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O60934 (NBN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nibrin
Alternative name(s):
Cell cycle regulatory protein p95
Nijmegen breakage syndrome protein 1
Gene names
Name:NBN
Synonyms:NBS, NBS1, P95
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length754 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex. Ref.11 Ref.16 Ref.22 Ref.30 Ref.36

Subunit structure

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. Interacts with histone H2AFX this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with HJURP, INTS3, KPNA2 and TERF2. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection. Interacts with SP100; recruits NBN to PML bodies. Interacts with ATF2. Interacts with MTOR, MAPKAP1 isoform 2and RICTOR; indicative for an association with the mTORC2 complex. Ref.2 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.26 Ref.30 Ref.31 Ref.36

Subcellular location

Nucleus By similarity. NucleusPML body. Chromosometelomere By similarity. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents By similarity. Ref.17 Ref.20

Tissue specificity

Ubiquitous. Expressed at high levels in testis.

Induction

Up-regulated by ionizing radiation (IR). Ref.36

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. Ref.21

The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex. Ref.21

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. Ref.21

Post-translational modification

Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance. Ref.13 Ref.14 Ref.15

Involvement in disease

Nijmegen breakage syndrome (NBS) [MIM:251260]: A disorder characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.38

Aplastic anemia (AA) [MIM:609135]: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.

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.

Sequence similarities

Contains 1 BRCT domain.

Contains 1 FHA domain.

Sequence caution

The sequence AAI08651.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence starting in position 550.

The sequence CAH56160.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
Meiosis
   Cellular componentChromosome
Nucleus
Telomere
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from direct assay PubMed 12529385. Source: MGI

DNA damage response, signal transduction by p53 class mediator

Traceable author statement Ref.2. Source: UniProtKB

DNA duplex unwinding

Inferred from mutant phenotype PubMed 15790808. Source: BHF-UCL

DNA repair

Traceable author statement. Source: Reactome

blastocyst growth

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Traceable author statement Ref.2. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: Ensembl

double-strand break repair

Inferred from direct assay Ref.2. Source: UniProtKB

double-strand break repair via homologous recombination

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

isotype switching

Inferred from electronic annotation. Source: Ensembl

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic G2 DNA damage checkpoint

Inferred from direct assay PubMed 11438675. Source: UniProtKB

mitotic cell cycle checkpoint

Inferred from direct assay PubMed 10766245. Source: UniProtKB

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

positive regulation of kinase activity

Inferred from direct assay PubMed 15790808. Source: BHF-UCL

positive regulation of protein autophosphorylation

Inferred from direct assay PubMed 15790808. Source: BHF-UCL

regulation of DNA-dependent DNA replication initiation

Traceable author statement Ref.2. Source: UniProtKB

telomere maintenance

Inferred from mutant phenotype PubMed 11448772. Source: UniProtKB

   Cellular_componentMre11 complex

Inferred from direct assay Ref.2. Source: UniProtKB

PML body

Inferred from direct assay Ref.17. Source: UniProtKB

nuclear chromosome, telomeric region

Inferred from direct assay Ref.16. Source: BHF-UCL

nuclear inclusion body

Inferred from direct assay PubMed 12447371. Source: UniProtKB

nucleolus

Inferred from direct assay Ref.16. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.16. Source: BHF-UCL

replication fork

Inferred from electronic annotation. Source: Ensembl

site of double-strand break

Inferred from direct assay Ref.20. Source: UniProtKB

   Molecular_functiondamaged DNA binding

Inferred from electronic annotation. Source: Ensembl

protein N-terminus binding

Inferred from physical interaction Ref.2. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 11486038. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 754754Nibrin
PRO_0000231043

Regions

Domain24 – 8360FHA
Domain105 – 18177BRCT
Region111 – 328218Mediates interaction with SP100 By similarity
Region221 – 402182Interaction with MTOR, MAPKAP1 and RICTOR
Motif461 – 4677Nuclear localization signal
Motif736 – 7438EEXXXDDL motif
Compositional bias448 – 4514Poly-Gln

