RNF8
entrez
9025
canonical
uniprot
O76064
canonical
ensembl
ENSG00000112130
resolver
ensp
ENSP00000362578
resolver
ensp
ENSP00000418879
resolver
genesymbol
RNF8
resolver
genesymbol_syn
KIAA0646
resolver
hgnc
HGNC:10071
resolver
uniprot
A6NN24
resolver
uniprot
A8MYC0
resolver
uniprot
B4DPG0
resolver
uniprot
Q53H16
resolver
uniprot
Q5NKW5
resolver
uniprot_entry
RNF8_HUMAN
resolver
uniprot_sec
A6NN24
resolver
uniprot_sec
A8MYC0
resolver
uniprot_sec
B4DPG0
resolver
uniprot_sec
Q53H16
resolver
uniprot_sec
Q5NKW5
resolver
amino_acid_sequence
MGEPGFFVTGDRAGGRSWCLRRVGMSAGWLLLEDGCEVTVGRGFGVTYQLVSKICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPLRVYSIHQGDYIQLGVPLENKENAEYEYEVTEEDWETIYPCLSPKNDQMIEKNKELRTKRKFSLDELAGPGAEGPSNLKSKINKVSCESGQPVKSQGKGEVASTPSDNLDPKLTALEPSKTTGAPIYPGFPKVTEVHHEQKASNSSASQRSLQMFKVTMSRILRLKIQMQEKHEAVMNVKKQTQKGNSKKVVQMEQELQDLQSQLCAEQAQQQARVEQLEKTFQEEEQHLQGLEIAQGEKDLKQQLAQALQEHWALMEELNRSKKDFEAIIQAKNKELEQTKEEKEKMQAQKEEVLSHMNDVLENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSKTYSLVLDNCINKMVNNLSSEVKERRIVLIRERKAKRLF
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) (PubMed:18001824, PubMed:18006705). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites (PubMed:18077395, PubMed:19202061). Promotes the recruitment of NBN to DNA damage sites by catalyzing 'Lys-6'-linked ubiquitination of NBN (PubMed:23115235). 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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001825, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22980979). 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 (PubMed:23233665). 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 (PubMed:22865450). 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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001825, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22980979). {ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:17724460, ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825, ECO:0000269|PubMed:18006705, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:18337245, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:21558560, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:21911360, ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22531782, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22865450, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:23233665}.
uniprot
proteins
mass_dalton
55518
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="R->A: Abolishes interaction with ATM-phosphorylated MDC1. Abolishes interaction with human herpesvirus 1 ICP0. Abolishes recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent. Does not affect ubiquitination of NBN."; /evidence="ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22405594, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:23233665"; MUTAGEN 403; /note="C->S: Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization."; /evidence="ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:18001824"; MUTAGEN 405; /note="I->A: Impairs interaction with UBE2L6/UBCH8 and ability to mediate 'Lys-48'-linked ubiquitination E3 ligase activity, while it still catalyzes 'Lys-63'-linked ubiquitination and still interacts with UBE2N/UBC13."; /evidence="ECO:0000269|PubMed:21911360, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22589545"; MUTAGEN 406; /note="C->S: Abolishes ubiquitin-ligase activity."; /evidence="ECO:0000269|PubMed:21857671"; MUTAGEN 443; /note="D->R: Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes."; /evidence="ECO:0000269|PubMed:22980979
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:23115235}.
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, ECO:0000269|PubMed:16215985}.
uniprot
proteins
protein_family
RNF8 family
uniprot
proteins
pubmed
11322894
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14981089
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16215985
uniprot
proteins
pubmed
17724460
uniprot
proteins
pubmed
18001824
uniprot
proteins
pubmed
18001825
uniprot
proteins
pubmed
18006705
uniprot
proteins
pubmed
18077395
uniprot
proteins
pubmed
18337245
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18678647
uniprot
proteins
pubmed
18948756
uniprot
proteins
pubmed
19015238
uniprot
proteins
pubmed
19124460
uniprot
proteins
pubmed
19202061
uniprot
proteins
pubmed
19203578
uniprot
proteins
pubmed
19203579
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20023648
uniprot
proteins
pubmed
20550933
uniprot
proteins
pubmed
21558560
uniprot
proteins
pubmed
21857671
uniprot
proteins
pubmed
21911360
uniprot
proteins
pubmed
22266820
uniprot
proteins
pubmed
22373579
uniprot
proteins
pubmed
22405594
uniprot
proteins
pubmed
22531782
uniprot
proteins
pubmed
22589545
uniprot
proteins
pubmed
22705371
uniprot
proteins
pubmed
22865450
uniprot
proteins
pubmed
22980979
uniprot
proteins
pubmed
23115235
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23233665
uniprot
proteins
pubmed
25512560
uniprot
proteins
pubmed
9734811
uniprot
proteins
pubmed
9852682
uniprot
proteins
sequence_length
485
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:23233665}. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03067}. Midbody {ECO:0000255|HAMAP-Rule:MF_03067}. Chromosome, telomere {ECO:0000255|HAMAP-Rule:MF_03067}. Note=Recruited at uncapped telomeres (By similarity). Following DNA damage, such as double-strand breaks, recruited to the sites of damage (PubMed:18001824, PubMed:18077395, PubMed:22266820, PubMed:23233665). 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. During spermatogenesis, sequestered in the cytoplasm by PIWIL1: RNF8 is released following ubiquitination and degradation of PIWIL1. {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:23233665}.
uniprot
proteins