Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000725
UniProt IDQ13618
Primary gene name(s)CUL3
Synonym gene name(s)KIAA0617
Protein nameCullin-3
Protein functionCore component of multiple cullin-RING-based BCR, BTB-CUL3-RBX1 E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, PubMed:27565346. 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 BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42 is involved in ubiquitination of KATNA1. BCR(SPOP is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR, BTB-CUL3-RBX1 E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13 controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12 is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem, ES cells division: BCR(KLHL12 acts by mediating monoubiquitination of SEC31, SEC31A or SEC31B, PubMed:22358839. BCR(KLHL3 acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4. The BCR(KLHL20 E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination, PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539. The BCR(KLHL21 E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex, CPC from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. The BCR(KLHL22 ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint, SAC and chromosome segregation. The BCR(KLHL25 ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1, 4E-BP1. Involved in ubiquitination of cyclin E and of cyclin D1, in vitro thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17 E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis, PubMed:25270598. {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:27565346}.
Subcellular locationNucleus. Golgi apparatus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13618
Gene Ontology
(Biological Process)
Complete annatation
anaphase-promoting complex-dependent catabolic process [GO:0031145];
cell cycle arrest [GO:0007050];
cell migration [GO:0016477];
cell projection organization [GO:0030030];
COPII vesicle coating [GO:0048208];
embryonic cleavage [GO:0040016];
ER to Golgi vesicle-mediated transport [GO:0006888];
fibroblast apoptotic process [GO:0044346];
G1/S transition of mitotic cell cycle [GO:0000082];
gastrulation [GO:0007369];
integrin-mediated signaling pathway [GO:0007229];
intrinsic apoptotic signaling pathway [GO:0097193];
liver morphogenesis [GO:0072576];
MAPK cascade [GO:0000165];
mitotic metaphase plate congression [GO:0007080];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of Rho protein signal transduction [GO:0035024];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
nucleus-associated proteasomal ubiquitin-dependent protein catabolic process [GO:0071630];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cytokinesis [GO:0032467];
positive regulation of mitotic metaphase/anaphase transition [GO:0045842];
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];
stem cell division [GO:0017145];
stress fiber assembly [GO:0043149];
trophectodermal cellular morphogenesis [GO:0001831];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
POZ domain binding [GO:0031208];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
Cul3-RING ubiquitin ligase complex [GO:0031463];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
Golgi membrane [GO:0000139];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
polar microtubule [GO:0005827]
Protein-protein interaction114030
Phylogenetic treeQ13618
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. CD30.8954653192112940.006613304636207460.0183564875648101
AZA vs. DISU-0.002275949629838480.9928196973838310.999297613676408
AZA vs. IL70.09086829647686120.6367924493743020.999311006273513
AZA vs. SAHA-0.166234988279060.4958521466898580.818851364943352
DISU vs. CD3-0.9099200543997820.01268312287650030.0354375151511336
DISU vs. IL70.08410156472316220.7384426604051160.935156881173568
DISU vs. SAHA-0.1631929067739820.5753877980427060.862423620517317
DMSO vs. AZA-0.1259846117121210.4529920692800121
DMSO vs. CD3-1.030248131252770.001417570751284790.00463649660618875
DMSO vs. DISU-0.1249705293928890.6085330895747790.939289650701039
DMSO vs. IL70.2238491584253080.2138917918016090.723450074518295
DMSO vs. SAHA-0.0481967154966720.8380787885117110.956430027749415
HIV vs. Mock in Activation-0.08677996480472640.8889543493916130.999983755607037
HIV vs. Mock in Latency0.03018498660460970.8550305327188470.999834320637052
IL7 vs. CD3-0.7963982814948520.01374609431853050.0387207773618407
SAHA vs. CD3-1.08721060736140.002323903481585290.00736358819753791
SAHA vs. IL7-0.2608596899682070.2845574924243820.532318148523844
(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 -0.143929 0.346274
(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
0.965 0.951 0.942 0.917 0.851
(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
2MYL NMR - A=49-68.
2MYM NMR - A=49-68.
4AP2 X-ray 2.8Å B=1-388.
4APF X-ray 3.1Å B=23-388.
4EOZ X-ray 2.4Å B/D=20-381.
4HXI X-ray 3.5Å B=20-381.

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
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)