Rnf8
entrez
58230
canonical
uniprot
Q8VC56
canonical
ensembl
ENSMUSG00000090083
resolver
ensp
ENSMUSP00000024817
resolver
enst
ENSMUST00000024817
resolver
genesymbol
Rnf8
resolver
uniprot
Q4FJV7
resolver
uniprot
Q9JK13
resolver
uniprot_entry
RNF8_MOUSE
resolver
uniprot_sec
Q4FJV7
resolver
uniprot_sec
Q9JK13
resolver
amino_acid_sequence
MGEPDPLVSGQLAARRSWCLRRLGMDCEWLQLEAGTEVTIGRGLSVTYQLISKVCPLMISRSHCVLKQNPEGQWTIMDNKSLNGVWLNRERLAPLQGYCIRKGDHIQLGVPLESRETAEYEYEVIEEDWESLAPCLAPKNDQRMEKHKGSRTKRKFSSPGLENLPAEGSSDLRCPLANVASKPIEPEKLHGKGDASSQSLGCLCPGLTSLKASERAAGPHACSALPKVLELSCPKKQKACRPSASQNSLELFKVTMSRMLKLKTQMQEKQIAVLNVKRQTRKGSSKKIVRMEKELRNLQSQLYAEQAQQQARVEQLEKTFQEEAHYLQGLEKEQGECDLKQQLVQALQEHQALMEELNCSKKDFEKIIQAKNKELEQTKEEKDKVQAQKEEVLSHMNDLLENELQCIICSEYFIEAVTLNCAHSFCSFCINEWMKRKVECPICRKDIESRTNSLVLDNCISKMVDNLSSDVKERRSVLIRERRAKRLS
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: 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. Promotes the recruitment of NBN to DNA damage sites by catalyzing 'Lys-6'-linked ubiquitination of NBN. 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 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 (PubMed:20153262, PubMed:28552346). 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. {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:20080757, ECO:0000269|PubMed:20153262, ECO:0000269|PubMed:21706008, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:24953653, ECO:0000269|PubMed:28552346}.
uniprot
proteins
mass_dalton
55517
uniprot
proteins
mutagenesis
MUTAGEN 68..72; /note="QNPEG->AAAAA: Abolishes interaction with PIWIL1."; /evidence="ECO:0000269|PubMed:28552346
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000255|HAMAP-Rule:MF_03067}.
uniprot
proteins
post_translational_modification
PTM: Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger. {ECO:0000255|HAMAP-Rule:MF_03067}.
uniprot
proteins
protein_family
RNF8 family
uniprot
proteins
pubmed
11207567
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
20080757
uniprot
proteins
pubmed
20153262
uniprot
proteins
pubmed
21706008
uniprot
proteins
pubmed
21857671
uniprot
proteins
pubmed
22101936
uniprot
proteins
pubmed
22266820
uniprot
proteins
pubmed
24953653
uniprot
proteins
pubmed
28552346
uniprot
proteins
sequence_length
488
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:28552346}. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:28552346}. Midbody {ECO:0000255|HAMAP-Rule:MF_03067}. Chromosome, telomere {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22101936}. Note=Recruited at uncapped telomeres (PubMed:21857671, PubMed:22101936). Following DNA double-strand breaks, recruited to the sites of damage. During prophase, concomitant with nuclear envelope breakdown, localizes throughout the cell, with a dotted pattern. In telophase, again in the nucleus and also with a discrete dotted pattern in the cytoplasm. In late telophase and during cytokinesis, localizes in the midbody of the tubulin bridge joining the daughter cells. Does not seem to be associated with condensed chromosomes at any time during the cell cycle (By similarity). During spermatogenesis, sequestered in the cytoplasm by PIWIL1: RNF8 is released following ubiquitination and degradation of PIWIL1 (PubMed:28552346). {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22101936, ECO:0000269|PubMed:28552346}.
uniprot
proteins