Protein Information (annotations from UniProt)
| Database ID | HIV0001907 |
| UniProt ID | O60934 |
| Primary gene name(s) | NBN |
| Synonym gene name(s) | NBS, NBS1, P95 |
| Protein name | Nibrin |
| Protein 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:0000269|PubMed:10888888, ECO:0000269|PubMed:15616588, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:9705271}. |
| Subcellular location | Nucleus {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 code | Click here for more information. |
| Amino acid sequence FASTA format: O60934 |
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| 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 interaction | 110763 |
| Phylogenetic tree | O60934 |
| HIV replication factor status |
Zhou et al., Cell. Host. Microbe., 2008 unknown Brass et al., Science, 2008 unknown Smith et al., J. Immunol, 2010 unknown |
| Interferon-stimulated 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 |
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| Experimental Condition | Log2 Fold Change | P value | Adjusted P value |
| AZA vs. CD3 | 1.20880749569299 | 0.000278762813742173 | 0.00118989326783405 |
| AZA vs. DISU | 0.177191718865675 | 0.484615927501025 | 0.931429104131977 |
| AZA vs. IL7 | 0.20645403534754 | 0.285498903481513 | 0.999311006273513 |
| AZA vs. SAHA | -0.482951137306888 | 0.0505188903040446 | 0.272849069309626 |
| DISU vs. CD3 | -1.0438438997152 | 0.00441465352778503 | 0.0146223878878997 |
| DISU vs. IL7 | 0.0204035414595795 | 0.935548770591605 | 0.988186499206029 |
| DISU vs. SAHA | -0.659834007043377 | 0.0252287526103437 | 0.186475002741781 |
| DMSO vs. AZA | -0.0551137986641796 | 0.744187136697625 | 1 |
| DMSO vs. CD3 | -1.27420569502153 | 8.97287710327488e-05 | 0.000408018091037839 |
| DMSO vs. DISU | -0.233861147891673 | 0.339036137252028 | 0.83759035206982 |
| DMSO vs. IL7 | 0.268645797683911 | 0.137556918789361 | 0.635679171613318 |
| DMSO vs. SAHA | -0.435543710895926 | 0.067945875388151 | 0.303411048288837 |
| HIV vs. Mock in Activation | -0.0489694707787896 | 0.937389988390543 | 0.999983755607037 |
| HIV vs. Mock in Latency | 0.107061841179384 | 0.519173161277985 | 0.999834320637052 |
| IL7 vs. CD3 | -0.993662431738255 | 0.00218977997168468 | 0.00832447755692388 |
| SAHA vs. CD3 | -1.71732265157784 | 2.27512118533557e-06 | 1.69733050806966e-05 |
| SAHA vs. IL7 | -0.693951025036725 | 0.00484555603783554 | 0.0375283168819825 |
| (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 |
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| 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 |
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| 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) |
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| Log2 Fold Change | unknown | ||||
| (3). Li et al., J. Immunol., 2013 Lymphatic tissue |
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| 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 |
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| 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 |
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| 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) |
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| 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 |
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| 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 |
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| 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 |
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| Affymetrix Prob ID | Fold Change | In CD8? | Category | |||
| unknown | unknown | unknown | unknown | |||
Protein Overview top
Drug-protein Interaction (annotations from DrugBank) top
Protein Secondary Structure (annotations from PDB) top
HIV-1 Interaction (annotations from NCBI HIV-1 Interaction Database) top
Metabolic/Signalling Pathway (annotations from KEGG database) top
| Pathway Accession Number | Description |
|---|---|
| hsa03440 | Homologous recombination - Homo sapiens (human) |
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