CTIP_HUMAN
ID CTIP_HUMAN Reviewed; 897 AA.
AC Q99708; A6NKN2; A8K8W6; E7ETY1; O75371; Q8NHQ3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=DNA endonuclease RBBP8;
DE EC=3.1.-.-;
DE AltName: Full=CtBP-interacting protein;
DE Short=CtIP;
DE AltName: Full=Retinoblastoma-binding protein 8;
DE Short=RBBP-8;
DE AltName: Full=Retinoblastoma-interacting protein and myosin-like;
DE Short=RIM;
DE AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog;
DE Short=SAE2;
GN Name=RBBP8; Synonyms=CTIP;
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 [MRNA] (ISOFORM 1), AND INTERACTION WITH RB1.
RX PubMed=9721205; DOI=10.1006/geno.1998.5368;
RA Fusco C., Reymond A., Zervos A.S.;
RT "Molecular cloning and characterization of a novel retinoblastoma-binding
RT protein.";
RL Genomics 51:351-358(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH CTBP1.
RX PubMed=9535825; DOI=10.1074/jbc.273.15.8549;
RA Schaeper U., Subramanian T., Lim L., Boyd J.M., Chinnadurai G.;
RT "Interaction between a cellular protein that binds to the C-terminal region
RT of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A
RT through a conserved PLDLS motif.";
RL J. Biol. Chem. 273:8549-8552(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Endometrial cancer;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRCA1.
RX PubMed=10764811; DOI=10.1074/jbc.m909494199;
RA Yu X., Baer R.;
RT "Nuclear localization and cell cycle-specific expression of CtIP, a protein
RT that associates with the BRCA1 tumor suppressor.";
RL J. Biol. Chem. 275:18541-18549(2000).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-664 AND SER-745, AND MUTAGENESIS OF
RP SER-664 AND SER-745.
RX PubMed=10910365; DOI=10.1038/35018134;
RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., Lee E.Y.-H.P.,
RA Lee W.-H.;
RT "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA
RT damage response.";
RL Nature 406:210-215(2000).
RN [10]
RP INTERACTION WITH LMO4.
RX PubMed=11751867; DOI=10.1074/jbc.m110603200;
RA Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J., Visvader J.E.;
RT "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor
RT suppressor BRCA1 and inhibits BRCA1 activity.";
RL J. Biol. Chem. 277:7849-7856(2002).
RN [11]
RP INTERACTION WITH SIAH1, AND UBIQUITINATION.
RX PubMed=14654780; DOI=10.1038/sj.onc.1206994;
RA Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A.,
RA Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F.,
RA Bruzzoni-Giovanelli H.;
RT "SIAH-1 interacts with CtIP and promotes its degradation by the proteasome
RT pathway.";
RL Oncogene 22:8845-8851(2003).
RN [12]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15084581; DOI=10.1074/jbc.m313974200;
RA Dubin M.J., Stokes P.H., Sum E.Y., Williams R.S., Valova V.A.,
RA Robinson P.J., Lindeman G.J., Glover J.N., Visvader J.E., Matthews J.M.;
RT "Dimerization of CtIP, a BRCA1- and CtBP-interacting protein, is mediated
RT by an N-terminal coiled-coil motif.";
RL J. Biol. Chem. 279:26932-26938(2004).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT SER-327, INTERACTION WITH BRCA1, AND
RP MUTAGENESIS OF SER-327.
RX PubMed=15485915; DOI=10.1128/mcb.24.21.9478-9486.2004;
RA Yu X., Chen J.;
RT "DNA damage-induced cell cycle checkpoint control requires CtIP, a
RT phosphorylation-dependent binding partner of BRCA1 C-terminal domains.";
RL Mol. Cell. Biol. 24:9478-9486(2004).
RN [14]
RP INTERACTION WITH BRCA1, FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, AND
RP MUTAGENESIS OF SER-327.
RX PubMed=16818604; DOI=10.1101/gad.1431006;
RA Yu X., Fu S., Lai M., Baer R., Chen J.;
RT "BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.";
RL Genes Dev. 20:1721-1726(2006).
RN [15]
RP FUNCTION.
RX PubMed=16581787; DOI=10.1128/mcb.26.8.3124-3134.2006;
RA Liu F., Lee W.H.;
RT "CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway
RT during G1/S progression.";
RL Mol. Cell. Biol. 26:3124-3134(2006).
RN [16]
RP DISEASE, AND TISSUE SPECIFICITY.
RX PubMed=18171986; DOI=10.1158/1541-7786.mcr-07-0126;
RA Wu M., Soler D.R., Abba M.C., Nunez M.I., Baer R., Hatzis C.,
RA Llombart-Cussac A., Llombart-Bosch A., Aldaz C.M.;
RT "CtIP silencing as a novel mechanism of tamoxifen resistance in breast
RT cancer.";
RL Mol. Cancer Res. 5:1285-1295(2007).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT SER-326; SER-349 AND SER-679, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH BRCA1; MRE11 AND RAD50.
RX PubMed=17965729; DOI=10.1038/nature06337;
RA Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J., Baer R.,
RA Lukas J., Jackson S.P.;
RT "Human CtIP promotes DNA end resection.";
RL Nature 450:509-514(2007).
