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.

ERCC3
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4ERN, 5IY9, 5IVW, 5IY7, 5IY8, 5IY6

Identifikatori
AliasiERCC3
Vanjski ID-jeviOMIM: 133510 MGI: 95414 HomoloGene: 96 GeneCards: ERCC3
Lokacija gena (čovjek)
Hromosom 2 (čovjek)
Hrom.Hromosom 2 (čovjek)[1]
Hromosom 2 (čovjek)
Genomska lokacija za ERCC3
Genomska lokacija za ERCC3
Bend2q14.3Početak127,257,290 bp[1]
Kraj127,294,166 bp[1]
Lokacija gena (miš)
Hromosom 18 (miš)
Hrom.Hromosom 18 (miš)[2]
Hromosom 18 (miš)
Genomska lokacija za ERCC3
Genomska lokacija za ERCC3
Bend18|18 B1Početak32,373,353 bp[2]
Kraj32,403,204 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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
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 MbChr 18: 32.37 – 32.4 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Struktura

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

Aminokiselinska sekvenca

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

1020304050
MGKRDRADRDKKKSRKRHYEDEEDDEEDAPGNDPQEAVPSAAGKQVDESG
TKVDEYGAKDYRLQMPLKDDHTSRPLWVAPDGHIFLEAFSPVYKYAQDFL
VAIAEPVCRPTHVHEYKLTAYSLYAAVSVGLQTSDITEYLRKLSKTGVPD
GIMQFIKLCTVSYGKVKLVLKHNRYFVESCHPDVIQHLLQDPVIRECRLR
NSEGEATELITETFTSKSAISKTAESSGGPSTSRVTDPQGKSDIPMDLFD
FYEQMDKDEEEEEETQTVSFEVKQEMIEELQKRCIHLEYPLLAEYDFRND
SVNPDINIDLKPTAVLRPYQEKSLRKMFGNGRARSGVIVLPCGAGKSLVG
VTAACTVRKRCLVLGNSAVSVEQWKAQFKMWSTIDDSQICRFTSDAKDKP
IGCSVAISTYSMLGHTTKRSWEAERVMEWLKTQEWGLMILDEVHTIPAKM
FRRVLTIVQAHCKLGLTATLVREDDKIVDLNFLIGPKLYEANWMELQNNG
YIAKVQCAEVWCPMSPEFYREYVAIKTKKRILLYTMNPNKFRACQFLIKF
HERRNDKIIVFADNVFALKEYAIRLNKPYIYGPTSQGERMQILQNFKHNP
KINTIFISKVGDTSFDLPEANVLIQISSHGGSRRQEAQRLGRVLRAKKGM
VAEEYNAFFYSLVSQDTQEMAYSTKRQRFLVDQGYSFKVITKLAGMEEED
LAFSTKEEQQQLLQKVLAATDLDAEEEVVAGEFGSRSSQASRRFGTMSSM
SGADDTVYMEYHSSRSKAPSKHVHPLFKRFRK

Funkcija

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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

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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

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Pokazalo se da je XPB u interakciji sa:

Inhibitori malih molekula

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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

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163161 - Ensembl, maj 2017
  2. ^ a b c 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. ^ a b 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. ^ a b c d e f 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. ^ a b 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. ^ a b c d 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

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Vanjski linkovi

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