RNF8_HUMAN
ID RNF8_HUMAN Reviewed; 485 AA.
AC O76064; A6NN24; A8MYC0; B4DPG0; Q53H16; Q5NKW5;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=E3 ubiquitin-protein ligase RNF8 {ECO:0000255|HAMAP-Rule:MF_03067};
DE Short=hRNF8;
DE EC=2.3.2.27 {ECO:0000255|HAMAP-Rule:MF_03067};
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}; Synonyms=KIAA0646;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9852682; DOI=10.1007/s100380050088;
RA Seki N., Hattori A., Sugano S., Suzuki Y., Nakagawara A., Ohhira M.,
RA Muramatsu M., Hori T., Saito T.;
RT "Isolation, tissue expression, and chromosomal assignment of a novel human
RT gene which encodes a protein with RING finger motif.";
RL J. Hum. Genet. 43:272-274(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INTERACTION WITH UBE2E2 AND UBE2N, AUTOUBIQUITINATION, AND
RP MUTAGENESIS OF CYS-403.
RC TISSUE=Fetal brain;
RX PubMed=16215985; DOI=10.1002/jcb.20587;
RA Plans V., Scheper J., Soler M., Loukili N., Okano Y., Thomson T.M.;
RT "The RING finger protein RNF8 recruits UBC13 for lysine 63-based self
RT polyubiquitylation.";
RL J. Cell. Biochem. 97:572-582(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hepatoma;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [10]
RP PROTEIN SEQUENCE OF 81-89; 156-173 AND 215-226, FUNCTION, SUBCELLULAR
RP LOCATION, MASS SPECTROMETRY, AND MUTAGENESIS OF ARG-42.
RX PubMed=23233665; DOI=10.1074/jbc.m112.423392;
RA Zhang S., Zhou Y., Sarkeshik A., Yates J.R. III, Thomson T.M., Zhang Z.,
RA Lee E.Y., Lee M.Y.;
RT "Identification of RNF8 as a ubiquitin ligase involved in targeting the p12
RT subunit of DNA polymerase delta for degradation in response to DNA
RT damage.";
RL J. Biol. Chem. 288:2941-2950(2013).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH UBE2E1; UBE2E2 AND UBE2E3,
RP AND MUTAGENESIS OF CYS-403.
RX PubMed=11322894; DOI=10.1046/j.1432-1327.2001.02169.x;
RA Ito K., Adachi S., Iwakami R., Yasuda H., Muto Y., Seki N., Okano Y.;
RT "N-terminally extended human ubiquitin-conjugating enzymes (E2s) mediate
RT the ubiquitination of RING-finger proteins, ARA54 and RNF8.";
RL Eur. J. Biochem. 268:2725-2732(2001).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RXRA, AND MUTAGENESIS OF
RP CYS-403.
RX PubMed=14981089; DOI=10.1074/jbc.m309148200;
RA Takano Y., Adachi S., Okuno M., Muto Y., Yoshioka T.,
RA Matsushima-Nishiwaki R., Tsurumi H., Ito K., Friedman S.L., Moriwaki H.,
RA Kojima S., Okano Y.;
RT "The RING finger protein, RNF8, interacts with retinoid X receptor alpha
RT and enhances its transcription-stimulating activity.";
RL J. Biol. Chem. 279:18926-18934(2004).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH MDC1,
RP DOMAIN, AND MUTAGENESIS OF ARG-42 AND CYS-403.
RX PubMed=18001824; DOI=10.1016/j.cell.2007.09.040;
RA Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J.,
RA Lukas C., Lukas J.;
RT "RNF8 ubiquitylates histones at DNA double-strand breaks and promotes
RT assembly of repair proteins.";
RL Cell 131:887-900(2007).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18077395; DOI=10.1073/pnas.0710061104;
RA Wang B., Elledge S.J.;
RT "Ubc13/Rnf8 ubiquitin ligases control foci formation of the
RT Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20759-20763(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH MDC1.
RX PubMed=18006705; DOI=10.1126/science.1150034;
RA Kolas N.K., Chapman J.R., Nakada S., Ylanko J., Chahwan R., Sweeney F.D.,
RA Panier S., Mendez M., Wildenhain J., Thomson T.M., Pelletier L.,
RA Jackson S.P., Durocher D.;
RT "Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.";
RL Science 318:1637-1640(2007).