RN [18]
RP ASSOCIATION WITH OVARIAN CANCER SURVIVAL.
RX PubMed=19270026; DOI=10.1093/hmg/ddp107;
RA Quaye L., Dafou D., Ramus S.J., Song H., Gentry-Maharaj A., Notaridou M.,
RA Hogdall E., Kjaer S.K., Christensen L., Hogdall C., Easton D.F., Jacobs I.,
RA Menon U., Pharoah P.D., Gayther S.A.;
RT "Functional complementation studies identify candidate genes and common
RT genetic variants associated with ovarian cancer survival.";
RL Hum. Mol. Genet. 18:1869-1878(2009).
RN [19]
RP FUNCTION, DNA-BINDING, PHOSPHORYLATION AT THR-847, AND MUTAGENESIS OF
RP THR-847.
RX PubMed=19202191; DOI=10.1074/jbc.m808906200;
RA Huertas P., Jackson S.P.;
RT "Human CtIP mediates cell cycle control of DNA end resection and double
RT strand break repair.";
RL J. Biol. Chem. 284:9558-9565(2009).
RN [20]
RP FUNCTION, INTERACTION WITH MRE11; RAD50 AND NBN, AND MUTAGENESIS OF HIS-31;
RP VAL-35; LYS-41 AND LEU-45.
RX PubMed=19759395; DOI=10.1074/jbc.m109.023424;
RA Yuan J., Chen J.;
RT "N terminus of CtIP is critical for homologous recombination-mediated
RT double-strand break repair.";
RL J. Biol. Chem. 284:31746-31752(2009).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF LYS-513 AND LYS-515.
RX PubMed=20064462; DOI=10.1016/j.molcel.2009.12.002;
RA You Z., Shi L.Z., Zhu Q., Wu P., Zhang Y.W., Basilio A., Tonnu N.,
RA Verma I.M., Berns M.W., Hunter T.;
RT "CtIP links DNA double-strand break sensing to resection.";
RL Mol. Cell 36:954-969(2009).
RN [22]
RP IDENTIFICATION BY 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP RETRACTED PAPER.
RX PubMed=20829486; DOI=10.1126/science.1192049;
RA Kaidi A., Weinert B.T., Choudhary C., Jackson S.P.;
RT "Human SIRT6 promotes DNA end resection through CtIP deacetylation.";
RL Science 329:1348-1353(2010).
RN [25]
RP RETRACTION NOTICE OF PUBMED:20829486.
RX PubMed=30975768; DOI=10.1126/science.aax4558;
RA Kaidi A., Weinert B.T., Choudhary C., Jackson S.P.;
RL Science 364:247-247(2019).
RN [26]
RP ASSOCIATION WITH BREAST CANCER.
RX PubMed=21799032; DOI=10.1158/0008-5472.can-11-0773;
RA Rebbeck T.R., Mitra N., Domchek S.M., Wan F., Friebel T.M., Tran T.V.,
RA Singer C.F., Tea M.K., Blum J.L., Tung N., Olopade O.I., Weitzel J.N.,
RA Lynch H.T., Snyder C.L., Garber J.E., Antoniou A.C., Peock S., Evans D.G.,
RA Paterson J., Kennedy M.J., Donaldson A., Dorkins H., Easton D.F.,
RA Rubinstein W.S., Daly M.B., Isaacs C., Nevanlinna H., Couch F.J.,
RA Andrulis I.L., Freidman E., Laitman Y., Ganz P.A., Tomlinson G.E.,
RA Neuhausen S.L., Narod S.A., Phelan C.M., Greenberg R., Nathanson K.L.;
RT "Modification of BRCA1-associated breast and ovarian cancer risk by BRCA1-
RT interacting genes.";
RL Cancer Res. 71:5792-5805(2011).
RN [27]
RP INVOLVEMENT IN JWDS, AND INVOLVEMENT IN SCKL2.
RX PubMed=21998596; DOI=10.1371/journal.pgen.1002310;
RA Jackson S.P., Borglum A.D.;
RT "CtIP mutations cause Seckel and Jawad syndromes.";
RL PLoS Genet. 7:E1002310-E1002310(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; THR-315; SER-327;
RP SER-379 AND SER-723, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [29]
RP INTERACTION WITH BRCA1; MRE11 AND PIN1, SUBCELLULAR LOCATION, MUTAGENESIS
RP OF SER-276 AND THR-315, AND PHOSPHORYLATION AT SER-276 AND THR-315.
RX PubMed=23623683; DOI=10.1016/j.molcel.2013.03.023;
RA Steger M., Murina O., Huehn D., Ferretti L.P., Walser R., Haenggi K.,
RA Lafranchi L., Neugebauer C., Paliwal S., Janscak P., Gerrits B.,
RA Del Sal G., Zerbe O., Sartori A.A.;
RT "Prolyl isomerase PIN1 regulates DNA double-strand break repair by
RT counteracting DNA end resection.";
RL Mol. Cell 50:333-343(2013).
RN [30]
RP INTERACTION WITH FZR1, SUBCELLULAR LOCATION, INDUCTION DURING THE CELL
RP CYCLE, AND MUTAGENESIS OF LYS-179 AND LYS-467.