Amino acid modifications

Modified residue2781Phosphoserine; by ATM Ref.14
Modified residue3431Phosphoserine; by ATM Ref.13 Ref.15
Modified residue3971Phosphoserine Ref.15 Ref.27 Ref.28 Ref.33
Modified residue4021Phosphothreonine Ref.33
Modified residue4321Phosphoserine Ref.25 Ref.28 Ref.33
Modified residue6151Phosphoserine Ref.15

Natural variations

Natural variant931S → L in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. Ref.37
Corresponds to variant rs12721593 [ dbSNP | Ensembl ].
VAR_025792
Natural variant951D → N in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. Ref.37
Corresponds to variant rs61753720 [ dbSNP | Ensembl ].
VAR_025793
Natural variant1051K → N. Ref.7
Corresponds to variant rs13312858 [ dbSNP | Ensembl ].
VAR_025794
Natural variant1421N → S.
Corresponds to variant rs769414 [ dbSNP | Ensembl ].
VAR_051226
Natural variant1501L → F in BC. Ref.38
VAR_025795
Natural variant1711I → V in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity. Ref.37 Ref.40
Corresponds to variant rs61754966 [ dbSNP | Ensembl ].
VAR_025796
Natural variant1851E → Q. Ref.1 Ref.2 Ref.5 Ref.7 Ref.38 Ref.39
Corresponds to variant rs1805794 [ dbSNP | Ensembl ].
VAR_025797
Natural variant2101V → F. Ref.37
Corresponds to variant rs61754796 [ dbSNP | Ensembl ].
VAR_025798
Natural variant2151R → W. Ref.37
Corresponds to variant rs34767364 [ dbSNP | Ensembl ].
VAR_025799
Natural variant2161Q → K. Ref.7
Corresponds to variant rs769416 [ dbSNP | Ensembl ].
VAR_025800
Natural variant2661P → L. Ref.7
Corresponds to variant rs769420 [ dbSNP | Ensembl ].
VAR_025801
Natural variant4081K → E.
Corresponds to variant rs34120922 [ dbSNP | Ensembl ].
VAR_051227
Natural variant4971T → A. Ref.7
Corresponds to variant rs3026268 [ dbSNP | Ensembl ].
VAR_025802
Natural variant5741L → I. Ref.38
Corresponds to variant rs142334798 [ dbSNP | Ensembl ].
VAR_025803
Natural variant6791Y → H Found in a renal cell carcinoma sample; somatic mutation. Ref.41
VAR_064738

Experimental info

Mutagenesis281R → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.21
Mutagenesis451H → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.21
Mutagenesis136 – 1372GG → EE: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.21
Mutagenesis1761Y → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.21
Mutagenesis3431S → A: Abrogates ATM-dependent phosphorylation. Ref.15 Ref.21
Mutagenesis3971S → A: Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2. Ref.15 Ref.19 Ref.21
Mutagenesis465 – 4662KR → AA: Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation. Ref.21
Mutagenesis5831Q → K: No loss of interaction with KPNA2. Ref.19 Ref.21
Mutagenesis6151S → A: Abrogates ATM-dependent phosphorylation. Ref.15 Ref.21
Mutagenesis736 – 7372EE → AA: Decreases ATM binding. Ref.21
Mutagenesis741 – 7422DD → AA: Decreases ATM binding. Ref.21
Mutagenesis745 – 7462RY → AA: Decreases ATM binding. Ref.21
Sequence conflict2471G → R in BAD96976. Ref.6

Sequences

Sequence LengthMass (Da)Tools
O60934 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: CD602F09BA73DAB6