RN [16]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17724460; DOI=10.1038/sj.onc.1210782;
RA Plans V., Guerra-Rebollo M., Thomson T.M.;
RT "Regulation of mitotic exit by the RNF8 ubiquitin ligase.";
RL Oncogene 27:1355-1365(2008).
RN [17]
RP FUNCTION.
RX PubMed=18948756; DOI=10.4161/cc.7.21.6949;
RA Zhang S., Chea J., Meng X., Zhou Y., Lee E.Y.C., Lee M.Y.W.T.;
RT "PCNA is ubiquitinated by RNF8.";
RL Cell Cycle 7:3399-3404(2008).
RN [18]
RP FUNCTION.
RX PubMed=18337245; DOI=10.1074/jbc.m710197200;
RA Sakasai R., Tibbetts R.;
RT "RNF8-dependent and RNF8-independent regulation of 53BP1 in response to DNA
RT damage.";
RL J. Biol. Chem. 283:13549-13555(2008).
RN [19]
RP INTERACTION WITH UBE2N.
RX PubMed=18678647; DOI=10.1128/mcb.00987-08;
RA Huen M.S.Y., Huang J., Yuan J., Yamamoto M., Akira S., Ashley C., Xiao W.,
RA Chen J.;
RT "Noncanonical E2 variant-independent function of UBC13 in promoting
RT checkpoint protein assembly.";
RL Mol. Cell. Biol. 28:6104-6112(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP INTERACTION WITH HERC2.
RX PubMed=20023648; DOI=10.1038/ncb2008;
RA Bekker-Jensen S., Rendtlew Danielsen J., Fugger K., Gromova I.,
RA Nerstedt A., Lukas C., Bartek J., Lukas J., Mailand N.;
RT "HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on
RT damaged chromosomes.";
RL Nat. Cell Biol. 12:80-86(2010).
RN [23]
RP FUNCTION.
RX PubMed=19203578; DOI=10.1016/j.cell.2008.12.042;
RA Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K.,
RA Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C.,
RA Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A.,
RA Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D.;
RT "The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling
RT cascade at sites of DNA damage.";
RL Cell 136:420-434(2009).
RN [24]
RP FUNCTION.
RX PubMed=19203579; DOI=10.1016/j.cell.2008.12.041;
RA Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H.,
RA Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J.,
RA Lukas C.;
RT "RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to
RT allow accumulation of repair proteins.";
RL Cell 136:435-446(2009).
RN [25]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19124460; DOI=10.1074/jbc.m809158200;
RA Gong Z., Cho Y.-W., Kim J.-E., Ge K., Chen J.;
RT "Accumulation of Pax2 transactivation domain interaction protein (PTIP) at
RT sites of DNA breaks via RNF8-dependent pathway is required for cell
RT survival after DNA damage.";
RL J. Biol. Chem. 284:7284-7293(2009).
RN [26]
RP FUNCTION.
RX PubMed=19015238; DOI=10.1128/mcb.01302-08;
RA Wu J., Huen M.S.Y., Lu L.-Y., Ye L., Dou Y., Ljungman M., Chen J., Yu X.;
RT "Histone ubiquitination associates with BRCA1-dependent DNA damage
RT response.";
RL Mol. Cell. Biol. 29:849-860(2009).
RN [27]
RP FUNCTION.
RX PubMed=19202061; DOI=10.1073/pnas.0807485106;
RA Shao G., Lilli D.R., Patterson-Fortin J., Coleman K.A., Morrissey D.E.,
RA Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-
RT dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [28]
RP FUNCTION.
RX PubMed=20550933; DOI=10.1016/j.cell.2010.04.038;
RA Shanbhag N.M., Rafalska-Metcalf I.U., Balane-Bolivar C., Janicki S.M.,
RA Greenberg R.A.;
RT "ATM-dependent chromatin changes silence transcription in cis to DNA
RT double-strand breaks.";
RL Cell 141:970-981(2010).
RN [29]
RP FUNCTION.
RX PubMed=21558560; DOI=10.1074/jbc.m111.232041;
RA Sy S.M., Jiang J., Dong S.S., Lok G.T., Wu J., Cai H., Yeung E.S.,
RA Huang J., Chen J., Deng Y., Huen M.S.;
RT "Critical roles of ring finger protein RNF8 in replication stress
RT responses.";
RL J. Biol. Chem. 286:22355-22361(2011).
