Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004435
UniProt IDQ13619
Primary gene name(s)CUL4A
Synonym gene name(s)unknown
Protein nameCullin-4A
Protein functionCore component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1 directs ubiquitination of JUN. DCX(DDB2 directs ubiquitination of XPC. DCX(DDB2 ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled, H3.1 and replication-independent, H3.3 nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL directs autoubiquitination of DTL. {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13619
Gene Ontology
(Biological Process)
Complete annatation
cell cycle arrest [GO:0007050];
cellular response to DNA damage stimulus [GO:0006974];
DNA damage response, detection of DNA damage [GO:0042769];
G1/S transition of mitotic cell cycle [GO:0000082];
global genome nucleotide-excision repair [GO:0070911];
hemopoiesis [GO:0030097];
intrinsic apoptotic signaling pathway [GO:0097193];
in utero embryonic development [GO:0001701];
negative regulation of cell proliferation [GO:0008285];
negative regulation of granulocyte differentiation [GO:0030853];
nucleotide-excision repair, DNA damage recognition [GO:0000715];
nucleotide-excision repair, DNA duplex unwinding [GO:0000717];
nucleotide-excision repair, DNA incision [GO:0033683];
nucleotide-excision repair, DNA incision, 3'-to lesion [GO:0006295];
nucleotide-excision repair, DNA incision, 5'-to lesion [GO:0006296];
nucleotide-excision repair, preincision complex assembly [GO:0006294];
nucleotide-excision repair, preincision complex stabilization [GO:0006293];
positive regulation of cell proliferation [GO:0008284];
positive regulation of G1/S transition of mitotic cell cycle [GO:1900087];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of DNA damage checkpoint [GO:2000001];
regulation of nucleotide-excision repair [GO:2000819];
regulation of protein metabolic process [GO:0051246];
somatic stem cell population maintenance [GO:0035019];
transcription-coupled nucleotide-excision repair [GO:0006283];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
Cul4A-RING E3 ubiquitin ligase complex [GO:0031464];
Cul4-RING E3 ubiquitin ligase complex [GO:0080008];
nucleoplasm [GO:0005654]
Protein-protein interaction114029
Phylogenetic treeQ13619
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. CD30.4450968205416120.1744335231637310.274375084650778
AZA vs. DISU-0.1305591022460440.6054115580236740.955305607396123
AZA vs. IL70.1215110534506590.5269748791727040.999311006273513
AZA vs. SAHA-0.426334200636810.08157116041224520.355699358836122
DISU vs. CD3-0.5886564639429770.1051429587878470.194088288117561
DISU vs. IL70.2431773302643050.3340994327848690.714381428874275
DISU vs. SAHA-0.2943847773172780.3135695957865910.696097713669128
DMSO vs. AZA-0.01001597201962650.9522811181178941
DMSO vs. CD3-0.4667217265852010.1449456506706210.230801780372145
DMSO vs. DISU0.1188214241617320.6259285770409530.944952148943607
DMSO vs. IL70.1387023527082320.4400338390789570.862615100665185
DMSO vs. SAHA-0.4229265896297530.07365934510427890.316995999447912
HIV vs. Mock in Activation0.03764693521091850.9517118403350080.999983755607037
HIV vs. Mock in Latency0.05248143692211830.7502580451591960.999834320637052
IL7 vs. CD3-0.3158471253425660.3257219197482180.463870606232511
SAHA vs. CD3-0.8960087551737340.01214223918737540.0302402155930835
SAHA vs. IL7-0.5513498693324620.02407293619446160.113226908086918
(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) unknown
(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 -0.071754 0.676606
(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
0.987 0.952 0.848 0.822 0.928
(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

PDB Accession Method Resolution Chain Structure Preview
2HYE X-ray 3.1Å C=1-759.
4A0K X-ray 5.9Å A=38-759.

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

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03420 Nucleotide excision repair - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)