XPB

ERCC3
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 4ERN, 5IY9, 5IVW, 5IY7, 5IY8, 5IY6
Identifikatori
Aliasi	ERCC3
Vanjski ID-jevi	OMIM: 133510 MGI: 95414 HomoloGene: 96 GeneCards: ERCC3
Lokacija gena (čovjek) Hrom. Hromosom 2 (čovjek)[1] Bend 2q14.3 Početak 127,257,290 bp[1] Kraj 127,294,166 bp[1]
Lokacija gena (miš) Hrom. Hromosom 18 (miš)[2] Bend 18|18 B1 Početak 32,373,353 bp[2] Kraj 32,403,204 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • protein C-terminus binding • nucleotide binding • GO:0004003 DNA helicase activity • protein kinase activity • hydrolase activity • ATP-dependent activity, acting on DNA • protein N-terminus binding • GO:0043140 3'-5' DNA helicase activity • ATP binding • oštećeno vezivanje sa DNK • vezivanje sa DNK • transcription factor binding • GO:0001948, GO:0016582 vezivanje za proteine • GO:0008026 helicase activity • RNA polymerase II CTD heptapeptide repeat kinase activity • ATPase activity • DNA translocase activity Ćelijska komponenta • GO:0000441 transcription factor TFIIH core complex • jedro • nukleoplazma • transcription factor TFIIH holo complex • transcription factor TFIID complex • nucleotide-excision repair factor 3 complex • transcription preinitiation complex Biološki proces • response to hypoxia • termination of RNA polymerase I transcription • embryonic organ development • transcription, DNA-templated • response to UV • 7-methylguanosine mRNA capping • nucleotide-excision repair, DNA incision • regulation of mitotic cell cycle phase transition • GO:0097285 apoptoza • positive regulation of apoptotic process • protein phosphorylation • hair cell differentiation • GO:0001306 response to oxidative stress • UV protection • cellular response to DNA damage stimulus • transcription initiation from RNA polymerase II promoter • global genome nucleotide-excision repair • GO:0034613 protein localization • transcription elongation from RNA polymerase II promoter • GO:0009373 regulation of transcription, DNA-templated • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • DNA topological change • transcription initiation from RNA polymerase I promoter • transcription by RNA polymerase II • transcription-coupled nucleotide-excision repair • Popravak ekscizijom nukleotida • nucleotide-excision repair, preincision complex stabilization • GO:0100026 Popravka DNK • GO:0022415 viral process • nucleotide-excision repair, preincision complex assembly • nucleotide-excision repair, DNA incision, 5'-to lesion • nucleotide-excision repair, DNA duplex unwinding • regulation of mitotic recombination • promoter clearance from RNA polymerase II promoter • transcription open complex formation at RNA polymerase II promoter • regulation of transposition, RNA-mediated • phosphorylation of RNA polymerase II C-terminal domain • regulation of RNA polymerase II regulatory region sequence-specific DNA binding • nucleotide-excision repair, DNA incision, 3'-to lesion • GO:0001183 transcription elongation from RNA polymerase I promoter Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	2071	13872
Ensembl	ENSG00000163161	ENSMUSG00000024382
UniProt	P19447	P49135
RefSeq (mRNK)	NM_000122 NM_001303416 NM_001303418	NM_133658
RefSeq (bjelančevina)	NP_000113 NP_001290345 NP_001290347	NP_598419
Lokacija (UCSC)	Chr 2: 127.26 – 127.29 Mb	Chr 18: 32.37 – 32.4 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

XPB (xeroderma pigmentosum tip B) je ATP-ovisna DNK helikaza , kod ljudi koji je dio kompleksa transkripcijskog faktora TFIIH, Kod ljudi, gen XPB nalazi se na hromosomu 2.

