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Tag Content
UUCD2 ID IUUC-Ptr-091029
UUCD1 version UUC-PaT-00690
Ensembl Protein ID ENSPTRP00000057853.2
UniProt Accession H2RCV3; H2RCV3_PANTR
Genbank Protein ID ENSPTRP00000057853
Protein Name E3 ubiquitin-protein ligase RNF8; RING finger protein 8; RING-type E3 ubiquitin transferase RNF8
Genbank Nucleotide ID AACZ03049037
Gene Name RNF8
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSPTRG00000018121.5 ENSPTRT00000066277.2 ENSPTRP00000057853.2
Status Unreviewed
Classification
Family E-Value Score Start End
E3 activity/RING/RING 1.30e-07 32.1 375 413
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   E3 activity/RING/RING

   S: 1    CaiCledfkdgplvlpCgHvfhadClqkwpglknssskefrCPlCr 46
    C+iC e f + ++l+C H f+ C++ w ++++ CP+Cr
   Q: 375 CIICSEYFIE-AVTLNCAHSFCSYCINEW------MKRKIECPICR 413
    ********99.899***************......**********8 PP
   

Organism Pan troglodytes
Functional Description
(View)

Functional Description



     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. 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.
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. 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.
Protein Sequence
(Fasta)
FLALLLSSQV TVGRGFGVTY QLVSKICPLM ISRNHCVLKQ NPEGQWTIMD NKSLNGVWLN 60
RARLEPLRVY SIQQGDYIQL GVPLENKENA EYEYEVTEED WETIYPCLSP KNDQMIEKNK 120
It may take some time, please wait.

Protein Fasta Sequence



>IUUC-Ptr-091029|E3,RING|Pan troglodytes
Please wait for a moment...
Nucleotide Sequence
(Fasta)
TTTCTTGCAT TGTTGTTGTC TTCCCAGGTG ACTGTAGGAC GAGGATTTGG TGTCACATAC 60
CAACTGGTAT CAAAAATCTG CCCCCTGATG ATTTCTCGAA ACCACTGTGT TTTGAAGCAG 120
It may take some time, please wait.

Nucleotide Fasta Sequence



>IUUC-Ptr-091029|E3,RING|Pan troglodytes
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0131--Cell cycle
KW-0132--Cell division
KW-0156--Chromatin regulator
KW-0158--Chromosome
KW-0175--Coiled coil
KW-0181--Complete proteome
KW-0227--DNA damage
KW-0234--DNA repair
KW-0479--Metal-binding
KW-0498--Mitosis
KW-0539--Nucleus
KW-1185--Reference proteome
KW-0779--Telomere
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
KW-0862--Zinc
KW-0863--Zinc-finger

Interpro

IPR000253--FHA_dom
IPR017335--RNF8
IPR008984--SMAD_FHA_domain
IPR001841--Znf_RING
IPR013083--Znf_RING/FYVE/PHD
IPR017907--Znf_RING_CS

PROSITE

PS50006--FHA_DOMAIN
PS00518--ZF_RING_1
PS50089--ZF_RING_2

Pfam

PF00498--FHA

SMART

SM00240--FHA
SM00184--RING

Gene Ontology

GO:0005829--C:cytosol
GO:0005634--C:nucleus
GO:0035861--C:site of double-strand break
GO:0000151--C:ubiquitin ligase complex
GO:0003682--F:chromatin binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0008270--F:zinc ion binding
GO:0006302--P:double-strand break repair
GO:0070535--P:histone H2A K63-linked ubiquitination
GO:0034244--P:negative regulation of transcription elongation from RNA polymerase II promoter
GO:0045739--P:positive regulation of DNA repair
GO:0051865--P:protein autoubiquitination
GO:0070936--P:protein K48-linked ubiquitination
GO:0010212--P:response to ionizing radiation
GO:0006511--P:ubiquitin-dependent protein catabolic process

Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-002124 Ailuropoda melanoleuca 83.30 2.00e-172 598.00
IUUC-Apl-003664 Anas platyrhynchos 80.00 1.00e-39 154.00
IUUC-Aca-005036 Anolis carolinensis 56.64 6.00e-119 421.00
IUUC-Ame-011537 Astyanax mexicanus 42.45 2.00e-81 296.00
IUUC-Bta-013297 Bos taurus 83.22 4.00e-166 577.00
IUUC-Cel-018658 Caenorhabditis elegans 41.07 1.00e-07 51.60
IUUC-Cja-019201 Callithrix jacchus 90.79 0.00e+00 691.00
IUUC-Cfa-021041 Canis familiaris 83.19 0.00e+00 642.00
IUUC-Csa-024133 Chlorocebus sabaeus 96.28 0.00e+00 779.00
IUUC-Cho-024624 Choloepus hoffmanni 74.88 1.00e-133 469.00
IUUC-Dre-027918 Danio rerio 41.92 4.00e-75 275.00
IUUC-Dno-029774 Dasypus novemcinctus 83.62 0.00e+00 626.00
IUUC-Dor-030190 Dipodomys ordii 71.33 2.00e-145 508.00
IUUC-Ete-032301 Echinops telfairi 73.95 6.00e-137 480.00
IUUC-Eca-033607 Equus caballus 86.00 1.00e-174 605.00
IUUC-Eeu-034888 Erinaceus europaeus 81.73 7.00e-120 423.00
IUUC-Fca-036075 Felis catus 82.31 0.00e+00 637.00
IUUC-Fal-037569 Ficedula albicollis 61.27 8.00e-120 423.00
IUUC-Gmo-038588 Gadus morhua 39.09 6.00e-67 248.00
IUUC-Gga-040777 Gallus gallus 58.41 1.00e-119 423.00
IUUC-Gac-042463 Gasterosteus aculeatus 42.51 1.00e-60 226.00
IUUC-Ggo-045269 Gorilla gorilla 97.82 0.00e+00 787.00
IUUC-Hsa-046249 Homo sapiens 97.59 0.00e+00 773.00
IUUC-Itr-048314 Ictidomys tridecemlineatus 83.01 0.00e+00 634.00
IUUC-Lch-049805 Latimeria chalumnae 49.15 1.00e-107 383.00
IUUC-Loc-052377 Lepisosteus oculatus 48.68 4.00e-84 305.00
IUUC-Mcc-055344 Macaca mulatta 96.29 0.00e+00 777.00
IUUC-Meu-055950 Macropus eugenii 63.24 3.00e-119 421.00
IUUC-Mla-059052 Melampsora laricipopulina 35.38 7.00e-10 57.00
IUUC-Mga-060049 Meleagris gallopavo 59.20 3.00e-119 421.00
IUUC-Mmr-061431 Microcebus murinus 83.92 3.00e-170 591.00
IUUC-Mdo-062016 Monodelphis domestica 68.81 2.00e-123 437.00
IUUC-Mmu-063235 Mus musculus 71.02 4.00e-165 574.00
IUUC-Mpu-066449 Mustela putorius furo 85.62 0.00e+00 673.00
IUUC-Mlu-067588 Myotis lucifugus 79.34 7.00e-164 570.00
IUUC-Nle-069192 Nomascus leucogenys 97.38 0.00e+00 785.00
IUUC-Opr-070300 Ochotona princeps 62.88 9.00e-127 446.00
IUUC-Ont-071998 Oreochromis niloticus 41.96 7.00e-63 234.00
IUUC-Oan-073610 Ornithorhynchus anatinus 66.09 3.00e-67 247.00
IUUC-Ocu-074603 Oryctolagus cuniculus 79.04 3.00e-169 588.00
IUUC-Ola-086681 Oryzias latipes 38.85 1.00e-68 253.00
IUUC-Oga-088183 Otolemur garnettii 84.25 0.00e+00 652.00
IUUC-Oar-090255 Ovis aries 83.93 2.00e-164 572.00
IUUC-Pan-092241 Papio anubis 96.07 0.00e+00 775.00
IUUC-Psi-093506 Pelodiscus sinensis 62.55 3.00e-128 451.00
IUUC-Pma-094579 Petromyzon marinus 56.67 2.00e-26 113.00
IUUC-Pfo-097014 Poecilia formosa 41.76 8.00e-60 224.00
IUUC-Pab-098530 Pongo abelii 95.85 0.00e+00 772.00
IUUC-Pca-100939 Procavia capensis 67.24 8.00e-127 447.00
IUUC-Pva-103148 Pteropus vampyrus 77.51 4.00e-168 583.00
IUUC-Rno-105338 Rattus norvegicus 73.20 8.00e-173 599.00
IUUC-Sha-107187 Sarcophilus harrisii 66.67 3.00e-106 378.00
IUUC-Sar-113356 Sorex araneus 64.85 1.00e-127 449.00
IUUC-Ssc-116290 Sus scrofa 83.52 0.00e+00 677.00
IUUC-Tru-117910 Takifugu rubripes 40.95 4.00e-57 215.00
IUUC-Tsy-119329 Tarsius syrichta 79.02 7.00e-167 580.00
IUUC-Tni-120521 Tetraodon nigroviridis 39.25 4.00e-58 218.00
IUUC-Tme-126989 Tuber melanosporum 32.76 5.00e-07 49.70
IUUC-Ttr-128997 Tursiops truncatus 78.84 5.00e-179 620.00
IUUC-Vpa-130154 Vicugna pacos 81.00 0.00e+00 628.00
IUUC-Xtr-132805 Xenopus tropicalis 51.74 6.00e-103 367.00
Created Date 25-Jun-2017

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