RN [30]
RP FUNCTION, AND MUTAGENESIS OF ARG-42 AND CYS-406.
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 [31]
RP FUNCTION.
RX PubMed=22865450; DOI=10.1158/0008-5472.can-12-1057;
RA Nakada S., Yonamine R.M., Matsuo K.;
RT "RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the
RT absence of BRCA1 and 53BP1.";
RL Cancer Res. 72:4974-4983(2012).
RN [32]
RP FUNCTION IN UBIQUITINATION OF KDM4A, AND MUTAGENESIS OF ILE-405.
RX PubMed=22373579; DOI=10.1038/emboj.2012.47;
RA Mallette F.A., Mattiroli F., Cui G., Young L.C., Hendzel M.J., Mer G.,
RA Sixma T.K., Richard S.;
RT "RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1
RT recruitment to DNA damage sites.";
RL EMBO J. 31:1865-1878(2012).
RN [33]
RP FUNCTION.
RX PubMed=22531782; DOI=10.1038/emboj.2012.104;
RA Luijsterburg M.S., Acs K., Ackermann L., Wiegant W.W., Bekker-Jensen S.,
RA Larsen D.H., Khanna K.K., van Attikum H., Mailand N., Dantuma N.P.;
RT "A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-
RT order chromatin structure.";
RL EMBO J. 31:2511-2527(2012).
RN [34]
RP INTERACTION WITH HUMAN HERPESVIRUS 1 ICP0 (MICROBIAL INFECTION), AND
RP MUTAGENESIS OF ARG-42.
RX PubMed=22405594; DOI=10.1016/j.molcel.2012.02.004;
RA Chaurushiya M.S., Lilley C.E., Aslanian A., Meisenhelder J., Scott D.C.,
RA Landry S., Ticau S., Boutell C., Yates J.R. III, Schulman B.A., Hunter T.,
RA Weitzman M.D.;
RT "Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral
RT mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain.";
RL Mol. Cell 46:79-90(2012).
RN [35]
RP FUNCTION.
RX PubMed=22705371; DOI=10.1016/j.molcel.2012.05.026;
RA Yan Z., Guo R., Paramasivam M., Shen W., Ling C., Fox D. III, Wang Y.,
RA Oostra A.B., Kuehl J., Lee D.Y., Takata M., Hoatlin M.E., Schindler D.,
RA Joenje H., de Winter J.P., Li L., Seidman M.M., Wang W.;
RT "A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to
RT the Fanconi anemia DNA repair network.";
RL Mol. Cell 47:61-75(2012).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH UBE2N.
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 [37]
RP FUNCTION, AND MUTAGENESIS OF ILE-405.
RX PubMed=21911360; DOI=10.1093/nar/gkr655;
RA Lok G.T., Sy S.M., Dong S.S., Ching Y.P., Tsao S.W., Thomson T.M.,
RA Huen M.S.;
RT "Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-
RT ubiquitylation.";
RL Nucleic Acids Res. 40:196-205(2012).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [39]
RP INTERACTION WITH WRAP53.
RX PubMed=25512560; DOI=10.1101/gad.246546.114;
RA Henriksson S., Rassoolzadeh H., Hedstroem E., Coucoravas C., Julner A.,
RA Goldstein M., Imreh G., Zhivotovsky B., Kastan M.B., Helleday T.,
RA Farnebo M.;
RT "The scaffold protein WRAP53beta orchestrates the ubiquitin response
RT critical for DNA double-strand break repair.";
RL Genes Dev. 28:2726-2738(2014).
RN [40]
RP STRUCTURE BY NMR OF 8-139.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the FHA domain of human ubiquitin ligase protein
RT RNF8.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 13-146 IN COMPLEX WITH
RP PHOSPHOPEPTIDE, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=18001825; DOI=10.1016/j.cell.2007.09.041;
RA Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J.;
RT "RNF8 transduces the DNA-damage signal via histone ubiquitylation and
RT checkpoint protein assembly.";
RL Cell 131:901-914(2007).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 351-483 IN COMPLEX WITH ZINC,
RP SUBUNIT, FUNCTION, AND MUTAGENESIS OF ASP-443.
RX PubMed=22980979; DOI=10.1016/j.cell.2012.08.005;
RA Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E.,
RA Vermeulen W., Marteijn J.A., Sixma T.K.;
RT "RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling.";
RL Cell 150:1182-1195(2012).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (4.8 ANGSTROMS) OF 345-485 IN COMPLEX WITH UBE2N, AND
RP MUTAGENESIS OF ILE-405.
