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ERCC5
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	5EKF, 5EKG
Identifikatori
Aliasi	ERCC5
Vanjski ID-jevi	OMIM: 133530 MGI: 103582 HomoloGene: 133551 GeneCards: ERCC5
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	102,875,995 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	44,220,420 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje sa DNK; • protein homodimerization activity; • hydrolase activity, acting on ester bonds; • protein N-terminus binding; • bubble DNA binding; • vezivanje iona metala; • single-stranded DNA binding; • GO:0001948, GO:0016582 vezivanje za proteine; • catalytic activity; • nuclease activity; • endonuclease activity; • double-stranded DNA binding; • endodeoxyribonuclease activity; • hydrolase activity; • RNA polymerase II complex binding; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• RNA polymerase II, holoenzyme; • transcription factor TFIIH holo complex; • Replikacijski protein A; • jedro; • nukleoplazma; • nucleotide-excision repair complex;
Biološki proces	• negative regulation of apoptotic process; • cellular response to DNA damage stimulus; • UV protection; • transcription-coupled nucleotide-excision repair; • nucleotide-excision repair, DNA incision; • response to UV; • response to UV-C; • Popravak ekscizijom nukleotida; • nucleotide-excision repair, preincision complex stabilization; • GO:0100026 Popravka DNK; • nucleotide-excision repair, preincision complex assembly; • nucleotide-excision repair, DNA incision, 5'-to lesion; • nucleotide-excision repair, DNA incision, 3'-to lesion;
	Izvori:Amigo / QuickGO
Ortolozi
	2073
	22592
	ENSG00000134899
	ENSMUSG00000026048
	P28715
	P35689
	NM_000123
	NM_011729
	NP_000114
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Komplementarni protein za popravak DNK XP-G ćelija jest protein koji je kod ljudi kodiran genom ERCC5 sa hromosoma 13.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.186 aminokiselina, a molekulska težina 133.108 Da.^[6]

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
MGVQGLWKLL	ECSGRQVSPE	ALEGKILAVD	ISIWLNQALK	GVRDRHGNSI
ENPHLLTLFH	RLCKLLFFRI	RPIFVFDGDA	PLLKKQTLVK	RRQRKDLASS
DSRKTTEKLL	KTFLKRQAIK	TAFRSKRDEA	LPSLTQVRRE	NDLYVLPPLQ
EEEKHSSEEE	DEKEWQERMN	QKQALQEEFF	HNPQAIDIES	EDFSSLPPEV
KHEILTDMKE	FTKRRRTLFE	AMPEESDDFS	QYQLKGLLKK	NYLNQHIEHV
QKEMNQQHSG	HIRRQYEDEG	GFLKEVESRR	VVSEDTSHYI	LIKGIQAKTV
AEVDSESLPS	SSKMHGMSFD	VKSSPCEKLK	TEKEPDATPP	SPRTLLAMQA
ALLGSSSEEE	LESENRRQAR	GRNAPAAVDE	GSISPRTLSA	IKRALDDDED
VKVCAGDDVQ	TGGPGAEEMR	INSSTENSDE	GLKVRDGKGI	PFTATLASSS
VNSAEEHVAS	TNEGREPTDS	VPKEQMSLVH	VGTEAFPISD	ESMIKDRKDR
LPLESAVVRH	SDAPGLPNGR	ELTPASPTCT	NSVSKNETHA	EVLEQQNELC
PYESKFDSSL	LSSDDETKCK	PNSASEVIGP	VSLQETSSIV	SVPSEAVDNV
ENVVSFNAKE	HENFLETIQE	QQTTESAGQD	LISIPKAVEP	MEIDSEESES
DGSFIEVQSV	ISDEELQAEF	PETSKPPSEQ	GEEELVGTRE	GEAPAESESL
LRDNSERDDV	DGEPQEAEKD	AEDSLHEWQD	INLEELETLE	SNLLAQQNSL
KAQKQQQERI	AATVTGQMFL	ESQELLRLFG	IPYIQAPMEA	EAQCAILDLT
DQTSGTITDD	SDIWLFGARH	VYRNFFNKNK	FVEYYQYVDF	HNQLGLDRNK
LINLAYLLGS	DYTEGIPTVG	CVTAMEILNE	FPGHGLEPLL	KFSEWWHEAQ
KNPKIRPNPH	DTKVKKKLRT	LQLTPGFPNP	AVAEAYLKPV	VDDSKGSFLW
GKPDLDKIRE	FCQRYFGWNR	TKTDESLFPV	LKQLDAQQTQ	LRIDSFFRLA
QQEKEDAKRI	KSQRLNRAVT	CMLRKEKEAA	ASEIEAVSVA	MEKEFELLDK
AKGKTQKRGI	TNTLEESSSL	KRKRLSDSKG	KNTCGGFLGE	TCLSESSDGS
SSEDAESSSL	MNVQRRTAAK	EPKTSASDSQ	NSVKEAPVKN	GGATTSSSSD
SDDDGGKEKM	VLVTARSVFG	KKRRKLRRAR	GRKRKT

