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Q9R207 (NBN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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 homolog
Gene names
Name:Nbn
Synonyms:Nbs1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length751 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 By similarity.

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.7

Subcellular location

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

Tissue specificity

High expression in the liver, heart and testis. Low expression in all other tissues analyzed. In the cerebellum the postmitotic Purkinje cells are marked specifically. Ref.6

Developmental stage

A low level of expression is observed in all tissues. Highly specific expression was observed in organs with physiologic DNA double strand breakage (DSB), such as testis, thymus and spleen. Enhanced expression is also found at sites of high proliferative activity. These are the subventricular layer of the telencephalon and the diencephalon, the liver, lung, kidney and gut, as well as striated and smooth muscle cells in various organs. Ref.6

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 By similarity.

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

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 By similarity.

Post-translational modification

Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance By similarity. Ref.8

Sequence similarities

Contains 1 BRCT domain.

Contains 1 FHA domain.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
Meiosis
   Cellular componentChromosome
Nucleus
Telomere
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from sequence orthology PubMed 12529385. Source: MGI

blastocyst growth

Inferred from mutant phenotype PubMed 14612522. Source: UniProtKB

cell proliferation

Inferred from mutant phenotype PubMed 15821748. Source: MGI

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

in utero embryonic development

Inferred from mutant phenotype PubMed 14612522. Source: UniProtKB

intrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 18614044. Source: MGI

isotype switching

Inferred from direct assay PubMed 15668383. Source: UniProtKB

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic G2 DNA damage checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic cell cycle checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular process controlling balance

Inferred from mutant phenotype PubMed 15821748. Source: MGI

positive regulation of kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of fibroblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

telomere maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentMre11 complex

Inferred from sequence or structural similarity. Source: UniProtKB

PML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear chromosome, telomeric region

Inferred from electronic annotation. Source: Ensembl

nuclear inclusion body

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 11555636. Source: MGI

replication fork

Inferred from direct assay PubMed 11934988. Source: MGI

site of double-strand break

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP-dependent DNA helicase activity

Inferred from electronic annotation. Source: Ensembl

damaged DNA binding

Inferred from direct assay PubMed 11934988. Source: MGI

protein N-terminus binding

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 751751Nibrin
PRO_0000231044

Regions

Domain24 – 8360FHA
Domain105 – 18177BRCT
Region111 – 328218Mediates interaction with SP100
Region221 – 403183Interaction with MTOR, MAPKAP1 and RICTOR By similarity
Motif461 – 4677Nuclear localization signal By similarity
Motif734 – 7418EEXXXDDL motif
Compositional bias449 – 4524Poly-Gln

Amino acid modifications

Modified residue3431Phosphoserine; by ATM Ref.8
Modified residue3981Phosphoserine By similarity
Modified residue4331Phosphoserine By similarity

Experimental info

Sequence conflict91G → S in AAH44773. Ref.4
Sequence conflict11 – 122AP → SL in AAC62113. Ref.3
Sequence conflict3251P → Q in BAE22356. Ref.5
Sequence conflict3661D → E in BAA76298. Ref.2
Sequence conflict4551I → F in BAA76298. Ref.2
Sequence conflict5131L → Q in AAH44773. Ref.4
Sequence conflict6641N → K in AAH44773. Ref.4
Sequence conflict6761E → D in AAH44773. Ref.4
Sequence conflict6791P → S in AAH44773. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q9R207 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: C9F597CC08227B2C

FASTA75183,795
        10         20         30         40         50         60 
MWKLLPAAGA APGEPYRLLA GVEYVVGRKN CGILIENDQS ISRNHAVLTV NFPVTSLSQT 

        70         80         90        100        110        120 
DEIPTLTIKD NSKYGTFVNE EKMQTGLSCT LKTGDRVTFG VFESKFRVEY EPLVVCSSCL 

       130        140        150        160        170        180 
DVSGKTVLNQ AILQLGGLTA NNWTEECTHL VMSAVKVTIK TICALICGRP IIKPEYFSEF 

       190        200        210        220        230        240 
LKAVESKKQP PDIESFYPPI DEPAIGSKSV DLSGRHERKQ IFKGKTFVFL NAKQHKKLSS 

       250        260        270        280        290        300 
AVAFGGGEAR LMAEDDEEEQ SFFSAPGTCV VDVGITNTQL IISHSQKKWI HLIMDTLQRN 

       310        320        330        340        350        360 
GLRPIPEAEI GLAVIFMTTE NYCNPQGQPC TELKTTTPGP SLSQVLSANG KIIPSAPVNM 

       370        380        390        400        410        420 
TTYVADTESE PADTCMPLSE RPEEVKIPGL EQSSRKLSQE TFNIKEAPKP SSKANNVASD 

       430        440        450        460        470        480 
TLVRGKTPSY QLSPMKFPVA NKNKDWTSQQ QQNSIKNYFQ PCTRKRERDE DNPELSSCKS 

       490        500        510        520        530        540 
SRMELSCSLL EQTQPAGPSL WKSKEHQSQN ATLDREADTS SVGGMDIELN RKSPDRKPLP 

       550        560        570        580        590        600 
TETLRPRKRK DVDLATEEEV LEELLRSTKP ELAVQVKVEK QEADDTIRKK PRMDAERNRP 

       610        620        630        640        650        660 
LNGGSEPESN SALQEDEREK KDELQTESWS TKHEIANSDG LQDSSEELPR KLLLTEFRSL 

       670        680        690        700        710        720 
VVSNHNSTSR NLCVNECGPL KNFKKFKKAT FPGAGKLPHI IGGSDLVGHH ARKNTELEEW 

       730        740        750 
LKQEMEVQKQ QAKEESLADD LFRYNPNVKR R 

« Hide

References

« Hide 'large scale' references
[1]"Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome."
Vissinga C.S., Yeo T.C., Woessner J., Massa H.F., Wilson R.K., Trask B.J., Concannon P.
Cytogenet. Cell Genet. 87:80-84(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the mouse Nijmegen breakage syndrome (Nibrin/Nbs1) protein."
Saito T.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Testis.
[3]"Isolation of 50 cDNAs differentially expressed in embryonic forebrain as compared to mid and hindbrain: a strategy to identify candidate genes involved in human neurodevelopmental diseases."
Mas C., Bourgeois F., Simonneau M.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain stem.
[4]"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].
Strain: Czech II and FVB/N.
Tissue: Colon and Mammary gland.
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-613.
Strain: C57BL/6J.
Tissue: Medulla oblongata.
[6]"Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development."
Wilda M., Demuth I., Concannon P., Sperling K., Hameister H.
Hum. Mol. Genet. 9:1739-1744(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]"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.
[8]"Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest."
Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.
J. Biol. Chem. 282:14690-14694(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-343.
[9]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF076687 mRNA. Translation: AAD20943.1.
AB016988 mRNA. Translation: BAA76298.1.
AF092840 mRNA. Translation: AAC62113.1.
BC044773 mRNA. Translation: AAH44773.1.
BC055061 mRNA. Translation: AAH55061.1.
AK134960 mRNA. Translation: BAE22356.1.
AK031933 mRNA. Translation: BAC27610.1.
CCDSCCDS17986.1.
RefSeqNP_038780.3. NM_013752.3.
UniGeneMm.20866.

3D structure databases

ProteinModelPortalQ9R207.
SMRQ9R207. Positions 217-326.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid205163. 7 interactions.
DIPDIP-46804N.
IntActQ9R207. 1 interaction.
MINTMINT-4084511.

PTM databases

PhosphoSiteQ9R207.

Proteomic databases

PaxDbQ9R207.
PRIDEQ9R207.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029879; ENSMUSP00000029879; ENSMUSG00000028224.
GeneID27354.
KEGGmmu:27354.
UCSCuc008sbn.1. mouse.

Organism-specific databases

CTD4683.
MGIMGI:1351625. Nbn.

Phylogenomic databases

eggNOGNOG84999.
GeneTreeENSGT00390000000521.
HOGENOMHOG000231654.
HOVERGENHBG053070.
InParanoidQ9R207.
KOK10867.
OMAKLPHIIG.
OrthoDBEOG7B5WV7.
PhylomeDBQ9R207.
TreeFamTF101103.

Gene expression databases

ArrayExpressQ9R207.
BgeeQ9R207.
CleanExMM_NBN.
GenevestigatorQ9R207.

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

NextBio305208.
PROQ9R207.
SOURCESearch...

Entry information

Entry nameNBN_MOUSE
AccessionPrimary (citable) accession number: Q9R207
Secondary accession number(s): O88981 expand/collapse secondary AC list , Q3UY57, Q811I6, Q8CCY0, Q9R1X1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot