Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000724
UniProt IDQ13616
Primary gene name(s)CUL1
Synonym gene name(s)unknown
Protein nameCullin-1
Protein functionCore component of multiple cullin-RING-based SCF, SKP1-CUL1-F-box protein E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, PubMed:27565346. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. 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 exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC and SCF(FBXW11 direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11 directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC and/or SCF(FBXW11 direct ubiquitination of CEP68, PubMed:25704143, PubMed:25503564. SCF(SKP2 directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2 directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7 directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain, NICD, and probably PSEN1. SCF(FBXW2 directs ubiquitination of GCM1. SCF(FBXO32 directs ubiquitination of MYOD1. SCF(FBXO7 directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33 directs ubiquitination of YBX1. SCF(FBXO1 directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF directs ubiquitination of CCP110. SCF(FBXL3 and SCF(FBXL21 direct ubiquitination of CRY1 and CRY2. SCF(FBXO9 directs ubiquitination of TTI1 and TELO2. SCF(FBXO10 directs ubiquitination of BCL2. {ECO:0000269|PubMed:15531760, ECO:0000269|PubMed:15640526, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23263282, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:9663463}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13616
Gene Ontology
(Biological Process)
Complete annatation
animal organ morphogenesis [GO:0009887];
cell cycle arrest [GO:0007050];
cell proliferation [GO:0008283];
Fc-epsilon receptor signaling pathway [GO:0038095];
G1/S transition of mitotic cell cycle [GO:0000082];
G2/M transition of mitotic cell cycle [GO:0000086];
intrinsic apoptotic signaling pathway [GO:0097193];
negative regulation of cell proliferation [GO:0008285];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition [GO:0051437];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein monoubiquitination [GO:0006513];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process [GO:0031146];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
viral process [GO:0016032];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cullin-RING ubiquitin ligase complex [GO:0031461];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
Parkin-FBXW7-Cul1 ubiquitin ligase complex [GO:1990452];
SCF ubiquitin ligase complex [GO:0019005]
Protein-protein interaction114032
Phylogenetic treeQ13616
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. CD30.8911128934937770.006847932858554560.0189171634978252
AZA vs. DISU0.08583319497625030.7344367851757280.974560663114398
AZA vs. IL70.1453491353024590.449796754785440.999311006273513
AZA vs. SAHA-0.1681119778683120.4908769567890460.815100159356474
DISU vs. CD3-0.8184199530686640.02479226577772140.0613256669401662
DISU vs. IL70.05087806797493050.8399317531540330.966339509210192
DISU vs. SAHA-0.2525360974962630.3862650573378450.752618252986357
DMSO vs. AZA-0.04425263673977740.7918789355655341
DMSO vs. CD3-0.9481419381245270.003248405816615010.00952086257340566
DMSO vs. DISU-0.1322079199719890.5879772945501280.934701463289767
DMSO vs. IL70.1969638640779220.2736341215982420.769860685669313
DMSO vs. SAHA-0.1303602892350730.5803327812375410.855834825775551
HIV vs. Mock in Activation0.008630388141018620.9889286414148910.999983755607037
HIV vs. Mock in Latency-0.08534691084115110.6053872911223740.999834320637052
IL7 vs. CD3-0.7374919105710370.02220880890464150.0569060205965142
SAHA vs. CD3-1.084162973936260.002381209032438210.00752144626259566
SAHA vs. IL7-0.3168361671335590.1935343541703310.424401637294672
(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 0.233904 0.0994466
(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
1.033 1.173 1.314 1.436 1.32
(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
1LDJ X-ray 3.0Å A=17-776.
1LDK X-ray 3.1Å A=15-410# B=411-776.
1U6G X-ray 3.1Å A=1-776.
3RTR X-ray 3.2Å A/C/E/G=411-776.
3TDU X-ray 1.5Å C/D=702-776.
3TDZ X-ray 2.0Å C/D=702-776.
4F52 X-ray 3.0Å A/C=411-690.
4P5O X-ray 3.1Å A/C=411-776.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 22190034

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04110 Cell cycle - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04350 TGF-beta signaling pathway - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)