RX PubMed=25349192; DOI=10.15252/embj.201489017;
RA Lafranchi L., de Boer H.R., de Vries E.G., Ong S.E., Sartori A.A.,
RA van Vugt M.A.;
RT "APC/C(Cdh1) controls CtIP stability during the cell cycle and in response
RT to DNA damage.";
RL EMBO J. 33:2860-2879(2014).
RN [31]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-869, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [32]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-193; LYS-378; LYS-604; LYS-613
RP AND LYS-869, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [33]
RP INTERACTION WITH CUL3 AND KLHL15, UBIQUITINATION, AND MUTAGENESIS OF
RP SER-276; THR-315; LYS-467; ARG-839; PHE-840 AND TYR-842.
RX PubMed=27561354; DOI=10.1038/ncomms12628;
RA Ferretti L.P., Himmels S.F., Trenner A., Walker C., von Aesch C.,
RA Eggenschwiler A., Murina O., Enchev R.I., Peter M., Freire R., Porro A.,
RA Sartori A.A.;
RT "Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-
RT tune DNA-end resection.";
RL Nat. Commun. 7:12628-12628(2016).
RN [34]
RP FUNCTION, AND INTERACTION WITH HDGFL2.
RX PubMed=26721387; DOI=10.1093/nar/gkv1526;
RA Baude A., Aaes T.L., Zhai B., Al-Nakouzi N., Oo H.Z., Daugaard M.,
RA Rohde M., Jaeaettelae M.;
RT "Hepatoma-derived growth factor-related protein 2 promotes DNA repair by
RT homologous recombination.";
RL Nucleic Acids Res. 44:2214-2226(2016).
RN [35]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-115; LYS-193; LYS-360;
RP LYS-378; LYS-396; LYS-404; LYS-410; LYS-438; LYS-449; LYS-526; LYS-530;
RP LYS-572; LYS-578; LYS-604; LYS-613; LYS-638; LYS-640; LYS-676; LYS-719;
RP LYS-782 AND LYS-869, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [36]
RP VARIANT SCKL2 TRP-100.
RX PubMed=24389050; DOI=10.1101/gr.160572.113;
RA Shaheen R., Faqeih E., Ansari S., Abdel-Salam G., Al-Hassnan Z.N.,
RA Al-Shidi T., Alomar R., Sogaty S., Alkuraya F.S.;
RT "Genomic analysis of primordial dwarfism reveals novel disease genes.";
RL Genome Res. 24:291-299(2014).
RN [37]
RP UBIQUITINATION, INTERACTION WITH RNF138, AND MUTAGENESIS OF LYS-62; LYS-78;
RP LYS-115; LYS-132; LYS-133; LYS-404; LYS-572; LYS-578; LYS-640; LYS-759;
RP LYS-760 AND LYS-782.
RX PubMed=26502057; DOI=10.1038/ncb3260;
RA Schmidt C.K., Galanty Y., Sczaniecka-Clift M., Coates J., Jhujh S.,
RA Demir M., Cornwell M., Beli P., Jackson S.P.;
RT "Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA
RT repair.";
RL Nat. Cell Biol. 17:1458-1470(2015).
RN [38]
RP INTERACTION WITH EXD2.
RX PubMed=26807646; DOI=10.1038/ncb3303;
RA Broderick R., Nieminuszczy J., Baddock H.T., Deshpande R.A., Gileadi O.,
RA Paull T.T., McHugh P.J., Niedzwiedz W.;
RT "EXD2 promotes homologous recombination by facilitating DNA end
RT resection.";
RL Nat. Cell Biol. 18:271-280(2016).
RN [39]
RP INTERACTION WITH SAMHD1.
RX PubMed=28834754; DOI=10.1016/j.celrep.2017.08.008;
RA Daddacha W., Koyen A.E., Bastien A.J., Head P.E., Dhere V.R., Nabeta G.N.,
RA Connolly E.C., Werner E., Madden M.Z., Daly M.B., Minten E.V., Whelan D.R.,
RA Schlafstein A.J., Zhang H., Anand R., Doronio C., Withers A.E., Shepard C.,
RA Sundaram R.K., Deng X., Dynan W.S., Wang Y., Bindra R.S., Cejka P.,
RA Rothenberg E., Doetsch P.W., Kim B., Yu D.S.;
RT "SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous
RT recombination.";
RL Cell Rep. 20:1921-1935(2017).
RN [40]
RP INTERACTION WITH AUNIP, AND SUBCELLULAR LOCATION.
RX PubMed=29042561; DOI=10.1038/s41467-017-01151-w;
RA Lou J., Chen H., Han J., He H., Huen M.S.Y., Feng X.H., Liu T., Huang J.;
RT "AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous
RT recombination repair pathway.";
RL Nat. Commun. 8:985-985(2017).
CC -!- FUNCTION: Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN)
CC complex in DNA-end resection, the first step of double-strand break
CC (DSB) repair through the homologous recombination (HR) pathway
CC (PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462,
CC PubMed:26721387). HR is restricted to S and G2 phases of the cell cycle
CC and preferentially repairs DSBs resulting from replication fork
CC collapse (PubMed:17965729, PubMed:19202191). Key determinant of DSB
CC repair pathway choice, as it commits cells to HR by preventing
CC classical non-homologous end-joining (NHEJ) (PubMed:19202191).
