RNF8 cdna clone
RNF8 cDNA Clone
NCBI and Uniprot Product Information
NCBI Description
The protein encoded by this gene contains a RING finger motif and an FHA domain. This protein has been shown to interact with several class II ubiquitin-conjugating enzymes (E2), including UBE2E1/UBCH6, UBE2E2, and UBE2E3, and may act as an ubiquitin ligase (E3) in the ubiquitination of certain nuclear proteins. This protein is also known to play a role in the DNA damage response and depletion of this protein causes cell growth inhibition and cell cycle arrest. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
Uniprot Description
RNF8: E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'- linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin- conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2. Belongs to the RNF8 family. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: Ligase; Nuclear receptor co-regulator; Histone-binding; EC 6.3.2.-; EC 6.3.2.19; Ubiquitin conjugating system; Transcription, coactivator/corepressor; Ubiquitin ligase; DNA repair, damage
Chromosomal Location of Human Ortholog: 6p21.3
Cellular Component: chromosome, telomeric region; cytoplasm; nucleoplasm; nucleus; ubiquitin ligase complex
Molecular Function: chromatin binding; histone binding; protein binding; protein homodimerization activity; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; zinc ion binding
Biological Process: double-strand break repair; double-strand break repair via nonhomologous end joining; histone exchange; histone H2A ubiquitination; histone H2B ubiquitination; isotype switching; positive regulation of DNA repair; protein autoubiquitination; response to DNA damage stimulus; response to ionizing radiation; spermatid development; ubiquitin-dependent protein catabolic process
Research Articles on RNF8
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Product Notes
The RNF8 rnf8 (Catalog #AAA1274646) is a cDNA Clone and is intended for research purposes only. The product is available for immediate purchase. The amino acid sequence is listed below: atgggggagc ccggcttctt cgtcacagga gaccgcgccg gtggccggag ctggtgcctg cggcgggtgg ggatgagcgc cgggtggctg ctgctggaag atgggtgcga ggtgactgta ggacgaggat ttggtgtcac ataccaactg gtatcaaaaa tctgccccct gatgatttct cgaaaccact gtgttttgaa gcagaatcct gagggccaat ggacaattat ggacaacaag agtctaaatg gtgtttggct gaacagagcg cgtctggaac ctttaagggt ctattccatt catcagggag actacatcca acttggagtg cctctggaaa ataaggagaa tgcggagtat gaatatgaag ttactgaaga agactgggag acaatatatc cttgtctttc cccaaagaat gaccaaatga tagaaaaaaa taaggaattg agaactaaaa ggaaattcag tttggatgaa ttagcaggtc ctggagctga aggcccctca aatttgaaat ccaaaataaa taaagtgtct tgtgaatctg gtcagccagt gaaatcacag gggaaaggtg aagtggccag tacaccctct gacaatttgg atcctaagtt gactgccctt gagccaagta agaccacagg ggctcccatt taccctggct tccccaaagt cacagaggtt catcatgagc agaaagcctc aaactcttca gcatctcaga gaagcttaca gatgtttaag gtgaccatgt ccaggattct gaggctcaaa atacagatgc aggaaaaaca tgaagccgtt atgaatgtga aaaagcagac ccaaaagggg aactcaaaga aagttgtgca aatggagcag gaacttcagg acttacagtc ccagctgtgt gcagagcagg ctcagcagca ggcaagagtg gagcaactag agaagacttt ccaggaagag gaacagcatc ttcagggttt ggagatagcc caaggagaaa aggacctgaa gcaacagctg gcccaggctc tgcaggagca ttgggctcta atggaagagc taaatcgcag caagaaggac tttgaagcaa tcattcaagc caagaacaaa gaattagagc agaccaagga agagaaggag aagatgcaag cacagaagga agaagttctt agccacatga atgatgtgct agagaatgag ctccaatgta ttatttgttc agaatacttc attgaggctg tcaccttgaa ctgtgcccac agtttctgct cctactgtat caatgaatgg atgaagcgga agatagaatg ccccatttgt cggaaggaca ttaagtccaa aacatactct ttggttctgg acaattgcat taataagatg gtaaataatc tgagctcaga agtgaaagaa cgacgaattg ttctcattag ggaacgaaaa gcaaagagat tgttctga. It is sometimes possible for the material contained within the vial of "RNF8, cDNA Clone" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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