Struktura

Dr. John Tainer i njegova grupa u The Scripps Research Institute riješili su 3D strukturu arhejskog homologa XPB rendgenskom kristalografijom.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 782 aminokiseline, a molekulska težina 89.278 Da.^[5]

• 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
MGKRDRADRD		KKKSRKRHYE		DEEDDEEDAP		GNDPQEAVPS		AAGKQVDESG
TKVDEYGAKD		YRLQMPLKDD		HTSRPLWVAP		DGHIFLEAFS		PVYKYAQDFL
VAIAEPVCRP		THVHEYKLTA		YSLYAAVSVG		LQTSDITEYL		RKLSKTGVPD
GIMQFIKLCT		VSYGKVKLVL		KHNRYFVESC		HPDVIQHLLQ		DPVIRECRLR
NSEGEATELI		TETFTSKSAI		SKTAESSGGP		STSRVTDPQG		KSDIPMDLFD
FYEQMDKDEE		EEEETQTVSF		EVKQEMIEEL		QKRCIHLEYP		LLAEYDFRND
SVNPDINIDL		KPTAVLRPYQ		EKSLRKMFGN		GRARSGVIVL		PCGAGKSLVG
VTAACTVRKR		CLVLGNSAVS		VEQWKAQFKM		WSTIDDSQIC		RFTSDAKDKP
IGCSVAISTY		SMLGHTTKRS		WEAERVMEWL		KTQEWGLMIL		DEVHTIPAKM
FRRVLTIVQA		HCKLGLTATL		VREDDKIVDL		NFLIGPKLYE		ANWMELQNNG
YIAKVQCAEV		WCPMSPEFYR		EYVAIKTKKR		ILLYTMNPNK		FRACQFLIKF
HERRNDKIIV		FADNVFALKE		YAIRLNKPYI		YGPTSQGERM		QILQNFKHNP
KINTIFISKV		GDTSFDLPEA		NVLIQISSHG		GSRRQEAQRL		GRVLRAKKGM
VAEEYNAFFY		SLVSQDTQEM		AYSTKRQRFL		VDQGYSFKVI		TKLAGMEEED
LAFSTKEEQQ		QLLQKVLAAT		DLDAEEEVVA		GEFGSRSSQA		SRRFGTMSSM
SGADDTVYME		YHSSRSKAPS		KHVHPLFKRF		RK

Funkcija

XPB ima značajnu ulogu u normalnoj baznoj transkripciji, transkripcijski spojenom popravku (TCR) i popravak ekscizijom nukleotida (NER). Pokazalo se da pročišćeni XPB odmotava DNK sa 3’-5’ polarnosti.

Funkcija XPB(ERCC3) proteina u NER-u je da pomogne u odmotavanju DNK dvostruke spirale nakon što se oštećenje prvobitno prepozna. NER je put u više koraka koji uklanja širok spektar različitih oštećenja DNK koja narušavaju normalno uparivanje baza. Takva oštećenja uključuju glomazne hemijske adukte, UV-inducirane pirimidinske dimere i nekoliko oblika oksidativnog oštećenja. Mutacije gena XPB(ERCC3) mogu kod ljudi dovesti do bolesti xeroderma pigmentosum (XP) ili XP u kombinaciji sa Cockayneovim sindromom (XPCS).^[6] Mutantne XPB ćelije pojedinaca sa XPCS fenotipom su osjetljive na UV-zračenje i akutni oksidativni stres.^[7]

Poremećaji

Mutacije u XPB i drugim srodnim komplementarnim grupama, XPA-XPG, dovode do brojnih genetički poremećaj|genetičkih poremećaja]] kao što su Xeroderma pigmentosum, Cockayneov sindrom i trihotiodistrofija.

Interakcije

Pokazalo se da je XPB u interakciji sa:

• BCR,^[8]
• CDK7,^[9][10][11]
• ERCC2,^{[9][12][13][14]}
• GTF2H1,^[9][10][12]
• GTF2H2,^[9][12]
• GTF2H4,^[9][12]
• GTF2H5,^[9]
• P53,^[15]
• PSMC5,^[16] i
• XPC.^[17]

Inhibitori malih molekula

Snažni, bioaktivni prirodni proizvodi poput triptolida koji inhibiraju transkripciju sisara putem inhibicije XPB podjedinice općeg transkripcijskog faktora TFIIH nedavno su prijavljeni kao konjugat glukoze za ciljanje hipoksijskih ćelija raka s povećanom ekspresijom transportera glukoze.^[18]

Također pogledajte

• Xeroderma pigmentosum, komplementarna grupa G

Reference

1. GRCh38: Ensembl release 89: ENSG00000163161 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024382 - 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.
5. Fan L, Arvai AS, Cooper PK, Iwai S, Hanaoka F, Tainer JA (april 2006). "Conserved XPB Core Structure and Motifs for DNA Unwinding: Implications for Pathway Selection of Transcription or Excision Repair". Molecular Cell. 22 (1): 27–37. doi:10.1016/j.molcel.2006.02.017. PMID 16600867.
6. Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH (2006). "Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome". Hum. Mutat. 27 (11): 1092–103. doi:10.1002/humu.20392. PMID 16947863. S2CID 22852219.
7. Andressoo JO, Weeda G, de Wit J, Mitchell JR, Beems RB, van Steeg H, van der Horst GT, Hoeijmakers JH (2009). "An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair". Mol. Cell. Biol. 29 (5): 1276–90. doi:10.1128/MCB.01229-08. PMC 2643825. PMID 19114557.
8. Takeda N, Shibuya M, Maru Y (januar 1999). "The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 203–7. Bibcode:1999PNAS...96..203T. doi:10.1073/pnas.96.1.203. PMC 15117. PMID 9874796.
9. Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W (juli 2004). "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. doi:10.1038/ng1387. PMID 15220921.
10. Rossignol M, Kolb-Cheynel I, Egly JM (april 1997). "Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH". EMBO J. 16 (7): 1628–37. doi:10.1093/emboj/16.7.1628. PMC 1169767. PMID 9130708.
11. Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y (decembar 1995). "Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Res. 55 (24): 6058–62. PMID 8521393.
12. Marinoni JC, Roy R, Vermeulen W, Miniou P, Lutz Y, Weeda G, Seroz T, Gomez DM, Hoeijmakers JH, Egly JM (mart 1997). "Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH". EMBO J. 16 (5): 1093–102. doi:10.1093/emboj/16.5.1093. PMC 1169708. PMID 9118947.
13. Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D (april 1994). "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature. 368 (6473): 769–72. Bibcode:1994Natur.368..769D. doi:10.1038/368769a0. PMID 8152490. S2CID 4363484.
14. 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.
15. Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG (juni 1995). "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. doi:10.1038/ng0695-188. hdl:1765/54884. PMID 7663514. S2CID 38325851.
16. Weeda G, Rossignol M, Fraser RA, Winkler GS, Vermeulen W, van 't Veer LJ, Ma L, Hoeijmakers JH, Egly JM (juni 1997). "The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor". Nucleic Acids Res. 25 (12): 2274–83. doi:10.1093/nar/25.12.2274. PMC 146752. PMID 9173976.
17. Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F (mart 2000). "The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA". J. Biol. Chem. 275 (13): 9870–5. doi:10.1074/jbc.275.13.9870. PMID 10734143.
18. Datan E, Minn I, Peng X, He QL, Ahn H, Yu B, Pomper MG, Liu JO (2020). "A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience. 23 (9): 101536. Bibcode:2020iSci...23j1536D. doi:10.1016/j.isci.2020.101536. PMC 7509213. PMID 33083765.

