Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0012251
UniProt IDQ14999
Primary gene name(s)CUL7
Synonym gene name(s)KIAA0076
Protein nameCullin-7
Protein functionCore component of the 3M and Cul7-RING(FBXW8 complexes, which mediates the ubiquitination of target proteins. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer, PubMed:24793695. Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5, PubMed:24793696. Core component of a Cul7-RING ubiquitin-protein ligase with FBXW8, which mediates ubiquitination and consequent degradation of target proteins such as GORASP1, IRS1 and MAP4K1/HPK1, PubMed:21572988, PubMed:24362026. Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain, PubMed:21572988. Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8 complex recognizes and binds IRS1 previously phosphorylated by S6 kinase, RPS6KB1 or RPS6KB2, PubMed:18498745. The Cul7-RING(FBXW8 complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradatation, thereby affecting cell proliferation and differentiation, PubMed:24362026. Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development, PubMed:20139075. Does not promote polyubiquitination and proteasomal degradation of p53/TP53, PubMed:16547496, PubMed:17332328. While the Cul7-RING(FBXW8 and the 3M complexes are associated and involved in common processes, CUL7 and the Cul7-RING(FBXW8 complex may be have additional functions. {ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:20139075, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
Subcellular locationCytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear region. Golgi apparatus. Note=Colocalizes with FBXW8 at the Golgi apparatus in neurons;
localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus, PubMed:24793695. CCDC8 is required for centrosomal location, PubMed:24793695. {ECO:0000269|PubMed:24793695}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q14999
Gene Ontology
(Biological Process)
Complete annatation
epithelial to mesenchymal transition [GO:0001837];
Golgi organization [GO:0007030];
IRE1-mediated unfolded protein response [GO:0036498];
microtubule cytoskeleton organization [GO:0000226];
mitotic cytokinesis [GO:0000281];
placenta development [GO:0001890];
positive regulation of dendrite morphogenesis [GO:0050775];
protein ubiquitination [GO:0016567];
proteolysis [GO:0006508];
regulation of mitotic nuclear division [GO:0007088];
ubiquitin-dependent protein catabolic process [GO:0006511];
vasculogenesis [GO:0001570];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
unknown
Gene Ontology
(Cellular Component)
Complete annatation
3M complex [GO:1990393];
anaphase-promoting complex [GO:0005680];
centrosome [GO:0005813];
Cul7-RING ubiquitin ligase complex [GO:0031467];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
Golgi apparatus [GO:0005794];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction115159
Phylogenetic treeQ14999
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.06731496293243320.8389848588500550.891698737225021
AZA vs. DISU-0.2993788097868850.243840669626830.827346002615447
AZA vs. IL7-0.3278819157625870.09362831731413860.821322439338236
AZA vs. SAHA-0.422763879009770.08816744635285480.371966438937289
DISU vs. CD3-0.3793202104102940.3113911828258370.443449285773893
DISU vs. IL7-0.03886990862518380.8789660148101870.976664898154608
DISU vs. SAHA-0.1210302018477010.6865694428697080.907113040373488
DMSO vs. AZA0.08075563252018250.6360645104637811
DMSO vs. CD30.0006639099291796880.9983601116258220.998757891071321
DMSO vs. DISU0.377663335561690.1273276153734180.613181252319969
DMSO vs. IL7-0.4009888142832250.02843060371330090.343893900447525
DMSO vs. SAHA-0.5085169428053780.03383064122037090.199588661812131
HIV vs. Mock in Activation0.1276971481506290.8377308342224260.999983755607037
HIV vs. Mock in Latency0.1700441372421790.3090129162632450.999834320637052
IL7 vs. CD3-0.3899905901900420.2319328137726610.361186414091881
SAHA vs. CD3-0.5137145793456110.1484650940932540.239189510665005
SAHA vs. IL7-0.09754275187794370.6936555557219990.857079777293007
(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 -0.365858 0.109626
(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
unknown unknown unknown unknown unknown
(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
2JNG NMR - A=360-460.

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)
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