InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NBN

Summary

InnateDB Protein

IDBP-293062.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NBN

Protein Name

nibrin

Synonyms

AT-V1; AT-V2; ATV; NBS; NBS1; P95;

Species

Homo sapiens

Ensembl Protein

ENSP00000386924

InnateDB Gene

IDBG-28009 (NBN)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10888888, ECO:0000269PubMed:15616588, ECO:0000269PubMed:19759395, ECO:0000269PubMed:23762398, ECO:0000269PubMed:9705271}.

Subcellular Localization

Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000269PubMed:12470659, ECO:0000269PubMed:15916964}. Chromosome, telomere {ECO:0000250}. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents. {ECO:0000250}.

Disease Associations

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. {ECO:0000269PubMed:9590180}. 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. {ECO:0000269PubMed:14684699}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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.Note=Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).

Tissue Specificity

Ubiquitous. Expressed at high levels in testis.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 111 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	112 [view]
Protein-Protein	112 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003684	damaged DNA binding
GO:0004003	ATP-dependent DNA helicase activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0047485	protein N-terminus binding

Biological Process

GO:0000077	DNA damage checkpoint
GO:0000723	telomere maintenance
GO:0000724	double-strand break repair via homologous recombination
GO:0006281	DNA repair
GO:0006302	double-strand break repair
GO:0007050	cell cycle arrest
GO:0007093	mitotic cell cycle checkpoint
GO:0007095	mitotic G2 DNA damage checkpoint
GO:0007126	meiotic nuclear division
GO:0030174	regulation of DNA-dependent DNA replication initiation
GO:0030330	DNA damage response, signal transduction by p53 class mediator
GO:0031954	positive regulation of protein autophosphorylation
GO:0032508	DNA duplex unwinding
GO:0033674	positive regulation of kinase activity

Cellular Component

GO:0000784	nuclear chromosome, telomeric region
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0016605	PML body
GO:0030870	Mre11 complex
GO:0035861	site of double-strand break
GO:0042405	nuclear inclusion body