[1]	NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN NIJMEGEN BREAKAGE SYNDROME, AND VARIANT GLN-185. DOI=10.1016/S0092-8674(00)81174-5; PubMed=9590180 [NCBI, ExPASy, EBI, Israel, Japan] Varon R., Vissinga C., Platzer M., Cerosaletti K.M., Chrzanowska K.H., Saar K., Beckmann G., Seemanova E., Cooper P.R., Nowak N.J., Stumm M., Weemaes C.M.R., Gatti R.A., Wilson R.K., Digweed M., Rosenthal A., Sperling K., Concannon P., Reis A.; "Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome."; Cell 93:467-476(1998).
[2]	NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 189-209; 238-250; 289-299; 300-320; 335-351; 395-405; 409-423; 426-441; 457-465; 503-529; 552-568; 595-613; 625-635; 653-660; 671-683 AND 736-745, VARIANT GLN-185, AND INTERACTION WITH MRE11 AND RAD50. DOI=10.1016/S0092-8674(00)81175-7; PubMed=9590181 [NCBI, ExPASy, EBI, Israel, Japan] Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M., Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J.; "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response."; Cell 93:477-486(1998).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1038/549; PubMed=9620777 [NCBI, ExPASy, EBI, Israel, Japan] Matsuura S., Tauchi H., Nakamura A., Kondo N., Sakamoto S., Endo S., Smeets D., Solder B., Belohradsky B.H., Kaloustian V.M., Oshimura M., Isomura M., Nakamura Y., Komatsu K.; "Positional cloning of the gene for Nijmegen breakage syndrome."; Nat. Genet. 19:179-181(1998).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. TISSUE=Fibroblast; DOI=10.1006/geno.1998.5657; PubMed=9933573 [NCBI, ExPASy, EBI, Israel, Japan] Tauchi H., Matsuura S., Isomura M., Kinjo T., Nakamura A., Sakamoto S., Kondo N., Endo S., Komatsu K., Nakamura Y.; "Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1."; Genomics 55:242-247(1999).
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-185. TISSUE=Brain; DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan] Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; "Complete sequencing and characterization of 21,243 full-length human cDNAs."; Nat. Genet. 36:40-45(2004).
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Synovial cell; Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[7]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-105; GLN-185; LYS-216; LEU-266 AND ALA-497. NIEHS SNPs program; Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-754. TISSUE=Colon endothelium; DOI=10.1186/1471-2164-8-399; PubMed=17974005 [NCBI, ExPASy, EBI, Israel, Japan] Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.; "The full-ORF clone resource of the German cDNA consortium."; BMC Genomics 8:399-399(2007).
[9]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-550. TISSUE=Skin; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[10]	FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH MRE11A AND RAD50. DOI=10.1074/jbc.273.34.21447; PubMed=9705271 [NCBI, ExPASy, EBI, Israel, Japan] Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.; "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95."; J. Biol. Chem. 273:21447-21450(1998).
[11]	INTERACTION WITH MRE11. DOI=10.1128/MCB.21.6.2184-2191.2001; PubMed=11238951 [NCBI, ExPASy, EBI, Israel, Japan] Desai-Mehta A., Cerosaletti K.M., Concannon P.; "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization."; Mol. Cell. Biol. 21:2184-2191(2001).
[12]	PHOSPHORYLATION AT SER-343, AND MUTAGENESIS OF ARG-28; HIS-45; 136-GLY-GLY-137 AND TYR-176. DOI=10.1038/75508; PubMed=10802669 [NCBI, ExPASy, EBI, Israel, Japan] Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S., Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.; "ATM-dependent phosphorylation of nibrin in response to radiation exposure."; Nat. Genet. 25:115-119(2000).
[13]	PHOSPHORYLATION AT SER-278. DOI=10.1038/35013083; PubMed=10839544 [NCBI, ExPASy, EBI, Israel, Japan] Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C., Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y., Shiloh Y., Lee E.Y.-H.P.; "Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products."; Nature 405:473-477(2000).
[14]	PHOSPHORYLATION AT SER-343; SER-397 AND SER-615, AND MUTAGENESIS OF SER-343; SER-397 AND SER-615. DOI=10.1038/35013089; PubMed=10839545 [NCBI, ExPASy, EBI, Israel, Japan] Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N., O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G., Livingston D.M., Weaver D.T.; "ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response."; Nature 405:477-482(2000).
