LLPS-Cap-2593
RNF8
Integrated Annotations
▼ OVERVIEW
| Status: | Unreviewed |
| Protein Name: | E3 ubiquitin-protein ligase RNF8; RING finger protein 8; RING-type E3 ubiquitin transferase RNF8 |
| Gene Name: | RNF8 |
| Ensembl Gene: | ENSCPOG00000040177.1 |
| Ensembl Protein: | ENSCPOP00000031394.1 |
| Organism: | Cavia porcellus |
| Taxa ID: | 10141 |
| LLPS Type: | LLPS regulator |
▼ Classification
Condensates:
| Condensate | Evidence | Orthologs |
|---|---|---|
| PML nuclear body | Predicted from orthologs | (View) |
▼ 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. 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. 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. |
▼ CROSS REFERENCE
| Database | Nucleotide ID | Protein ID |
|---|---|---|
| Ensembl | ENSCPOT00000032403.1 | ENSCPOP00000031394.1 |
| UniProt | A0A286Y0Q7, A0A286Y0Q7_CAVPO | |
| GeneBank | AAKN02021438, AAKN02021437 | |
| RefSeq | XM_005005410.2 | XP_005005467.1 |
▼ SEQUENCE
| Protein Sequence (FASTA) |
|---|
1 MGEPGCQDSG DPAAVRSWCL RRVGMEAEWL PLEDGREVSI GRGFGVTYQL VSKICPLMIS 60 61 RNHCVLKQNP EGRWTIMDNK SLNGVWLNRE RLEPLKFYLI REGDHIQLGV PLQNKEHAEF 120 121 EYEVSEEDWE RLFPCLALQS RQMVEKNKGW RTKRKSSMEE LESLGCGGPS GSKAKMSKVS 180 181 CAPDQPGRPP GPGEMASQPR ECLDPGLAPP EAGRKTMRAR TYPGPPKAPQ LYPKKQKASK 240 241 PSASQSSLEL FKVTMSRIMK LKKQLQEKQV AVMNVKNQTR AGNARRIVRM ERELQELQAQ 300 301 LCTEQAQQQA RVEQLEKTFQ EEENHLQGLE KEQVEDLKQQ LAQALQEHQA LMEELNRSKK 360 361 DFETIIQAKN KELEQTKEEK EKVQAQKEEV LSHMNDVLEN ELQCIICSEY FIEAVTLNCA 420 421 HSFCSYCISE WMKRKVECPI CRKDIKSKTH SLVLDNCIAK LVDNLSPEVK ERRVVLTRER 480 481 KAKRLS 486 |
| Nucleotide CDS Sequence (FASTA) |
1 ATGGGGGAGC CCGGTTGTCA GGACTCAGGA GACCCCGCCG CTGTCCGGAG CTGGTGCCTG 60 61 CGGCGGGTGG GAATGGAGGC CGAGTGGCTG CCGCTGGAGG ACGGGCGCGA AGTGTCCATA 120 121 GGACGAGGAT TTGGTGTCAC ATACCAACTG GTATCAAAAA TTTGCCCTCT GATGATTTCT 180 181 CGAAACCACT GTGTTTTGAA GCAGAATCCT GAGGGCCGCT GGACAATTAT GGACAACAAG 240 241 AGTCTGAATG GTGTTTGGCT GAACAGAGAG CGTCTGGAAC CACTAAAGTT TTATCTCATC 300 301 CGTGAGGGAG ACCACATCCA GCTCGGAGTG CCTCTGCAGA ATAAGGAGCA CGCAGAGTTC 360 361 GAATACGAAG TTAGCGAAGA AGACTGGGAG AGGCTGTTTC CTTGTCTTGC CCTACAGAGT 420 421 AGACAGATGG TGGAGAAAAA CAAGGGCTGG AGAACTAAAA GGAAAAGCAG CATGGAGGAG 480 481 TTAGAGAGCC TTGGCTGTGG GGGCCCCTCA GGCTCAAAAG CCAAGATGAG TAAAGTGTCT 540 541 TGTGCACCTG ACCAGCCGGG GAGGCCACCG GGGCCTGGTG AAATGGCCAG TCAGCCCCGT 600 601 GAGTGTTTGG ATCCGGGGCT GGCTCCTCCT GAGGCAGGCA GGAAGACCAT GAGAGCTCGT 660 661 ACTTACCCTG GGCCTCCAAA AGCCCCGCAG CTTTATCCCA AGAAGCAGAA AGCCTCAAAG 720 721 CCTTCTGCGT CTCAGAGCAG CCTGGAGCTG TTTAAGGTGA CCATGTCCAG AATCATGAAG 780 781 CTGAAAAAGC AGCTGCAAGA AAAACAGGTT GCTGTTATGA ATGTGAAAAA CCAAACCCGG 840 841 GCAGGGAATG CACGGAGGAT CGTGAGGATG GAGCGGGAGC TGCAGGAGCT GCAGGCCCAG 900 901 CTGTGCACAG AGCAGGCCCA GCAGCAGGCG AGAGTGGAGC AGCTCGAAAA GACTTTCCAG 960 961 GAGGAGGAGA ATCACCTCCA GGGTTTGGAG AAAGAGCAAG TAGAGGACCT GAAGCAGCAG 1020 1021 CTGGCCCAGG CTCTGCAGGA GCATCAGGCC CTCATGGAGG AGCTAAATCG CAGCAAGAAG 1080 1081 GACTTTGAAA CAATCATTCA AGCGAAGAAC AAAGAACTGG AGCAGACCAA GGAAGAAAAG 1140 1141 GAGAAGGTAC AGGCCCAGAA GGAGGAGGTT CTGAGCCACA TGAACGACGT GCTGGAGAAT 1200 1201 GAGCTGCAGT GCATCATCTG CTCAGAGTAC TTCATCGAGG CTGTCACCTT GAACTGCGCC 1260 1261 CACAGCTTCT GCTCCTATTG CATCAGTGAG TGGATGAAGC GGAAGGTGGA ATGCCCCATC 1320 1321 TGCCGGAAGG ACATCAAGTC CAAAACCCAC TCCCTGGTTC TAGACAACTG CATTGCTAAG 1380 1381 CTGGTGGATA ATTTGAGCCC AGAAGTGAAG GAGCGAAGAG TGGTCCTCAC TAGGGAACGG 1440 1441 AAAGCCAAGA GGCTGTCATG A 1461 |
▼ KEYWORD
ID | Family |
Cell cycle | |
Cell division | |
Chromatin regulator | |
Chromosome | |
Coiled coil | |
Complete proteome | |
Cytoplasm | |
DNA damage | |
DNA repair | |
Metal-binding | |
Mitosis | |
Nucleus | |
Reference proteome | |
Telomere | |
Transferase | |
Ubl conjugation | |
Ubl conjugation pathway | |
Zinc | |
Zinc-finger
|
▼ GENE ONTOLOGY
ID | Classification | Description |
Cellular Component | Chromosome, telomeric region | |
Cellular Component | Cytosol | |
Cellular Component | Midbody | |
Cellular Component | Nucleus | |
Cellular Component | Site of double-strand break | |
Cellular Component | Ubiquitin ligase complex | |
Molecular Function | Chromatin binding | |
Molecular Function | Histone binding | |
Molecular Function | Protein homodimerization activity | |
Molecular Function | Ubiquitin binding | |
Molecular Function | Ubiquitin protein ligase binding | |
Molecular Function | Ubiquitin-protein transferase activity | |
Molecular Function | Zinc ion binding | |
Biological Process | Cell cycle | |
Biological Process | Cell division | |
Biological Process | Double-strand break repair | |
Biological Process | Histone H2A K63-linked ubiquitination | |
Biological Process | Histone H2B ubiquitination | |
Biological Process | Negative regulation of transcription elongation from RNA polymerase II promoter | |
Biological Process | Positive regulation of DNA repair | |
Biological Process | Protein autoubiquitination | |
Biological Process | Protein K48-linked ubiquitination | |
Biological Process | Response to ionizing radiation | |
Biological Process | Ubiquitin-dependent protein catabolic process |
▼ ORTHOLOGY
| DrLLPS ID | Organism | Identity | E-value | Score |
|---|---|---|---|---|
| LLPS-Ict-1894 | Ictidomys tridecemlineatus | 82.19 | 6e-34 | 127 |
| LLPS-Fud-2928 | Fukomys damarensis | 80.4 | 0.0 | 583 |
| LLPS-Urm-1957 | Ursus maritimus | 78.84 | 1e-177 | 513 |
| LLPS-Mup-1013 | Mustela putorius furo | 78.72 | 0.0 | 622 |
| LLPS-Eqc-2185 | Equus caballus | 77.87 | 0.0 | 622 |
| LLPS-Fec-0911 | Felis catus | 77.82 | 0.0 | 605 |
| LLPS-Aim-2156 | Ailuropoda melanoleuca | 77.64 | 0.0 | 585 |
| LLPS-Dio-0558 | Dipodomys ordii | 77.5 | 6e-37 | 136 |
| LLPS-Sus-1595 | Sus scrofa | 77.02 | 0.0 | 614 |
| LLPS-Caf-1350 | Canis familiaris | 76.95 | 0.0 | 612 |
| LLPS-Otg-1793 | Otolemur garnettii | 75.72 | 0.0 | 602 |
| LLPS-Ova-2508 | Ovis aries | 75.67 | 0.0 | 561 |
| LLPS-Caj-0842 | Callithrix jacchus | 75.36 | 0.0 | 597 |
| LLPS-Mam-3303 | Macaca mulatta | 75.1 | 0.0 | 596 |
| LLPS-Nol-1265 | Nomascus leucogenys | 75.1 | 0.0 | 595 |
| LLPS-Man-0576 | Macaca nemestrina | 75.1 | 0.0 | 597 |
| LLPS-Paa-1645 | Papio anubis | 75.1 | 0.0 | 598 |
| LLPS-Cea-1252 | Cercocebus atys | 75.1 | 0.0 | 598 |
| LLPS-Maf-0091 | Macaca fascicularis | 75.1 | 0.0 | 597 |
| LLPS-Gog-0987 | Gorilla gorilla | 75.1 | 0.0 | 597 |
| LLPS-Mal-2269 | Mandrillus leucophaeus | 75.06 | 0.0 | 543 |
| LLPS-Hos-1659 | Homo sapiens | 74.9 | 0.0 | 593 |
| LLPS-Pat-0448 | Pan troglodytes | 74.9 | 0.0 | 592 |
| LLPS-Pap-1715 | Pan paniscus | 74.9 | 0.0 | 592 |
| LLPS-Chs-1882 | Chlorocebus sabaeus | 74.9 | 0.0 | 591 |
| LLPS-Orc-0428 | Oryctolagus cuniculus | 74.54 | 0.0 | 590 |
| LLPS-Poa-1325 | Pongo abelii | 74.24 | 0.0 | 555 |
| LLPS-Bot-0793 | Bos taurus | 74.12 | 0.0 | 584 |
| LLPS-Mea-1097 | Mesocricetus auratus | 73.77 | 0.0 | 568 |
| LLPS-Ran-3900 | Rattus norvegicus | 73.05 | 0.0 | 564 |
| LLPS-Aon-2971 | Aotus nancymaae | 73.02 | 9e-175 | 506 |
| LLPS-Myl-1352 | Myotis lucifugus | 72.46 | 0.0 | 559 |
| LLPS-Mum-2880 | Mus musculus | 71.11 | 0.0 | 544 |
| LLPS-Rhb-1885 | Rhinopithecus bieti | 70.25 | 0.0 | 535 |
| LLPS-Sah-2610 | Sarcophilus harrisii | 65.19 | 1e-112 | 346 |
| LLPS-Ora-2121 | Ornithorhynchus anatinus | 60.43 | 7e-50 | 176 |
