ERCC8

ERCC8
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4A11
Identifikatori
Aliasi	ERCC8
Vanjski ID-jevi	OMIM: 609412 MGI: 1919241 HomoloGene: 62 GeneCards: ERCC8
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	60,945,073 bp
Lokacija gena (miš)
Hrom.	Hromosom 13 (miš)
Kraj	108,331,898 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• ATP-dependent activity, acting on DNA; • GO:0004003 DNA helicase activity; • GO:0050372 aktivnost sa transferazom ubikvitina; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• nukleoplazma; • nucleotide-excision repair complex; • nuclear matrix; • Cul4A-RING E3 ubiquitin ligase complex; • jedro; • Cul4-RING E3 ubiquitin ligase complex; • citoplazma; • perikaryon; • GO:0009327 makromolekulani kompleks;
Biološki proces	• response to X-ray; • protein polyubiquitination; • GO:1900404 positive regulation of DNA repair; • proteasome-mediated ubiquitin-dependent protein catabolic process; • protein ubiquitination; • protein autoubiquitination; • transcription-coupled nucleotide-excision repair; • GO:0001306 response to oxidative stress; • response to UV; • cellular response to DNA damage stimulus; • Popravak ekscizijom nukleotida; • GO:0100026 Popravka DNK; • Posttranslacione modifikacije; • response to auditory stimulus; • GO:1904578 response to organic cyclic compound; • DNA duplex unwinding;
	Izvori:Amigo / QuickGO
Ortolozi
	1161
	71991
	ENSG00000049167
	ENSMUSG00000021694
	Q13216
	Q8CFD5
	NM_001290285; NM_000082; NM_001007233; NM_001007234
	NM_028042; NM_001362403
	NP_000073; NP_001007234; NP_001007235; NP_001277214
	NP_082318; NP_001349332
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein ERCC-8 ekscizijke popravke DNK jest protein koji je kod ljudi kodiran genom ERCC8.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 396 aminokiselina, а molekulska težina 44.055 Da.^[7]

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
MLGFLSARQT	GLEDPLRLRR	AESTRRVLGL	ELNKDRDVER	IHGGGINTLD
IEPVEGRYML	SGGSDGVIVL	YDLENSSRQS	YYTCKAVCSI	GRDHPDVHRY
SVETVQWYPH	DTGMFTSSSF	DKTLKVWDTN	TLQTADVFNF	EETVYSHHMS
PVSTKHCLVA	VGTRGPKVQL	CDLKSGSCSH	ILQGHRQEIL	AVSWSPRYDY
ILATASADSR	VKLWDVRRAS	GCLITLDQHN	GKKSQAVESA	NTAHNGKVNG
LCFTSDGLHL	LTVGTDNRMR	LWNSSNGENT	LVNYGKVCNN	SKKGLKFTVS
CGCSSEFVFV	PYGSTIAVYT	VYSGEQITML	KGHYKTVDCC	VFQSNFQELY
SGSRDCNILA	WVPSLYEPVP	DDDETTTKSQ	LNPAFEDAWS	SSDEEG

Funkcija

Ovaj gen kodira protein ponovljenog WD-a, koji stupa u interakciju s Cockayneovim sindromom tipa B (CSB) i p44 proteinima, a potonji je podjedinica RNK-polimeraze II transkripcijskog faktora II H . Mutacije u ovom genu identificirane su kod pacijenata s nasljednom bolešću Cockayneov sindrom (CS). CS je poremećaj ubrzanog starenja koji karakterizira fotoosjetljivost, poremećen razvoj i višesistemska progresivna degeneracija. CS ćelije su abnormalno osjetljive na ultraljubičasto zračenje i neispravne su u popravljanju transkripcijski aktivnih gena. Alternativno je za ovaj gen pronađeno više prerađenih varijanti transkripta koje kodiraju različite izoforme.^[6]

