• Disorder▼
  • Domain▼
  • PTM▼
  • Variation▼
  • Mutation▼
  • Interaction▼
  • Disease▼
  • Drug▼
  • Physicochemical▼
  • Function▼
  • Proteomics▼
  • Structure▼
  • Localization▼
  • Expression▼
  • Element▼
  • Methylation▼

LLPS-Caf-1350
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: ENSCAFG00000030176.2
Ensembl Protein: ENSCAFP00000002119.3
Organism: Canis familiaris
Taxa ID: 9615
LLPS Type: LLPS regulator


▼ PROPERTY


——— Disorder propensity (calculated by IUPred2A)

▼ Classification

Condensates:
CondensateEvidenceOrthologs
PML nuclear bodyPredicted 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

▼ SEQUENCE

Protein Sequence (FASTA)
1     MEEPGSLVTG  DRAGGRRWCL  RRARMNAEWL  LLEDGNEVTI  GRGFGVTYQL  VSKICPLMIS  60
61    RNHCVLKQNV  EGQWTIMDNK  SLNGVWLNRE  RLEPLKVYSI  HKGDHIQLGV  PLENKENAEY  120
121   EYEVTEEDWE  RMYPCLAPKN  DQIIGKNRGL  RTKRKFSLDE  LEGPGAEGPS  HLKSKISKVS  180
181   YKPGQPVKSH  GKGEVASQPS  EYLDPKLTSL  ELSEKATDAH  VYPSSTKVVA  LHHKKQKASS  240
241   PSASQSSLEL  FKVTMSRILK  LKTQMQEKQV  AVLNVKRQTQ  KGNSKKIVKM  EKELQDLQSQ  300
301   LCAEQAQQQA  RVEQLEKTFQ  EEEQHLQGLE  KDQGEEDLKQ  QLAQALQEHR  ALMEELNRSK  360
361   KDFEAIIQAK  NKELEQTKEE  KEKMQAQKEE  VLSHVNDVLE  NELQCIICSE  YFIEAVTLNC  420
421   AHSFCSYCIN  EWMKRKVECP  ICRKDIKSKT  HSLVLDNCIN  KMVDNLSSEV  KDRRIVLIRE  480
481   RKGMRMH  487
Nucleotide CDS Sequence (FASTA)
1     ATGGAGGAGC  CCGGCTCGTT  GGTCACGGGA  GACCGCGCCG  GTGGCCGGAG  GTGGTGCTTG  60
61    CGGCGGGCCA  GGATGAACGC  CGAGTGGCTG  CTGCTGGAGG  ACGGAAACGA  GGTGACTATA  120
121   GGGCGAGGAT  TTGGTGTCAC  ATACCAACTG  GTATCAAAAA  TCTGCCCTCT  GATGATTTCC  180
181   CGAAACCACT  GTGTTTTGAA  GCAGAACGTC  GAGGGCCAGT  GGACAATTAT  GGATAACAAG  240
241   AGTCTGAATG  GTGTTTGGCT  GAACAGAGAA  CGTCTAGAAC  CTTTAAAGGT  CTATTCTATC  300
301   CATAAAGGAG  ACCACATCCA  GCTCGGGGTA  CCTCTAGAGA  ATAAGGAGAA  TGCGGAGTAT  360
361   GAGTATGAAG  TTACTGAAGA  AGACTGGGAG  AGGATGTATC  CTTGTCTTGC  TCCAAAGAAT  420
421   GATCAGATTA  TAGGAAAAAA  TAGGGGTTTG  AGAACTAAAA  GGAAATTCAG  TTTGGATGAA  480
481   TTGGAGGGTC  CTGGAGCTGA  AGGCCCCTCA  CATTTGAAAT  CCAAAATAAG  TAAAGTGTCT  540
541   TACAAACCTG  GTCAGCCGGT  GAAATCTCAT  GGAAAAGGTG  AGGTGGCCAG  TCAGCCTTCT  600
601   GAATATTTGG  ATCCTAAGTT  GACATCTCTT  GAGCTAAGTG  AGAAGGCCAC  AGATGCTCAT  660
661   GTTTACCCTT  CCTCCACAAA  AGTCGTAGCG  CTTCATCATA  AGAAGCAGAA  AGCCTCAAGT  720
721   CCTTCAGCAT  CTCAGAGCAG  CTTAGAGCTG  TTCAAGGTGA  CTATGTCCAG  GATTCTGAAG  780
781   CTGAAAACAC  AAATGCAGGA  AAAACAGGTA  GCTGTCCTGA  ATGTGAAAAG  GCAGACCCAA  840
841   AAAGGGAACT  CAAAGAAAAT  TGTGAAAATG  GAGAAGGAAC  TGCAGGACTT  ACAGTCCCAG  900
901   CTGTGTGCAG  AGCAGGCCCA  GCAGCAGGCC  AGAGTGGAAC  AGCTAGAGAA  GACTTTCCAA  960
961   GAAGAGGAGC  AGCATCTCCA  GGGTTTGGAG  AAGGATCAAG  GAGAAGAGGA  CCTGAAGCAA  1020
1021  CAGCTGGCCC  AGGCGCTGCA  GGAGCATCGG  GCTCTAATGG  AAGAGCTAAA  TCGCAGCAAG  1080
1081  AAGGACTTTG  AAGCAATCAT  TCAAGCCAAG  AACAAAGAAT  TGGAACAGAC  CAAGGAAGAG  1140
1141  AAGGAGAAGA  TGCAAGCCCA  GAAGGAGGAA  GTCCTTAGCC  ACGTGAATGA  TGTGCTAGAG  1200
1201  AATGAGCTCC  AGTGTATTAT  TTGCTCAGAA  TACTTCATTG  AGGCTGTCAC  CTTGAACTGT  1260
1261  GCCCACAGTT  TCTGCTCCTA  CTGTATCAAT  GAATGGATGA  AGCGGAAGGT  AGAATGCCCC  1320
1321  ATTTGTCGGA  AGGACATCAA  GTCCAAAACC  CACTCCCTGG  TTCTGGACAA  TTGCATTAAT  1380
1381  AAGATGGTAG  ATAATCTGAG  CTCAGAAGTG  AAAGACCGAC  GAATTGTCCT  CATTAGGGAA  1440
1441  CGAAAAGGGA  TGAGAATGCA  C  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
Cytoplasm
Cellular Component
Midbody
Cellular Component
Nucleus
Cellular Component
Ubiquitin ligase complex
Molecular Function
Chromatin binding
Molecular Function
Histone binding
Molecular Function
Metal ion binding
Molecular Function
Protein homodimerization activity
Molecular Function
Ubiquitin binding
Molecular Function
Ubiquitin-protein transferase activity
Biological Process
Cell cycle
Biological Process
Cell division
Biological Process
Double-strand break repair
Biological Process
Histone H2A ubiquitination
Biological Process
Histone H2B ubiquitination
Biological Process
Positive regulation of DNA repair
Biological Process
Protein K63-linked ubiquitination
Biological Process
Response to ionizing radiation

▼ ORTHOLOGY

DrLLPS IDOrganismIdentityE-valueScore
LLPS-Mup-1013Mustela putorius furo94.410.0 793
LLPS-Urm-1957Ursus maritimus93.240.0 671
LLPS-Fec-0911Felis catus92.390.0 779
LLPS-Aim-2156Ailuropoda melanoleuca90.680.0 757
LLPS-Eqc-2185Equus caballus88.910.0 739
LLPS-Sus-1595Sus scrofa87.890.0 729
LLPS-Ict-1894Ictidomys tridecemlineatus87.679e-37 135
LLPS-Otg-1793Otolemur garnettii87.270.0 707
LLPS-Ova-2508Ovis aries86.830.0 663
LLPS-Bot-0793Bos taurus86.190.0 687
LLPS-Caj-0842Callithrix jacchus85.60.0 699
LLPS-Gog-0987Gorilla gorilla84.980.0 702
LLPS-Nol-1265Nomascus leucogenys84.980.0 699
LLPS-Hos-1659Homo sapiens84.980.0 698
LLPS-Aon-2971Aotus nancymaae84.740.0 591
LLPS-Pat-0448Pan troglodytes84.570.0 693
LLPS-Pap-1715Pan paniscus84.570.0 693
LLPS-Paa-1645Papio anubis84.360.0 695
LLPS-Cea-1252Cercocebus atys84.360.0 694
LLPS-Chs-1882Chlorocebus sabaeus84.360.0 689
LLPS-Maf-0091Macaca fascicularis84.160.0 691
LLPS-Mam-3303Macaca mulatta84.160.0 691
LLPS-Man-0576Macaca nemestrina84.160.0 691
LLPS-Dio-0558Dipodomys ordii83.751e-39 143
LLPS-Mal-2269Mandrillus leucophaeus83.30.0 631
LLPS-Poa-1325Pongo abelii83.120.0 654
LLPS-Myl-1352Myotis lucifugus82.680.0 689
LLPS-Orc-0428Oryctolagus cuniculus80.860.0 664
LLPS-Rhb-1885Rhinopithecus bieti79.50.0 648
LLPS-Fud-2928Fukomys damarensis79.290.0 577
LLPS-Mea-1097Mesocricetus auratus78.230.0 631
LLPS-Cap-2593Cavia porcellus76.950.0 617
LLPS-Ran-3900Rattus norvegicus76.540.0 597
LLPS-Mum-2880Mus musculus74.950.0 588
LLPS-Sah-2610Sarcophilus harrisii68.328e-136 405
LLPS-Ora-2121Ornithorhynchus anatinus67.111e-66 220
LLPS-Pes-1071Pelodiscus sinensis63.455e-168 491
LLPS-Fia-3308Ficedula albicollis62.682e-134 404
LLPS-Gaga-2327Gallus gallus60.847e-134 405
LLPS-Meg-0912Meleagris gallopavo60.085e-143 426
LLPS-Anp-0555Anas platyrhynchos59.553e-52 181
LLPS-Tar-2729Takifugu rubripes59.044e-41 159
LLPS-Anc-0530Anolis carolinensis58.614e-141 422
LLPS-Lac-1946Latimeria chalumnae51.491e-119 368
LLPS-Xet-0740Xenopus tropicalis50.623e-119 365
LLPS-Tag-1483Taeniopygia guttata50.613e-54 189
LLPS-Leo-0738Lepisosteus oculatus49.694e-104 326
LLPS-Scf-0935Scleropages formosus44.786e-93 300
LLPS-Scj-1269Schizosaccharomyces japonicus44.681e-0655.1
LLPS-Met-2469Medicago truncatula43.486e-0650.4
LLPS-Chr-1715Chlamydomonas reinhardtii43.482e-0653.9
LLPS-Scp-1160Schizosaccharomyces pombe42.225e-0858.9
LLPS-Ten-1439Tetraodon nigroviridis41.825e-0653.5
LLPS-Loa-4335Loxodonta africana40.859e-0755.8
LLPS-Orn-1700Oreochromis niloticus40.844e-74 250
LLPS-Orl-2740Oryzias latipes40.829e-1065.1
LLPS-Asm-3125Astyanax mexicanus40.715e-90 291
LLPS-Dar-3019Danio rerio40.669e-84 275
LLPS-Icp-2455Ictalurus punctatus40.426e-84 274
LLPS-Xim-0408Xiphophorus maculatus40.35e-74 248
LLPS-Scc-0039Schizosaccharomyces cryophilus40.03e-0756.6
LLPS-Scm-1368Scophthalmus maximus39.667e-77 257
LLPS-Gaa-2362Gasterosteus aculeatus39.534e-76 254
LLPS-Pof-0388Poecilia formosa39.152e-73 247
LLPS-Fuv-1179Fusarium verticillioides39.137e-0650.8
LLPS-Mod-3286Monodelphis domestica38.714e-0653.5
LLPS-Amt-2057Amborella trichopoda36.495e-0653.5
LLPS-Tut-0114Tursiops truncatus36.479e-0651.6
LLPS-Cii-2079Ciona intestinalis36.472e-0653.9
LLPS-Cas-4083Carlito syrichta36.479e-0651.6
LLPS-Mel-0611Melampsora laricipopulina35.292e-0962.0