CC Functions downstream of the MRN complex and ATM, promotes ATR
CC activation and its recruitment to DSBs in the S/G2 phase facilitating
CC the generation of ssDNA (PubMed:16581787, PubMed:17965729,
CC PubMed:19759395, PubMed:20064462). Component of the BRCA1-RBBP8 complex
CC that regulates CHEK1 activation and controls cell cycle G2/M
CC checkpoints on DNA damage (PubMed:15485915, PubMed:16818604). During
CC immunoglobulin heavy chain class-switch recombination, promotes
CC microhomology-mediated alternative end joining (A-NHEJ) and plays an
CC essential role in chromosomal translocations (By similarity).
CC {ECO:0000250|UniProtKB:Q80YR6, ECO:0000269|PubMed:15485915,
CC ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191,
CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462,
CC ECO:0000269|PubMed:26721387}.
CC -!- SUBUNIT: Homodimer; dimerizes via the coiled coil domain
CC (PubMed:15084581). Interacts (via the PXDLS motif) with CTBP1; the
CC interaction is disrupted via binding of the adenovirus E1A to CTBP1
CC (PubMed:9535825). Component of the BRCA1-RBBP8 complex. Interacts (the
CC Ser-327 phosphorylated form) with BRCA1 (via the C-terminal BRCA1
CC domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8
CC and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA
CC damage (PubMed:10764811, PubMed:15485915, PubMed:16818604,
CC PubMed:17965729, PubMed:23623683). Interacts with RB1 (PubMed:9721205).
CC Interacts with the MRN complex. Interacts directly with MRE11; the
CC interaction is required for efficient homologous recombination (HR) and
CC regulation of the MRN complex (PubMed:19759395, PubMed:23623683).
CC Interacts directly with RAD50 (PubMed:19759395). Interacts directly
CC with NBN (PubMed:19759395). Interacts with LM04 (via the LIM zinc-
CC binding 1 domain) (PubMed:11751867). Interacts with SIAH1
CC (PubMed:14654780). Interacts with RNF138 (PubMed:26502057). Interacts
CC with EXD2 (PubMed:26807646). Interacts with CUL3 and KLHL15; this
CC interaction leads to RBBP8 proteasomal degradation (PubMed:27561354).
CC Directly interacts with PIN1; this interaction depends upon RBBP8
CC phosphorylation, predominantly at Thr-315 (PubMed:23623683). Interacts
CC with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal
CC degradation (PubMed:25349192). Interacts with AUNIP; leading to recruit
CC RBBP8 to sites of DNA damage (PubMed:29042561, PubMed:10764811,
CC PubMed:11751867, PubMed:14654780, PubMed:15084581, PubMed:15485915,
CC PubMed:16818604, PubMed:17965729, PubMed:19759395, PubMed:23623683,
CC PubMed:25349192, PubMed:26502057, PubMed:26807646, PubMed:27561354,
CC PubMed:9535825, PubMed:9721205). Interacts with SAMHD1
CC (PubMed:28834754). Interacts with HDGFL2 (PubMed:26721387).
CC {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:11751867,
CC ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15084581,
CC ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19759395,
CC ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:25349192,
CC ECO:0000269|PubMed:26502057, ECO:0000269|PubMed:26721387,
CC ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:27561354,
CC ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:29042561,
CC ECO:0000269|PubMed:9535825, ECO:0000269|PubMed:9721205}.
CC -!- INTERACTION:
CC Q99708; P38398: BRCA1; NbExp=12; IntAct=EBI-745715, EBI-349905;
CC Q99708; Q9NVH0: EXD2; NbExp=3; IntAct=EBI-745715, EBI-11324738;
CC Q99708; Q9UQ84: EXO1; NbExp=4; IntAct=EBI-745715, EBI-944667;
CC Q99708; P49959: MRE11; NbExp=3; IntAct=EBI-745715, EBI-396513;
CC Q99708; O60934: NBN; NbExp=2; IntAct=EBI-745715, EBI-494844;
CC Q99708; O75475: PSIP1; NbExp=4; IntAct=EBI-745715, EBI-1801773;
CC Q99708; P06400: RB1; NbExp=2; IntAct=EBI-745715, EBI-491274;
CC Q99708; Q99708: RBBP8; NbExp=4; IntAct=EBI-745715, EBI-745715;
CC Q99708-2; P25800: LMO1; NbExp=3; IntAct=EBI-10203615, EBI-8639312;
CC Q99708-2; P61968: LMO4; NbExp=3; IntAct=EBI-10203615, EBI-2798728;
CC Q99708-2; Q13526: PIN1; NbExp=3; IntAct=EBI-10203615, EBI-714158;
CC Q99708-2; Q08999: RBL2; NbExp=3; IntAct=EBI-10203615, EBI-971439;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10764811,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:23623683}. Chromosome
CC {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:29042561}. Note=Associates with sites of DNA damage
CC in S/G2 phase (PubMed:10764811, PubMed:25349192). Ubiquitinated RBBP8
CC binds to chromatin following DNA damage (PubMed:16818604).
CC {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:25349192}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q99708-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99708-2; Sequence=VSP_043220;
CC Name=3;
CC IsoId=Q99708-3; Sequence=VSP_045247, VSP_045248;
CC -!- TISSUE SPECIFICITY: Expressed in ER-positive breast cancer lines, but
CC tends to be down-regulated ER-negative cells (at protein level).