RX PubMed=22589545; DOI=10.1074/jbc.m112.359653;
RA Campbell S.J., Edwards R.A., Leung C.C., Neculai D., Hodge C.D.,
RA Dhe-Paganon S., Glover J.N.;
RT "Molecular insights into the function of RING Finger (RNF)-containing
RT proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation.";
RL J. Biol. Chem. 287:23900-23910(2012).
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/C1orf86 and
CC Fanconi anemia (FA) complex, followed by interstrand cross-link repair.
CC H2A 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 (PubMed:11322894, PubMed:14981089, PubMed:17724460,
CC PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395,
CC PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460,
CC PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933,
CC PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820,
CC PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450,
CC PubMed:22980979). 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 (PubMed:23233665). In addition to its function in
CC damage signaling, also plays a role in higher-order chromatin structure
CC by mediating extensive chromatin decondensation. Involved in the
CC activation of ATM by promoting histone H2B ubiquitination, which
CC indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac),
CC establishing a chromatin environment that promotes efficient activation
CC of ATM kinase. Required in the testis, where it plays a role in the
CC replacement of histones during spermatogenesis. At uncapped telomeres,
CC promotes the joining of deprotected chromosome ends by inducing H2A
CC ubiquitination and TP53BP1 recruitment, suggesting that it may enhance
CC cancer development by aggravating telomere-induced genome instability
CC in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs
CC in the absence of BRCA1 and TP53BP1 Also involved in class switch
CC recombination in immune system, via its role in regulation of DSBs
CC 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 (PubMed:11322894, PubMed:14981089,
CC PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705,
CC PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238,
CC PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579,
CC PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360,
CC PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371,
CC PubMed:22865450, PubMed:22980979). {ECO:0000269|PubMed:11322894,
CC ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:17724460,
CC ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825,
CC ECO:0000269|PubMed:18006705, ECO:0000269|PubMed:18077395,
CC ECO:0000269|PubMed:18337245, ECO:0000269|PubMed:18948756,
CC ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19124460,
CC ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19203578,
CC ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933,
CC ECO:0000269|PubMed:21558560, ECO:0000269|PubMed:21857671,
CC ECO:0000269|PubMed:21911360, ECO:0000269|PubMed:22266820,
CC ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22531782,
CC ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22865450,
CC ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23233665}.
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-4827'
CC phosphorylated HERC2 (via C-terminus). Interacts with PIWIL1; leading
CC to sequester RNF8 in the cytoplasm (By similarity). Interacts with
CC WRAP53/TCAB1 (PubMed:25512560). {ECO:0000250|UniProtKB:Q8VC56,
CC ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089,
CC ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:18001824,
CC ECO:0000269|PubMed:18001825, ECO:0000269|PubMed:18006705,
CC ECO:0000269|PubMed:18678647, ECO:0000269|PubMed:20023648,
CC ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:22589545,
CC ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:25512560}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via FHA domain) with
CC phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8
CC degradation by the proteasome. {ECO:0000269|PubMed:22405594}.