Smatra se da proteini CSA i CSB funkcioniraju u transkripciji i popravkama DNK, ponajviše u popravljanju ekscizije (isijecanja) nukleotida povezanih s transkripcijom. Ćelije s nedostatkom CSA i CSB pokazuju nedostatak preferencijalne popravke UV-induciranih ciklobutanskih pirimidinskih dimera u aktivno transkribiranim genima, u skladu s neuspjelim odgovorom popravljanja ekscizije vezanih nukleotida pri transkripciji.^[8] Unutar ćelije, CSA protein nalazi se na mjestima oštećenja DNK, posebno međulančanim unakrsnim vezama, dvolančanim prekidima i nekim monoadodacima.^[9]

CS nastaje zbog mutacija zametne linije u bilo kojem od dva gena, CSA (ERCC8) ili CSB (ERCC6) . Mutacije CSA općenito uzrokuju umjereniji oblik CS-a od mutacija CSB.^[9] Mutacije u genu CSA čine oko 20% slučajeva CS-a.^[10]

Interakcije

Za ERCC8 pokazano je daima interakcije sa XAB2.^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000049167 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021694 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Itoh T, Shiomi T, Shiomi N, Harada Y, Wakasugi M, Matsunaga T, Nikaido O, Friedberg EC, Yamaizumi M (april 1996). "Rodent complementation group 8 (ERCC8) corresponds to Cockayne syndrome complementation group A". Mutat Res. 362 (2): 167–74. doi:10.1016/0921-8777(95)00046-1. PMID 8596535.
^ ^a ^b "Entrez Gene: ERCC8 excision repair cross-complementing rodent repair deficiency, complementation group 8".
^ "UniProt, Q13216" (jezik: engleski). Pristupljeno 14. 10. 2021.
^ van Hoffen A, Natarajan AT, Mayne LV, van Zeeland AA, Mullenders LH, Venema J (1993). "Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells". Nucleic Acids Res. 21 (25): 5890–5. doi:10.1093/nar/21.25.5890. PMC 310470. PMID 8290349.
^ ^a ^b Iyama T, Wilson DM (2016). "Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome". J. Mol. Biol. 428 (1): 62–78. doi:10.1016/j.jmb.2015.11.020. PMC 4738086. PMID 26616585.
^ Koch S, Garcia Gonzalez O, Assfalg R, Schelling A, Schäfer P, Scharffetter-Kochanek K, Iben S (2014). "Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth". Cell Cycle. 13 (13): 2029–37. doi:10.4161/cc.29018. PMC 4111694. PMID 24781187.
^ 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 (novembar 2000). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". J. Biol. Chem. UNITED STATES. 275 (45): 34931–7. doi:10.1074/jbc.M004936200. ISSN 0021-9258. PMID 10944529.

