XPA

For the ISO 639-3 code, see Pirriya language.

XPA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1D4U, 1XPA, 2JNW
Identifiers
Aliases	XPA , XP1, XPAC, xeroderma pigmentosum, complementation group A, DNA damage recognition and repair factor
External IDs	OMIM: 611153; MGI: 99135; HomoloGene: 37298; GeneCards: XPA; OMA:XPA - orthologs
Gene location (Mouse) Chr. Chromosome 4 (mouse) [1] Band 4 B1|4 24.49 cM Start 46,155,347 bp [1] End 46,196,311 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in granulocyte genital tubercle neural layer of retina ventricular zone right kidney ganglionic eminence muscle of thigh embryo tail of embryo proximal tubule BioGPS More reference expression data
Gene ontology Molecular function metal ion binding protein domain specific binding protein homodimerization activity DNA binding protein binding damaged DNA binding Cellular component intercellular bridge DNA replication factor A complex nucleotide-excision repair factor 1 complex nucleus nucleoplasm cytoplasm Biological process nucleotide-excision repair, DNA incision intrinsic apoptotic signaling pathway in response to DNA damage transcription-coupled nucleotide-excision repair response to oxidative stress cellular response to DNA damage stimulus response to auditory stimulus multicellular organism growth global genome nucleotide-excision repair response to toxic substance response to UV nucleotide-excision repair, preincision complex assembly nucleotide-excision repair nucleotide-excision repair, DNA incision, 5'-to lesion nucleotide-excision repair involved in interstrand cross-link repair UV-damage excision repair base-excision repair nucleotide-excision repair, preincision complex stabilization nucleotide-excision repair, DNA damage recognition DNA repair UV protection protein localization to nucleus regulation of autophagy nucleotide-excision repair, DNA duplex unwinding nucleotide-excision repair, DNA incision, 3'-to lesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7507 22590 Ensembl ENSG00000136936 ENSMUSG00000028329 UniProt P23025 Q64267 RefSeq (mRNA) NM_000380 NM_011728 RefSeq (protein) NP_000371 NP_001341904 NP_035858 Location (UCSC) n/a Chr 4: 46.16 – 46.2 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the XPA gene. ^[4]

Function

Nucleotide excision repair (NER) is a major pathway for repairing a variety of bulky DNA damages including those introduced by UV irradiation. The XPA protein appears to play a key role in NER at sites of damage as a scaffold for other repair proteins in order to ensure that the damages are appropriately excised. ^[5] Among the repair proteins with which XPA interacts is a protein complex (including the ERCC1 protein) that is capable of incising DNA at sites of damage. ^[6]

Xpa mutant individuals often show the severe clinical symptoms of xeroderma pigmentosum, a condition involving extreme sensitivity to sunlight and a high incidence of skin cancer.

Interactions

XPA has been shown to interact with ERCC1, ^{[6] [7]} Replication protein A1 ^[8] and XAB2. ^[9]

References

1. GRCm38: Ensembl release 89: ENSMUSG00000028329 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: XPA xeroderma pigmentosum, complementation group A".
5. Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ (2016). "XPA: A key scaffold for human nucleotide excision repair". DNA Repair (Amst.). 44: 123–35. doi:10.1016/j.dnarep.2016.05.018. PMC   4958585 . PMID   27247238.
6. Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ (May 1994). "Specific association between the human DNA repair proteins XPA and ERCC1". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 5012–6. Bibcode:1994PNAS...91.5012L. doi: 10.1073/pnas.91.11.5012 . PMC   43920 . PMID   8197174.
7. Nagai A, Saijo M, Kuraoka I, Matsuda T, Kodo N, Nakatsu Y, Mimaki T, Mino M, Biggerstaff M, Wood RD (Jun 1995). "Enhancement of damage-specific DNA binding of XPA by interaction with the ERCC1 DNA repair protein". Biochemical and Biophysical Research Communications. 211 (3): 960–6. doi:10.1006/bbrc.1995.1905. hdl: 1765/60251 . PMID   7598728.
8. Li L, Lu X, Peterson CA, Legerski RJ (Oct 1995). "An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair". Molecular and Cellular Biology. 15 (10): 5396–402. doi:10.1128/mcb.15.10.5396. PMC   230789 . PMID   7565690.
9. 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 (Nov 2000). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". The Journal of Biological Chemistry. 275 (45): 34931–7. doi: 10.1074/jbc.M004936200 . hdl: 1765/3168 . PMID   10944529.

Further reading

• Cleaver JE, Thompson LH, Richardson AS, States JC (1999). "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy". Human Mutation. 14 (1): 9–22. doi: 10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6 . PMID   10447254. S2CID   24148589.
• Morikawa K, Shirakawa M (Aug 2000). "Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA". Mutation Research. 460 (3–4): 257–75. doi:10.1016/s0921-8777(00)00031-8. PMID   10946233.
• Satokata I, Tanaka K, Okada Y (Mar 1992). "Molecular basis of group A xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene". Human Genetics. 88 (6): 603–7. doi:10.1007/BF02265282. PMID   1339397. S2CID   36814493.
• Satokata I, Tanaka K, Yuba S, Okada Y (Mar 1992). "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". Mutation Research. 273 (2): 203–12. doi:10.1016/0921-8777(92)90081-d. PMID   1372103.
• Miyamoto I, Miura N, Niwa H, Miyazaki J, Tanaka K (Jun 1992). "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". The Journal of Biological Chemistry. 267 (17): 12182–7. doi: 10.1016/S0021-9258(19)49821-9 . PMID   1601884.
• Satokata I, Tanaka K, Miura N, Miyamoto I, Satoh Y, Kondo S, Okada Y (Dec 1990). "Characterization of a splicing mutation in group A xeroderma pigmentosum". Proceedings of the National Academy of Sciences of the United States of America. 87 (24): 9908–12. Bibcode:1990PNAS...87.9908S. doi: 10.1073/pnas.87.24.9908 . PMC   55283 . PMID   1702221.
• Miura N, Miyamoto I, Asahina H, Satokata I, Tanaka K, Okada Y (Oct 1991). "Identification and characterization of xpac protein, the gene product of the human XPAC (xeroderma pigmentosum group A complementing) gene". The Journal of Biological Chemistry. 266 (29): 19786–9. doi: 10.1016/S0021-9258(18)55060-2 . PMID   1918083.
• Tanaka K, Miura N, Satokata I, Miyamoto I, Yoshida MC, Satoh Y, Kondo S, Yasui A, Okayama H, Okada Y (Nov 1990). "Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain". Nature. 348 (6296): 73–6. Bibcode:1990Natur.348...73T. doi:10.1038/348073a0. PMID   2234061. S2CID   4346999.
• Li L, Lu X, Peterson CA, Legerski RJ (Oct 1995). "An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair". Molecular and Cellular Biology. 15 (10): 5396–402. doi:10.1128/mcb.15.10.5396. PMC   230789 . PMID   7565690.
• Nagai A, Saijo M, Kuraoka I, Matsuda T, Kodo N, Nakatsu Y, Mimaki T, Mino M, Biggerstaff M, Wood RD (Jun 1995). "Enhancement of damage-specific DNA binding of XPA by interaction with the ERCC1 DNA repair protein". Biochemical and Biophysical Research Communications. 211 (3): 960–6. doi:10.1006/bbrc.1995.1905. hdl: 1765/60251 . PMID   7598728.
• Farndon PA, Morris DJ, Hardy C, McConville CM, Weissenbach J, Kilpatrick MW, Reis A (Sep 1994). "Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3". Genomics. 23 (2): 486–9. doi:10.1006/geno.1994.1528. PMID   7835901.
• Park CH, Mu D, Reardon JT, Sancar A (Mar 1995). "The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor". The Journal of Biological Chemistry. 270 (9): 4896–902. doi: 10.1074/jbc.270.9.4896 . PMID   7876263.
• Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ (May 1994). "Specific association between the human DNA repair proteins XPA and ERCC1". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 5012–6. Bibcode:1994PNAS...91.5012L. doi: 10.1073/pnas.91.11.5012 . PMC   43920 . PMID   8197174.
• Park CH, Sancar A (May 1994). "Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 5017–21. Bibcode:1994PNAS...91.5017P. doi: 10.1073/pnas.91.11.5017 . PMC   43921 . PMID   8197175.
• Satokata I, Iwai K, Matsuda T, Okada Y, Tanaka K (Dec 1993). "Genomic characterization of the human DNA excision repair-controlling gene XPAC". Gene. 136 (1–2): 345–8. doi:10.1016/0378-1119(93)90493-M. PMID   8294029.
• Tanaka K (Mar 1993). "The Japan Society of Human Genetics Award Lecture. Molecular analysis of xeroderma pigmentosum group A gene". The Japanese Journal of Human Genetics. 38 (1): 1–14. doi: 10.1007/BF01891230 . PMID   8504220.
• Topping RS, Myrand SP, Williams BL, Albert JC, States JC (Dec 1995). "Characterization of the human XPA promoter". Gene. 166 (2): 341–2. doi:10.1016/0378-1119(95)00649-4. PMID   8543191.
• Lench NJ, Telford EA, Andersen SE, Moynihan TP, Robinson PA, Markham AF (Dec 1996). "An EST and STS-based YAC contig map of human chromosome 9q22.3". Genomics. 38 (2): 199–205. doi:10.1006/geno.1996.0616. PMID   8954802.
• Selby CP, Sancar A (Jan 1997). "Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II". The Journal of Biological Chemistry. 272 (3): 1885–90. doi: 10.1074/jbc.272.3.1885 . PMID   8999876.
• Hayashi T, Takao M, Tanaka K, Yasui A (Jun 1998). "ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines". Mutation Research. 407 (3): 269–76. doi:10.1016/s0921-8777(98)00013-5. PMID   9653453.

External links

• GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum