NBN_HUMAN
ID NBN_HUMAN Reviewed; 754 AA.
AC O60934; B2R626; B2RNC5; O60672; Q32NF7; Q53FM6; Q63HR6; Q7LDM2;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Nibrin;
DE AltName: Full=Cell cycle regulatory protein p95;
DE AltName: Full=Nijmegen breakage syndrome protein 1;
GN Name=NBN; Synonyms=NBS, NBS1, P95;
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], TISSUE SPECIFICITY, INVOLVEMENT IN NIJMEGEN
RP BREAKAGE SYNDROME, AND VARIANT GLN-185.
RX PubMed=9590180; DOI=10.1016/s0092-8674(00)81174-5;
RA Varon R., Vissinga C., Platzer M., Cerosaletti K.M., Chrzanowska K.H.,
RA Saar K., Beckmann G., Seemanova E., Cooper P.R., Nowak N.J., Stumm M.,
RA Weemaes C.M.R., Gatti R.A., Wilson R.K., Digweed M., Rosenthal A.,
RA Sperling K., Concannon P., Reis A.;
RT "Nibrin, a novel DNA double-strand break repair protein, is mutated in
RT Nijmegen breakage syndrome.";
RL Cell 93:467-476(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 189-209; 238-250; 289-299;
RP 300-320; 335-351; 395-405; 409-423; 426-441; 457-465; 503-529; 552-568;
RP 595-613; 625-635; 653-660; 671-683 AND 736-745, VARIANT GLN-185, AND
RP INTERACTION WITH MRE11 AND RAD50.
RX PubMed=9590181; DOI=10.1016/s0092-8674(00)81175-7;
RA Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M.,
RA Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J.;
RT "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage
RT of double-strand break repair to the cellular DNA damage response.";
RL Cell 93:477-486(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9620777; DOI=10.1038/549;
RA Matsuura S., Tauchi H., Nakamura A., Kondo N., Sakamoto S., Endo S.,
RA Smeets D., Solder B., Belohradsky B.H., Kaloustian V.M., Oshimura M.,
RA Isomura M., Nakamura Y., Komatsu K.;
RT "Positional cloning of the gene for Nijmegen breakage syndrome.";
RL Nat. Genet. 19:179-181(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Fibroblast;
RX PubMed=9933573; DOI=10.1006/geno.1998.5657;
RA Tauchi H., Matsuura S., Isomura M., Kinjo T., Nakamura A., Sakamoto S.,
RA Kondo N., Endo S., Komatsu K., Nakamura Y.;
RT "Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that
RT contains the Nijmegen breakage syndrome gene, NBS1.";
RL Genomics 55:242-247(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-185.
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovial cell;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-105; GLN-185; LYS-216;
RP LEU-266 AND ALA-497.
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Skin, and 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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-754.
RC TISSUE=Colon endothelium;
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 [11]
RP FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH MRE11
RP AND RAD50.
RX PubMed=9705271; DOI=10.1074/jbc.273.34.21447;
RA Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.;
RT "Nuclease activities in a complex of human recombination and DNA repair
RT factors Rad50, Mre11, and p95.";
RL J. Biol. Chem. 273:21447-21450(1998).
RN [12]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE BASC COMPLEX WITH BRCA1;
RP MSH2; MSH6; MLH1; ATM; BLM; RAD50 AND MRE11.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [13]
RP INTERACTION WITH MRE11.
RX PubMed=11238951; DOI=10.1128/mcb.21.6.2184-2191.2001;
RA Desai-Mehta A., Cerosaletti K.M., Concannon P.;
RT "Distinct functional domains of nibrin mediate Mre11 binding, focus
RT formation, and nuclear localization.";
RL Mol. Cell. Biol. 21:2184-2191(2001).
RN [14]
RP PHOSPHORYLATION AT SER-343, AND MUTAGENESIS OF ARG-28; HIS-45;
RP 136-GLY-GLY-137 AND TYR-176.
RX PubMed=10802669; DOI=10.1038/75508;
RA Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S.,
RA Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.;
RT "ATM-dependent phosphorylation of nibrin in response to radiation
RT exposure.";
RL Nat. Genet. 25:115-119(2000).
RN [15]
RP PHOSPHORYLATION AT SER-278.
RX PubMed=10839544; DOI=10.1038/35013083;
RA Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C.,
RA Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y.,
RA Shiloh Y., Lee E.Y.-H.P.;
RT "Functional link between ataxia-telangiectasia and Nijmegen breakage
RT syndrome gene products.";
RL Nature 405:473-477(2000).
RN [16]
RP PHOSPHORYLATION AT SER-343; SER-397 AND SER-615, AND MUTAGENESIS OF
RP SER-343; SER-397 AND SER-615.
RX PubMed=10839545; DOI=10.1038/35013089;
RA Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N.,
RA O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G.,
RA Livingston D.M., Weaver D.T.;
RT "ATM phosphorylation of Nijmegen breakage syndrome protein is required in a
RT DNA damage response.";
RL Nature 405:477-482(2000).
RN [17]
RP FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION
RP IN A COMPLEX WITH TERF2, AND SUBCELLULAR LOCATION.
RX PubMed=10888888; DOI=10.1038/77139;
RA Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.;
RT "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human
RT telomeres.";
RL Nat. Genet. 25:347-352(2000).
RN [18]
RP INTERACTION WITH SP100, AND SUBCELLULAR LOCATION.
RX PubMed=12470659; DOI=10.1016/s0006-291x(02)02755-9;
RA Naka K., Ikeda K., Motoyama N.;
RT "Recruitment of NBS1 into PML oncogenic domains via interaction with SP100
RT protein.";
RL Biochem. Biophys. Res. Commun. 299:863-871(2002).
RN [19]
RP INTERACTION WITH H2AX.
RX PubMed=12419185; DOI=10.1016/s0960-9822(02)01259-9;
RA Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K.,
RA Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.;
RT "NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT
RT domain.";
RL Curr. Biol. 12:1846-1851(2002).
RN [20]
RP INTERACTION WITH KPNA2, AND MUTAGENESIS OF SER-397; 465-LYS-ARG-466 AND
RP GLN-583.
RX PubMed=16188882; DOI=10.1074/jbc.m508425200;
RA Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C.;
RT "Importin KPNA2 is required for proper nuclear localization and multiple
RT functions of NBS1.";
RL J. Biol. Chem. 280:39594-39600(2005).
RN [21]
RP INTERACTION WITH ATF2, AND SUBCELLULAR LOCATION.
RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT response.";
RL Mol. Cell 18:577-587(2005).
RN [22]
RP DOMAIN, AND MUTAGENESIS OF 736-GLU-GLU-737; 741-ASP-ASP-742 AND
RP 745-ARG-TYR-746.
RX PubMed=15758953; DOI=10.1038/nature03442;
RA Falck J., Coates J., Jackson S.P.;
RT "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA
RT damage.";
RL Nature 434:605-611(2005).
RN [23]
RP FUNCTION.
RX PubMed=15616588; DOI=10.1038/sj.emboj.7600504;
RA Stiff T., Reis C., Alderton G.K., Woodbine L., O'Driscoll M., Jeggo P.A.;
RT "Nbs1 is required for ATR-dependent phosphorylation events.";
RL EMBO J. 24:199-208(2005).
RN [24]
RP REVIEW.
RX PubMed=16467875; DOI=10.1038/sj.cr.7310007;
RA Zhang Y., Zhou J., Lim C.U.;
RT "The role of NBS1 in DNA double strand break repair, telomere stability,
RT and cell cycle checkpoint control.";
RL Cell Res. 16:45-54(2006).
RN [25]
RP INACTIVATION BY ADENOVIRUS ONCOPROTEINS.
RX PubMed=12124628; DOI=10.1038/nature00863;
RA Stracker T.H., Carson C.T., Weitzman M.D.;
RT "Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair
RT complex.";
RL Nature 418:348-352(2002).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [27]
RP INTERACTION WITH HJURP.
RX PubMed=17823411; DOI=10.1158/0008-5472.can-07-1307;
RA Kato T., Sato N., Hayama S., Yamabuki T., Ito T., Miyamoto M., Kondo S.,
RA Nakamura Y., Daigo Y.;
RT "Activation of Holliday junction recognizing protein involved in the
RT chromosomal stability and immortality of cancer cells.";
RL Cancer Res. 67:8544-8553(2007).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397 AND SER-432, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [31]
RP FUNCTION, AND INTERACTION WITH RBBP8.
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 [32]
RP INTERACTION WITH INTS3.
RX PubMed=19683501; DOI=10.1016/j.molcel.2009.06.011;
RA Huang J., Gong Z., Ghosal G., Chen J.;
RT "SOSS complexes participate in the maintenance of genomic stability.";
RL Mol. Cell 35:384-393(2009).
RN [33]
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 [34]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12 (MICROBIAL INFECTION).