CC -!- INTERACTION:
CC O76064; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-373337, EBI-746752;
CC O76064; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-373337, EBI-739879;
CC O76064; Q9P1Z2: CALCOCO1; NbExp=3; IntAct=EBI-373337, EBI-749920;
CC O76064; Q49A88-3: CCDC14; NbExp=3; IntAct=EBI-373337, EBI-12105646;
CC O76064; Q8IVM0: CCDC50; NbExp=3; IntAct=EBI-373337, EBI-723996;
CC O76064; Q9C0F1: CEP44; NbExp=4; IntAct=EBI-373337, EBI-744115;
CC O76064; Q6P2H3-3: CEP85; NbExp=3; IntAct=EBI-373337, EBI-12368239;
CC O76064; P49760: CLK2; NbExp=5; IntAct=EBI-373337, EBI-750020;
CC O76064; P49761: CLK3; NbExp=3; IntAct=EBI-373337, EBI-745579;
CC O76064; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-373337, EBI-742054;
CC O76064; P50570: DNM2; NbExp=3; IntAct=EBI-373337, EBI-346547;
CC O76064; Q5QJE6: DNTTIP2; NbExp=3; IntAct=EBI-373337, EBI-5666736;
CC O76064; O95208-2: EPN2; NbExp=3; IntAct=EBI-373337, EBI-12135243;
CC O76064; I6L9I8: EPN3; NbExp=3; IntAct=EBI-373337, EBI-12866582;
CC O76064; Q9BPY3: FAM118B; NbExp=3; IntAct=EBI-373337, EBI-726822;
CC O76064; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-373337, EBI-10175124;
CC O76064; A1L4K1: FSD2; NbExp=3; IntAct=EBI-373337, EBI-5661036;
CC O76064; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-373337, EBI-473189;
CC O76064; V9HW80: HEL-S-70; NbExp=3; IntAct=EBI-373337, EBI-10175326;
CC O76064; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-373337, EBI-10172004;
CC O76064; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-373337, EBI-2556193;
CC O76064; Q5T7B8-2: KIF24; NbExp=3; IntAct=EBI-373337, EBI-10213781;
CC O76064; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-373337, EBI-10171774;
CC O76064; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-373337, EBI-1044640;
CC O76064; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-373337, EBI-11958364;
CC O76064; P61968: LMO4; NbExp=3; IntAct=EBI-373337, EBI-2798728;
CC O76064; Q9Y6D9: MAD1L1; NbExp=7; IntAct=EBI-373337, EBI-742610;
CC O76064; P28482: MAPK1; NbExp=3; IntAct=EBI-373337, EBI-959949;
CC O76064; Q14676: MDC1; NbExp=11; IntAct=EBI-373337, EBI-495644;
CC O76064; P49585: PCYT1A; NbExp=3; IntAct=EBI-373337, EBI-2563309;
CC O76064; O15173: PGRMC2; NbExp=3; IntAct=EBI-373337, EBI-1050125;
CC O76064; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-373337, EBI-79165;
CC O76064; Q9UL42: PNMA2; NbExp=7; IntAct=EBI-373337, EBI-302355;
CC O76064; Q96CD2: PPCDC; NbExp=3; IntAct=EBI-373337, EBI-724333;
CC O76064; P20618: PSMB1; NbExp=3; IntAct=EBI-373337, EBI-372273;
CC O76064; O43251: RBFOX2; NbExp=3; IntAct=EBI-373337, EBI-746056;
CC O76064; O43251-10: RBFOX2; NbExp=3; IntAct=EBI-373337, EBI-11963050;
CC O76064; O76064: RNF8; NbExp=6; IntAct=EBI-373337, EBI-373337;
CC O76064; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-373337, EBI-17247926;
CC O76064; Q9UH03: SEPTIN3; NbExp=7; IntAct=EBI-373337, EBI-727037;
CC O76064; Q8IVP1: SH3GL3; NbExp=3; IntAct=EBI-373337, EBI-6503765;
CC O76064; O75558: STX11; NbExp=6; IntAct=EBI-373337, EBI-714135;
CC O76064; Q9BSE2: TMEM79; NbExp=10; IntAct=EBI-373337, EBI-8649725;
CC O76064; Q15025: TNIP1; NbExp=3; IntAct=EBI-373337, EBI-357849;
CC O76064; Q6UXN7: TOMM20L; NbExp=3; IntAct=EBI-373337, EBI-11954062;
CC O76064; P62837: UBE2D2; NbExp=4; IntAct=EBI-373337, EBI-347677;
CC O76064; Q99986: VRK1; NbExp=2; IntAct=EBI-373337, EBI-1769146;
CC O76064; Q9Y3C0: WASHC3; NbExp=3; IntAct=EBI-373337, EBI-712969;
CC O76064; O00401: WASL; NbExp=8; IntAct=EBI-373337, EBI-957615;
CC O76064; Q96DT7-3: ZBTB10; NbExp=3; IntAct=EBI-373337, EBI-12017160;
CC O76064; Q9UL40: ZNF346; NbExp=3; IntAct=EBI-373337, EBI-2462313;
CC O76064; Q96IT1: ZNF496; NbExp=3; IntAct=EBI-373337, EBI-743906;
CC O76064-1; Q14676: MDC1; NbExp=2; IntAct=EBI-15964690, EBI-495644;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067,
CC ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089,
CC ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:23233665}. Cytoplasm
CC {ECO:0000255|HAMAP-Rule:MF_03067}. Midbody {ECO:0000255|HAMAP-
CC Rule:MF_03067}. Chromosome, telomere {ECO:0000255|HAMAP-Rule:MF_03067}.
CC Note=Recruited at uncapped telomeres (By similarity). Following DNA
CC damage, such as double-strand breaks, recruited to the sites of damage
CC (PubMed:18001824, PubMed:18077395, PubMed:22266820, PubMed:23233665).
CC During prophase, concomitant with nuclear envelope breakdown, localizes
CC throughout the cell, with a dotted pattern. In telophase, again in the
CC nucleus and also with a discrete dotted pattern in the cytoplasm. In
CC late telophase and during cytokinesis, localizes in the midbody of the
CC tubulin bridge joining the daughter cells. Does not seem to be
CC associated with condensed chromosomes at any time during the cell
CC cycle. During spermatogenesis, sequestered in the cytoplasm by PIWIL1:
CC RNF8 is released following ubiquitination and degradation of PIWIL1.
CC {ECO:0000255|HAMAP-Rule:MF_03067, ECO:0000269|PubMed:18001824,
CC ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:22266820,
CC ECO:0000269|PubMed:23233665}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O76064-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O76064-2; Sequence=VSP_036671, VSP_037831;
CC Name=3;
CC IsoId=O76064-3; Sequence=VSP_054037, VSP_054038;
CC -!- TISSUE SPECIFICITY: Ubiquitous. In fetal tissues, highest expression in
CC brain, thymus and liver. In adult tissues, highest levels in brain and
CC testis, lowest levels in peripheral blood cells.
CC {ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:9852682}.
CC -!- DEVELOPMENTAL STAGE: Low levels at the G1-S boundary increase in
CC intensity during S phase and until the end of the G2 phase. Abruptly
CC decreases in late mitosis (at protein level). Barely detectable in
CC anaphase. {ECO:0000269|PubMed:17724460}.
CC -!- DOMAIN: The FHA domain specifically recognizes and binds ATM-
CC phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2
CC (PubMed:18001824). This domain is required for proper recruitment to
CC DNA damage sites after UV irradiation, ionizing radiation, or treatment
CC with an alkylating agent (PubMed:23233665).
CC {ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:23233665}.
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 ECO:0000269|PubMed:16215985}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the RNF8 family. {ECO:0000255|HAMAP-
CC Rule:MF_03067}.
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 (PubMed:19203578 and
CC PubMed:19203579). However, other data suggest that RNF168 is the
CC priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13'
CC and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub
CC respectively) (PubMed:22980979). These data suggest that RNF168 might
CC be recruited to DSBs sites in a RNF8-dependent manner by binding to
CC non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates
CC monoubiquitination of H2A, which is then amplified by RNF8
CC (PubMed:22980979). Additional evidence is however required to confirm
CC these data. {ECO:0000255|HAMAP-Rule:MF_03067,
CC ECO:0000305|PubMed:22980979}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31621.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG60572.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=EAX03945.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AB012770; BAA33557.1; -; Genomic_DNA.
DR EMBL; AF334675; AAQ14887.1; -; mRNA.
DR EMBL; AB014546; BAA31621.2; ALT_INIT; mRNA.
DR EMBL; AK298319; BAG60572.1; ALT_SEQ; mRNA.
DR EMBL; BT007446; AAP36114.1; -; mRNA.
DR EMBL; AK222765; BAD96485.1; -; mRNA.
DR EMBL; AL096712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03944.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03945.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC007517; AAH07517.1; -; mRNA.
DR CCDS; CCDS4833.1; -. [O76064-3]
DR CCDS; CCDS4834.1; -. [O76064-1]
DR RefSeq; NP_003949.1; NM_003958.3. [O76064-1]
DR RefSeq; NP_898901.1; NM_183078.2. [O76064-3]
DR PDB; 2CSW; NMR; -; A=8-139.
DR PDB; 2PIE; X-ray; 1.35 A; A=13-146.
DR PDB; 4AYC; X-ray; 1.90 A; A/B=351-485.
DR PDB; 4ORH; X-ray; 4.80 A; C/G/H/K/L=345-485.
DR PDB; 4WHV; X-ray; 8.30 A; C/D/I/J=345-485.
DR PDBsum; 2CSW; -.
DR PDBsum; 2PIE; -.
DR PDBsum; 4AYC; -.
DR PDBsum; 4ORH; -.
DR PDBsum; 4WHV; -.
DR AlphaFoldDB; O76064; -.
DR BMRB; O76064; -.
DR SASBDB; O76064; -.
DR SMR; O76064; -.
DR BioGRID; 114492; 121.
DR CORUM; O76064; -.
DR DIP; DIP-31265N; -.
DR IntAct; O76064; 78.
DR MINT; O76064; -.
DR STRING; 9606.ENSP00000362578; -.
DR iPTMnet; O76064; -.
DR PhosphoSitePlus; O76064; -.
DR BioMuta; RNF8; -.
DR EPD; O76064; -.
DR jPOST; O76064; -.
DR MassIVE; O76064; -.
DR MaxQB; O76064; -.
DR PaxDb; O76064; -.
DR PeptideAtlas; O76064; -.
DR PRIDE; O76064; -.
DR ProteomicsDB; 50370; -. [O76064-1]
DR ProteomicsDB; 50371; -. [O76064-2]
DR Antibodypedia; 15585; 336 antibodies from 38 providers.
DR DNASU; 9025; -.
DR Ensembl; ENST00000229866.10; ENSP00000229866.6; ENSG00000112130.17. [O76064-2]
DR Ensembl; ENST00000373479.9; ENSP00000362578.4; ENSG00000112130.17. [O76064-1]
DR Ensembl; ENST00000469731.5; ENSP00000418879.1; ENSG00000112130.17. [O76064-3]
DR GeneID; 9025; -.
DR KEGG; hsa:9025; -.
DR MANE-Select; ENST00000373479.9; ENSP00000362578.4; NM_003958.4; NP_003949.1.
DR UCSC; uc003onq.4; human. [O76064-1]
DR CTD; 9025; -.
DR DisGeNET; 9025; -.
DR GeneCards; RNF8; -.
DR HGNC; HGNC:10071; RNF8.
DR HPA; ENSG00000112130; Low tissue specificity.
DR MIM; 611685; gene.
DR neXtProt; NX_O76064; -.
DR OpenTargets; ENSG00000112130; -.
DR PharmGKB; PA34445; -.
DR VEuPathDB; HostDB:ENSG00000112130; -.
DR eggNOG; KOG3872; Eukaryota.
DR GeneTree; ENSGT00400000022349; -.
DR HOGENOM; CLU_023453_1_0_1; -.
DR InParanoid; O76064; -.
DR OMA; YCIKQWR; -.
DR OrthoDB; 1585372at2759; -.
DR PhylomeDB; O76064; -.
DR TreeFam; TF330957; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; O76064; -.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR SignaLink; O76064; -.
DR SIGNOR; O76064; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9025; 373 hits in 1127 CRISPR screens.
DR ChiTaRS; RNF8; human.
DR EvolutionaryTrace; O76064; -.
DR GeneWiki; RNF8; -.
DR GenomeRNAi; 9025; -.
DR Pharos; O76064; Tbio.
DR PRO; PR:O76064; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O76064; protein.
DR Bgee; ENSG00000112130; Expressed in cortical plate and 194 other tissues.
DR ExpressionAtlas; O76064; baseline and differential.
DR Genevisible; O76064; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0043486; P:histone exchange; ISS:UniProtKB.
DR GO; GO:0070535; P:histone H2A K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; IDA:UniProtKB.
DR GO; GO:0033523; P:histone H2B ubiquitination; ISS:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; TAS:UniProtKB.
DR GO; GO:0045190; P:isotype switching; ISS:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR HAMAP; MF_03067; RNF8; 1.
DR IDEAL; IID00118; -.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR017335; RNF8.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00498; FHA; 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 3D-structure; Alternative splicing; Cell cycle; Cell division;
KW Chromatin regulator; Chromosome; Cytoplasm; Direct protein sequencing;
KW DNA damage; DNA repair; Host-virus interaction; Metal-binding; Mitosis;
KW Nucleus; Phosphoprotein; Reference proteome; Telomere; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..485
FT /note="E3 ubiquitin-protein ligase RNF8"
FT /id="PRO_0000056048"
FT DOMAIN 38..92
FT /note="FHA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT ZN_FING 403..441
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 REGION 181..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 81..98
FT /note="SLNGVWLNRARLEPLRVY -> SFPSEKAEDFTAAGERFL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036671"
FT VAR_SEQ 99..485
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037831"
FT VAR_SEQ 413..448
FT /note="AVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSKT -> QRDCSEDRALRA
FT FERLPGSASLRWSGGFSLAVTPLL (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054037"
FT VAR_SEQ 449..485
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054038"
FT VARIANT 162
FT /note="A -> T (in dbSNP:rs34338974)"
FT /id="VAR_052096"
FT VARIANT 473
FT /note="I -> V (in dbSNP:rs1139944)"
FT /id="VAR_052097"
FT MUTAGEN 42
FT /note="R->A: Abolishes interaction with ATM-phosphorylated
FT MDC1. Abolishes interaction with human herpesvirus 1 ICP0.