CC {ECO:0000269|PubMed:18171986}.
CC -!- INDUCTION: Expression is cell-cycle regulated. Levels increase as
CC dividing cells traverse the G1/S boundary (PubMed:18171986). The
CC protein is degraded by the proteasome pathway during mitotic exit. Also
CC degraded in response to DNA damage in G2 cells; this degradation is
CC mediated by the E3 FZR1/APC/C complex (PubMed:25349192).
CC {ECO:0000269|PubMed:18171986, ECO:0000269|PubMed:25349192}.
CC -!- DOMAIN: The PXDLS motif binds to a cleft in CtBP proteins.
CC -!- DOMAIN: The damage-recruitment motif is required for DNA binding and
CC translocation to sites of DNA damage.
CC -!- PTM: Hyperphosphorylation upon ionizing radiation results in
CC dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is
CC essential for the recruitment to DNA and the DNA repair function.
CC Phosphorylated on Ser-327 as cells enter G2 phase. This phosphorylation
CC is required for binding BRCA1 and for the G2/M DNA damage transition
CC checkpoint control. Phosphorylation at Thr-315, probably catalyzed by
CC CDK2, is required for PIN1-binding, while phosphorylation at Ser-276
CC serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is
CC cell-cycle dependent. It steadily increases during S phase, peaks at
CC late S/G2 phase, and drops at G1 (PubMed:23623683).
CC {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191,
CC ECO:0000269|PubMed:23623683}.
CC -!- PTM: Ubiquitinated (PubMed:14654780, PubMed:16818604, PubMed:27561354).
CC Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING
CC domain) does not lead to its proteasomal degradation but instead the
CC ubiquitinated RBBP8 binds to chromatin following DNA damage and may
CC play a role in G2/M checkpoint control (PubMed:16818604). Ubiquitinated
CC by RNF138 at its N-terminus (PubMed:26502057). Ubiquitinated through
CC 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to
CC proteasomal degradation (PubMed:27561354). Ubiquitinated by the E3
CC FZR1/APC/C complex; this modification leads to proteasomal degradation
CC (PubMed:25349192). {ECO:0000269|PubMed:14654780,
CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:25349192,
CC ECO:0000269|PubMed:26502057, ECO:0000269|PubMed:27561354}.
CC -!- DISEASE: Seckel syndrome 2 (SCKL2) [MIM:606744]: A rare autosomal
CC recessive disorder characterized by proportionate dwarfism of prenatal
CC onset associated with low birth weight, growth retardation, severe
CC microcephaly with a bird-headed like appearance, and intellectual
CC disability. {ECO:0000269|PubMed:21998596, ECO:0000269|PubMed:24389050}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Jawad syndrome (JWDS) [MIM:251255]: A syndrome characterized
CC by congenital microcephaly, moderately severe intellectual disability,
CC and symmetrical digital anomalies. Digital malformations of variable
CC degree include hallux valgus, syndactyly of toes 4 and 5, short fifth
CC fingers, single flexion crease of fifth fingers, polydactyly and
CC synpolydactyly. {ECO:0000269|PubMed:21998596}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=Genetic variability in RBBP8 is noted as a factor in
CC BRCA1-associated breast cancer risk (PubMed:21799032). Associated with
CC sensitivity to tamoxifen in certain breast cancer cell lines
CC (PubMed:18171986). {ECO:0000269|PubMed:18171986,
CC ECO:0000269|PubMed:21799032}.
CC -!- SIMILARITY: Belongs to the COM1/SAE2/CtIP family. {ECO:0000305}.
CC -!- CAUTION: Upon DNA damage, was shown to interact with SIRT6 resulting in
CC its deacetylation. However, this study was later retracted.
CC {ECO:0000305|PubMed:20829486, ECO:0000305|PubMed:30975768}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RBBP8ID42066ch18q11.html";
CC ---------------------------------------------------------------------------
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DR EMBL; AF043431; AAC34368.1; -; mRNA.
DR EMBL; U72066; AAC14371.1; -; mRNA.
DR EMBL; AK292481; BAF85170.1; -; mRNA.
DR EMBL; BX648221; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC091147; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471088; EAX01144.1; -; Genomic_DNA.
DR EMBL; BC030590; AAH30590.1; -; mRNA.
DR CCDS; CCDS11874.1; -. [Q99708-3]
DR CCDS; CCDS11875.1; -. [Q99708-1]
DR RefSeq; NP_002885.1; NM_002894.2. [Q99708-1]
DR RefSeq; NP_976036.1; NM_203291.1. [Q99708-1]
DR RefSeq; NP_976037.1; NM_203292.1. [Q99708-3]
DR RefSeq; XP_006722582.1; XM_006722519.2. [Q99708-1]
DR RefSeq; XP_006722583.1; XM_006722520.2. [Q99708-1]
DR RefSeq; XP_006722584.1; XM_006722521.2. [Q99708-1]
DR RefSeq; XP_011524434.1; XM_011526132.2. [Q99708-1]
DR PDB; 2L4Z; NMR; -; A=641-685.
DR PDB; 4D2H; X-ray; 1.90 A; A/B/C/D/E/F/G/H=18-52.
DR PDB; 7BGF; X-ray; 2.80 A; A/B=31-152.
DR PDBsum; 2L4Z; -.
DR PDBsum; 4D2H; -.
DR PDBsum; 7BGF; -.
DR AlphaFoldDB; Q99708; -.
DR SMR; Q99708; -.
DR BioGRID; 111867; 108.
DR ComplexPortal; CPX-4441; BRCA1-C complex.
DR CORUM; Q99708; -.
DR DIP; DIP-24244N; -.
DR ELM; Q99708; -.
DR IntAct; Q99708; 44.
DR MINT; Q99708; -.
DR STRING; 9606.ENSP00000382628; -.
DR iPTMnet; Q99708; -.
DR PhosphoSitePlus; Q99708; -.
DR BioMuta; RBBP8; -.
DR DMDM; 116242745; -.
DR EPD; Q99708; -.
DR jPOST; Q99708; -.
DR MassIVE; Q99708; -.
DR MaxQB; Q99708; -.
DR PaxDb; Q99708; -.
DR PeptideAtlas; Q99708; -.
DR PRIDE; Q99708; -.
DR ProteomicsDB; 1422; -.
DR ProteomicsDB; 78424; -. [Q99708-1]
DR ProteomicsDB; 78425; -. [Q99708-2]
DR Antibodypedia; 7316; 460 antibodies from 42 providers.
DR DNASU; 5932; -.
DR Ensembl; ENST00000327155.10; ENSP00000323050.5; ENSG00000101773.19. [Q99708-1]
DR Ensembl; ENST00000399722.6; ENSP00000382628.2; ENSG00000101773.19. [Q99708-1]
DR Ensembl; ENST00000399725.6; ENSP00000382630.2; ENSG00000101773.19. [Q99708-3]
DR GeneID; 5932; -.
DR KEGG; hsa:5932; -.
DR MANE-Select; ENST00000327155.10; ENSP00000323050.5; NM_002894.3; NP_002885.1.
DR UCSC; uc002ktw.4; human. [Q99708-1]
DR CTD; 5932; -.
DR DisGeNET; 5932; -.
DR GeneCards; RBBP8; -.
DR HGNC; HGNC:9891; RBBP8.
DR HPA; ENSG00000101773; Low tissue specificity.
DR MalaCards; RBBP8; -.
DR MIM; 251255; phenotype.
DR MIM; 604124; gene.
DR MIM; 606744; phenotype.
DR neXtProt; NX_Q99708; -.
DR OpenTargets; ENSG00000101773; -.
DR Orphanet; 313795; Jawad syndrome.
DR Orphanet; 808; Seckel syndrome.
DR PharmGKB; PA34255; -.
DR VEuPathDB; HostDB:ENSG00000101773; -.
DR eggNOG; ENOG502QTV5; Eukaryota.
DR GeneTree; ENSGT00530000063835; -.
DR HOGENOM; CLU_019262_0_0_1; -.
DR InParanoid; Q99708; -.
DR OMA; FKIPLCP; -.
DR PhylomeDB; Q99708; -.
DR TreeFam; TF106469; -.
DR PathwayCommons; Q99708; -.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; Q99708; -.
DR SIGNOR; Q99708; -.
DR BioGRID-ORCS; 5932; 660 hits in 1090 CRISPR screens.
DR ChiTaRS; RBBP8; human.
DR EvolutionaryTrace; Q99708; -.
DR GeneWiki; RBBP8; -.
DR GenomeRNAi; 5932; -.
DR Pharos; Q99708; Tbio.
DR PRO; PR:Q99708; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q99708; protein.
DR Bgee; ENSG00000101773; Expressed in choroid plexus epithelium and 182 other tissues.
DR ExpressionAtlas; Q99708; baseline and differential.
DR Genevisible; Q99708; HS.
DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0035861; C:site of double-strand break; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; IDA:BHF-UCL.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0000406; F:double-strand/single-strand DNA junction binding; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0070336; F:flap-structured DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IMP:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0000403; F:Y-form DNA binding; IBA:GO_Central.
DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IC:ComplexPortal.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0035825; P:homologous recombination; IC:ComplexPortal.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR IDEAL; IID00340; -.
DR InterPro; IPR019518; CtIP_N.
DR InterPro; IPR013882; Ctp1_C.
DR InterPro; IPR033594; RBBP8.
DR InterPro; IPR033316; RBBP8-like.
DR PANTHER; PTHR15107; PTHR15107; 1.
DR PANTHER; PTHR15107:SF4; PTHR15107:SF4; 1.
DR Pfam; PF10482; CtIP_N; 1.