FASTA75484,959
        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 

« Hide

References

« Hide 'large scale' references
[1]"Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome."
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.
Cell 93:467-476(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN NIJMEGEN BREAKAGE SYNDROME, VARIANT GLN-185.
[2]"The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response."
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.
Cell 93:477-486(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: 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, INTERACTION WITH MRE11 AND RAD50.
[3]"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 B.H., Kaloustian V.M., Oshimura M., Isomura M., Nakamura Y., Komatsu K.
Nat. Genet. 19:179-181(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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 55:242-247(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Fibroblast.
[5]"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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-185.
Tissue: Brain.
[6]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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Synovial cell.
[7]NIEHS SNPs program
Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-105; GLN-185; LYS-216; LEU-266 AND ALA-497.
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Skin and Testis.
[10]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-754.
Tissue: Colon endothelium.
[11]"Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95."
Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.
J. Biol. Chem. 273:21447-21450(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DSB REPAIR, IDENTIFICATION IN THE MRN COMPLEX WITH MRE11A AND RAD50.
[12]"Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization."
Desai-Mehta A., Cerosaletti K.M., Concannon P.
Mol. Cell. Biol. 21:2184-2191(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MRE11.
[13]"ATM-dependent phosphorylation of nibrin in response to radiation exposure."
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.
Nat. Genet. 25:115-119(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-343, MUTAGENESIS OF ARG-28; HIS-45; 136-GLY-GLY-137 AND TYR-176.
[14]"Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products."
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.
Nature 405:473-477(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-278.
[15]"ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response."
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.
Nature 405:477-482(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-343; SER-397 AND SER-615, MUTAGENESIS OF SER-343; SER-397 AND SER-615.
[16]"Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres."
Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.
Nat. Genet. 25:347-352(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH TERF2.
[17]"Recruitment of NBS1 into PML oncogenic domains via interaction with SP100 protein."
Naka K., Ikeda K., Motoyama N.
Biochem. Biophys. Res. Commun. 299:863-871(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SP100, SUBCELLULAR LOCATION.
[18]"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. 12:1846-1851(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH H2AFX.
[19]"Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1."
Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C.
J. Biol. Chem. 280:39594-39600(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KPNA2, MUTAGENESIS OF SER-397; 465-LYS-ARG-466 AND GLN-583.
[20]"ATM-dependent phosphorylation of ATF2 is required for the DNA damage response."
Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.
Mol. Cell 18:577-587(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATF2, SUBCELLULAR LOCATION.
[21]"Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."
Falck J., Coates J., Jackson S.P.
Nature 434:605-611(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, MUTAGENESIS OF 736-GLU-GLU-737; 741-ASP-ASP-742 AND 745-ARG-TYR-746.
[22]"Nbs1 is required for ATR-dependent phosphorylation events."
Stiff T., Reis C., Alderton G.K., Woodbine L., O'Driscoll M., Jeggo P.A.
EMBO J. 24:199-208(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control."
Zhang Y., Zhou J., Lim C.U.
Cell Res. 16:45-54(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[24]"Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex."
Stracker T.H., Carson C.T., Weitzman M.D.
Nature 418:348-352(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INACTIVATION BY ADENOVIRUS ONCOPROTEINS.
[25]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"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. 67:8544-8553(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HJURP.
[27]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
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.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[28]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397 AND SER-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair."
Yuan J., Chen J.
J. Biol. Chem. 284:31746-31752(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RBBP8.
[31]"SOSS complexes participate in the maintenance of genomic stability."
Huang J., Gong Z., Ghosal G., Chen J.
Mol. Cell 35:384-393(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INTS3.
[32]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[33]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397; THR-402 AND SER-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[34]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains."
Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C., Wu K.J.
PLoS ONE 8:E65586-E65586(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AKT1 PHOSPHORYLATION, INTERACTION WITH MTOR; MAPKAP1 AND RICTOR, INDUCTION BY IONIZING RADIATION.
[37]"Mutations in the Nijmegen breakage syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL)."
Varon R., Reis A., Henze G., von Einsiedel H.G., Sperling K., Seeger K.
Cancer Res. 61:3570-3572(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-93; ASN-95; VAL-171; PHE-210 AND TRP-215, POSSIBLE INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA.
[38]"Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility."
Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.
J. Med. Genet. 40:E131-E131(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BC PHE-150, VARIANTS GLN-185 AND ILE-574.
[39]"Polymorphisms in DNA repair and metabolic genes in bladder cancer."
Sanyal S., Festa F., Sakano S., Zhang Z., Steineck G., Norming U., Wijkstroem H., Larsson P., Kumar R., Hemminki K.
Carcinogenesis 25:729-734(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-185.
[40]"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. 115:372-376(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-171.
[41]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-679.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF051334 mRNA. Translation: AAC39732.1.
AF058696 mRNA. Translation: AAC39752.1.
AB013139 Genomic DNA. Translation: BAA28616.1.
AF069291 Genomic DNA. Translation: AAC62232.1.
AK312410 mRNA. Translation: BAG35323.1.
AK223256 mRNA. Translation: BAD96976.1.
AY566246 Genomic DNA. Translation: AAS59158.1.
CH471060 Genomic DNA. Translation: EAW91660.1.
BC108650 mRNA. Translation: AAI08651.1. Sequence problems.
BC136802 mRNA. Translation: AAI36803.1.
BC136803 mRNA. Translation: AAI36804.1.
BX640816 mRNA. Translation: CAH56160.1. Different initiation.
PIRT00393.
RefSeqNP_002476.2. NM_002485.4.
XP_005250980.1. XM_005250923.1.
UniGeneHs.492208.

