XPA

XPA
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1D4U, 1XPA, 2JNW
Identifikatori
Aliasi	XPA
Vanjski ID-jevi	OMIM: 611153 MGI: 99135 HomoloGene: 37298 GeneCards: XPA
Lokacija gena (miš) Hrom. Hromosom 4 (miš)[1] Bend 4 B1|4 24.49 cM Početak 46,155,347 bp[1] Kraj 46,196,311 bp[1]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • vezivanje iona metala • protein domain specific binding • protein homodimerization activity • vezivanje sa DNK • GO:0001948, GO:0016582 vezivanje za proteine • oštećeno vezivanje sa DNK Ćelijska komponenta • intercellular bridge • Replikacijski protein A • nucleotide-excision repair factor 1 complex • jedro • nukleoplazma • citoplazma Biološki proces • nucleotide-excision repair, DNA incision • intrinsic apoptotic signaling pathway in response to DNA damage • transcription-coupled nucleotide-excision repair • GO:0001306 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 • Popravak ekscizijom nukleotida • 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 • GO:0100026 Popravka DNK • UV protection • protein localization to nucleus • regulation of autophagy • nucleotide-excision repair, DNA duplex unwinding • nucleotide-excision repair, DNA incision, 3'-to lesion Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	7507	22590
Ensembl	ENSG00000136936	ENSMUSG00000028329
UniProt	P23025	Q64267
RefSeq (mRNK)	NM_000380	NM_011728
RefSeq (bjelančevina)	NP_000371 NP_001341904	NP_035858
Lokacija (UCSC)	n/a	Chr 4: 46.16 – 46.2 Mb
PubMed pretraga	[2]	[3]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Protein za popravku DNK koji nadopunjuje ćelije XP-A je protein koji je kod ljudi kodiran genom XPA , sa hromosoma 9.^[4]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 273 aminokiseline, а molekulska masa — 31.368 Da.^[4]

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MAAADGALPE		AAALEQPAEL		PASVRASIER		KRQRALMLRQ		ARLAARPYSA
TAAAATGGMA		NVKAAPKIID		TGGGFILEEE		EEEEQKIGKV		VHQPGPVMEF
DYVICEECGK		EFMDSYLMNH		FDLPTCDNCR		DADDKHKLIT		KTEAKQEYLL
KDCDLEKREP		PLKFIVKKNP		HHSQWGDMKL		YLKLQIVKRS		LEVWGSQEAL
EEAKEVRQEN		REKMKQKKFD		KKVKELRRAV		RSSVWKRETI		VHQHEYGPEE
NLEDDMYRKT		CTMCGHELTY		EKM

Funkcija

Nukleotidni ekscizijski popravak (NER) je glavni put za popravak raznih glomaznih oštećenja DNK, uključujući i ona unesena UV zračenjem. Čini se da XPA protein ima ključnu ulogu u NER-u na mjestima oštećenja kao skela za druge proteine za popravak kako bi se osiguralo da su oštećenja na odgovarajući način izrezana.^[5] Među proteinima za popravak s kojima XPA stupa u interakciju je proteinski kompleks (uključujući ERCC1 protein) koji je sposoban urezati DNK na mjestima oštećenja.^[6]

Xpa mutantne osobe često pokazuju teške kliničke simptome xeroderma pigmentosum, stanja koje uključuje ekstremnu osjetljivost na sunčevu svjetlost i visoku učestalost raka kože.

Interakcije

Pokazano je da XPA ima interakcije sa ERCC1,^[6][7] replikacijskim proteinom A1^[8] i XAB2.^[9]

Reference

1. GRCm38: Ensembl release 89: ENSMUSG00000028329 - Ensembl, maj 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 (maj 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. PMID 10944529.

Dopunska literatura

• 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 (maj 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 (maj 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.

Vanjski linkovi

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