[15]	FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A COMPLEX WITH TERF2. DOI=10.1038/77139; PubMed=10888888 [NCBI, ExPASy, EBI, Israel, Japan] Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.; "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres."; Nat. Genet. 25:347-352(2000).
[16]	INTERACTION WITH H2AFX. DOI=10.1016/S0960-9822(02)01259-9; PubMed=12419185 [NCBI, ExPASy, EBI, Israel, Japan] Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K., Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.; "NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain."; Curr. Biol. 12:1846-1851(2002).
[17]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan] Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.; "Large-scale characterization of HeLa cell nuclear phosphoproteins."; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[18]	INTERACTION WITH KPNA2, AND MUTAGENESIS OF SER-397; 465-LYS-ARG-466 AND GLN-583. DOI=10.1074/jbc.M508425200; PubMed=16188882 [NCBI, ExPASy, EBI, Israel, Japan] Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C.; "Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1."; J. Biol. Chem. 280:39594-39600(2005).
[19]	DOMAIN, AND MUTAGENESIS OF 736-GLU-GLU-737; 741-ASP-ASP-742 AND 745-ARG-TYR-746. DOI=10.1038/nature03442; PubMed=15758953 [NCBI, ExPASy, EBI, Israel, Japan] Falck J., Coates J., Jackson S.P.; "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."; Nature 434:605-611(2005).
[20]	FUNCTION. DOI=10.1038/sj.emboj.7600504; PubMed=15616588 [NCBI, ExPASy, EBI, Israel, Japan] Stiff T., Reis C., Alderton G.K., Woodbine L., O'Driscoll M., Jeggo P.A.; "Nbs1 is required for ATR-dependent phosphorylation events."; EMBO J. 24:199-208(2005).
[21]	REVIEW. DOI=10.1038/sj.cr.7310007; PubMed=16467875 [NCBI, ExPASy, EBI, Israel, Japan] Zhang Y., Zhou J., Lim C.U.; "The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control."; Cell Res. 16:45-54(2006).
[22]	INACTIVATION BY ADENOVIRUS ONCOPROTEINS. DOI=10.1038/nature00863; PubMed=12124628 [NCBI, ExPASy, EBI, Israel, Japan] Stracker T.H., Carson C.T., Weitzman M.D.; "Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex."; Nature 418:348-352(2002).
[23]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan] Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; "A probability-based approach for high-throughput protein phosphorylation analysis and site localization."; Nat. Biotechnol. 24:1285-1292(2006).
[24]	INTERACTION WITH HJURP. DOI=10.1158/0008-5472.CAN-07-1307; PubMed=17823411 [NCBI, ExPASy, EBI, Israel, Japan] Kato T., Sato N., Hayama S., Yamabuki T., Ito T., Miyamoto M., Kondo S., Nakamura Y., Daigo Y.; "Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells."; Cancer Res. 67:8544-8553(2007).
[25]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343 AND SER-397, AND MASS SPECTROMETRY. DOI=10.1126/science.1140321; PubMed=17525332 [NCBI, ExPASy, EBI, Israel, Japan] Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."; Science 316:1160-1166(2007).
[26]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397 AND SER-432, AND MASS SPECTROMETRY. DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan] Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.; "A quantitative atlas of mitotic phosphorylation."; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[27]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.
[28]	VARIANTS LEU-93; ASN-95; VAL-171; PHE-210 AND TRP-215, AND POSSIBLE INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC ANEMIA. PubMed=11325820 [NCBI, ExPASy, EBI, Israel, Japan] Varon R., Reis A., Henze G., von Einsiedel H.G., Sperling K., Seeger K.; "Mutations in the Nijmegen breakage syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL)."; Cancer Res. 61:3570-3572(2001).
[29]	VARIANT BC PHE-150, AND VARIANTS GLN-185 AND ILE-574. DOI=10.1136/jmg.40.12.e131; PubMed=14684699 [NCBI, ExPASy, EBI, Israel, Japan] Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.; "Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility."; J. Med. Genet. 40:E131-E131(2003).
[30]	VARIANT GLN-185. DOI=10.1093/carcin/bgh058; PubMed=14688016 [NCBI, ExPASy, EBI, Israel, Japan] Sanyal S., Festa F., Sakano S., Zhang Z., Steineck G., Norming U., Wijkstroem H., Larsson P., Kumar R., Hemminki K.; "Polymorphisms in DNA repair and metabolic genes in bladder cancer."; Carcinogenesis 25:729-734(2004).
[31]	VARIANT VAL-171. DOI=10.1007/s00439-004-1155-1; PubMed=15338273 [NCBI, ExPASy, EBI, Israel, Japan] Shimada H., Shimizu K., Mimaki S., Sakiyama T., Mori T., Shimasaki N., Yokota J., Nakachi K., Ohta T., Ohki M.; "First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability."; Hum. Genet. 115:372-376(2004).

Comments

FUNCTION: Component of the MRE11/RAD50/NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability.
SUBUNIT: Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50 and MRE11A (By similarity). Interacts with histone H2AFX this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with HJURP, KPNA2 and TERF2.
INTERACTION:
P24864:CCNE1; NbExp=1; IntAct=EBI-494844, EBI-519526;
P16104:H2AFX; NbExp=6; IntAct=EBI-494844, EBI-494830;
Q14676:MDC1; NbExp=2; IntAct=EBI-494844, EBI-495644;
P49959:MRE11A; NbExp=1; IntAct=EBI-494844, EBI-396513;
SUBCELLULAR LOCATION: Nucleus (By similarity). Telomere (By similarity). Note=Localizes to discrete nuclear foci after treatment with genotoxic agents (By similarity).
TISSUE SPECIFICITY: Ubiquitous. Expressed at high levels in testis.
DOMAIN: The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AFX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage.
DOMAIN: The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.
DOMAIN: The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.
PTM: Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.
DISEASE: Defects in NBN are the cause of Nijmegen breakage syndrome (NBS) [MIM:251260]. NBS is an autosomal recessive syndrome characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies.
DISEASE: Defects in NBN are a cause of genetic susceptibility to breast cancer (BC) [MIM:114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime. A positive family history has been identified as major contributor to risk of development of the disease, and this link is striking for early-onset breast cancer.
DISEASE: Defects in NBN may be associated with aplastic anemia [MIM:609135]. Aplastic anemia is a disease of bone-marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. Most of the cases of aplastic anemia are idiopathic, some are familial and some are due to a viral infection or to exposure to chemicals and radiation.
DISEASE: Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).
MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.
SIMILARITY: Contains 1 BRCT domain.
SIMILARITY: Contains 1 FHA domain.
SEQUENCE CAUTION:
- Sequence=AAI08651.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 550
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NBS1ID160.html";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=NBN";.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nbs1/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF051334; AAC39732.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF058696; AAC39752.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB013139; BAA28616.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF069291; AAC62232.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AK312410; BAG35323.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AK223256; BAD96976.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY566246; AAS59158.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC108650; AAI08651.1; ALT_SEQ; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BX640816; CAH56160.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00299463; -.

T00393; T00393.

NP_002476.2; -.

3D structure databases

ModBase

O60934.

Protein-protein interaction databases

IntAct

O60934; 5.

PTM databases

PhosphoSite

O60934; -.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway; BARD1 signaling events.
telomerasepathway; Regulation of Telomerase.

Reactome

REACT_216; DNA Repair.

Organism-specific databases

GC08M091015; -.

HIX0007638; -.

HGNC:7652; NBN.

NBN.

CAB003836; -.
HPA001429; -.

MIM

114480; phenotype. [NCBI / EBI]
251260; phenotype. [NCBI / EBI]
602667; gene. [NCBI / EBI]
609135; phenotype. [NCBI / EBI]

Orphanet

647; Nijmegen breakage syndrome.

