Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001582
UniProt IDQ9Y2M5
Primary gene name(s)KLHL20
Synonym gene name(s)KLEIP
Protein nameKelch-like protein 20
Protein functionSubstrate-specific adapter of a BCR, BTB-CUL3-RBX1 E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20 E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis, PubMed:20389280. The BCR(KLHL20 E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination, PubMed:24768539. Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking, PubMed:24768539. Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20 E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11, PubMed:21670212. In case of tumor, the BCR(KLHL20 E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression, PubMed:21840486. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:17395875, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:24768539}.
Subcellular locationCytoplasm, perinuclear region. Nucleus. Golgi apparatus, trans-Golgi network. Cell projection, axon {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Note=Localizes in the perinuclear region in normal conditions. Following IFN-alpha or IFN-gamma treatment, it is relocalized and sequestrated to the PML nuclear bodies, preventing DAPK1 ubiquitination, PubMed:20389280. {ECO:0000269|PubMed:20389280}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y2M5
Gene Ontology
(Biological Process)
Complete annatation
cytoskeleton organization [GO:0007010];
Golgi to endosome transport [GO:0006895];
negative regulation of apoptotic process [GO:0043066];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein K33-linked ubiquitination [GO:1990390];
protein transport [GO:0015031];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
response to interferon-alpha [GO:0035455]
Gene Ontology
(Molecular Function)
Complete annatation
interferon-gamma binding [GO:0019964];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
actin cytoskeleton [GO:0015629];
axon [GO:0030424];
Cul3-RING ubiquitin ligase complex [GO:0031463];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendrite [GO:0030425];
Golgi apparatus [GO:0005794];
perinuclear region of cytoplasm [GO:0048471];
PML body [GO:0016605];
trans-Golgi network [GO:0005802]
Protein-protein interaction118100
Phylogenetic treeQ9Y2M5
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. CD3-0.5424686879288950.0998426780319770.175597481150522
AZA vs. DISU0.2984676392286310.2410498626040990.825177556396647
AZA vs. IL7-0.03041282179961670.875617197518390.999311006273513
AZA vs. SAHA0.1016639113944780.6787702604655560.90621672242426
DISU vs. CD30.8281782917862520.0234208697245940.0586260694501046
DISU vs. IL7-0.3377225549701980.1834711933219770.554718860675651
DISU vs. SAHA-0.1956999000590990.5045460617678460.827517071827669
DMSO vs. AZA-0.01745554045596110.9181881706929791
DMSO vs. CD30.5131228999314250.1110349955086410.185860245259742
DMSO vs. DISU-0.3179950827782580.1957857652333730.713270904924328
DMSO vs. IL7-0.005542837224618040.9756726060482590.995635115004222
DMSO vs. SAHA0.1123524025069430.635581292609180.882166384918945
HIV vs. Mock in Activation0.06350120362600480.9190266269567320.999983755607037
HIV vs. Mock in Latency-0.04921862484943790.767937796978980.999834320637052
IL7 vs. CD30.5200036525670130.1080552171696750.201265257836896
SAHA vs. CD30.6192139109718620.08223548045434560.148809881177592
SAHA vs. IL70.1283395829271540.6001823872094780.797316410046327
(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) TRUE
(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 -0.124686 0.623038
(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

not found

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
not found
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