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O60934

- NBN_HUMAN

UniProt

O60934 - NBN_HUMAN

Protein

Nibrin

Gene

NBN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    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.5 Publications

    GO - Molecular functioni

    1. damaged DNA binding Source: Ensembl
    2. protein binding Source: UniProtKB
    3. protein N-terminus binding Source: UniProtKB
    4. transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. blastocyst growth Source: Ensembl
    2. cell cycle arrest Source: UniProtKB
    3. cell proliferation Source: Ensembl
    4. DNA damage checkpoint Source: MGI
    5. DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
    6. DNA duplex unwinding Source: BHF-UCL
    7. DNA repair Source: Reactome
    8. double-strand break repair Source: UniProtKB
    9. double-strand break repair via homologous recombination Source: Reactome
    10. intrinsic apoptotic signaling pathway Source: Ensembl
    11. isotype switching Source: Ensembl
    12. meiotic nuclear division Source: UniProtKB-KW
    13. mitotic cell cycle checkpoint Source: UniProtKB
    14. mitotic G2 DNA damage checkpoint Source: UniProtKB
    15. neuromuscular process controlling balance Source: Ensembl
    16. positive regulation of kinase activity Source: BHF-UCL
    17. positive regulation of protein autophosphorylation Source: BHF-UCL
    18. regulation of DNA-dependent DNA replication initiation Source: UniProtKB
    19. telomere maintenance Source: UniProtKB

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA repair, Meiosis

    Enzyme and pathway databases

    ReactomeiREACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_1884. MRN complex relocalizes to nuclear foci.
    REACT_1924. ATM mediated phosphorylation of repair proteins.
    REACT_27271. Meiotic recombination.
    REACT_486. Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nibrin
    Alternative name(s):
    Cell cycle regulatory protein p95
    Nijmegen breakage syndrome protein 1
    Gene namesi
    Name:NBN
    Synonyms:NBS, NBS1, P95
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:7652. NBN.

    Subcellular locationi

    Nucleus By similarity. NucleusPML body 2 Publications. Chromosometelomere By similarity
    Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.By similarity

    GO - Cellular componenti

    1. Mre11 complex Source: UniProtKB
    2. nuclear chromosome, telomeric region Source: BHF-UCL
    3. nuclear inclusion body Source: UniProtKB
    4. nucleolus Source: BHF-UCL
    5. nucleoplasm Source: Reactome
    6. nucleus Source: BHF-UCL
    7. PML body Source: UniProtKB
    8. replication fork Source: Ensembl
    9. site of double-strand break Source: UniProtKB

    Keywords - Cellular componenti

    Chromosome, Nucleus, Telomere

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    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.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti150 – 1501L → F in BC. 1 Publication
    VAR_025795
    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).

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi28 – 281R → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. 2 Publications
    Mutagenesisi45 – 451H → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. 2 Publications
    Mutagenesisi136 – 1372GG → EE: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. 1 Publication
    Mutagenesisi176 – 1761Y → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. 2 Publications
    Mutagenesisi343 – 3431S → A: Abrogates ATM-dependent phosphorylation. 2 Publications
    Mutagenesisi397 – 3971S → A: Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2. 3 Publications
    Mutagenesisi465 – 4662KR → AA: Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation. 1 Publication
    Mutagenesisi583 – 5831Q → K: No loss of interaction with KPNA2. 2 Publications
    Mutagenesisi615 – 6151S → A: Abrogates ATM-dependent phosphorylation. 2 Publications
    Mutagenesisi736 – 7372EE → AA: Decreases ATM binding. 1 Publication
    Mutagenesisi741 – 7422DD → AA: Decreases ATM binding. 1 Publication
    Mutagenesisi745 – 7462RY → AA: Decreases ATM binding. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi114480. phenotype.
    251260. phenotype.
    609135. phenotype.
    Orphaneti1331. Familial prostate cancer.
    145. Hereditary breast and ovarian cancer syndrome.
    647. Nijmegen breakage syndrome.
    PharmGKBiPA31457.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 754754NibrinPRO_0000231043Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei278 – 2781Phosphoserine; by ATM1 Publication
    Modified residuei343 – 3431Phosphoserine; by ATM2 Publications
    Modified residuei397 – 3971Phosphoserine4 Publications
    Modified residuei402 – 4021Phosphothreonine1 Publication
    Modified residuei432 – 4321Phosphoserine3 Publications
    Modified residuei615 – 6151Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.7 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO60934.
    PaxDbiO60934.
    PRIDEiO60934.

    PTM databases

    PhosphoSiteiO60934.

    Expressioni

    Tissue specificityi

    Ubiquitous. Expressed at high levels in testis.

    Inductioni

    Up-regulated by ionizing radiation (IR).1 Publication

    Gene expression databases

    ArrayExpressiO60934.
    BgeeiO60934.
    CleanExiHS_NBN.
    GenevestigatoriO60934.

    Organism-specific databases

    HPAiCAB003836.
    HPA001429.

