Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001550
UniProt IDQ8N163
Primary gene name(s)CCAR2
Synonym gene name(s)DBC1, KIAA1967
Protein nameCell cycle and apoptosis regulator protein 2
Protein functionCore component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II, RNAPII and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in, A + T-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3-specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation, PubMed:18235501, PubMed:18235502, PubMed:19131338, PubMed:19218236, PubMed:22446626, PubMed:23352644, PubMed:23398316. Represses the ligand-dependent transcriptional activation function of ESR2, PubMed:20074560. Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1, PubMed:24415752. Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization, PubMed:21030595. Positively regulates the beta-catenin pathway, canonical Wnt signaling pathway and is required for MCC-mediated repression of the beta-catenin pathway, PubMed:24824780. Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3, PubMed:25661920. Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2, PubMed:25732823. Represses the transcriptional activator activity of BRCA1, PubMed:20160719. Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro, PubMed:25361978. {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}.
Subcellular locationNucleus {ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:25661920}. Cytoplasm {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:24824780}. Note=Recruited to chromatin, post-UV irradiation. Sequestered to the cytoplasm in the presence of MCC. Translocated to the cytoplasm during UV-induced apoptosis. {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:24824780}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8N163
Gene Ontology
(Biological Process)
Complete annatation
cell cycle [GO:0007049];
cellular response to DNA damage stimulus [GO:0006974];
mitochondrial fragmentation involved in apoptotic process [GO:0043653];
mRNA processing [GO:0006397];
negative regulation of catalytic activity [GO:0043086];
negative regulation of cell growth [GO:0030308];
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage [GO:1902230];
negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435];
negative regulation of transcription, DNA-templated [GO:0045892];
positive regulation of apoptotic process [GO:0043065];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of DNA damage checkpoint [GO:2000003];
regulation of cellular response to heat [GO:1900034];
regulation of circadian rhythm [GO:0042752];
regulation of DNA-templated transcription, elongation [GO:0032784];
regulation of protein deacetylation [GO:0090311];
regulation of protein stability [GO:0031647];
response to UV [GO:0009411];
rhythmic process [GO:0048511];
RNA splicing [GO:0008380];
transcription, DNA-templated [GO:0006351];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
Gene Ontology
(Cellular Component)
Complete annatation
Protein-protein interaction121775
Phylogenetic treeQ8N163
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. CD30.2149566222067990.5117338832471450.62746933682891
AZA vs. DISU-0.02689139536830010.9151898746089610.994271142470137
AZA vs. IL70.05323775486328750.7814432264659090.999311006273513
AZA vs. SAHA-0.1768653475889170.4678480563808370.804237777175215
DISU vs. CD3-0.2539646538043040.4839734854069040.611329047500419
DISU vs. IL70.0706847205531990.7786642643067090.948619491765825
DISU vs. SAHA-0.1477065939718040.6117223226280520.877759294853684
DMSO vs. AZA0.0385206456841270.8177337491202031
DMSO vs. CD3-0.1882269581741790.5566327104873870.659919380911908
DMSO vs. DISU0.06352106702999160.7942529269527950.97560211472989
DMSO vs. IL70.02210631192581370.9019399799569050.979228917441583
DMSO vs. SAHA-0.2208889950265510.3482252790115930.699001291478855
HIV vs. Mock in Activation0.1312116060873320.8329436754891990.999983755607037
HIV vs. Mock in Latency-0.03114922921466580.850062935342180.999834320637052
IL7 vs. CD3-0.1556182461075410.6287081252042790.74064224862869
SAHA vs. CD3-0.4153688191011940.2405500814614520.348868225158703
SAHA vs. IL7-0.232657382431880.3389012921486680.588751651244557
(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 -0.177319 0.274336
(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
1.017 1.017 0.98 0.96 1.003
(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
Vpr downregulates 23874603
Pol interacts with 22190034
retropepsin interacts with 22190034

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found