Funkcija

Ekscizijska popravka unakrsne komplementarne reparacije glodara, komplementacijska grupa 5 (xeroderma pigmentosum, komplementacijska grupa G) uključena je u ekscizijsku popravku oštećenja DNK izazvane UV zračenjem. Mutacije uzrokuju Cockayneov sindrom, koji se karakterizira teškim defektima rasta, mentalnom retardacijom i kaheksijom. Opisano je više alternativno prerađenih varijanti transkripta koje kodiraju različite izoforme, ali biološka valjanost svih varijanti nije utvrđena.^[6]

Mutacije u ERCC5 uzrokuju artrogripozu.^[7]

XPG je strukturno specifična endonukleaza koja urezuje DNK na 3’ strani oštećenog nukleotida tokom reparacije ekscizijom nukleotida.

Sindromi

Mutacijski defekti gena Ercc5(Xpg) mogu uzrokovati stanje sklono karcinomu xeroderma pigmentosum (XP) samostalno ili u kombinaciji s teškim neurorazvojnim poremećajem Cockayneov sindrom (CS) ili infantilnim smrtonosnim cerebro-okulo-facio-skeletnim sindromom.^[8]

Model miša

Model mutantnog miša Ercc5(Xpg) predstavio je karakteristike preranog starenja, uključujući kaheksiju i osteoporozu sa izraženim degenerativnim fenotipovima u jetri i mozgu.^[8] Ovi mutirani miševi su razvili multisistemski degenerativni fenotip preranog starenja koji izgleda jača vezu između oštećenja DNK i starenja.^[8] (vidi Teorija oštećenja DNK starenjem).

Ograničenje u ishrani, koje produžava životni vijek miševa divljeg tipa, također je značajno produžilo životni vijek Ercc5(Xpg) mutantnih miševa.^[9] Ograničenje ishrane mutantnih miševa, dok je odlagalo starenje, također je usporilo akumulaciju oštećenja DNK u čitavom genomu i očuvalo transkripcioni izlaz, doprinoseći tako poboljšanoj vitalnosti ćelija.

Interakcije

Pokazalo se da ERCC5 u interakciji sa ERCC2.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134899 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026048 - 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.
^ Samec S, Jones TA, Corlet J, Scherly D, Sheer D, Wood RD, Clarkson SG (maj 1994). "The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization". Genomics. 21 (1): 283–5. doi:10.1006/geno.1994.1261. PMID 8088806.
^ ^a ^b ^c "Entrez Gene: ERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))".
^ Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH (juli 2014). "A novel homozygous ERCC5 truncating mutation in a family with prenatal arthrogryposis--further evidence of genotype-phenotype correlation". American Journal of Medical Genetics. Part A. 164A (7): 1777–83. doi:10.1002/ajmg.a.36506. PMID 24700531. S2CID 8023991.
^ ^a ^b ^c Barnhoorn S, Uittenboogaard LM, Jaarsma D, Vermeij WP, Tresini M, Weymaere M, Menoni H, Brandt RM, de Waard MC, Botter SM, Sarker AH, Jaspers NG, van der Horst GT, Cooper PK, Hoeijmakers JH, van der Pluijm I (oktobar 2014). "Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency". PLOS Genetics. 10 (10): e1004686. doi:10.1371/journal.pgen.1004686. PMC 4191938. PMID 25299392.
^ Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH (septembar 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC 5161687. PMID 27556946.
^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.