DR Pfam; PF08573; SAE2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Chromosome;
KW Coiled coil; Disease variant; DNA damage; DNA repair; DNA-binding;
KW Dwarfism; Endonuclease; Hydrolase; Intellectual disability;
KW Isopeptide bond; Meiosis; Mitosis; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..897
FT /note="DNA endonuclease RBBP8"
FT /id="PRO_0000097179"
FT REGION 22..45
FT /note="Essential for binding to the MRN complex and for RPA
FT focus formation on DNA damage"
FT REGION 292..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..557
FT /note="Damage-recruitment motif"
FT REGION 704..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 873..897
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 28..157
FT /evidence="ECO:0000255"
FT MOTIF 490..494
FT /note="PXDLS motif"
FT MOTIF 840..842
FT /note="KLHL15-binding"
FT /evidence="ECO:0000269|PubMed:27561354"
FT COMPBIAS 305..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..462
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23623683"
FT MOD_RES 315
FT /note="Phosphothreonine; by CDK2"
FT /evidence="ECO:0000269|PubMed:23623683,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965729"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15485915,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965729"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 664
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:10910365"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965729"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 745
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:10910365"
FT MOD_RES 847
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:19202191"
FT CROSSLNK 62
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 115
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 193
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 360
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 378
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 396
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 404
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 410
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 449
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 526
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 530
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 572
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 578
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 604
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 613
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 638
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 640
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 676
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 719
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 782
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 869
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT VAR_SEQ 714
FT /note="S -> SMLFYI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043220"
FT VAR_SEQ 786..867
FT /note="RETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAEEREKKLASCSR
FT HRFRYIPPNTPENFWEVGFPSTQTCMERGY -> SIMQICQQKKEKRNWLPAQDTDSAT
FT FHPTHQRIFGKLVFLPLRLVWKEVILRKILILVLVQKDVSLTTQYFLQKARSRRHRR
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_045247"
FT VAR_SEQ 868..897
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_045248"
FT VARIANT 100
FT /note="R -> W (in SCKL2; dbSNP:rs373804633)"
FT /evidence="ECO:0000269|PubMed:24389050"
FT /id="VAR_075824"
FT VARIANT 357
FT /note="K -> N (in dbSNP:rs34678569)"
FT /id="VAR_051308"
FT VARIANT 387
FT /note="H -> Y (in dbSNP:rs1804732)"
FT /id="VAR_028308"
FT MUTAGEN 31
FT /note="H->A: No effect on RPA focus formation on DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:19759395"
FT MUTAGEN 35
FT /note="V->A: No effect on RPA focus formation on DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:19759395"
FT MUTAGEN 41
FT /note="K->A: No effect on RPA focus formation on DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:19759395"
FT MUTAGEN 45
FT /note="L->A: No effect on RPA focus formation on DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:19759395"
FT MUTAGEN 62
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640;
FT R-759; R-760 and R-782. In K5R; defects in ability to
FT promoting DNA resection and homologous recombination; when
FT associated with R-78; R-115; R-132 and R-133."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 78
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-115; R-132; R-133; R-404; R-572; R-578; R-640;
FT R-759; R-760 and R-782. In K5R; defects in ability to
FT promoting DNA resection and homologous recombination; when
FT associated with R-62; R-115; R-132 and R-133."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 115
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-132; R-133; R-404; R-572; R-578; R-640;
FT R-759; R-760 and R-782. In K5R; defects in ability to
FT promoting DNA resection and homologous recombination; when
FT associated with R-62; R-78; R-132 and R-133."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 132
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640;
FT R-759; R-760 and R-782. In K5R; defects in ability to
FT promoting DNA resection and homologous recombination; when
FT associated with R-62; R-78; R-115 and R-133."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 133
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640;
FT R-759; R-760 and R-782. In K5R; defects in ability to
FT promoting DNA resection and homologous recombination; when
FT associated with R-62; R-78; R-115 and R-132."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 179
FT /note="K->A: No effect on FZR1-binding."
FT /evidence="ECO:0000269|PubMed:25349192"
FT MUTAGEN 276
FT /note="S->A: No effect on PIN1-binding. Impaired PIN1-
FT binding, partially decreased CUL3/KLHL15-mediated
FT proteasomal degradation, no effect on BRCA1-, MRE11-, nor
FT on KLHL15-binding; when associated with A-315."
FT /evidence="ECO:0000269|PubMed:23623683,
FT ECO:0000269|PubMed:27561354"
FT MUTAGEN 315
FT /note="T->A: Decreased PIN1-binding. Impaired PIN1-binding,
FT partially decreased CUL3/KLHL15-mediated proteasomal
FT degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-
FT binding; when associated with A-276."
FT /evidence="ECO:0000269|PubMed:23623683,
FT ECO:0000269|PubMed:27561354"
FT MUTAGEN 327
FT /note="S->A: Abolishes BRCA1 interaction and
FT ubiquitination. No activation of CHEK1 after DNA damage."
FT /evidence="ECO:0000269|PubMed:15485915,
FT ECO:0000269|PubMed:16818604"
FT MUTAGEN 404
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-572; R-578; R-640;
FT R-759; R-760 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 467
FT /note="K->A: Impaired FZR1-binding and APC/C-mediated
FT polyubiquitination. Increased stability. No effect on
FT MRE11-binding, nor on CUL3/KLHL15-mediated proteasomal
FT degradation. No effect on DNA-en resection activity."
FT /evidence="ECO:0000269|PubMed:25349192,
FT ECO:0000269|PubMed:27561354"
FT MUTAGEN 513
FT /note="K->A: Abolishes damage recruitment capability."
FT /evidence="ECO:0000269|PubMed:20064462"
FT MUTAGEN 515
FT /note="K->A: Abolishes damage recruitment capability."