RX PubMed=20943970; DOI=10.1128/jvi.01506-10;
RA Balasubramanian N., Bai P., Buchek G., Korza G., Weller S.K.;
RT "Physical interaction between the herpes simplex virus type 1 exonuclease,
RT UL12, and the DNA double-strand break-sensing MRN complex.";
RL J. Virol. 84:12504-12514(2010).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397; THR-402 AND SER-432, AND
RP IDENTIFICATION BY 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 [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-337; SER-343; SER-347;
RP SER-397; SER-432; SER-509; SER-518 AND SER-673, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [39]
RP FUNCTION IN AKT1 PHOSPHORYLATION, INTERACTION WITH MTOR; MAPKAP1 AND
RP RICTOR, AND INDUCTION BY IONIZING RADIATION.
RX PubMed=23762398; DOI=10.1371/journal.pone.0065586;
RA Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C., Wu K.J.;
RT "Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific
RT domains.";
RL PLoS ONE 8:E65586-E65586(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [41]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26438602; DOI=10.1128/mcb.00757-15;
RA Ikura M., Furuya K., Matsuda S., Matsuda R., Shima H., Adachi J.,
RA Matsuda T., Shiraki T., Ikura T.;
RT "Acetylation of histone H2AX at Lys 5 by the TIP60 histone
RT acetyltransferase complex is essential for the dynamic binding of NBS1 to
RT damaged chromatin.";
RL Mol. Cell. Biol. 35:4147-4157(2015).
RN [42]
RP IDENTIFICATION IN THE MRN COMPLEX, INTERACTION WITH MCM9, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26215093; DOI=10.1038/ncomms8744;
RA Lee K.Y., Im J.S., Shibata E., Park J., Handa N., Kowalczykowski S.C.,
RA Dutta A.;
RT "MCM8-9 complex promotes resection of double-strand break ends by MRE11-
RT RAD50-NBS1 complex.";
RL Nat. Commun. 6:7744-7744(2015).
RN [43]
RP INTERACTION WITH MRNIP.
RX PubMed=27568553; DOI=10.1016/j.celrep.2016.07.087;
RA Staples C.J., Barone G., Myers K.N., Ganesh A., Gibbs-Seymour I.,
RA Patil A.A., Beveridge R.D., Daye C., Beniston R., Maslen S., Ahel I.,
RA Skehel J.M., Collis S.J.;
RT "MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA
RT damage response.";
RL Cell Rep. 16:2565-2575(2016).
RN [44]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-529; LYS-571 AND LYS-582, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [45]
RP INTERACTION WITH UFL1.
RX PubMed=30886146; DOI=10.1038/s41467-019-09175-0;
RA Qin B., Yu J., Nowsheen S., Wang M., Tu X., Liu T., Li H., Wang L., Lou Z.;
RT "UFL1 promotes histone H4 ufmylation and ATM activation.";
RL Nat. Commun. 10:1242-1242(2019).
RN [46]
RP VARIANTS LEU-93; ASN-95; VAL-171; PHE-210 AND TRP-215, AND POSSIBLE
RP INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA.
RX PubMed=11325820;
RA Varon R., Reis A., Henze G., von Einsiedel H.G., Sperling K., Seeger K.;
RT "Mutations in the Nijmegen breakage syndrome gene (NBS1) in childhood acute
RT lymphoblastic leukemia (ALL).";
RL Cancer Res. 61:3570-3572(2001).
RN [47]
RP VARIANT BC PHE-150, AND VARIANTS GLN-185 AND ILE-574.
RX PubMed=14684699; DOI=10.1136/jmg.40.12.e131;
RA Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.;
RT "Mutation screening of Mre11 complex genes: indication of RAD50 involvement
RT in breast and ovarian cancer susceptibility.";
RL J. Med. Genet. 40:E131-E131(2003).
RN [48]
RP VARIANT GLN-185.
RX PubMed=14688016; DOI=10.1093/carcin/bgh058;
RA Sanyal S., Festa F., Sakano S., Zhang Z., Steineck G., Norming U.,
RA Wijkstroem H., Larsson P., Kumar R., Hemminki K.;
RT "Polymorphisms in DNA repair and metabolic genes in bladder cancer.";
RL Carcinogenesis 25:729-734(2004).
RN [49]
RP POSSIBLE INVOLVEMENT IN AA, AND VARIANT VAL-171.
