RNF8_MOUSE
ID RNF8_MOUSE Reviewed; 488 AA.
AC Q8VC56; Q4FJV7; Q9JK13;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=E3 ubiquitin-protein ligase RNF8 {ECO:0000255|HAMAP-Rule:MF_03067};
DE EC=2.3.2.27 {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=ActA-interacting protein 37;
DE Short=AIP37;
DE AltName: Full=LaXp180;
DE AltName: Full=RING finger protein 8 {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=RING-type E3 ubiquitin transferase RNF8 {ECO:0000255|HAMAP-Rule:MF_03067};
GN Name=Rnf8 {ECO:0000255|HAMAP-Rule:MF_03067};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Extraembryonic tissue, Liver, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-283, AND INTERACTION WITH ACTA (MICROBIAL
RP INFECTION).
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=11207567; DOI=10.1046/j.1462-5822.2000.00034.x;
RA Pfeuffer T., Goebel W., Laubinger J., Bachmann M., Kuhn M.;
RT "LaXp180, a mammalian ActA-binding protein, identified with the yeast two-
RT hybrid system co-localizes with intracellular Listeria monocytogenes.";
RL Cell. Microbiol. 2:101-114(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20153262; DOI=10.1016/j.devcel.2010.01.010;
RA Lu L.Y., Wu J., Ye L., Gavrilina G.B., Saunders T.L., Yu X.;
RT "RNF8-dependent histone modifications regulate nucleosome removal during
RT spermatogenesis.";
RL Dev. Cell 18:371-384(2010).
RN [6]
RP FUNCTION.
RX PubMed=20080757; DOI=10.1073/pnas.0913790107;
RA Ramachandran S., Chahwan R., Nepal R.M., Frieder D., Panier S., Roa S.,
RA Zaheen A., Durocher D., Scharff M.D., Martin A.;
RT "The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch
RT recombination.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:809-814(2010).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21706008; DOI=10.1038/nsmb.2078;
RA Wu J., Chen Y., Lu L.Y., Wu Y., Paulsen M.T., Ljungman M., Ferguson D.O.,
RA Yu X.;
RT "Chfr and RNF8 synergistically regulate ATM activation.";
RL Nat. Struct. Mol. Biol. 18:761-768(2011).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21857671; DOI=10.1038/ncb2326;
RA Peuscher M.H., Jacobs J.J.;
RT "DNA-damage response and repair activities at uncapped telomeres depend on
RT RNF8.";
RL Nat. Cell Biol. 13:1139-1145(2011).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=22101936; DOI=10.1038/nsmb.2172;
RA Rai R., Li J.M., Zheng H., Lok G.T., Deng Y., Huen M.S., Chen J., Jin J.,
RA Chang S.;
RT "The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end
RT protection.";
RL Nat. Struct. Mol. Biol. 18:1400-1407(2011).
RN [10]
RP FUNCTION.
RX PubMed=22266820; DOI=10.1038/nsmb.2211;
RA Feng L., Chen J.;
RT "The E3 ligase RNF8 regulates KU80 removal and NHEJ repair.";
RL Nat. Struct. Mol. Biol. 19:201-206(2012).
RN [11]
RP FUNCTION.
RX PubMed=24953653; DOI=10.1016/j.celrep.2014.05.041;
RA Cardamone M.D., Tanasa B., Chan M., Cederquist C.T., Andricovich J.,
RA Rosenfeld M.G., Perissi V.;
RT "GPS2/KDM4A pioneering activity regulates promoter-specific recruitment of
RT PPARgamma.";
RL Cell Rep. 8:163-176(2014).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH PIWIL1, AND MUTAGENESIS OF
RP 68-GLN--GLY-72.
RX PubMed=28552346; DOI=10.1016/j.cell.2017.04.034;
RA Gou L.T., Kang J.Y., Dai P., Wang X., Li F., Zhao S., Zhang M., Hua M.M.,
RA Lu Y., Zhu Y., Li Z., Chen H., Wu L.G., Li D., Fu X.D., Li J., Shi H.J.,
RA Liu M.F.;
RT "Ubiquitination-deficient mutations in human Piwi cause male infertility by
RT impairing histone-to-protamine exchange during spermiogenesis.";
RL Cell 169:1090-1104(2017).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in DNA
CC damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX and promoting the recruitment
CC of DNA repair proteins at double-strand breaks (DSBs) sites, and by
CC catalyzing 'Lys-48'-linked ubiquitination to remove target proteins
CC from DNA damage sites. Following DNA DSBs, it is recruited to the sites
CC of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX, thereby promoting the
CC formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF).
