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 27-MAR-2024, entry version 207. 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). RN [41] RP FUNCTION, SUBUNIT, PHOSPHORYLATION, AND MUTAGENESIS OF LEU-27 AND ARG-839. RX PubMed=30601117; DOI=10.7554/elife.42129; RA Wilkinson O.J., Martin-Gonzalez A., Kang H., Northall S.J., Wigley D.B., RA Moreno-Herrero F., Dillingham M.S.; RT "CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA RT end structures for double-strand break repair."; RL Elife 8:0-0(2019). RN [42] RP UBIQUITINATION, AND MUTAGENESIS OF TYR-842. RX PubMed=35219381; DOI=10.1016/j.molcel.2022.01.020; RA Zhang C., Zhou B., Gu F., Liu H., Wu H., Yao F., Zheng H., Fu H., Chong W., RA Cai S., Huang M., Ma X., Guo Z., Li T., Deng W., Zheng M., Ji Q., Zhao Y., RA Ma Y., Wang Q.E., Tang T.S., Guo C.; RT "Micropeptide PACMP inhibition elicits synthetic lethal effects by RT decreasing CtIP and poly(ADP-ribosyl)ation."; RL Mol. Cell 82:1297-1312(2022). RN [43] {ECO:0007744|PDB:2L4Z} RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 322-333 IN PHOSPHORYLATED FORM IN RP COMPLEX WITH BRCA1, AND INTERACTION WITH BRCA1. RX PubMed=16101277; DOI=10.1021/bi0509651; RA Varma A.K., Brown R.S., Birrane G., Ladias J.A.; RT "Structural basis for cell cycle checkpoint control by the BRCA1-CtIP RT complex."; RL Biochemistry 44:10941-10946(2005). RN [44] {ECO:0007744|PDB:2L4Z} RP STRUCTURE BY NMR OF 641-685 IN COMPLEX WITH MOUSE LMO4, AND INTERACTION RP WITH LMO4. RX PubMed=23353824; DOI=10.1016/j.jmb.2013.01.017; RA Stokes P.H., Liew C.W., Kwan A.H., Foo P., Barker H.E., Djamirze A., RA O'Reilly V., Visvader J.E., Mackay J.P., Matthews J.M.; RT "Structural basis of the interaction of the breast cancer oncogene LMO4 RT with the tumour suppressor CtIP/RBBP8."; RL J. Mol. Biol. 425:1101-1110(2013). RN [45] {ECO:0007744|PDB:4D2H} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 18-52, SUBUNIT, INTERACTION WITH RP MRE11; NBN AND RAD50, ZN(2+)-BINDING, AND MUTAGENESIS OF LEU-27; CYS-89 AND RP CYS-92. RX PubMed=25558984; DOI=10.1038/nsmb.2937; RA Davies O.R., Forment J.V., Sun M., Belotserkovskaya R., Coates J., RA Galanty Y., Demir M., Morton C.R., Rzechorzek N.J., Jackson S.P., RA Pellegrini L.; RT "CtIP tetramer assembly is required for DNA-end resection and repair."; RL Nat. Struct. Mol. Biol. 22:150-157(2015). RN [46] {ECO:0007744|PDB:7BGF} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 31-152 OF MUTANT ALA-89 AND RP ALA-93, AND SUBUNIT. RX PubMed=34129781; DOI=10.1098/rsob.210060; RA Morton C.R., Rzechorzek N.J., Maman J.D., Kuramochi M., Sekiguchi H., RA Rambo R., Sasaki Y.C., Davies O.R., Pellegrini L.; RT "Structural basis for the coiled-coil architecture of human CtIP."; RL Open Biol. 11:210060-210060(2021). 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). Binds CC preferentially to DNA Y-junctions and to DNA substrates with blocked CC ends and promotes intermolecular DNA bridging (PubMed:30601117). 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, ECO:0000269|PubMed:30601117}. CC -!- SUBUNIT: Homotetramer; formed by antiparallel association of helical CC extensions protruding from the N-termini of two parallel coiled-coil CC dimers (PubMed:25558984, PubMed:34129781, PubMed:30601117, CC PubMed:15084581). Forms a dumbbell-shaped particle in which polar CC globular domains are held about 30 nm apart by a central rod CC (PubMed:30601117). Homotetramerization is required for DNA-end CC resection and repair (PubMed:25558984). Interacts (via the PXDLS motif) CC with CTBP1; the interaction is disrupted via binding of the adenovirus CC E1A to CTBP1 (PubMed:9535825). Component of the BRCA1-RBBP8 complex. CC Interacts (the Ser-327 phosphorylated form) with BRCA1 (via the C- CC terminal BRCT domains): the interaction occurs in the G2 phase, CC ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M CC checkpoint control on DNA damage (PubMed:10764811, PubMed:15485915, CC PubMed:16818604, PubMed:17965729, PubMed:23623683, PubMed:16101277). CC Interacts with RB1 (PubMed:9721205). Interacts with the MRN complex. CC Interacts directly with MRE11; the interaction is required for CC efficient homologous recombination (HR) and regulation of the MRN CC complex (PubMed:19759395, PubMed:23623683, PubMed:25558984). Interacts CC directly with RAD50 (PubMed:19759395, PubMed:25558984). Interacts CC directly with NBN (PubMed:19759395, PubMed:25558984). Interacts with CC LM04 (via the LIM zinc-binding 1 domain) (PubMed:11751867, CC PubMed:23353824). Interacts with SIAH1 (PubMed:14654780). Interacts CC with RNF138 (PubMed:26502057). Interacts with EXD2 (PubMed:26807646). CC Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 CC proteasomal degradation (PubMed:27561354). Directly interacts with CC PIN1; this interaction depends upon RBBP8 phosphorylation, CC predominantly at Thr-315 (PubMed:23623683). Interacts with FZR1; this CC interaction leads to APC/C-mediated RBBP8 proteasomal degradation CC (PubMed:25349192). Interacts with AUNIP; leading to recruitment of 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:16101277, CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:23353824, CC ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:25349192, CC ECO:0000269|PubMed:25558984, ECO:0000269|PubMed:26502057, CC ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:26807646, CC ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:28834754, CC ECO:0000269|PubMed:29042561, ECO:0000269|PubMed:30601117, CC ECO:0000269|PubMed:34129781, ECO:0000269|PubMed:9535825, CC ECO:0000269|PubMed:9721205}. CC -!- INTERACTION: CC Q99708; P38398: BRCA1; NbExp=15; 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). Phosphorylation is CC not required for tetramerization (PubMed:30601117). Binds to DNA more CC strongly when dephosphorylated (PubMed:30601117). CC {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, CC ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:30601117}. 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, PubMed:35219381). CC Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to CC proteasomal degradation (PubMed:25349192). CC {ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:16818604, CC ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:26502057, CC ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:35219381}. 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 -!- MISCELLANEOUS: Binds one Zn(2+) atom per dimer. Zn(2+)-binding is not CC required for homotetramerization. {ECO:0000269|PubMed:25558984}. 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="https://atlasgeneticsoncology.org/gene/42066/RBBP8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 1Y98; X-ray; 2.50 A; B=322-333. 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; 1Y98; -. DR PDBsum; 2L4Z; -. DR PDBsum; 4D2H; -. DR PDBsum; 7BGF; -. DR AlphaFoldDB; Q99708; -. DR SMR; Q99708; -. DR BioGRID; 111867; 122. DR ComplexPortal; CPX-4441; BRCA1-C complex. DR CORUM; Q99708; -. DR DIP; DIP-24244N; -. DR ELM; Q99708; -. DR IntAct; Q99708; 45. DR MINT; Q99708; -. DR STRING; 9606.ENSP00000382628; -. DR GlyGen; Q99708; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000382628; -. DR PeptideAtlas; Q99708; -. DR ProteomicsDB; 1422; -. DR ProteomicsDB; 78424; -. [Q99708-1] DR ProteomicsDB; 78425; -. [Q99708-2] DR Antibodypedia; 7316; 489 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 AGR; HGNC:9891; -. 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; LENFQWS; -. DR OrthoDB; 1222852at2759; -. 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 homologous recombination repair (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; 681 hits in 1168 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 183 other cell types or tissues. DR ExpressionAtlas; Q99708; baseline and differential. DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. 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:0017053; C:transcription repressor complex; IDA:BHF-UCL. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. 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: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; NAS:ComplexPortal. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0035825; P:homologous recombination; NAS:ComplexPortal. DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW. DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; NAS:ComplexPortal. 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; IPR033316; RBBP8-like. DR PANTHER; PTHR15107:SF4; DNA ENDONUCLEASE RBBP8; 1. DR PANTHER; PTHR15107; RETINOBLASTOMA BINDING PROTEIN 8; 1. DR Pfam; PF10482; CtIP_N; 1. DR Pfam; PF08573; SAE2; 1. DR Genevisible; Q99708; HS. 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; Metal-binding; Mitosis; Nuclease; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. 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 45..160 FT /note="Required for interaction with LMO4, probably by FT stabilizing the interaction through RPPB8 dimerization" FT /evidence="ECO:0000269|PubMed:23353824" 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 641..685 FT /note="Required for interaction with LMO4, probably by FT making physical contact with LMO4" FT /evidence="ECO:0000269|PubMed:23353824" 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 35..84 FT /evidence="ECO:0000269|PubMed:34129781" FT COILED 117..138 FT /evidence="ECO:0000269|PubMed:34129781" 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 27 FT /note="L->E: Can form homodimers but not homotetramers. FT Abolishes ability to promote homologous recombination and FT DNA resection. Defective binding to DNA. Defective in FT localizing to sites of DNA damage. Does not affect FT interaction with MRN complex components MRE11, NBN or FT RAD50." FT /evidence="ECO:0000269|PubMed:25558984, FT ECO:0000269|PubMed:30601117" 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 89 FT /note="C->A: Reduces Zn(2+) content; when associated with FT A-92." FT /evidence="ECO:0000269|PubMed:25558984" FT MUTAGEN 92 FT /note="C->A: Reduces Zn(2+) content; when associated with FT A-89." FT /evidence="ECO:0000269|PubMed:25558984" 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 FT PIN1-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 FT KLHL15-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: Defective binding to DNA. No effect on FT CUL3/KLHL15-mediated proteasomal degradation. Does not FT affect tetramerization." FT /evidence="ECO:0000269|PubMed:27561354, FT ECO:0000269|PubMed:30601117" 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 ECO:0000269|PubMed:35219381" 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 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 //