Dopunska literatura

Miura M (mart 1999). "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair". Journal of Radiation Research. 40 (1): 1–12. Bibcode:1999JRadR..40....1M. doi:10.1269/jrr.40.1. PMID 10408173.
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.
Takahashi E, Shiomi N, Shiomi T (novembar 1992). "Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization". Japanese Journal of Cancer Research. 83 (11): 1117–9. doi:10.1111/j.1349-7006.1992.tb02731.x. PMC 5918714. PMID 1483924.
Mudgett JS, MacInnes MA (decembar 1990). "Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination". Genomics. 8 (4): 623–33. doi:10.1016/0888-7543(90)90248-S. PMID 2276736.
Shiomi T, Harada Y, Saito T, Shiomi N, Okuno Y, Yamaizumi M (mart 1994). "An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum". Mutation Research. 314 (2): 167–75. doi:10.1016/0921-8777(94)90080-9. PMID 7510366.
Lehmann AR, Bootsma D, Clarkson SG, Cleaver JE, McAlpine PJ, Tanaka K, Thompson LH, Wood RD (juli 1994). "Nomenclature of human DNA repair genes". Mutation Research. 315 (1): 41–2. doi:10.1016/0921-8777(94)90026-4. PMID 7517009.
Cloud KG, Shen B, Strniste GF, Park MS (juli 1995). "XPG protein has a structure-specific endonuclease activity". Mutation Research. 347 (2): 55–60. doi:10.1016/0165-7992(95)90070-5. PMID 7651464.
Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A (septembar 1995). "Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies". The Journal of Biological Chemistry. 270 (35): 20862–9. doi:10.1074/jbc.270.35.20862. PMID 7657672.
Nouspikel T, Clarkson SG (juni 1994). "Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient" (PDF). Human Molecular Genetics. 3 (6): 963–7. doi:10.1093/hmg/3.6.963. PMID 7951246.
Habraken Y, Sung P, Prakash L, Prakash S (august 1994). "Human xeroderma pigmentosum group G gene encodes a DNA endonuclease". Nucleic Acids Research. 22 (16): 3312–6. doi:10.1093/nar/22.16.3312. PMC 523723. PMID 8078765.
O'Donovan A, Davies AA, Moggs JG, West SC, Wood RD (septembar 1994). "XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair". Nature. 371 (6496): 432–5. Bibcode:1994Natur.371..432O. doi:10.1038/371432a0. PMID 8090225. S2CID 4328388.
O'Donovan A, Scherly D, Clarkson SG, Wood RD (juni 1994). "Isolation of active recombinant XPG protein, a human DNA repair endonuclease". The Journal of Biological Chemistry. 269 (23): 15965–8. doi:10.1016/S0021-9258(17)33956-X. PMID 8206890.
MacInnes MA, Dickson JA, Hernandez RR, Learmonth D, Lin GY, Mudgett JS, Park MS, Schauer S, Reynolds RJ, Strniste GF (oktobar 1993). "Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe". Molecular and Cellular Biology. 13 (10): 6393–402. doi:10.1128/MCB.13.10.6393. PMC 364698. PMID 8413238.
Scherly D, Nouspikel T, Corlet J, Ucla C, Bairoch A, Clarkson SG (maj 1993). "Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2". Nature. 363 (6425): 182–5. Bibcode:1993Natur.363..182S. doi:10.1038/363182a0. PMID 8483504. S2CID 9713824.
O'Donovan A, Wood RD (maj 1993). "Identical defects in DNA repair in xeroderma pigmentosum group G and rodent ERCC group 5". Nature. 363 (6425): 185–8. Bibcode:1993Natur.363..185O. doi:10.1038/363185a0. PMID 8483505. S2CID 4372167.
Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
Park MS, Knauf JA, Pendergrass SH, Coulon CH, Strniste GF, Marrone BL, MacInnes MA (august 1996). "Ultraviolet-induced movement of the human DNA repair protein, Xeroderma pigmentosum type G, in the nucleus". Proceedings of the National Academy of Sciences of the United States of America. 93 (16): 8368–73. Bibcode:1996PNAS...93.8368P. doi:10.1073/pnas.93.16.8368. PMC 38677. PMID 8710877.

Vanjski linkovi

GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134899 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026048 - 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.

[pmid8088806-5] Samec S, Jones TA, Corlet J, Scherly D, Sheer D, Wood RD, Clarkson SG (maj 1994). "The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization". Genomics. 21 (1): 283–5. doi:10.1006/geno.1994.1261. PMID 8088806.

[entrez-6] "Entrez Gene: ERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))".

[7] Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH (juli 2014). "A novel homozygous ERCC5 truncating mutation in a family with prenatal arthrogryposis--further evidence of genotype-phenotype correlation". American Journal of Medical Genetics. Part A. 164A (7): 1777–83. doi:10.1002/ajmg.a.36506. PMID 24700531. S2CID 8023991.

[pmid25299392-8] Barnhoorn S, Uittenboogaard LM, Jaarsma D, Vermeij WP, Tresini M, Weymaere M, Menoni H, Brandt RM, de Waard MC, Botter SM, Sarker AH, Jaspers NG, van der Horst GT, Cooper PK, Hoeijmakers JH, van der Pluijm I (oktobar 2014). "Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency". PLOS Genetics. 10 (10): e1004686. doi:10.1371/journal.pgen.1004686. PMC 4191938. PMID 25299392.

[pmid27556946-9] Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH (septembar 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC 5161687. PMID 27556946.

[pmid8652557-10] Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.

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