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Q9JIL9 (NBN_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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):
Nijmegen breakage syndrome protein 1 homolog
Gene names
Name:Nbn
Synonyms:Nbs1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length750 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 and RICTOR; indicative for an association with the mTORC2 complex By similarity.

Subcellular location

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

Tissue specificity

Present at approximately equal levels in the heart at fetal day 17, at relatively constant levels at postnatal days 10, 17 and 21 and at slightly lower levels in the adult heart. Barely detectable in the brain. Not detected in kidney, very low levels in liver and skeletal muscle and moderate levels in heart, lung and brain (at protein level). Ref.1

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.

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_processblastocyst growth

Inferred from sequence or structural similarity. Source: UniProtKB

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

in utero embryonic development

Inferred from sequence or structural similarity. Source: UniProtKB

isotype switching

Inferred from sequence or structural similarity. Source: UniProtKB

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

negative regulation of neuron differentiation

Inferred from mutant phenotype PubMed 17442057. Source: RGD

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 17442057. Source: RGD

reciprocal meiotic recombination

Traceable author statement Ref.1. Source: RGD

regulation of fibroblast proliferation

Inferred from direct assay PubMed 12637527. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 18253720. Source: RGD

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

chromosome, telomeric region

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear inclusion body

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionprotein 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 – 750750Nibrin
PRO_0000231046

Regions

Domain24 – 8360FHA
Domain105 – 18177BRCT
Region111 – 328218Mediates interaction with SP100 By similarity
Region221 – 403183Interaction with MTOR, MAPKAP1 and RICTOR By similarity
Motif461 – 4677Nuclear localization signal By similarity
Motif733 – 7408EEXXXDDL motif

Amino acid modifications

Modified residue3431Phosphoserine; by ATM By similarity
Modified residue4331Phosphoserine By similarity

Experimental info

Sequence conflict671T → I in AAF91228. Ref.1
Sequence conflict841Q → L in AAH85700. Ref.2
Sequence conflict2771N → H in AAH85700. Ref.2
Sequence conflict3011G → D in AAF91228. Ref.1
Sequence conflict4971G → E in AAF91228. Ref.1
Sequence conflict5141D → G in AAF91228. Ref.1
Sequence conflict6191G → E in AAF91228. Ref.1
Sequence conflict6421Q → P in AAH85700. Ref.2
Sequence conflict6721V → P in AAF91228. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9JIL9 [UniParc].

Last modified April 4, 2006. Version 2.
Checksum: 43A93B5497102A4A

FASTA75083,150
        10         20         30         40         50         60 
MWKLLPAASA APGEPCRLLA GVEYIVGRKN CAILIENDQS ISRNHAVLRV NFPVTSLSQT 

        70         80         90        100        110        120 
DEIPTLTIKD NSKYGTFINE EKMQNGLSST LKTGDRVTFG VFESKFRVEY EPLVVCSSCL 

       130        140        150        160        170        180 
DVSGKTVLNQ AILQLGGLTA NSWTEECTHL AMSSVKVTIK TICALICGRP IVKPEYFSEF 

       190        200        210        220        230        240 
LKAVESKTQP PEIESFYPPI DEPAIGNKSV DLSGRRERKQ IFKGKTFVFL NAKQHKKLGS 

       250        260        270        280        290        300 
AVVFGGGEAR LMAEGGEEEQ SFFSAPGTCV VDVGITNTQL IITDSQRKWI HLIMDILQRH 

       310        320        330        340        350        360 
GLRPIPEAEI GLAVIFMTTE SYCNPQGQPC TEVKTTTPGP SLSQGLSANG KVIPSAPMNM 

       370        380        390        400        410        420 
TTYVADTESE PADTCMSLSE RPEEVKIFGL DQNSRKLLQG TCNIKETSNQ SSNSNNAASN 

       430        440        450        460        470        480 
TLVRGKAPNY QLSPMKCPAA SKNKDWSSQQ QLNSIKNYFQ PCSRKRERDE ENPEQSSCKS 

       490        500        510        520        530        540 
SRVELSCSLL EQTQPAGPSL WKSKDHESQS ETLDRASNAS SVGGIDIKPN GKSPDSKSFS 

       550        560        570        580        590        600 
TEDLRARKRK EVDLSTEEEV LEELLRSTKP ELAVQVKVEK QEADVSIRKK PRMDAERNQH 

       610        620        630        640        650        660 
LNGGPVPESN SALQEDETGK KDELQIEAWS TKREVSNTDE LQDSSEELPR KLLLTEFRSL 

       670        680        690        700        710        720 
VVHNNSSRNL CVLNGRGELK NFKKFKKATC PGAGKLPHII GGSDLIGHHA RKNTELEEWL 

       730        740        750 
KHEMEVQKQQ AKEDSLADDL FRYNPNVKRR 

« Hide

References

« Hide 'large scale' references
[1]"The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes."
Lanson N.A. Jr., Egeland D.B., Royals B.A., Claycomb W.C.
Nucleic Acids Res. 28:2882-2892(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"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: Testis.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF218575 mRNA. Translation: AAF91228.1.
BC085700 mRNA. Translation: AAH85700.1.
RefSeqNP_620228.1. NM_138873.2.
UniGeneRn.25214.

3D structure databases

ProteinModelPortalQ9JIL9.
SMRQ9JIL9. Positions 217-327.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ9JIL9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID85482.
KEGGrno:85482.
UCSCRGD:621420. rat.

Organism-specific databases

CTD4683.
RGD621420. Nbn.

Phylogenomic databases

eggNOGNOG84999.
HOGENOMHOG000231654.
HOVERGENHBG053070.
InParanoidQ9JIL9.
KOK10867.
PhylomeDBQ9JIL9.

Gene expression databases

GenevestigatorQ9JIL9.

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

NextBio617562.
PROQ9JIL9.

Entry information

Entry nameNBN_RAT
AccessionPrimary (citable) accession number: Q9JIL9
Secondary accession number(s): Q5RKL2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: April 16, 2014
This is version 91 of the entry and version 2 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