PharmGKB

PA31457; -.

Gene expression databases

O60934; -.

O60934; -.

HS_NBN; -.

ENSG00000104320; Homo sapiens.

Ontologies

GO:0005794;	Cellular component: Golgi apparatus (inferred from direct assay from HPA).
GO:0030870;	Cellular component: Mre11 complex (inferred from direct assay from UniProtKB).
GO:0000784;	Cellular component: nuclear chromosome, telomeric region (inferred from direct assay from UniProtKB).
GO:0042405;	Cellular component: nuclear inclusion body (inferred from direct assay from UniProtKB).
GO:0005730;	Cellular component: nucleolus (inferred from direct assay from UniProtKB).
GO:0005654;	Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0047485;	Molecular function: protein N-terminus binding (inferred from physical interaction from UniProtKB).
GO:0008134;	Molecular function: transcription factor binding (inferred from physical interaction from UniProtKB).
GO:0007050;	Biological process: cell cycle arrest (traceable author statement from UniProtKB).
GO:0030330;	Biological process: DNA damage response, signal transduction by p53 class mediator (traceable author statement from UniProtKB).
GO:0006302;	Biological process: double-strand break repair (inferred from direct assay from UniProtKB).
GO:0031575;	Biological process: G1/S transition checkpoint (inferred from direct assay from UniProtKB).
GO:0007126;	Biological process: meiosis (inferred from electronic annotation from UniProtKB-KW).
GO:0007095;	Biological process: mitotic cell cycle G2/M transition DNA damage checkpoint (inferred from direct assay from UniProtKB).
GO:0030174;	Biological process: regulation of DNA replication initiation (traceable author statement from UniProtKB).
GO:0000723;	Biological process: telomere maintenance (inferred from mutant phenotype from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR001357; BRCT.
IPR013908; DNA-repair_Nbs1_C.
IPR000253; FHA.
IPR016592; Nibrin_met.
Graphical view of domain structure.

Gene3D

G3DSA:2.60.200.20; FHA; 1.

Pfam

PF00533; BRCT; 1.
PF00498; FHA; 1.
PF08599; Nbs1_C; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF011869; Nibrin_animal; 1.

SMART

SM00292; BRCT; 1.
SM00240; FHA; 1.
SMART graphical view of domain structure.

PROSITE

PS50172; BRCT; FALSE_NEG.
PS50006; FHA_DOMAIN; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

O60934; -.

Genome annotation databases

Ensembl

ENSG00000104320; Homo sapiens. [Contig view]

GeneID

4683; -.

KEGG

hsa:4683; -.

Phylogenomic databases

HOGENOM

O60934; -.

HOVERGEN

O60934; -.

OMA

O60934; QEMEVQN.

Other

18054; -.

