Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001907
UniProt IDO60934
Primary gene name(s)NBN
Synonym gene name(s)NBS, NBS1, P95
Protein nameNibrin
Protein functionComponent 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:0000269|PubMed:10888888, ECO:0000269|PubMed:15616588, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:9705271}.
Subcellular locationNucleus {ECO:0000269|PubMed:10783165}. Nucleus, PML body {ECO:0000269|PubMed:12470659, ECO:0000269|PubMed:15916964}. Chromosome, telomere {ECO:0000250}. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents. {ECO:0000269|PubMed:10783165}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O60934
Gene Ontology
(Biological Process)
Complete annatation
blastocyst growth [GO:0001832];
cell cycle arrest [GO:0007050];
cell proliferation [GO:0008283];
DNA damage checkpoint [GO:0000077];
DNA damage response, signal transduction by p53 class mediator [GO:0030330];
DNA double-strand break processing [GO:0000729];
DNA duplex unwinding [GO:0032508];
DNA replication [GO:0006260];
DNA synthesis involved in DNA repair [GO:0000731];
double-strand break repair [GO:0006302];
double-strand break repair via homologous recombination [GO:0000724];
double-strand break repair via nonhomologous end joining [GO:0006303];
intrinsic apoptotic signaling pathway [GO:0097193];
isotype switching [GO:0045190];
meiotic cell cycle [GO:0051321];
mitotic cell cycle checkpoint [GO:0007093];
mitotic G2 DNA damage checkpoint [GO:0007095];
negative regulation of telomere capping [GO:1904354];
neuromuscular process controlling balance [GO:0050885];
positive regulation of kinase activity [GO:0033674];
positive regulation of protein autophosphorylation [GO:0031954];
positive regulation of telomere maintenance [GO:0032206];
regulation of DNA-dependent DNA replication initiation [GO:0030174];
regulation of signal transduction by p53 class mediator [GO:1901796];
strand displacement [GO:0000732];
telomere maintenance [GO:0000723];
telomeric 3' overhang formation [GO:0031860]
Gene Ontology
(Molecular Function)
Complete annatation
damaged DNA binding [GO:0003684];
protein N-terminus binding [GO:0047485];
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
Mre11 complex [GO:0030870];
nuclear chromosome, telomeric region [GO:0000784];
nuclear inclusion body [GO:0042405];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605];
replication fork [GO:0005657];
site of double-strand break [GO:0035861]
Protein-protein interaction110763
Phylogenetic treeO60934
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.208807495692990.0002787628137421730.00118989326783405
AZA vs. DISU0.1771917188656750.4846159275010250.931429104131977
AZA vs. IL70.206454035347540.2854989034815130.999311006273513
AZA vs. SAHA-0.4829511373068880.05051889030404460.272849069309626
DISU vs. CD3-1.04384389971520.004414653527785030.0146223878878997
DISU vs. IL70.02040354145957950.9355487705916050.988186499206029
DISU vs. SAHA-0.6598340070433770.02522875261034370.186475002741781
DMSO vs. AZA-0.05511379866417960.7441871366976251
DMSO vs. CD3-1.274205695021538.97287710327488e-050.000408018091037839
DMSO vs. DISU-0.2338611478916730.3390361372520280.83759035206982
DMSO vs. IL70.2686457976839110.1375569187893610.635679171613318
DMSO vs. SAHA-0.4355437108959260.0679458753881510.303411048288837
HIV vs. Mock in Activation-0.04896947077878960.9373899883905430.999983755607037
HIV vs. Mock in Latency0.1070618411793840.5191731612779850.999834320637052
IL7 vs. CD3-0.9936624317382550.002189779971684680.00832447755692388
SAHA vs. CD3-1.717322651577842.27512118533557e-061.69733050806966e-05
SAHA vs. IL7-0.6939510250367250.004845556037835540.0375283168819825
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.299651 0.0232363
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.926 0.946 0.785 0.813 1.062
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp160; precursor cooperates with 19164952

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03440 Homologous recombination - Homo sapiens (human)