| LLPS-Pes-1071 | Pelodiscus sinensis | 59.34 | 5e-141 | 422 |
| LLPS-Fia-3308 | Ficedula albicollis | 59.11 | 4e-112 | 347 |
| LLPS-Meg-0912 | Meleagris gallopavo | 57.84 | 2e-118 | 363 |
| LLPS-Gaga-2327 | Gallus gallus | 57.78 | 2e-114 | 355 |
| LLPS-Anp-0555 | Anas platyrhynchos | 56.65 | 1e-55 | 190 |
| LLPS-Anc-0530 | Anolis carolinensis | 54.21 | 2e-126 | 384 |
| LLPS-Tag-1483 | Taeniopygia guttata | 53.61 | 3e-59 | 202 |
| LLPS-Lac-1946 | Latimeria chalumnae | 52.12 | 3e-111 | 347 |
| LLPS-Xet-0740 | Xenopus tropicalis | 50.2 | 9e-103 | 323 |
| LLPS-Leo-0738 | Lepisosteus oculatus | 48.55 | 4e-94 | 300 |
| LLPS-Scj-1269 | Schizosaccharomyces japonicus | 44.68 | 3e-06 | 53.5 |
| LLPS-Scf-0935 | Scleropages formosus | 42.6 | 8e-86 | 281 |
| LLPS-Scp-1160 | Schizosaccharomyces pombe | 42.22 | 2e-07 | 57.4 |
| LLPS-Orl-2740 | Oryzias latipes | 42.11 | 4e-09 | 62.8 |
| LLPS-Asm-3125 | Astyanax mexicanus | 41.16 | 2e-78 | 260 |
| LLPS-Gaa-2362 | Gasterosteus aculeatus | 40.94 | 3e-70 | 239 |
| LLPS-Scm-1368 | Scophthalmus maximus | 40.42 | 3e-73 | 247 |
| LLPS-Scc-0039 | Schizosaccharomyces cryophilus | 40.0 | 7e-07 | 55.5 |
| LLPS-Pyt-1066 | Pyrenophora teres | 39.77 | 1e-06 | 55.1 |
| LLPS-Pof-0388 | Poecilia formosa | 39.52 | 1e-71 | 242 |
| LLPS-Orn-1700 | Oreochromis niloticus | 39.34 | 7e-72 | 244 |
| LLPS-Dar-3019 | Danio rerio | 39.2 | 3e-71 | 241 |
| LLPS-Loa-4335 | Loxodonta africana | 39.06 | 2e-06 | 54.3 |
| LLPS-Mod-3286 | Monodelphis domestica | 39.06 | 2e-06 | 54.7 |
| LLPS-Xim-0408 | Xiphophorus maculatus | 38.65 | 6e-70 | 237 |
| LLPS-Icp-2455 | Ictalurus punctatus | 38.43 | 1e-75 | 253 |
| LLPS-Tar-2729 | Takifugu rubripes | 37.92 | 2e-63 | 221 |
| LLPS-Amt-2057 | Amborella trichopoda | 37.84 | 2e-06 | 55.1 |
| LLPS-Ten-0747 | Tetraodon nigroviridis | 37.65 | 6e-06 | 52.4 |
| LLPS-Cas-4083 | Carlito syrichta | 37.65 | 5e-06 | 52.8 |
| LLPS-Tut-0114 | Tursiops truncatus | 37.65 | 5e-06 | 52.8 |
| LLPS-Cii-2079 | Ciona intestinalis | 37.65 | 1e-06 | 54.7 |
| LLPS-Mel-0611 | Melampsora laricipopulina | 36.76 | 7e-08 | 57.0 |
| LLPS-Chr-1715 | Chlamydomonas reinhardtii | 33.7 | 4e-07 | 56.2 |
| LLPS-Ere-0020 | Erinaceus europaeus | 32.26 | 1e-06 | 55.5 |
| LLPS-Fus-0210 | Fusarium solani | 28.26 | 3e-06 | 53.9 |
| LLPS-Trv-0321 | Trichoderma virens | 27.22 | 1e-06 | 55.1 |
| LLPS-Fuo-1235 | Fusarium oxysporum | 26.98 | 6e-06 | 53.1 |
| LLPS-Fuv-0144 | Fusarium verticillioides | 26.98 | 4e-06 | 53.5 |