CC Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and
CC PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand
CC cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination
CC of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi
CC anemia (FA) complex, followed by interstrand cross-link repair. H2A
CC ubiquitination also mediates the ATM-dependent transcriptional
CC silencing at regions flanking DSBs in cis, a mechanism to avoid
CC collision between transcription and repair intermediates. Promotes the
CC formation of 'Lys-63'-linked polyubiquitin chains via interactions with
CC the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-
CC histone substrates such as PCNA. Substrates that are polyubiquitinated
CC at 'Lys-63' are usually not targeted for degradation. Also catalyzes
CC the formation of 'Lys-48'-linked polyubiquitin chains via interaction
CC with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of
CC substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is
CC still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-
CC linked ubiquitination is regulated but it could be due to RNF8 ability
CC to interact with specific E2 specific ligases. For instance,
CC interaction with phosphorylated HERC2 promotes the association between
CC RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-
CC linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by
CC promoting the 'Lys-48'-linked ubiquitination and degradation the of
CC KU80/XRCC5. Following DNA damage, mediates the ubiquitination and
CC degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to
CC unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA
CC damage sites. Following DNA damage, mediates the ubiquitination and
CC degradation of POLD4/p12, a subunit of DNA polymerase delta. In the
CC absence of POLD4, DNA polymerase delta complex exhibits higher
CC proofreading activity. In addition to its function in damage signaling,
CC also plays a role in higher-order chromatin structure by mediating
CC extensive chromatin decondensation. Involved in the activation of ATM
CC by promoting histone H2B ubiquitination, which indirectly triggers
CC histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin
CC environment that promotes efficient activation of ATM kinase. Required
CC in the testis, where it plays a role in the replacement of histones
CC during spermatogenesis (PubMed:20153262, PubMed:28552346). At uncapped
CC telomeres, promotes the joining of deprotected chromosome ends by
CC inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it
CC may enhance cancer development by aggravating telomere-induced genome
CC instability in case of telomeric crisis. Promotes the assembly of RAD51
CC at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class
CC switch recombination in immune system, via its role in regulation of
CC DSBs repair. May be required for proper exit from mitosis after spindle
CC checkpoint activation and may regulate cytokinesis. May play a role in
CC the regulation of RXRA-mediated transcriptional activity. Not involved
CC in RXRA ubiquitination by UBE2E2. {ECO:0000255|HAMAP-Rule:MF_03067,
CC ECO:0000269|PubMed:20080757, ECO:0000269|PubMed:20153262,
CC ECO:0000269|PubMed:21706008, ECO:0000269|PubMed:21857671,
CC ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:24953653,
CC ECO:0000269|PubMed:28552346}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000255|HAMAP-Rule:MF_03067};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SUBUNIT: Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of
CC the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts
CC with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with
CC UBE2N. Interacts with RXRA. Interacts (via FHA domain) with ATM-
CC phosphorylated MDC1. Interacts (via FHA domain) with 'Thr-4829'
CC phosphorylated HERC2 (via C-terminus) (By similarity). Interacts with
CC PIWIL1; leading to sequester RNF8 in the cytoplasm (PubMed:28552346).
CC Interacts with WRAP53/TCAB1 (By similarity). {ECO:0000255|HAMAP-
CC Rule:MF_03067, ECO:0000269|PubMed:28552346}.
CC -!- SUBUNIT: (Microbial infection) May interact with the L.monocytogenes
CC protein actA; however, given these errors in the sequence (AJ242721),
CC the relevance of the interaction with actA remains to be confirmed.
CC {ECO:0000269|PubMed:11207567}.