NBN; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Cell cycle; Chromosomal protein; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; Meiosis; Nucleus; Phosphoprotein; Polymorphism; Telomere.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 754`	`754`	`Nibrin.`	`PRO_0000231043`
`DOMAIN`	`24 83`	`60`	`FHA.`
`DOMAIN`	`105 181`	`77`	`BRCT.`
`MOTIF`	`461 467`	`7`	`Nuclear localization signal.`
`MOTIF`	`736 743`	`8`	`EEXXXDDL motif.`
`COMPBIAS`	`448 451`	`4`	`Poly-Gln.`
`MOD_RES`	`278 278`		`Phosphoserine; by ATM.`
`MOD_RES`	`343 343`		`Phosphoserine; by ATM.`
`MOD_RES`	`397 397`		`Phosphoserine.`
`MOD_RES`	`432 432`		`Phosphoserine.`
`MOD_RES`	`615 615`		`Phosphoserine.`
`VARIANT`	`93 93`	`1`	`S -> L (in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant).`	`VAR_025792`
`VARIANT`	`95 95`	`1`	`D -> N (in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant).`	`VAR_025793`
`VARIANT`	`105 105`	`1`	`K -> N (in dbSNP:rs13312858 [NCBI]).`	`VAR_025794`
`VARIANT`	`142 142`	`1`	`N -> S (in dbSNP:rs769414 [NCBI]).`	`VAR_051226`
`VARIANT`	`150 150`	`1`	`L -> F (in BC).`	`VAR_025795`
`VARIANT`	`171 171`	`1`	`I -> V (in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity).`	`VAR_025796`
`VARIANT`	`185 185`	`1`	`E -> Q (in dbSNP:rs1805794 [NCBI]).`	`VAR_025797`
`VARIANT`	`210 210`	`1`	`V -> F.`	`VAR_025798`
`VARIANT`	`215 215`	`1`	`R -> W.`	`VAR_025799`
`VARIANT`	`216 216`	`1`	`Q -> K (in dbSNP:rs769416 [NCBI]).`	`VAR_025800`
`VARIANT`	`266 266`	`1`	`P -> L (in dbSNP:rs769420 [NCBI]).`	`VAR_025801`
`VARIANT`	`408 408`	`1`	`K -> E (in dbSNP:rs34120922 [NCBI]).`	`VAR_051227`
`VARIANT`	`497 497`	`1`	`T -> A (in dbSNP:rs3026268 [NCBI]).`	`VAR_025802`
`VARIANT`	`574 574`	`1`	`L -> I.`	`VAR_025803`
`MUTAGEN`	`28 28`		`R->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.`
`MUTAGEN`	`45 45`		`H->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.`
`MUTAGEN`	`136 137`		`GG->EE: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.`
`MUTAGEN`	`176 176`		`Y->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.`
`MUTAGEN`	`343 343`		`S->A: Abrogates ATM-dependent phosphorylation.`
`MUTAGEN`	`397 397`		`S->A: Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2.`
`MUTAGEN`	`465 466`		`KR->AA: Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation.`
`MUTAGEN`	`583 583`		`Q->K: No loss of interaction with KPNA2.`
`MUTAGEN`	`615 615`		`S->A: Abrogates ATM-dependent phosphorylation.`
`MUTAGEN`	`736 737`		`EE->AA: Decreases ATM binding.`
`MUTAGEN`	`741 742`		`DD->AA: Decreases ATM binding.`
`MUTAGEN`	`745 746`		`RY->AA: Decreases ATM binding.`
`CONFLICT`	`247 247`		`G -> R (in Ref. 6; BAD96976).`

Sequence information

Length: 754 AA [This is the length of the unprocessed precursor]

Molecular weight: 84959 Da [This is the MW of the unprocessed precursor]

CRC64: CD602F09BA73DAB6 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT 

        70         80         90        100        110        120 
DEIPVLTLKD NSKYGTFVNE EKMQNGFSRT LKSGDGITFG VFGSKFRIEY EPLVACSSCL 

       130        140        150        160        170        180 
DVSGKTALNQ AILQLGGFTV NNWTEECTHL VMVSVKVTIK TICALICGRP IVKPEYFTEF 

       190        200        210        220        230        240 
LKAVESKKQP PQIESFYPPL DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS 

       250        260        270        280        290        300 
AVVFGGGEAR LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ 

       310        320        330        340        350        360 
GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGVSVDE KLMPSAPVNT 

       370        380        390        400        410        420 
TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA PTVKESCKTS SNNNSMVSNT 

       430        440        450        460        470        480 
LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS 

       490        500        510        520        530        540 
ARIETSCSLL EQTQPATPSL WKNKEQHLSE NEPVDTNSDN NLFTDTDLKS IVKNSASKSH 

       550        560        570        580        590        600 
AAEKLRSNKK REMDDVAIED EVLEQLFKDT KPELEIDVKV QKQEEDVNVR KRPRMDIETN 

       610        620        630        640        650        660 
DTFSDEAVPE SSKISQENEI GKKRELKEDS LWSAKEISNN DKLQDDSEML PKKLLLTEFR 

       670        680        690        700        710        720 
SLVIKNSTSR NPSGINDDYG QLKNFKKFKK VTYPGAGKLP HIIGGSDLIA HHARKNTELE 

       730        740        750 
EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL KRRR

O60934 in FASTA format

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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools