Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001510
UniProt IDQ14145
Primary gene name(s)KEAP1
Synonym gene name(s)INRF2, KIAA0132, KLHL19
Protein nameKelch-like ECH-associated protein 1
Protein functionActs as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:17046835}.
Subcellular locationCytoplasm. Nucleus. Note=Shuttles between cytoplasm and nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q14145
Gene Ontology
(Biological Process)
Complete annatation
cellular response to interleukin-4 [GO:0071353];
cytoplasmic sequestering of transcription factor [GO:0042994];
in utero embryonic development [GO:0001701];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
proteasomal ubiquitin-independent protein catabolic process [GO:0010499];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of epidermal cell differentiation [GO:0045604];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
actin filament [GO:0005884];
cell-cell adherens junction [GO:0005913];
Cul3-RING ubiquitin ligase complex [GO:0031463];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
focal adhesion [GO:0005925];
microtubule organizing center [GO:0005815];
midbody [GO:0030496];
nucleoplasm [GO:0005654]
Protein-protein interaction115156
Phylogenetic treeQ14145
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. CD30.7018116736071550.0331596423686130.070730558983829
AZA vs. DISU0.4243705732865530.09632949451759220.633569365578044
AZA vs. IL70.1070302638612440.5795233910292130.999311006273513
AZA vs. SAHA-0.8890469575897480.004538150877217540.0581163412292639
DISU vs. CD3-0.2904130900630080.4291048225100740.560853732291412
DISU vs. IL7-0.3271649014174360.1987474589475630.573217425451454
DISU vs. SAHA-1.310343123595860.0006908705569025340.0158479606743959
DMSO vs. AZA0.01796847069641360.9151659672312221
DMSO vs. CD3-0.6952297115155520.03056745340476150.0638249876357595
DMSO vs. DISU-0.4085608383292590.09732901104580540.563051131078805
DMSO vs. IL70.09658660655020840.592851610333350.910297977040248
DMSO vs. SAHA-0.9120425451512040.002593403438889470.0350539759887922
HIV vs. Mock in Activation0.09010578068311570.8849207708252140.999983755607037
HIV vs. Mock in Latency0.03688316777071750.8244730777022060.999834320637052
IL7 vs. CD3-0.5892285870270380.06754713936349050.139623975812657
SAHA vs. CD3-1.613466648275779.06627063457233e-065.75278730370547e-05
SAHA vs. IL7-0.9977797774116950.001238270953197730.0137641210372431
(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 -0.942703059
(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 0.0969585 0.568621
(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
0.907 1.007 0.874 0.791 0.918
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB08908 Dimethyl fumarate approved, investigational yes binder

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1U6D X-ray 1.8Å X=321-609.
1ZGK X-ray 1.3Å A=321-609.
2FLU X-ray 1.5Å X=321-609.
3VNG X-ray 2.1Å A=321-609.
3VNH X-ray 2.1Å A=321-609.
3ZGC X-ray 2.2Å A/B=321-609.
3ZGD X-ray 1.9Å A/B=321-609.
4CXI X-ray 2.3Å A=48-180.
4CXJ X-ray 2.8Å A=48-180.
4CXT X-ray 2.6Å A=48-180.
4IFJ X-ray 1.8Å A=321-609.
4IFL X-ray 1.8Å X=321-609.
4IFN X-ray 2.4Å X=321-609.
4IN4 X-ray 2.5Å A/B/C=321-609.
4IQK X-ray 1.9Å A=321-609.
4L7B X-ray 2.4Å A/B=321-609.
4L7C X-ray 2.4Å A/B/C=321-609.
4L7D X-ray 2.2Å A/B/C=321-609.
4N1B X-ray 2.5Å A/B/C=321-609.
4XMB X-ray 2.4Å A=321-609.
5DAD X-ray 2.6Å A=49-182.
5DAF X-ray 2.3Å A=49-182.

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

HIV Partner Interaction Type PubMed
Tat regulated by 19409485

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)