    Interactioni

    Subunit structurei

    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 2 and RICTOR; indicative for an association with the mTORC2 complex.12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EP300Q094725EBI-494844,EBI-447295
    FANCD2Q9BXW96EBI-494844,EBI-359343
    H2AFXP1610412EBI-494844,EBI-494830
    MDC1Q1467626EBI-494844,EBI-495644
    MRE11AP499592EBI-494844,EBI-396513
    SIRT1Q96EB65EBI-494844,EBI-1802965

    Protein-protein interaction databases

    BioGridi110763. 58 interactions.
    DIPiDIP-33605N.
    IntActiO60934. 17 interactions.
    MINTiMINT-203482.
    STRINGi9606.ENSP00000265433.

    Structurei

    3D structure databases

    ProteinModelPortaliO60934.
    SMRiO60934. Positions 8-109, 217-326.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 8360FHAPROSITE-ProRule annotationAdd
    BLAST
    Domaini105 – 18177BRCTAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni111 – 328218Mediates interaction with SP100By similarityAdd
    BLAST
    Regioni221 – 402182Interaction with MTOR, MAPKAP1 and RICTORAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi461 – 4677Nuclear localization signal
    Motifi736 – 7438EEXXXDDL motif

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi448 – 4514Poly-Gln

    Domaini

    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.1 Publication
    The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.1 Publication
    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.1 Publication

    Sequence similaritiesi

    Contains 1 BRCT domain.Curated
    Contains 1 FHA domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG84999.
    HOVERGENiHBG053070.
    InParanoidiO60934.
    KOiK10867.
    OMAiKLPHIIG.
    OrthoDBiEOG7B5WV7.
    PhylomeDBiO60934.
    TreeFamiTF101103.

    Family and domain databases

    Gene3Di2.60.200.20. 1 hit.
    3.40.50.10190. 1 hit.
    InterProiIPR001357. BRCT_dom.
    IPR013908. DNA-repair_Nbs1_C.
    IPR000253. FHA_dom.
    IPR016592. Nibrin_met.
    IPR008984. SMAD_FHA_domain.
    [Graphical view]
    PfamiPF00498. FHA. 1 hit.
    PF08599. Nbs1_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF011869. Nibrin_animal. 1 hit.
    SMARTiSM00292. BRCT. 1 hit.
    SM00240. FHA. 1 hit.
    [Graphical view]
    SUPFAMiSSF49879. SSF49879. 1 hit.
    SSF52113. SSF52113. 1 hit.
    PROSITEiPS50006. FHA_DOMAIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O60934-1 [UniParc]FASTAAdd to Basket

    « Hide

    MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA    50
    NFSVTNLSQT DEIPVLTLKD NSKYGTFVNE EKMQNGFSRT LKSGDGITFG 100
    VFGSKFRIEY EPLVACSSCL DVSGKTALNQ AILQLGGFTV NNWTEECTHL 150
    VMVSVKVTIK TICALICGRP IVKPEYFTEF LKAVESKKQP PQIESFYPPL 200
    DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS AVVFGGGEAR 250
    LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ 300
    GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGVSVDE 350
    KLMPSAPVNT TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA 400
    PTVKESCKTS SNNNSMVSNT LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ 450
    QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS ARIETSCSLL EQTQPATPSL 500
    WKNKEQHLSE NEPVDTNSDN NLFTDTDLKS IVKNSASKSH AAEKLRSNKK 550
    REMDDVAIED EVLEQLFKDT KPELEIDVKV QKQEEDVNVR KRPRMDIETN 600
    DTFSDEAVPE SSKISQENEI GKKRELKEDS LWSAKEISNN DKLQDDSEML 650
    PKKLLLTEFR SLVIKNSTSR NPSGINDDYG QLKNFKKFKK VTYPGAGKLP 700
    HIIGGSDLIA HHARKNTELE EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL 750
    KRRR 754
    Length:754
    Mass (Da):84,959
    Last modified:August 1, 1998 - v1
    Checksum:iCD602F09BA73DAB6
    GO

    Sequence cautioni

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti247 – 2471G → R in BAD96976. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti93 – 931S → L in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. 1 Publication
    Corresponds to variant rs12721593 [ dbSNP | Ensembl ].
    VAR_025792
    Natural varianti95 – 951D → N in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. 1 Publication
    Corresponds to variant rs61753720 [ dbSNP | Ensembl ].
    VAR_025793
    Natural varianti105 – 1051K → N.1 Publication
    Corresponds to variant rs13312858 [ dbSNP | Ensembl ].
    VAR_025794
    Natural varianti142 – 1421N → S.
    Corresponds to variant rs769414 [ dbSNP | Ensembl ].
    VAR_051226
    Natural varianti150 – 1501L → F in BC. 1 Publication
    VAR_025795
    Natural varianti171 – 1711I → V in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity. 2 Publications
    Corresponds to variant rs61754966 [ dbSNP | Ensembl ].
    VAR_025796
    Natural varianti185 – 1851E → Q.6 Publications
    Corresponds to variant rs1805794 [ dbSNP | Ensembl ].
    VAR_025797
    Natural varianti210 – 2101V → F.1 Publication
    Corresponds to variant rs61754796 [ dbSNP | Ensembl ].
    VAR_025798
    Natural varianti215 – 2151R → W.1 Publication
    Corresponds to variant rs34767364 [ dbSNP | Ensembl ].
    VAR_025799
    Natural varianti216 – 2161Q → K.1 Publication
    Corresponds to variant rs769416 [ dbSNP | Ensembl ].
    VAR_025800
    Natural varianti266 – 2661P → L.1 Publication
    Corresponds to variant rs769420 [ dbSNP | Ensembl ].
    VAR_025801
    Natural varianti408 – 4081K → E.
    Corresponds to variant rs34120922 [ dbSNP | Ensembl ].
    VAR_051227
    Natural varianti497 – 4971T → A.1 Publication
    Corresponds to variant rs3026268 [ dbSNP | Ensembl ].
    VAR_025802
    Natural varianti574 – 5741L → I.1 Publication
    Corresponds to variant rs142334798 [ dbSNP | Ensembl ].
    VAR_025803
    Natural varianti679 – 6791Y → H Found in a renal cell carcinoma sample; somatic mutation. 1 Publication
    VAR_064738

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS6249.1.
    PIRiT00393.
    RefSeqiNP_002476.2. NM_002485.4.
    XP_005250980.1. XM_005250923.1.
    UniGeneiHs.492208.

    Genome annotation databases

    EnsembliENST00000265433; ENSP00000265433; ENSG00000104320.
    ENST00000409330; ENSP00000386924; ENSG00000104320.
    GeneIDi4683.
    KEGGihsa:4683.
    UCSCiuc003yei.1. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS6249.1.
    PIRi T00393.
    RefSeqi NP_002476.2. NM_002485.4.
    XP_005250980.1. XM_005250923.1.
    UniGenei Hs.492208.

    3D structure databases

    ProteinModelPortali O60934.
    SMRi O60934. Positions 8-109, 217-326.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110763. 58 interactions.
    DIPi DIP-33605N.
    IntActi O60934. 17 interactions.
    MINTi MINT-203482.
    STRINGi 9606.ENSP00000265433.

    PTM databases

    PhosphoSitei O60934.

    Proteomic databases

    MaxQBi O60934.
    PaxDbi O60934.
    PRIDEi O60934.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000265433 ; ENSP00000265433 ; ENSG00000104320 .
    ENST00000409330 ; ENSP00000386924 ; ENSG00000104320 .
    GeneIDi 4683.
    KEGGi hsa:4683.
    UCSCi uc003yei.1. human.

    Organism-specific databases

    CTDi 4683.
    GeneCardsi GC08M091015.
    GeneReviewsi NBN.
    HGNCi HGNC:7652. NBN.
    HPAi CAB003836.
    HPA001429.
    MIMi 114480. phenotype.
    251260. phenotype.
    602667. gene.
    609135. phenotype.
    neXtProti NX_O60934.
    Orphaneti 1331. Familial prostate cancer.
    145. Hereditary breast and ovarian cancer syndrome.
    647. Nijmegen breakage syndrome.
    PharmGKBi PA31457.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG84999.
    HOVERGENi HBG053070.
    InParanoidi O60934.
    KOi K10867.
    OMAi KLPHIIG.
    OrthoDBi EOG7B5WV7.
    PhylomeDBi O60934.
    TreeFami TF101103.

    Enzyme and pathway databases

    Reactomei REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_1884. MRN complex relocalizes to nuclear foci.
    REACT_1924. ATM mediated phosphorylation of repair proteins.
    REACT_27271. Meiotic recombination.
    REACT_486. Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks.

    Miscellaneous databases

    GeneWikii Nibrin.
    GenomeRNAii 4683.
    NextBioi 18054.
    PROi O60934.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O60934.
    Bgeei O60934.
    CleanExi HS_NBN.
    Genevestigatori O60934.

    Family and domain databases

    Gene3Di 2.60.200.20. 1 hit.
    3.40.50.10190. 1 hit.
    InterProi IPR001357. BRCT_dom.
    IPR013908. DNA-repair_Nbs1_C.
    IPR000253. FHA_dom.
    IPR016592. Nibrin_met.
    IPR008984. SMAD_FHA_domain.
    [Graphical view ]
    Pfami PF00498. FHA. 1 hit.
    PF08599. Nbs1_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF011869. Nibrin_animal. 1 hit.
    SMARTi SM00292. BRCT. 1 hit.
    SM00240. FHA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    SSF52113. SSF52113. 1 hit.
    PROSITEi PS50006. FHA_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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. 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.
      , 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. 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. 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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    28. 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. 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. 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. Cited for: VARIANT HIS-679.

    Entry informationi

    Entry nameiNBN_HUMAN
    AccessioniPrimary (citable) accession number: O60934
    Secondary accession number(s): B2R626
    , B2RNC5, O60672, Q32NF7, Q53FM6, Q63HR6, Q7LDM2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 4, 2006
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 128 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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.

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3