RNF8 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0006303Biological processdouble-strand break repair via nonhomologous end joining
GO_0036297Biological processinterstrand cross-link repair
GO_0010212Biological processresponse to ionizing radiation
GO_0140861Biological processDNA repair-dependent chromatin remodeling
GO_0045739Biological processpositive regulation of DNA repair
GO_0006302Biological processdouble-strand break repair
GO_0006974Biological processDNA damage response
GO_0006511Biological processubiquitin-dependent protein catabolic process
GO_0051865Biological processprotein autoubiquitination
GO_0051301Biological processcell division
GO_0034244Biological processnegative regulation of transcription elongation by RNA polymerase II
GO_0070936Biological processprotein K48-linked ubiquitination
GO_0070534Biological processprotein K63-linked ubiquitination
GO_1905168Biological processpositive regulation of double-strand break repair via homologous recombination
GO_0035092Biological processsperm DNA condensation
GO_0045190Biological processisotype switching
GO_0040029Biological processepigenetic regulation of gene expression
GO_0042770Biological processsignal transduction in response to DNA damage
GO_0085020Biological processprotein K6-linked ubiquitination
GO_0000151Cellular componentubiquitin ligase complex
GO_0030496Cellular componentmidbody
GO_0005654Cellular componentnucleoplasm
GO_0005829Cellular componentcytosol
GO_0000781Cellular componentchromosome, telomeric region
GO_0035861Cellular componentsite of double-strand break
GO_0005634Cellular componentnucleus
GO_0061630Molecular functionubiquitin protein ligase activity
GO_0042803Molecular functionprotein homodimerization activity
GO_0042393Molecular functionhistone binding
GO_0003682Molecular functionchromatin binding
GO_0042802Molecular functionidentical protein binding
GO_0031625Molecular functionubiquitin protein ligase binding
GO_0008270Molecular functionzinc ion binding
GO_0005515Molecular functionprotein binding
GO_0043130Molecular functionubiquitin binding

IV. Literature review

[source]
Gene nameRNF8
Protein nameE3 ubiquitin-protein ligase RNF8 (hRNF8) (EC 2.3.2.27) (RING finger protein 8) (RING-type E3 ubiquitin transferase RNF8)
Alternative protein RNF8
Ring finger protein 8
SynonymsKIAA0646
DescriptionFUNCTION: 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 . Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity . 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 aggravating 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 . .

AccessionsH7C4L7
ENST00000373479.9 [O76064-1]
ENST00000498460.1
F8WDH8
F8WEW6
C9J858
ENST00000469316.5
ENST00000487950.1
L0R6N6
ENST00000229866.10 [O76064-2]
ENST00000469731.5 [O76064-3]
ENST00000494320.5
O76064