Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004434
UniProt IDQ13617
Primary gene name(s)CUL2
Synonym gene name(s)unknown
Protein nameCullin-2
Protein functionCore component of multiple cullin-RING-based ECS, ElonginB/C-CUL2/5-SOCS-box protein E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, PubMed:27565346. May serve as a rigid scaffold in the complex and 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 ECS complex depends on the substrate recognition component. ECS(VHL mediates the ubiquitination of hypoxia-inducible factor, HIF. {ECO:0000269|PubMed:10973499, ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:9122164}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13617
Gene Ontology
(Biological Process)
Complete annatation
cell cycle arrest [GO:0007050];
G1/S transition of mitotic cell cycle [GO:0000082];
intrinsic apoptotic signaling pathway [GO:0097193];
negative regulation of cell proliferation [GO:0008285];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061418];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
Cul2-RING ubiquitin ligase complex [GO:0031462];
cytosol [GO:0005829];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
VCB complex [GO:0030891]
Protein-protein interaction114031
Phylogenetic treeQ13617
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. CD31.224897979842230.0002313645217876250.00100871451327251
AZA vs. DISU0.09831701219616150.6980248362161010.969414628811637
AZA vs. IL70.2379388976212870.2176677797201830.985454595180332
AZA vs. SAHA-0.06738863688750170.782826453432740.942392971669428
DISU vs. CD3-1.139504609516550.001894483746298750.00715546178694746
DISU vs. IL70.1308867213135280.6037063063927380.877784777090135
DISU vs. SAHA-0.1647500003649480.5723422285809170.862012977061268
DMSO vs. AZA-0.09326509986496930.5800383802794931
DMSO vs. CD3-1.329743567807734.47673988737129e-050.000219824271197029
DMSO vs. DISU-0.1934266334437140.4290189354659250.881718877024027
DMSO vs. IL70.3384294191365650.06111211930153190.474873299629768
DMSO vs. SAHA0.01889843591100310.9362440006906050.9846317807625
HIV vs. Mock in Activation-0.08558482895469260.8906315561513160.999983755607037
HIV vs. Mock in Latency0.02420274645078840.8840173151190160.999834320637052
IL7 vs. CD3-0.9785139047633920.002544692092362520.00944732608575869
SAHA vs. CD3-1.317282639029190.0002509257425200580.00107549799197306
SAHA vs. IL7-0.3090695650980520.2056253780390810.439659141639874
(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 -0.0135798 0.951281
(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
1.066 0.954 0.946 1.011 0.917
(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
4WQO X-ray 3.2Å D=1-163.

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

HIV Partner Interaction Type PubMed
Vif interacts with 22190034

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)