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Protein FULL name:


NBN (NBS1) (Homo sapiens) is product of expression of NBN gene.

Human diseases related to this protein:

NBN (NBS1) is involved in:

DDS in Homo sapiens


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, INTS3, 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=4; 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 susceptibility to breast cancer (BC) [MIM:114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.

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: Note=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; Sequence=BAD96976.1; Type=Erroneous initiation; Sequence=CAH56160.1; Type=Erroneous initiation;

WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]

WEB RESOURCE: Name=GeneReviews; [LINK]


NCBI GenPept GI number(s): 33356172
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot O60934 O60934
PFAM: - O60934 (Link - using uniprot id)
InterPro: - O60934 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -

Protein sequence:

NBN (NBS1) (Homo sapiens) is able to recognize following damages:
NBN (NBS1) (Homo sapiens) belongs to following protein families:

Title Authors Journal
Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanova E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A Cell May 1, 1998
The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH Cell May 1, 1998
Positional cloning of the gene for Nijmegen breakage syndrome. Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, Smeets D, Solder B, Belohradsky BH, Der Kaloustian VM, Oshimura M, Isomura M, Nakamura Y, Komatsu K Nat Genet June 1, 1998
Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. Trujillo KM, Yuan SS, Lee EY, Sung P J Biol Chem Aug. 21, 1998
Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1. Tauchi H, Matsuura S, Isomura M, Kinjo T, Nakamura A, Sakamoto S, Kondo N, Endo S, Komatsu K, Nakamura Y Genomics Feb. 15, 1999
ATM-dependent phosphorylation of nibrin in response to radiation exposure. Gatei M, Young D, Cerosaletti KM, Desai-Mehta A, Spring K, Kozlov S, Lavin MF, Gatti RA, Concannon P, Khanna K Nat Genet May 1, 2000
ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Wu X, Ranganathan V, Weisman DS, Heine WF, Ciccone DN, O'Neill TB, Crick KE, Pierce KA, Lane WS, Rathbun G, Livingston DM, Weaver DT Nature May 25, 2000
Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Zhao S, Weng YC, Yuan SS, Lin YT, Hsu HC, Lin SC, Gerbino E, Song MH, Zdzienicka MZ, Gatti RA, Shay JW, Ziv Y, Shiloh Y, Lee EY Nature May 25, 2000
Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T Nat Genet July 1, 2000
Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization. Desai-Mehta A, Cerosaletti KM, Concannon P Mol Cell Biol March 1, 2001
Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL). Varon R, Reis A, Henze G, von Einsiedel HG, Sperling K, Seeger K Cancer Res May 1, 2001
Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Stracker TH, Carson CT, Weitzman MD Nature July 18, 2002
NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, Kobayashi T, Tamai K, Tanimoto K, Komatsu K Curr Biol Oct. 1, 2002
Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility. Heikkinen K, Karppinen SM, Soini Y, Makinen M, Winqvist R J Med Genet Dec. 1, 2003
Complete sequencing and characterization of 21,243 full-length human cDNAs. 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 TO, 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 Nat Genet Feb. 1, 2004
Polymorphisms in DNA repair and metabolic genes in bladder cancer. Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, Norming U, Wijkstrom H, Larsson P, Kumar R, Hemminki K Carcinogenesis May 1, 2004
Large-scale characterization of HeLa cell nuclear phosphoproteins. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP Proc Natl Acad Sci U S A Aug. 17, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability. Shimada H, Shimizu K, Mimaki S, Sakiyama T, Mori T, Shimasaki N, Yokota J, Nakachi K, Ohta T, Ohki M Hum Genet Oct. 1, 2004
Nbs1 is required for ATR-dependent phosphorylation events. Stiff T, Reis C, Alderton GK, Woodbine L, O'Driscoll M, Jeggo PA EMBO J Feb. 12, 2005
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Falck J, Coates J, Jackson SP Nature March 31, 2005
Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. Tseng SF, Chang CY, Wu KJ, Teng SC J Biol Chem Nov. 25, 2005
The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Zhang Y, Zhou J, Lim CU Cell Res Feb. 1, 2006
A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP Nat Biotechnol Oct. 1, 2006
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, 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 BMC Genomics Jan. 1, 2007
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007
Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells. Kato T, Sato N, Hayama S, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y, Daigo Y Cancer Res Sept. 15, 2007
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem June 1, 2009
SOSS complexes participate in the maintenance of genomic stability. Huang J, Gong Z, Ghosal G, Chen J Mol Cell Aug. 14, 2009

Last modification of this entry: Oct. 11, 2010.

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