RAD23B

RAD23B
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1P1A, 1PVE, 1UEL
Identifikatori
Aliasi	RAD23B
Vanjski ID-jevi	OMIM: 600062 MGI: 105128 HomoloGene: 37704 GeneCards: RAD23B
Lokacija gena (čovjek) Hrom. Hromosom 9 (čovjek)[1] Bend 9q31.2 Početak 107,283,137 bp[1] Kraj 107,332,192 bp[1]
Lokacija gena (miš) Hrom. Hromosom 4 (miš)[2] Bend 4|4 B3 Početak 55,350,043 bp[2] Kraj 55,392,237 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • single-stranded DNA binding • oštećeno vezivanje sa DNK • polyubiquitin modification-dependent protein binding • GO:0001948, GO:0016582 vezivanje za proteine • ubiquitin binding • proteasome binding Ćelijska komponenta • XPC complex • Proteasom • jedro • nukleoplazma • citoplazma • citosol Biološki proces • cellular response to DNA damage stimulus • Popravak ekscizijom nukleotida • global genome nucleotide-excision repair • nucleotide-excision repair, DNA damage recognition • Spermatogeneza • embryonic organ development • proteasome-mediated ubiquitin-dependent protein catabolic process • regulation of proteasomal ubiquitin-dependent protein catabolic process • GO:0100026 Popravka DNK • nucleotide-excision repair, preincision complex assembly • Savijanje proteina • protein deubiquitination • cellular response to interleukin-7 • nucleotide-excision repair, DNA duplex unwinding Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	5887	19359
Ensembl	ENSG00000119318	ENSMUSG00000028426
UniProt	P54727 Q5W0S4	P54728
RefSeq (mRNK)	NM_002874 NM_001244713 NM_001244724	NM_009011
RefSeq (bjelančevina)	NP_001231642 NP_001231653 NP_002865	NP_033037
Lokacija (UCSC)	Chr 9: 107.28 – 107.33 Mb	Chr 4: 55.35 – 55.39 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Homolog B UV-ekscizijskog popravka proteina RAD23 jest protein koji je kod ljudi kodiran genom RAD23B sa hromosoma 9.^[5][6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 409 aminokiselina, a molekulska težina 43.171 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
MQVTLKTLQQ		QTFKIDIDPE		ETVKALKEKI		ESEKGKDAFP		VAGQKLIYAG
KILNDDTALK		EYKIDEKNFV		VVMVTKPKAV		STPAPATTQQ		SAPASTTAVT
SSTTTTVAQA		PTPVPALAPT		STPASITPAS		ATASSEPAPA		SAAKQEKPAE
KPAETPVATS		PTATDSTSGD		SSRSNLFEDA		TSALVTGQSY		ENMVTEIMSM
GYEREQVIAA		LRASFNNPDR		AVEYLLMGIP		GDRESQAVVD		PPQAASTGAP
QSSAVAAAAA		TTTATTTTTS		SGGHPLEFLR		NQPQFQQMRQ		IIQQNPSLLP
ALLQQIGREN		PQLLQQISQH		QEHFIQMLNE		PVQEAGGQGG		GGGGGSGGIA
EAGSGHMNYI		QVTPQEKEAI		ERLKALGFPE		GLVIQAYFAC		EKNENLAANF
LLQQNFDED

Funkcija

Protein kodiran ovim genom jedan je od dva ljudska homologa Saccharomyces cerevisiae Rad23, proteina uključenog u popravak ekscizijom nukleotida (NER). Utvrđeno je da je ovaj protein komponenta proteinskog kompleksa koji specifično nadopunjuje NER defekt ekstrakta ćelija xeroderma pigmentosum grupe C (XP-c) in vitro. Pokazalo se i da ovaj protein stupa u interakciju sa i podiže ekscizijsku aktivnost 3-metiladenin-DNK glikozilaznog (MPG) nukleotida, što ukazuje na ulogu u prepoznavanju oštećenja DNK u popravci ekscizijom baze. Ovaj protein sadrži N-terminalni domen sličan ubikvitinu, za koji je objavljeno da interragira sa proteasomom 26S, te stoga ovaj protein može biti uključen u proteolitski put u ćelijama, posredovan ubikvitinom.^[7]