Dopunska literatura

van Gool AJ, van der Horst GT, Citterio E, Hoeijmakers JH (1997). "Cockayne syndrome: defective repair of transcription?". EMBO J. 16 (14): 4155–62. doi:10.1093/emboj/16.14.4155. PMC 1170041. PMID 9250659.
Henning KA, Li L, Iyer N, et al. (1995). "The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH". Cell. 82 (4): 555–64. doi:10.1016/0092-8674(95)90028-4. PMID 7664335. S2CID 16109644.
Bregman DB, et al. (1996). "UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells". Proc. Natl. Acad. Sci. U.S.A. 93 (21): 11586–90. Bibcode:1996PNAS...9311586B. doi:10.1073/pnas.93.21.11586. PMC 38101. PMID 8876179.
Selby CP, Sancar A (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". J. Biol. Chem. 272 (3): 1885–90. doi:10.1074/jbc.272.3.1885. PMID 8999876.
Nakatsu Y, Asahina H, Citterio E, et al. (2001). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". J. Biol. Chem. 275 (45): 34931–7. doi:10.1074/jbc.M004936200. PMID 10944529.
Kamiuchi S, et al. (2002). "Translocation of Cockayne syndrome group A protein to the nuclear matrix: possible relevance to transcription-coupled DNA repair" (PDF). Proc. Natl. Acad. Sci. U.S.A. 99 (1): 201–6. Bibcode:2002PNAS...99..201K. doi:10.1073/pnas.012473199. PMC 117539. PMID 11782547.
Strausberg RL, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Groisman R, Polanowska J, Kuraoka I, et al. (2003). "The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage". Cell. 113 (3): 357–67. doi:10.1016/S0092-8674(03)00316-7. PMID 12732143. S2CID 11639677.
Cao H, Williams C, Carter M, Hegele RA (2004). "CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism". J. Hum. Genet. 49 (1): 61–3. doi:10.1007/s10038-003-0107-2. PMID 14661080.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ (2005). "Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects". J. Hum. Genet. 50 (3): 151–4. doi:10.1007/s10038-004-0228-2. PMID 15744458.
Sarker AH, Tsutakawa SE, Kostek S, et al. (2006). "Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome". Mol. Cell. 20 (2): 187–98. doi:10.1016/j.molcel.2005.09.022. PMID 16246722.
Groisman R, Kuraoka I, Chevallier O, et al. (2006). "CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome". Genes Dev. 20 (11): 1429–34. doi:10.1101/gad.378206. PMC 1475755. PMID 16751180.
Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH (2006). "Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo". Mol. Cell. 23 (4): 471–82. doi:10.1016/j.molcel.2006.06.029. PMID 16916636.
Saijo M, Hirai T, Ogawa A, et al. (2007). "Functional TFIIH is required for UV-induced translocation of CSA to the nuclear matrix". Mol. Cell. Biol. 27 (7): 2538–47. doi:10.1128/MCB.01288-06. PMC 1899911. PMID 17242193.
D'Errico M, Parlanti E, Teson M, et al. (2007). "The role of CSA in the response to oxidative DNA damage in human cells". Oncogene. 26 (30): 4336–43. doi:10.1038/sj.onc.1210232. PMID 17297471.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Cockayne syndrome

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000049167 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021694 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8596535-5] Itoh T, Shiomi T, Shiomi N, Harada Y, Wakasugi M, Matsunaga T, Nikaido O, Friedberg EC, Yamaizumi M (april 1996). "Rodent complementation group 8 (ERCC8) corresponds to Cockayne syndrome complementation group A". Mutat Res. 362 (2): 167–74. doi:10.1016/0921-8777(95)00046-1. PMID 8596535.

[entrez-6] "Entrez Gene: ERCC8 excision repair cross-complementing rodent repair deficiency, complementation group 8".

[UniProt-7] "UniProt, Q13216" (jezik: engleski). Pristupljeno 14. 10. 2021.

[pmid8290349-8] van Hoffen A, Natarajan AT, Mayne LV, van Zeeland AA, Mullenders LH, Venema J (1993). "Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells". Nucleic Acids Res. 21 (25): 5890–5. doi:10.1093/nar/21.25.5890. PMC 310470. PMID 8290349.

[pmid26616585-9] Iyama T, Wilson DM (2016). "Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome". J. Mol. Biol. 428 (1): 62–78. doi:10.1016/j.jmb.2015.11.020. PMC 4738086. PMID 26616585.

[pmid24781187-10] Koch S, Garcia Gonzalez O, Assfalg R, Schelling A, Schäfer P, Scharffetter-Kochanek K, Iben S (2014). "Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth". Cell Cycle. 13 (13): 2029–37. doi:10.4161/cc.29018. PMC 4111694. PMID 24781187.

[pmid10944529-11] 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 (novembar 2000). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". J. Biol. Chem. UNITED STATES. 275 (45): 34931–7. doi:10.1074/jbc.M004936200. ISSN 0021-9258. PMID 10944529.

[1]