CC -!- INTERACTION:
CC Q8VC56; Q96AP0: ACD; Xeno; NbExp=2; IntAct=EBI-15954293, EBI-717666;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067,
CC ECO:0000269|PubMed:28552346}. Cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_03067, ECO:0000269|PubMed:28552346}. Midbody
CC {ECO:0000255|HAMAP-Rule:MF_03067}. Chromosome, telomere
CC {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:21857671,
CC ECO:0000269|PubMed:22101936}. Note=Recruited at uncapped telomeres
CC (PubMed:21857671, PubMed:22101936). Following DNA double-strand breaks,
CC recruited to the sites of damage. During prophase, concomitant with
CC nuclear envelope breakdown, localizes throughout the cell, with a
CC dotted pattern. In telophase, again in the nucleus and also with a
CC discrete dotted pattern in the cytoplasm. In late telophase and during
CC cytokinesis, localizes in the midbody of the tubulin bridge joining the
CC daughter cells. Does not seem to be associated with condensed
CC chromosomes at any time during the cell cycle (By similarity). During
CC spermatogenesis, sequestered in the cytoplasm by PIWIL1: RNF8 is
CC released following ubiquitination and degradation of PIWIL1
CC (PubMed:28552346). {ECO:0000255|HAMAP-Rule:MF_03067,
CC ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22101936,
CC ECO:0000269|PubMed:28552346}.
CC -!- DOMAIN: The FHA domain specifically recognizes and binds ATM-
CC phosphorylated MDC1 and phosphorylated HERC2 (By similarity). This
CC domain is also required for proper recruitment to DNA damage sites
CC after UV irradiation, ionizing radiation, or treatment with an
CC alkylating agent (By similarity). {ECO:0000250|UniProtKB:O76064,
CC ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- PTM: Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin.
CC 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type
CC polyubiquitination is also observed, but it doesn't require its own
CC functional RING-type zinc finger. {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- DISRUPTION PHENOTYPE: Male mice are infertile, while females do not
CC show defects. Male mice display defects in histone H2A and H2B
CC ubiquitination in testis cells. While meiotic sex chromosome
CC inactivation in the XY body prior to meiosis is not affected, H4K16ac
CC is decreased, leading to defects in the replacement of histones by
CC protamines during spermiogenesis. Mice lacking both Rnf8 and Chfr
CC develop thymic lymphomas and chromosomes are frequently altered, due to
CC defects in DNA damage response and defects in damage-induced activation
CC of ATM kinase. {ECO:0000269|PubMed:20153262,
CC ECO:0000269|PubMed:21706008}.
CC -!- SIMILARITY: Belongs to the RNF8 family. {ECO:0000255|HAMAP-
CC Rule:MF_03067}.
CC -!- CAUTION: The precise role of Rnf8 at telomeres is subject to debate. 2
CC publications reported recruitment of Rnf8 at uncapped telomeres
CC followed by regulation of non-homologous end joining (NHEJ), however
CC the 2 publications reported different data and conclusions. According
CC to a report, Rnf8 promotes telomere end protection and inhibits NHEJ by
CC mediating ubiquitination via 'Lys-63'-linked ubiquitin and
CC stabilization of Tpp1 at uncapped telomeres (PubMed:22101936).
CC According to another report, Rnf8 recruitment at uncapped telomeres
CC leads to promote NHEJ and the joining of deprotected chromosome ends by
CC inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that
CC Rnf8 may have a detrimental role in case of telomeric crisis and
CC enhance cancer development by aggravating telomere-induced genome
CC instability (PubMed:21857671). {ECO:0000305|PubMed:21857671,
CC ECO:0000305|PubMed:22101936}.
CC -!- CAUTION: According to a well-established model, RNF8 initiate H2A 'Lys-
CC 63'-linked ubiquitination leading to recruitment of RNF168 to amplify
CC H2A 'Lys-63'-linked ubiquitination. However, other data suggest that
CC RNF168 is the priming ubiquitin ligase by mediating monoubiquitination
CC of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and
CC H2AK15Ub respectively). These data suggest that RNF168 might be
CC recruited to DSBs sites in a RNF8-dependent manner by binding to non-
CC histone proteins ubiquitinated via 'Lys-63'-linked and initiates
CC monoubiquitination of H2A, which is then amplified by RNF8. Additional
CC evidence is however required to confirm these data. {ECO:0000255|HAMAP-
CC Rule:MF_03067}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB92239.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB92239.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK076180; BAC36236.1; -; mRNA.
DR EMBL; AK147168; BAE27732.1; -; mRNA.
DR EMBL; CT010295; CAJ18503.1; -; mRNA.
DR EMBL; BC021778; AAH21778.1; -; mRNA.
DR EMBL; AJ242721; CAB92239.1; ALT_FRAME; mRNA.
DR CCDS; CCDS37538.1; -.
DR RefSeq; NP_067394.1; NM_021419.2.
DR AlphaFoldDB; Q8VC56; -.
DR SMR; Q8VC56; -.
DR BioGRID; 208404; 7.
DR DIP; DIP-59448N; -.
DR IntAct; Q8VC56; 2.
DR MINT; Q8VC56; -.
DR STRING; 10090.ENSMUSP00000024817; -.
DR iPTMnet; Q8VC56; -.
DR PhosphoSitePlus; Q8VC56; -.
DR jPOST; Q8VC56; -.
DR MaxQB; Q8VC56; -.
DR PaxDb; Q8VC56; -.
DR PRIDE; Q8VC56; -.
DR DNASU; 58230; -.
DR Ensembl; ENSMUST00000024817; ENSMUSP00000024817; ENSMUSG00000090083.
DR GeneID; 58230; -.
DR KEGG; mmu:58230; -.
DR UCSC; uc008btf.1; mouse.
DR CTD; 9025; -.
DR MGI; MGI:1929069; Rnf8.
DR VEuPathDB; HostDB:ENSMUSG00000090083; -.
DR eggNOG; KOG3872; Eukaryota.
DR GeneTree; ENSGT00400000022349; -.
DR HOGENOM; CLU_023453_1_0_1; -.
DR InParanoid; Q8VC56; -.
DR OMA; YCIKQWR; -.
DR OrthoDB; 1585372at2759; -.
DR PhylomeDB; Q8VC56; -.
DR TreeFam; TF330957; -.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 58230; 15 hits in 109 CRISPR screens.
DR PRO; PR:Q8VC56; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8VC56; protein.
DR Bgee; ENSMUSG00000090083; Expressed in primary oocyte and 273 other tissues.
DR ExpressionAtlas; Q8VC56; baseline and differential.
DR Genevisible; Q8VC56; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0043486; P:histone exchange; IMP:UniProtKB.
DR GO; GO:0070535; P:histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; IMP:UniProtKB.
DR GO; GO:0033523; P:histone H2B ubiquitination; IMP:UniProtKB.
DR GO; GO:0045190; P:isotype switching; IMP:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISO:MGI.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR HAMAP; MF_03067; RNF8; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR017335; RNF8.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF037950; E3_ubiquit_lig_RNF8; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Chromatin regulator; Chromosome; Cytoplasm;
KW DNA damage; DNA repair; Metal-binding; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Telomere; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..488
FT /note="E3 ubiquitin-protein ligase RNF8"
FT /id="PRO_0000056049"
FT DOMAIN 38..92
FT /note="FHA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT ZN_FING 406..444
FT /note="RING-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT REGION 68..72
FT /note="Required for interaction with PIWIL1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067,
FT ECO:0000269|PubMed:28552346"
FT REGION 141..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O76064"
FT MUTAGEN 68..72
FT /note="QNPEG->AAAAA: Abolishes interaction with PIWIL1."
FT /evidence="ECO:0000269|PubMed:28552346"
SQ SEQUENCE 488 AA; 55517 MW; 428242204EBC44A1 CRC64;
MGEPDPLVSG QLAARRSWCL RRLGMDCEWL QLEAGTEVTI GRGLSVTYQL ISKVCPLMIS
RSHCVLKQNP EGQWTIMDNK SLNGVWLNRE RLAPLQGYCI RKGDHIQLGV PLESRETAEY
EYEVIEEDWE SLAPCLAPKN DQRMEKHKGS RTKRKFSSPG LENLPAEGSS DLRCPLANVA
SKPIEPEKLH GKGDASSQSL GCLCPGLTSL KASERAAGPH ACSALPKVLE LSCPKKQKAC
RPSASQNSLE LFKVTMSRML KLKTQMQEKQ IAVLNVKRQT RKGSSKKIVR MEKELRNLQS
QLYAEQAQQQ ARVEQLEKTF QEEAHYLQGL EKEQGECDLK QQLVQALQEH QALMEELNCS
KKDFEKIIQA KNKELEQTKE EKDKVQAQKE EVLSHMNDLL ENELQCIICS EYFIEAVTLN
CAHSFCSFCI NEWMKRKVEC PICRKDIESR TNSLVLDNCI SKMVDNLSSD VKERRSVLIR
ERRAKRLS