RX PubMed=15338273; DOI=10.1007/s00439-004-1155-1;
RA Shimada H., Shimizu K., Mimaki S., Sakiyama T., Mori T., Shimasaki N.,
RA Yokota J., Nakachi K., Ohta T., Ohki M.;
RT "First case of aplastic anemia in a Japanese child with a homozygous
RT missense mutation in the NBS1 gene (I171V) associated with genomic
RT instability.";
RL Hum. Genet. 115:372-376(2004).
RN [50]
RP VARIANT HIS-679.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Component of the MRE11-RAD50-NBN (MRN complex) which plays a
CC critical role in the cellular response to DNA damage and the
CC maintenance of chromosome integrity. The complex is involved in double-
CC strand break (DSB) repair, DNA recombination, maintenance of telomere
CC integrity, cell cycle checkpoint control and meiosis. The complex
CC possesses single-strand endonuclease activity and double-strand-
CC specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50
CC may be required to bind DNA ends and hold them in close proximity. NBN
CC modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase
CC family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites
CC and activating their functions. It can also recruit MRE11 and RAD50 to
CC the proximity of DSBs by an interaction with the histone H2AX. NBN also
CC functions in telomere length maintenance by generating the 3' overhang
CC which serves as a primer for telomerase dependent telomere elongation.
CC NBN is a major player in the control of intra-S-phase checkpoint and
CC there is some evidence that NBN is involved in G1 and G2 checkpoints.
CC The roles of NBS1/MRN encompass DNA damage sensor, signal transducer,
CC and effector, which enable cells to maintain DNA integrity and genomic
CC stability. Forms a complex with RBBP8 to link DNA double-strand break
CC sensing to resection. Enhances AKT1 phosphorylation possibly by
CC association with the mTORC2 complex. {ECO:0000269|PubMed:10888888,
CC ECO:0000269|PubMed:15616588, ECO:0000269|PubMed:19759395,
CC ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:26438602,
CC ECO:0000269|PubMed:9705271}.
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN (PubMed:26215093,
CC PubMed:9590181, PubMed:9705271, PubMed:11238951). As part of the MRN
CC complex, interacts with MCM9; the interaction recruits the complex to
CC DNA repair sites (PubMed:26215093). Component of the BASC complex, at
CC least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and
CC NBN (PubMed:10783165). Interacts with histone H2AX this requires
CC phosphorylation of H2AX on 'Ser-139' (PubMed:12419185). Interacts with
CC HJURP (PubMed:17823411). Interacts with INTS3 (PubMed:19683501).
CC Interacts with KPNA2 (PubMed:16188882). Interacts with TERF2
CC (PubMed:10888888). Interacts with RBBP8; the interaction links the role
CC of the MRN complex in DNA double-strand break sensing to resection
CC (PubMed:19759395). Interacts with SP100; recruits NBN to PML bodies
CC (PubMed:12470659). Interacts with ATF2 (PubMed:15916964). Interacts
CC with MTOR, MAPKAP1 isoform 2 and RICTOR; indicative for an association
CC with the mTORC2 complex (PubMed:23762398). Interacts with MRNIP
CC (PubMed:27568553). Interacts with UFL1; promoting UFL1 recruitment to
CC double-strand breaks following DNA damage (PubMed:30886146). Interacts
CC with CYREN (via XLF motif) (By similarity).
CC {ECO:0000250|UniProtKB:Q9R207, ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11238951,
CC ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12470659,
CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16188882,
CC ECO:0000269|PubMed:17823411, ECO:0000269|PubMed:19683501,
CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:23762398,
CC ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:27568553,
CC ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:9590181,
CC ECO:0000269|PubMed:9705271}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL12. {ECO:0000269|PubMed:20943970}.
CC -!- INTERACTION:
CC O60934; Q13315: ATM; NbExp=2; IntAct=EBI-494844, EBI-495465;
CC O60934; Q09472: EP300; NbExp=5; IntAct=EBI-494844, EBI-447295;
CC O60934; Q9BXW9: FANCD2; NbExp=6; IntAct=EBI-494844, EBI-359343;
CC O60934; P16104: H2AX; NbExp=14; IntAct=EBI-494844, EBI-494830;
CC O60934; Q68E01: INTS3; NbExp=2; IntAct=EBI-494844, EBI-2680854;
CC O60934; Q14676: MDC1; NbExp=33; IntAct=EBI-494844, EBI-495644;
CC O60934; P49959: MRE11; NbExp=5; IntAct=EBI-494844, EBI-396513;
CC O60934; O75943: RAD17; NbExp=5; IntAct=EBI-494844, EBI-968231;
CC O60934; Q99708: RBBP8; NbExp=2; IntAct=EBI-494844, EBI-745715;
CC O60934; Q96EB6: SIRT1; NbExp=5; IntAct=EBI-494844, EBI-1802965;
CC O60934; Q13428: TCOF1; NbExp=10; IntAct=EBI-494844, EBI-396105;
CC O60934; Q99986: VRK1; NbExp=13; IntAct=EBI-494844, EBI-1769146;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:26215093}. Nucleus, PML body
CC {ECO:0000269|PubMed:12470659, ECO:0000269|PubMed:15916964}. Chromosome,
CC telomere {ECO:0000269|PubMed:10888888}. Chromosome
CC {ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26438602}.
CC Note=Localizes to discrete nuclear foci after treatment with genotoxic
CC agents (PubMed:26438602, PubMed:10783165, PubMed:26215093). Acetylation
CC of 'Lys-5' of histone H2AX (H2AXK5ac) promotes NBN/NBS1 assembly at the
CC sites of DNA damage (PubMed:26438602). {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26438602}.
CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:9590180). Expressed at high
CC levels in testis (PubMed:9590180). {ECO:0000269|PubMed:9590180}.
CC -!- INDUCTION: Up-regulated by ionizing radiation (IR).
CC {ECO:0000269|PubMed:23762398}.
CC -!- DOMAIN: The FHA and BRCT domains are likely to have a crucial role for
CC both binding to histone H2AX and for relocalization of MRE11/RAD50
CC complex to the vicinity of DNA damage. {ECO:0000269|PubMed:15758953}.
CC -!- DOMAIN: The C-terminal domain contains a MRE11-binding site, and this
CC interaction is required for the nuclear localization of the MRN
CC complex. {ECO:0000269|PubMed:15758953}.
CC -!- DOMAIN: The EEXXXDDL motif at the C-terminus is required for the
CC interaction with ATM and its recruitment to sites of DNA damage and
CC promote the phosphorylation of ATM substrates, leading to the events of
CC DNA damage response. {ECO:0000269|PubMed:15758953}.
CC -!- PTM: Phosphorylated by ATM in response of ionizing radiation, and such
CC phosphorylation is responsible intra-S phase checkpoint control and
CC telomere maintenance. {ECO:0000269|PubMed:10802669,
CC ECO:0000269|PubMed:10839544, ECO:0000269|PubMed:10839545}.
CC -!- DISEASE: Nijmegen breakage syndrome (NBS) [MIM:251260]: A disorder
CC characterized by chromosomal instability, radiation sensitivity,
CC microcephaly, growth retardation, immunodeficiency and predisposition
CC to cancer, particularly to lymphoid malignancies.
CC {ECO:0000269|PubMed:9590180}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal carcinoma is
CC by far the most common type. Breast cancer is etiologically and
CC genetically heterogeneous. Important genetic factors have been
CC indicated by familial occurrence and bilateral involvement. Mutations
CC at more than one locus can be involved in different families or even in
CC the same case. {ECO:0000269|PubMed:14684699}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Aplastic anemia (AA) [MIM:609135]: A form of anemia in which
CC the bone marrow fails to produce adequate numbers of peripheral blood
CC elements. It is characterized by peripheral pancytopenia and marrow
CC hypoplasia. {ECO:0000269|PubMed:15338273}. Note=Disease susceptibility
CC may be associated with variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in NBN might play a role in the pathogenesis of
CC childhood acute lymphoblastic leukemia (ALL).
CC {ECO:0000269|PubMed:11325820}.
CC -!- MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex
CC is inactivated and degraded by viral oncoproteins, thereby preventing
CC concatenation of viral genomes in infected cells.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI08651.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 550.; Evidence={ECO:0000305};
CC Sequence=CAH56160.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NBS1ID160.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/nbs1/";
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; AF051334; AAC39732.1; -; mRNA.
DR EMBL; AF058696; AAC39752.1; -; mRNA.
DR EMBL; AB013139; BAA28616.1; -; Genomic_DNA.
DR EMBL; AF069291; AAC62232.1; -; Genomic_DNA.
DR EMBL; AK312410; BAG35323.1; -; mRNA.
DR EMBL; AK223256; BAD96976.1; -; mRNA.
DR EMBL; AY566246; AAS59158.1; -; Genomic_DNA.
DR EMBL; CH471060; EAW91660.1; -; Genomic_DNA.
DR EMBL; BC108650; AAI08651.1; ALT_SEQ; mRNA.
DR EMBL; BC136802; AAI36803.1; -; mRNA.
DR EMBL; BC136803; AAI36804.1; -; mRNA.
DR EMBL; BX640816; CAH56160.1; ALT_INIT; mRNA.
DR CCDS; CCDS6249.1; -.
DR PIR; T00393; T00393.
DR RefSeq; NP_001019859.1; NM_001024688.2.
DR RefSeq; NP_002476.2; NM_002485.4.
DR RefSeq; XP_011515347.1; XM_011517045.1.
DR PDB; 5WQD; X-ray; 3.00 A; H/I/J/K/L/M/N=423-438.
DR PDB; 7SID; EM; 2.53 A; B/D=727-754.
DR PDBsum; 5WQD; -.
DR PDBsum; 7SID; -.
DR AlphaFoldDB; O60934; -.
DR SMR; O60934; -.
DR BioGRID; 110763; 152.
DR ComplexPortal; CPX-4442; MRN complex.
DR CORUM; O60934; -.
DR DIP; DIP-33605N; -.
DR ELM; O60934; -.
DR IntAct; O60934; 50.
DR MINT; O60934; -.
DR STRING; 9606.ENSP00000265433; -.
DR GlyGen; O60934; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60934; -.
DR MetOSite; O60934; -.
DR PhosphoSitePlus; O60934; -.
DR BioMuta; NBN; -.
DR CPTAC; CPTAC-3236; -.
DR CPTAC; CPTAC-3237; -.
DR CPTAC; CPTAC-3238; -.
DR CPTAC; CPTAC-3239; -.
DR CPTAC; CPTAC-934; -.
DR CPTAC; CPTAC-935; -.
DR EPD; O60934; -.
DR jPOST; O60934; -.
DR MassIVE; O60934; -.
DR MaxQB; O60934; -.
DR PaxDb; O60934; -.
DR PeptideAtlas; O60934; -.
DR PRIDE; O60934; -.
DR ProteomicsDB; 49678; -.
DR Antibodypedia; 690; 1581 antibodies from 48 providers.
DR CPTC; O60934; 4 antibodies.
DR DNASU; 4683; -.
DR Ensembl; ENST00000265433.8; ENSP00000265433.4; ENSG00000104320.14.
DR GeneID; 4683; -.
DR KEGG; hsa:4683; -.
DR MANE-Select; ENST00000265433.8; ENSP00000265433.4; NM_002485.5; NP_002476.2.
DR UCSC; uc003yej.2; human.
DR CTD; 4683; -.
DR DisGeNET; 4683; -.
DR GeneCards; NBN; -.
DR GeneReviews; NBN; -.
DR HGNC; HGNC:7652; NBN.
DR HPA; ENSG00000104320; Low tissue specificity.
DR MalaCards; NBN; -.
DR MIM; 114480; phenotype.
DR MIM; 251260; phenotype.
DR MIM; 602667; gene.
DR MIM; 609135; phenotype.
DR neXtProt; NX_O60934; -.
DR OpenTargets; ENSG00000104320; -.
DR Orphanet; 1331; Familial prostate cancer.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 647; Nijmegen breakage syndrome.
DR PharmGKB; PA31457; -.
DR VEuPathDB; HostDB:ENSG00000104320; -.
DR eggNOG; ENOG502QQ7Y; Eukaryota.
DR GeneTree; ENSGT00390000000521; -.
DR HOGENOM; CLU_023410_0_0_1; -.
DR InParanoid; O60934; -.
DR OMA; LESPHSC; -.
DR OrthoDB; 831679at2759; -.
DR PhylomeDB; O60934; -.
DR TreeFam; TF101103; -.
DR PathwayCommons; O60934; -.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
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-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
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-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; O60934; -.
DR SIGNOR; O60934; -.
DR BioGRID-ORCS; 4683; 46 hits in 1083 CRISPR screens.
DR ChiTaRS; NBN; human.
DR GeneWiki; Nibrin; -.
DR GenomeRNAi; 4683; -.
DR Pharos; O60934; Tbio.
DR PRO; PR:O60934; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O60934; protein.
DR Bgee; ENSG00000104320; Expressed in endometrium epithelium and 209 other tissues.
DR ExpressionAtlas; O60934; baseline and differential.
DR Genevisible; O60934; HS.
DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal.
DR GO; GO:0098687; C:chromosomal region; IC:ComplexPortal.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030870; C:Mre11 complex; IDA:UniProtKB.
DR GO; GO:0042405; C:nuclear inclusion body; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0005657; C:replication fork; IEA:Ensembl.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0001832; P:blastocyst growth; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:MGI.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; TAS:UniProtKB.
DR GO; GO:0000729; P:DNA double-strand break processing; IC:ComplexPortal.
DR GO; GO:0032508; P:DNA duplex unwinding; IMP:BHF-UCL.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IC:ComplexPortal.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0035825; P:homologous recombination; IC:ComplexPortal.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:1904354; P:negative regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0033674; P:positive regulation of kinase activity; IDA:BHF-UCL.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; TAS:UniProtKB.
DR GO; GO:0090656; P:t-circle formation; IMP:BHF-UCL.
DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB.
DR GO; GO:0090737; P:telomere maintenance via telomere trimming; IGI:BHF-UCL.
DR GO; GO:0031860; P:telomeric 3' overhang formation; IMP:BHF-UCL.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.40.50.10190; -; 1.
DR Gene3D; 3.40.50.10980; -; 1.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR013908; DNA-repair_Nbs1_C.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR040227; Nibrin-rel.
DR InterPro; IPR032429; Nibrin_BRCT2.
DR InterPro; IPR043014; Nibrin_BRCT2_sf.
DR InterPro; IPR016592; Nibrin_met.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR PANTHER; PTHR12162; PTHR12162; 1.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF08599; Nbs1_C; 1.
DR Pfam; PF16508; NIBRIN_BRCT_II; 1.
DR PIRSF; PIRSF011869; Nibrin_animal; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM01348; Nbs1_C; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Chromosome; Direct protein sequencing;
KW Disease variant; DNA damage; DNA repair; Host-virus interaction;
KW Isopeptide bond; Meiosis; Nucleus; Phosphoprotein; Reference proteome;
KW Telomere; Ubl conjugation.
FT CHAIN 1..754
FT /note="Nibrin"
FT /id="PRO_0000231043"
FT DOMAIN 24..83
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 105..181
FT /note="BRCT"
FT REGION 111..328
FT /note="Mediates interaction with SP100"
FT /evidence="ECO:0000250|UniProtKB:Q9R207"
FT REGION 221..402
FT /note="Interaction with MTOR, MAPKAP1 and RICTOR"
FT /evidence="ECO:0000269|PubMed:23762398"
FT REGION 326..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 461..467
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:16188882"
FT MOTIF 736..743
FT /note="EEXXXDDL motif"
FT /evidence="ECO:0000269|PubMed:15758953"
FT COMPBIAS 326..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 278
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:10839544"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 343
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:10802669,
FT ECO:0000269|PubMed:10839545, ECO:0007744|PubMed:23186163"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10839545,
FT ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 402
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10839545"
FT MOD_RES 673
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 529
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 582
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 93
FT /note="S -> L (in some childhood acute lymphoblastic
FT leukemia patients; uncertain pathological significance;
FT rare variant; dbSNP:rs12721593)"
FT /evidence="ECO:0000269|PubMed:11325820"
FT /id="VAR_025792"
FT VARIANT 95
FT /note="D -> N (in some childhood acute lymphoblastic
FT leukemia patients; uncertain pathological significance;
FT rare variant; dbSNP:rs61753720)"
FT /evidence="ECO:0000269|PubMed:11325820"
FT /id="VAR_025793"
FT VARIANT 105
FT /note="K -> N (in dbSNP:rs13312858)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_025794"
FT VARIANT 142
FT /note="N -> S (in dbSNP:rs769414)"
FT /id="VAR_051226"
FT VARIANT 150
FT /note="L -> F (in BC; dbSNP:rs773119929)"
FT /evidence="ECO:0000269|PubMed:14684699"
FT /id="VAR_025795"
FT VARIANT 171
FT /note="I -> V (in some childhood acute lymphoblastic
FT leukemia patients; uncertain pathological significance;
FT rare variant; associated with aplastic anemia at
FT homozygosity; dbSNP:rs61754966)"
FT /evidence="ECO:0000269|PubMed:11325820,
FT ECO:0000269|PubMed:15338273"
FT /id="VAR_025796"
FT VARIANT 185
FT /note="E -> Q (in dbSNP:rs1805794)"
FT /evidence="ECO:0000269|PubMed:14684699,
FT ECO:0000269|PubMed:14688016, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:9590180, ECO:0000269|PubMed:9590181,
FT ECO:0000269|Ref.7"
FT /id="VAR_025797"
FT VARIANT 210
FT /note="V -> F (in dbSNP:rs61754796)"
FT /evidence="ECO:0000269|PubMed:11325820"
FT /id="VAR_025798"
FT VARIANT 215
FT /note="R -> W (in dbSNP:rs34767364)"
FT /evidence="ECO:0000269|PubMed:11325820"
FT /id="VAR_025799"
FT VARIANT 216
FT /note="Q -> K (in dbSNP:rs769416)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_025800"
FT VARIANT 266
FT /note="P -> L (in dbSNP:rs769420)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_025801"
FT VARIANT 408
FT /note="K -> E (in dbSNP:rs34120922)"
FT /id="VAR_051227"
FT VARIANT 497
FT /note="T -> A (in dbSNP:rs3026268)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_025802"
FT VARIANT 574
FT /note="L -> I (in dbSNP:rs142334798)"
FT /evidence="ECO:0000269|PubMed:14684699"
FT /id="VAR_025803"
FT VARIANT 679
FT /note="Y -> H (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064738"
FT MUTAGEN 28
FT /note="R->A: Disrupts nuclear foci formation and block
FT phosphorylation in response to ionizing radiation."
FT /evidence="ECO:0000269|PubMed:10802669"
FT MUTAGEN 45
FT /note="H->A: Disrupts nuclear foci formation and block
FT phosphorylation in response to ionizing radiation."
FT /evidence="ECO:0000269|PubMed:10802669"
FT MUTAGEN 136..137
FT /note="GG->EE: Disrupts nuclear foci formation and block
FT phosphorylation in response to ionizing radiation."
FT /evidence="ECO:0000269|PubMed:10802669"
FT MUTAGEN 176
FT /note="Y->A: Disrupts nuclear foci formation and block
FT phosphorylation in response to ionizing radiation."
FT /evidence="ECO:0000269|PubMed:10802669"
FT MUTAGEN 343
FT /note="S->A: Abrogates ATM-dependent phosphorylation."
FT /evidence="ECO:0000269|PubMed:10839545"
FT MUTAGEN 397
FT /note="S->A: Abrogates ATM-dependent phosphorylation. No
FT loss of interaction with KPNA2."
FT /evidence="ECO:0000269|PubMed:10839545,
FT ECO:0000269|PubMed:16188882"
FT MUTAGEN 465..466
FT /note="KR->AA: Blocks the association with KPNA2, and
FT reduces nuclear foci formation in response to ionizing
FT radiation."
FT /evidence="ECO:0000269|PubMed:16188882"
FT MUTAGEN 583
FT /note="Q->K: No loss of interaction with KPNA2."
FT /evidence="ECO:0000269|PubMed:16188882"
FT MUTAGEN 615
FT /note="S->A: Abrogates ATM-dependent phosphorylation."
FT /evidence="ECO:0000269|PubMed:10839545"
FT MUTAGEN 736..737
FT /note="EE->AA: Decreases ATM binding."
FT /evidence="ECO:0000269|PubMed:15758953"
FT MUTAGEN 741..742
FT /note="DD->AA: Decreases ATM binding."
FT /evidence="ECO:0000269|PubMed:15758953"
FT MUTAGEN 745..746
FT /note="RY->AA: Decreases ATM binding."
FT /evidence="ECO:0000269|PubMed:15758953"
FT CONFLICT 247
FT /note="G -> R (in Ref. 6; BAD96976)"
FT /evidence="ECO:0000305"
FT TURN 426..429
FT /evidence="ECO:0007829|PDB:5WQD"
SQ SEQUENCE 754 AA; 84959 MW; CD602F09BA73DAB6 CRC64;
MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT
DEIPVLTLKD NSKYGTFVNE EKMQNGFSRT LKSGDGITFG VFGSKFRIEY EPLVACSSCL
DVSGKTALNQ AILQLGGFTV NNWTEECTHL VMVSVKVTIK TICALICGRP IVKPEYFTEF
LKAVESKKQP PQIESFYPPL DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS
AVVFGGGEAR LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ
GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGVSVDE KLMPSAPVNT
TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA PTVKESCKTS SNNNSMVSNT
LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS
ARIETSCSLL EQTQPATPSL WKNKEQHLSE NEPVDTNSDN NLFTDTDLKS IVKNSASKSH
AAEKLRSNKK REMDDVAIED EVLEQLFKDT KPELEIDVKV QKQEEDVNVR KRPRMDIETN
DTFSDEAVPE SSKISQENEI GKKRELKEDS LWSAKEISNN DKLQDDSEML PKKLLLTEFR
SLVIKNSTSR NPSGINDDYG QLKNFKKFKK VTYPGAGKLP HIIGGSDLIA HHARKNTELE
EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL KRRR