Dopunska literatura

• Jeang KT (1998). "Tat, Tat-associated kinase, and transcription". J. Biomed. Sci. 5 (1): 24–7. doi:10.1007/BF02253352. PMID 9570510.
• Yankulov K, Bentley D (1998). "Transcriptional control: Tat cofactors and transcriptional elongation". Curr. Biol. 8 (13): R447–9. doi:10.1016/S0960-9822(98)70289-1. PMID 9651670. S2CID 15480646.
• Cleaver JE, Thompson LH, Richardson AS, States JC (1999). "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy". Hum. Mutat. 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.
• Ma L, Weeda G, Jochemsen AG, Bootsma D, Hoeijmakers JH, van der Eb AJ (1992). "Molecular and functional analysis of the XPBC/ERCC-3 promoter: transcription activity is dependent on the integrity of an Sp1-binding site". Nucleic Acids Res. 20 (2): 217–24. doi:10.1093/nar/20.2.217. PMC 310357. PMID 1741247.
• Weeda G, Wiegant J, van der Ploeg M, Geurts van Kessel AH, van der Eb AJ, Hoeijmakers JH (1991). "Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21". Genomics. 10 (4): 1035–1040. doi:10.1016/0888-7543(91)90195-K. hdl:1765/3025. PMID 1916809.
• Weeda G, Ma LB, van Ham RC, van der Eb AJ, Hoeijmakers JH (1991). "Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome". Nucleic Acids Res. 19 (22): 6301–6308. doi:10.1093/nar/19.22.6301. PMC 329143. PMID 1956789.
• Weeda G, van Ham RC, Masurel R, Westerveld A, Odijk H, de Wit J, Bootsma D, van der Eb AJ, Hoeijmakers JH (1990). "Molecular cloning and biological characterization of the human excision repair gene ERCC-3". Mol. Cell. Biol. 10 (6): 2570–2581. doi:10.1128/MCB.10.6.2570. PMC 360615. PMID 2111438.
• Weeda G, van Ham RC, Vermeulen W, Bootsma D, van der Eb AJ, Hoeijmakers JH (1990). "A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome". Cell. 62 (4): 777–91. doi:10.1016/0092-8674(90)90122-U. hdl:1765/3020. PMID 2167179. S2CID 31743602.
• Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG (1995). "p53 modulation of TFIIH-associated nucleotide excision repair activity". Nat. Genet. 10 (2): 188–95. doi:10.1038/ng0695-188. hdl:1765/54884. PMID 7663514. S2CID 38325851.
• Maxon ME, Goodrich JA, Tjian R (1994). "Transcription factor IIE binds preferentially to RNA polymerase IIa and recruits TFIIH: a model for promoter clearance". Genes Dev. 8 (5): 515–24. doi:10.1101/gad.8.5.515. PMID 7926747.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Drapkin R, Reardon JT, Ansari A, Huang JC, Zawel L, Ahn K, Sancar A, Reinberg D (1994). "Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II". Nature. 368 (6473): 769–72. Bibcode:1994Natur.368..769D. doi:10.1038/368769a0. PMID 8152490. S2CID 4363484.
• van Vuuren AJ, Vermeulen W, Ma L, Weeda G, Appeldoorn E, Jaspers NG, van der Eb AJ, Bootsma D, Hoeijmakers JH, Humbert S (1994). "Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH)". EMBO J. 13 (7): 1645–1653. doi:10.1002/j.1460-2075.1994.tb06428.x. PMC 394995. PMID 8157004.
• Schaeffer L, Moncollin V, Roy R, Staub A, Mezzina M, Sarasin A, Weeda G, Hoeijmakers JH, Egly JM (1994). "The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor". EMBO J. 13 (10): 2388–2392. doi:10.1002/j.1460-2075.1994.tb06522.x. PMC 395103. PMID 8194528.
• Guzder SN, Sung P, Bailly V, Prakash L, Prakash S (1994). "RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription". Nature. 369 (6481): 578–81. Bibcode:1994Natur.369..578G. doi:10.1038/369578a0. PMID 8202161. S2CID 4332757.
• Vermeulen W, Scott RJ, Rodgers S, Müller HJ, Cole J, Arlett CF, Kleijer WJ, Bootsma D, Hoeijmakers JH, Weeda G (1994). "Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3". Am. J. Hum. Genet. 54 (2): 191–200. PMC 1918172. PMID 8304337.
• Scott RJ, Itin P, Kleijer WJ, Kolb K, Arlett C, Muller H (1993). "Xeroderma pigmentosum-Cockayne syndrome complex in two patients: absence of skin tumors despite severe deficiency of DNA excision repair". J. Am. Acad. Dermatol. 29 (5 Pt 2): 883–9. doi:10.1016/0190-9622(93)70263-S. PMID 8408834.
• Blau J, Xiao H, McCracken S, O'Hare P, Greenblatt J, Bentley D (1996). "Three functional classes of transcriptional activation domain". Mol. Cell. Biol. 16 (5): 2044–2055. doi:10.1128/MCB.16.5.2044. PMC 231191. PMID 8628270.
• Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (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): 2157–2167. doi:10.1021/bi9524124. PMID 8652557.
• Hwang JR, Moncollin V, Vermeulen W, Seroz T, van Vuuren H, Hoeijmakers JH, Egly JM (1996). "A 3' --> 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription". J. Biol. Chem. 271 (27): 15898–904. doi:10.1074/jbc.271.27.15898. PMID 8663148.

Vanjski linkovi

• GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
• XPBC-ERCC-3 protein na US National Library of Medicine Medical Subject Headings (MeSH)

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