3D structure databases

ProteinModelPortalO60934.
SMRO60934. Positions 12-326.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110763. 55 interactions.
DIPDIP-33605N.
IntActO60934. 15 interactions.
MINTMINT-203482.
STRING9606.ENSP00000265433.

PTM databases

PhosphoSiteO60934.

Proteomic databases

PaxDbO60934.
PRIDEO60934.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265433; ENSP00000265433; ENSG00000104320.
ENST00000409330; ENSP00000386924; ENSG00000104320.
GeneID4683.
KEGGhsa:4683.
UCSCuc003yei.1. human.

Organism-specific databases

CTD4683.
GeneCardsGC08M091015.
HGNCHGNC:7652. NBN.
HPACAB003836.
HPA001429.
MIM114480. phenotype.
251260. phenotype.
602667. gene.
609135. phenotype.
neXtProtNX_O60934.
Orphanet1331. Familial prostate cancer.
145. Hereditary breast and ovarian cancer syndrome.
647. Nijmegen breakage syndrome.
PharmGKBPA31457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84999.
HOVERGENHBG053070.
InParanoidO60934.
KOK10867.
OMAKLPHIIG.
OrthoDBEOG7B5WV7.
PhylomeDBO60934.
TreeFamTF101103.

Enzyme and pathway databases

ReactomeREACT_111183. Meiosis.
REACT_120956. Cellular responses to stress.
REACT_216. DNA Repair.

Gene expression databases

ArrayExpressO60934.
BgeeO60934.
CleanExHS_NBN.
GenevestigatorO60934.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
3.40.50.10190. 1 hit.
InterProIPR001357. BRCT_dom.
IPR013908. DNA-repair_Nbs1_C.
IPR000253. FHA_dom.
IPR016592. Nibrin_met.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamPF00498. FHA. 1 hit.
PF08599. Nbs1_C. 1 hit.
[Graphical view]
PIRSFPIRSF011869. Nibrin_animal. 1 hit.
SMARTSM00292. BRCT. 1 hit.
SM00240. FHA. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF52113. SSF52113. 1 hit.
PROSITEPS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNibrin.
GenomeRNAi4683.
NextBio18054.
PROO60934.
SOURCESearch...

Entry information

Entry nameNBN_HUMAN
AccessionPrimary (citable) accession number: O60934
Secondary accession number(s): B2R626 expand/collapse secondary AC list , B2RNC5, O60672, Q32NF7, Q53FM6, Q63HR6, Q7LDM2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM