Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002450
UniProt IDQ99708
Primary gene name(s)RBBP8
Synonym gene name(s)CTIP
Protein nameDNA endonuclease RBBP8
Protein functionEndonuclease that cooperates with the MRE11-RAD50-NBN, MRN complex in DNA-end resection, the first step of double-strand break, DSB repair through the homologous recombination, HR pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining, NHEJ. Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage, PubMed:10764811, PubMed:10910365, PubMed:15485915, PubMed:16581787, PubMed:16818604, PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:20829486. During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining, A-NHEJ and plays an essential role in chromosomal translocations, By similarity. {ECO:0000250|UniProtKB:Q80YR6, ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462, ECO:0000269|PubMed:20829486}.
Subcellular locationNucleus {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:23623683}. Chromosome {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604}. Note=Associates with sites of DNA damage in S/G2 phase, PubMed:10764811, Ref.29. Ubiquitinated RBBP8 binds to chromatin following DNA damage, PubMed:16818604. {ECO:0000269|PubMed:10764811, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:25349192}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q99708
Gene Ontology
(Biological Process)
Complete annatation
blastocyst hatching [GO:0001835];
cell cycle checkpoint [GO:0000075];
cell division [GO:0051301];
DNA double-strand break processing [GO:0000729];
DNA double-strand break processing involved in repair via single-strand annealing [GO:0010792];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
DNA synthesis involved in DNA repair [GO:0000731];
double-strand break repair via homologous recombination [GO:0000724];
G1/S transition of mitotic cell cycle [GO:0000082];
G2 DNA damage checkpoint [GO:0031572];
meiotic cell cycle [GO:0051321];
mitotic nuclear division [GO:0007067];
nucleotide-excision repair [GO:0006289];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
response to estradiol [GO:0032355];
strand displacement [GO:0000732]
Gene Ontology
(Molecular Function)
Complete annatation
damaged DNA binding [GO:0003684];
RNA polymerase II repressing transcription factor binding [GO:0001103];
RNA polymerase II transcription corepressor activity [GO:0001106];
single-stranded DNA endodeoxyribonuclease activity [GO:0000014]
Gene Ontology
(Cellular Component)
Complete annatation
chromosome [GO:0005694];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcriptional repressor complex [GO:0017053]
Protein-protein interaction111867
Phylogenetic treeQ99708
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. CD32.269753427795592.65418102829429e-072.33394495090149e-06
AZA vs. DISU0.2183683008881810.3938441187772070.902524512989909
AZA vs. IL70.52670456633830.0249986373460420.505422034167827
AZA vs. SAHA-0.1688045074137680.4955742329430340.8187817287633
DISU vs. CD3-2.065259419003433.7793110723161e-063.13090760312481e-05
DISU vs. IL70.2998145285894310.2565410961378640.642311414097044
DISU vs. SAHA-0.386296947868830.1890197006625860.556281177247772
DMSO vs. AZA-0.1290113516194450.4553389412492251
DMSO vs. CD3-2.41092626627532.58359119653662e-082.53397144373855e-07
DMSO vs. DISU-0.3494581338786590.1578281200271120.663450423656506
DMSO vs. IL70.6627307317715580.002051730980861420.0883709843899598
DMSO vs. SAHA-0.04711210379101860.8440084814214810.958477782895368
HIV vs. Mock in Activation-0.2167284847085450.8172482897119330.999983755607037
HIV vs. Mock in Latency-0.108864504626750.5239265386207190.999834320637052
IL7 vs. CD3-1.733486952015750.0002134892586248550.00113068292173311
SAHA vs. CD3-2.464370324771582.06446101325142e-082.56272054939859e-07
SAHA vs. IL7-0.6993523432591630.004736015568168490.0370185221898928
(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
1.9 0.000187621 1.4 0.009627116 1.5 0.04949702
(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 0.61147 0.000305467
(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
unknown unknown unknown unknown unknown
(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
203344_s_at 1.43 Yes upregulated in CD4+ cells
203344_s_at 2.55 Yes upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2L4Z NMR - A=641-685.
4D2H X-ray 1.9Å A/B/C/D/E/F/G/H=18-52.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

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