FT Abolishes recruitment to DNA damage sites after UV
FT irradiation, ionizing radiation, or treatment with an
FT alkylating agent."
FT /evidence="ECO:0000269|PubMed:18001824,
FT ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:22405594,
FT ECO:0000269|PubMed:23233665"
FT MUTAGEN 403
FT /note="C->S: Marked reduction of E2-dependent
FT ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-
FT binding. Loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:11322894,
FT ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:16215985,
FT ECO:0000269|PubMed:18001824"
FT MUTAGEN 405
FT /note="I->A: Impairs interaction with UBE2L6/UBCH8 and
FT ability to mediate 'Lys-48'-linked ubiquitination E3 ligase
FT activity, while it still catalyzes 'Lys-63'-linked
FT ubiquitination and still interacts with UBE2N/UBC13."
FT /evidence="ECO:0000269|PubMed:21911360,
FT ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22589545"
FT MUTAGEN 406
FT /note="C->S: Abolishes ubiquitin-ligase activity."
FT /evidence="ECO:0000269|PubMed:21857671"
FT MUTAGEN 443
FT /note="D->R: Does not affect the monomeric structure but
FT abolishes ability to monoubiquitinate H2A in nucleosomes."
FT /evidence="ECO:0000269|PubMed:22980979"
FT CONFLICT 230
FT /note="V -> A (in Ref. 6; BAD96485)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="K -> R (in Ref. 6; BAD96485)"
FT /evidence="ECO:0000305"
FT STRAND 16..22
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 38..49
FT /evidence="ECO:0007829|PDB:2PIE"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:2CSW"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:2PIE"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:2PIE"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:2PIE"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:2PIE"
FT HELIX 351..400
FT /evidence="ECO:0007829|PDB:4AYC"
FT TURN 404..406
FT /evidence="ECO:0007829|PDB:4AYC"
FT STRAND 411..416
FT /evidence="ECO:0007829|PDB:4AYC"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:4AYC"
FT HELIX 424..430
FT /evidence="ECO:0007829|PDB:4AYC"
FT TURN 431..433
FT /evidence="ECO:0007829|PDB:4AYC"
FT TURN 438..440
FT /evidence="ECO:0007829|PDB:4AYC"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:4AYC"
FT HELIX 451..461
FT /evidence="ECO:0007829|PDB:4AYC"
FT HELIX 466..480
FT /evidence="ECO:0007829|PDB:4AYC"
SQ SEQUENCE 485 AA; 55518 MW; 54650B2FFC9948B1 CRC64;
MGEPGFFVTG DRAGGRSWCL RRVGMSAGWL LLEDGCEVTV GRGFGVTYQL VSKICPLMIS
RNHCVLKQNP EGQWTIMDNK SLNGVWLNRA RLEPLRVYSI HQGDYIQLGV PLENKENAEY
EYEVTEEDWE TIYPCLSPKN DQMIEKNKEL RTKRKFSLDE LAGPGAEGPS NLKSKINKVS
CESGQPVKSQ GKGEVASTPS DNLDPKLTAL EPSKTTGAPI YPGFPKVTEV HHEQKASNSS
ASQRSLQMFK VTMSRILRLK IQMQEKHEAV MNVKKQTQKG NSKKVVQMEQ ELQDLQSQLC
AEQAQQQARV EQLEKTFQEE EQHLQGLEIA QGEKDLKQQL AQALQEHWAL MEELNRSKKD
FEAIIQAKNK ELEQTKEEKE KMQAQKEEVL SHMNDVLENE LQCIICSEYF IEAVTLNCAH
SFCSYCINEW MKRKIECPIC RKDIKSKTYS LVLDNCINKM VNNLSSEVKE RRIVLIRERK
AKRLF