FT /evidence="ECO:0000269|PubMed:20064462"
FT MUTAGEN 572
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-578; R-640;
FT R-759; R-760 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 578
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-640;
FT R-759; R-760 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 640
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578;
FT R-759; R-760 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 664
FT /note="S->A: Abrogates dissociation of BRCA1."
FT /evidence="ECO:0000269|PubMed:10910365"
FT MUTAGEN 745
FT /note="S->A: Abrogates dissociation of BRCA1."
FT /evidence="ECO:0000269|PubMed:10910365"
FT MUTAGEN 759
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578;
FT R-640; R-760 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 760
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578;
FT R-640; R-759 and R-782."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 782
FT /note="K->R: In K12R; defects in ability to promoting DNA
FT resection and homologous recombination; when associated
FT with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578;
FT R-640; R-759 and R-760."
FT /evidence="ECO:0000269|PubMed:26502057"
FT MUTAGEN 839
FT /note="R->A: No effect on CUL3/KLHL15-mediated proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:27561354"
FT MUTAGEN 840
FT /note="F->A: Decreased CUL3/KLHL15-mediated proteasomal
FT degradation."
FT /evidence="ECO:0000269|PubMed:27561354"
FT MUTAGEN 842
FT /note="Y->A: Decreased interaction with KLHL15, decreased
FT polyubiquitination and CUL3/KLHL15-mediated proteasomal
FT degradation. No effect on DNA-end resection activity."
FT /evidence="ECO:0000269|PubMed:27561354"
FT MUTAGEN 842
FT /note="Y->F: No effect on KLHL15-binding, nor on
FT CUL3/KLHL15-mediated proteasomal degradation."
FT /evidence="ECO:0000269|PubMed:27561354"
FT MUTAGEN 847
FT /note="T->A: Impairs DNA resection."
FT /evidence="ECO:0000269|PubMed:19202191"
FT MUTAGEN 847
FT /note="T->E: Mimics constitutive phosphorylation."
FT /evidence="ECO:0000269|PubMed:19202191"
FT CONFLICT 4
FT /note="S -> L (in Ref. 1; AAC14371)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="H -> Q (in Ref. 4; BX648221)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="C -> Y (in Ref. 3; BAF85170)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="E -> G (in Ref. 3; BAF85170)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="D -> G (in Ref. 4; BX648221)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="K -> R (in Ref. 4; BX648221)"
FT /evidence="ECO:0000305"
FT CONFLICT 521
FT /note="L -> P (in Ref. 3; BAF85170)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="L -> P (in Ref. 4; BX648221)"
FT /evidence="ECO:0000305"
FT HELIX 18..50
FT /evidence="ECO:0007829|PDB:4D2H"
FT STRAND 648..650
FT /evidence="ECO:0007829|PDB:2L4Z"
FT HELIX 651..653
FT /evidence="ECO:0007829|PDB:2L4Z"
FT TURN 662..666
FT /evidence="ECO:0007829|PDB:2L4Z"
FT STRAND 677..679
FT /evidence="ECO:0007829|PDB:2L4Z"
FT CONFLICT Q99708-3:862
FT /note="S -> G (in Ref. 4; BX648221)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 897 AA; 101942 MW; E028DE56DE55C0F2 CRC64;
MNISGSSCGS PNSADTSSDF KDLWTKLKEC HDREVQGLQV KVTKLKQERI LDAQRLEEFF
TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR KKQQEFENIR QQNLKLITEL
MNERNTLQEE NKKLSEQLQQ KIENDQQHQA AELECEEDVI PDSPITAFSF SGVNRLRRKE
NPHVRYIEQT HTKLEHSVCA NEMRKVSKSS THPQHNPNEN EILVADTYDQ SQSPMAKAHG
TSSYTPDKSS FNLATVVAET LGLGVQEESE TQGPMSPLGD ELYHCLEGNH KKQPFEESTR
NTEDSLRFSD STSKTPPQEE LPTRVSSPVF GATSSIKSGL DLNTSLSPSL LQPGKKKHLK
TLPFSNTCIS RLEKTRSKSE DSALFTHHSL GSEVNKIIIQ SSNKQILINK NISESLGEQN
RTEYGKDSNT DKHLEPLKSL GGRTSKRKKT EEESEHEVSC PQASFDKENA FPFPMDNQFS
MNGDCVMDKP LDLSDRFSAI QRQEKSQGSE TSKNKFRQVT LYEALKTIPK GFSSSRKASD
GNCTLPKDSP GEPCSQECII LQPLNKCSPD NKPSLQIKEE NAVFKIPLRP RESLETENVL
DDIKSAGSHE PIKIQTRSDH GGCELASVLQ LNPCRTGKIK SLQNNQDVSF ENIQWSIDPG
ADLSQYKMDV TVIDTKDGSQ SKLGGETVDM DCTLVSETVL LKMKKQEQKG EKSSNEERKM
NDSLEDMFDR TTHEEYESCL ADSFSQAADE EEELSTATKK LHTHGDKQDK VKQKAFVEPY
FKGDERETSL QNFPHIEVVR KKEERRKLLG HTCKECEIYY ADMPAEEREK KLASCSRHRF
RYIPPNTPEN FWEVGFPSTQ TCMERGYIKE DLDPCPRPKR RQPYNAIFSP KGKEQKT
