NBN - Nibrin - human protein (Function)
 
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Protein
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NBN »  Nibrin
 
Protein also known as:  Nijmegen breakage syndrome protein 1.
Gene name:  NBN
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 126 1
GENE REF ISO

Function

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Overview 
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
  • CuratedUniProtKB
GO molecular function 
Contributes to ATP-dependent DNA helicase activitydefinition[GO:0004003]  
1
  • IMPBHF-UCL
Contributes to damaged DNA bindingdefinition[GO:0003684]  
1
  • ICUniProtKB
Protein bindingdefinition[GO:0005515]  
16
  • IPIIntAct
  • IPIUniProtKB
Protein N-terminus bindingdefinition[GO:0047485]  
1
  • IPIUniProtKB
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIUniProtKB
GO biological process 
Blastocyst growthdefinition[GO:0001832] silver  
  • IEAOrtholog Compara
Cell cycle arrestdefinition[GO:0007050]  
1
  • TASUniProtKB
Cell proliferationdefinition[GO:0008283] silver  
  • IEAOrtholog Compara
DNA damage checkpointdefinition[GO:0000077]  
1
  • IDAMGI
DNA damage response, signal transduction by p53 class mediatordefinition[GO:0030330]  
1
  • TASUniProtKB
DNA duplex unwindingdefinition[GO:0032508]  
1
  • IMPBHF-UCL
Double-strand break repairdefinition[GO:0006302]  
1
  • IDAUniProtKB
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193] silver  
  • IEAOrtholog Compara
Isotype switchingdefinition[GO:0045190] silver  
  • IEAOrtholog Compara
Meiotic nuclear divisiondefinition[GO:0007126]  
  • IEAUniProtKB KW
Mitotic cell cycle checkpointdefinition[GO:0007093]  
1
  • IDAUniProtKB
Mitotic G2 DNA damage checkpointdefinition[GO:0007095]  
1
  • IDAUniProtKB
Neuromuscular process controlling balancedefinition[GO:0050885] silver  
  • IEAOrtholog Compara
Positive regulation of kinase activitydefinition[GO:0033674]  
1
  • IDABHF-UCL
Positive regulation of protein autophosphorylationdefinition[GO:0031954]  
1
  • IDABHF-UCL
Regulation of DNA-dependent DNA replication initiationdefinition[GO:0030174]  
1
  • TASUniProtKB
Telomere maintenancedefinition[GO:0000723]  
1
  • IMPUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
Homologous recombination  hsa03440+4683  
According to Reactome, this protein belongs to the following pathways:
Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks  REACT_486  
ATM mediated phosphorylation of repair proteins  REACT_1924  
DNA Damage/Telomere Stress Induced Senescence  REACT_169185  
Meiotic recombination  REACT_27271  
MRN complex relocalizes to nuclear foci  REACT_1884  
Note 
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.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Meiosis  definition   [KW-0469]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Nibrin
GenomeRNAi: 4683
PRO: PR:O60934