ProtoNet

Search...

Other Resources

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:	November 3, 2009
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.