Uloga u popravku DNK

Kompleks XPC-RAD23B je početni faktor prepoznavanja oštećenja u globalnom popravku ekscizijom genomskih nukleotida (GG-NER). XPC-RAD23B prepoznaje širok spektar lezija koje termodinamički destabiliziraju DNK duplekse, uključujući UV-inducirane fotoproizvode (ciklopirimidinski dimeri i 6-4 fotoproizvodi), adukte formirane mutagenima iz okoliša, kao što su benzo[a]piren ili različiti aromatski amini, određene oksidativnne endogene lezije kao što su ciklopurini i adukti formirani hemoterapijskim lijekovima protiv raka kao što je cisplatin. Prisustvo XPC-RAD23B je potrebno za sklapanje drugih jedarnih faktora NER i progresiju kroz NER put i in vitro i in vivo.^[8] Although most studies have been performed with XPC-RAD23B, it is part of a trimeric complex with centrin-2, a calcium-binding protein of the calmodulin family.^[8]

Epigenetička represija

Nivo ekspresije proteina RAD23B može biti epigenetički potisnut, bilo promotora metilacije gena RAD23B ^[9][10] ili bilo kojom od dvije mikroRNK (miR -744-3p^[11] ili miR-373.^[12])

Nedostatak RAD23B kod raka

Nedostatak ekspresije gena za popravak DNK povećava rizik od raka (pogledajte nedostatak popravka DNK u karcinogenezi). Ekspresija RAD23B je smanjena u tumorskom tkivu žena sa rakom dojke.^[13] Uočen je i nizak postotak RAD23B pozitivnih jedara kod raka dojke visokog stepena.^[14]

RAD23B je značajno smanjen metilacijama promotora u ćelijskoj liniji koja potiče od multiplog mijeloma.^[9] i smanjen metilacijom promotora u malom udjelu [[rak pluća nemalih ćelija|raka pluća nemalih ćelijaa (NSCLC) tumours.^[10]

Čini se da je RAD23B jedan od 26 gena za popravak DNK koji su epigenetički potisnuti kod različitih karcinoma (vidi Epigenetika raka).

Interakcije

Pokazano je da RAD23B u interakcijama sa PSMD4^[15] i ataksinom 3.^[16]

Reference

1. GRCh38: Ensembl release 89: ENSG00000119318 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028426 - 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. van der Spek PJ, Smit EM, Beverloo HB, Sugasawa K, Masutani C, Hanaoka F, Hoeijmakers JH, Hagemeijer A (Oct 1994). "Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23". Genomics. 23 (3): 651–8. doi:10.1006/geno.1994.1554. hdl:1765/3069. PMID 7851894.
6. Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D (Apr 1994). "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23". The EMBO Journal. 13 (8): 1831–43. doi:10.1002/j.1460-2075.1994.tb06452.x. PMC 395023. PMID 8168482.
7. "Entrez Gene: RAD23B RAD23 homolog B (S. cerevisiae)".
8. Schärer OD (Oct 2013). "Nucleotide excision repair in eukaryotes". Cold Spring Harbor Perspectives in Biology. 5 (10): a012609. doi:10.1101/cshperspect.a012609. PMC 3783044. PMID 24086042.
9. Peng B, Hodge DR, Thomas SB, Cherry JM, Munroe DJ, Pompeia C, Xiao W, Farrar WL (Feb 2005). "Epigenetic silencing of the human nucleotide excision repair gene, hHR23B, in interleukin-6-responsive multiple myeloma KAS-6/1 cells". The Journal of Biological Chemistry. 280 (6): 4182–7. doi:10.1074/jbc.M412566200. PMID 15550378.
10. Do H, Wong NC, Murone C, John T, Solomon B, Mitchell PL, Dobrovic A (2014). "A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma". Scientific Reports. 4: 4186. Bibcode:2014NatSR...4E4186D. doi:10.1038/srep04186. PMC 3935198. PMID 24569633.
11. Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE (Apr 2015). "A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation". Nucleic Acids Research. 43 (8): 4075–86. doi:10.1093/nar/gkv273. PMC 4417178. PMID 25845598.
12. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM (Feb 2009). "MicroRNA regulation of DNA repair gene expression in hypoxic stress". Cancer Research. 69 (3): 1221–9. doi:10.1158/0008-5472.CAN-08-2516. PMC 2997438. PMID 19141645.
13. Matta J, Morales L, Dutil J, Bayona M, Alvarez C, Suarez E (Feb 2013). "Differential expression of DNA repair genes in Hispanic women with breast cancer". Molecular Cancer Biology. 1 (1): 54. doi:10.9777/mcb.2013.10006 (neaktivno 31. 12. 2022). PMC 4189824. PMID 25309843.
14. Linge A, Maurya P, Friedrich K, Baretton GB, Kelly S, Henry M, Clynes M, Larkin A, Meleady P (Jul 2014). "Identification and functional validation of RAD23B as a potential protein in human breast cancer progression". Journal of Proteome Research. 13 (7): 3212–22. doi:10.1021/pr4012156. PMID 24897598.
15. Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome" (PDF). The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID 10488153. S2CID 1757366.
16. Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.

Dopunska literatura

• Maruyama K, Sugano S (Jan 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.
• van der Spek PJ, Eker A, Rademakers S, Visser C, Sugasawa K, Masutani C, Hanaoka F, Bootsma D, Hoeijmakers JH (Jul 1996). "XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes". Nucleic Acids Research. 24 (13): 2551–9. doi:10.1093/nar/24.13.2551. PMC 145966. PMID 8692695.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH (Aug 1998). "Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair". Molecular Cell. 2 (2): 223–32. doi:10.1016/S1097-2765(00)80132-X. PMID 9734359.
• Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome" (PDF). The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID 10488153. S2CID 1757366.
• Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, O'Connor TR (Sep 2000). "3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins". The Journal of Biological Chemistry. 275 (37): 28433–8. doi:10.1074/jbc.M001064200. PMID 10854423.
• Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
• Araújo SJ, Nigg EA, Wood RD (Apr 2001). "Strong functional interactions of TFIIH with XPC and XPG in human DNA nucleotide excision repair, without a preassembled repairosome". Molecular and Cellular Biology. 21 (7): 2281–91. doi:10.1128/MCB.21.7.2281-2291.2001. PMC 86862. PMID 11259578.
• Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F (Jun 2001). "Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair". The Journal of Biological Chemistry. 276 (22): 18665–72. doi:10.1074/jbc.M100855200. PMID 11279143.
• Park H, Suzuki T, Lennarz WJ (Sep 2001). "Identification of proteins that interact with mammalian peptide:N-glycanase and implicate this hydrolase in the proteasome-dependent pathway for protein degradation". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11163–8. Bibcode:2001PNAS...9811163P. doi:10.1073/pnas.201393498. PMC 58701. PMID 11562482.
• Walters KJ, Kleijnen MF, Goh AM, Wagner G, Howley PM (Feb 2002). "Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a". Biochemistry. 41 (6): 1767–77. doi:10.1021/bi011892y. PMID 11827521.
• Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Waye MM (Sep 2002). "Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway". Life Sciences. 71 (19): 2267–77. doi:10.1016/S0024-3205(02)01962-8. PMID 12215374.
• Shimizu Y, Iwai S, Hanaoka F, Sugasawa K (Jan 2003). "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase". The EMBO Journal. 22 (1): 164–73. doi:10.1093/emboj/cdg016. PMC 140069. PMID 12505994.
• Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH (Jul 2003). "A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein". Genes & Development. 17 (13): 1630–45. doi:10.1101/gad.260003. PMC 196135. PMID 12815074.
• Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS (Sep 2003). "Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a". The Journal of Biological Chemistry. 278 (38): 36621–7. doi:10.1074/jbc.M304628200. PMID 12832454.
• Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M (Feb 2004). "Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B". The Journal of Biological Chemistry. 279 (6): 4760–7. doi:10.1074/jbc.M309448200. PMID 14585839.
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Vanjski linkovi