Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000469
UniProt IDQ13191
Primary gene name(s)CBLB
Synonym gene name(s)RNF56
Protein nameE3 ubiquitin-protein ligase CBL-B
Protein functionE3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR, T-cell receptor, BCR, B-cell receptor and FCER1, high affinity immunoglobulin epsilon receptor signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:12177062}. Note=Upon EGF stimulation, associates with endocytic vesicles.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13191
Gene Ontology
(Biological Process)
Complete annatation
epidermal growth factor receptor signaling pathway [GO:0007173];
negative regulation of epidermal growth factor-activated receptor activity [GO:0007175];
NLS-bearing protein import into nucleus [GO:0006607];
protein polyubiquitination [GO:0000209];
proteolysis [GO:0006508];
signal transduction [GO:0007165]
Gene Ontology
(Molecular Function)
Complete annatation
calcium ion binding [GO:0005509];
ligase activity [GO:0016874];
signal transducer activity [GO:0004871];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane raft [GO:0045121];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886]
Protein-protein interaction107316
Phylogenetic treeQ13191
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. CD30.7636227460036830.06349947896606470.12130090582719
AZA vs. DISU0.185173451038330.4641276286509090.925291573476315
AZA vs. IL7-0.3347277833924770.08205327174959210.792807883894659
AZA vs. SAHA-0.05472189172670540.8227094680043640.956625255596125
DISU vs. CD3-0.5908461085423160.1512072450337410.257635131868273
DISU vs. IL7-0.5295685746009530.03587361623294620.247851122600541
DISU vs. SAHA-0.2378431570819480.4141536193413520.770008202643197
DMSO vs. AZA-0.01945739997386820.9074904908372011
DMSO vs. CD3-0.7915684307101630.05935297341619220.111226837232857
DMSO vs. DISU-0.2056381222480610.3991521065841340.863407037405606
DMSO vs. IL7-0.3084431027494540.08654516175334080.550224883237125
DMSO vs. SAHA-0.04198536380811820.8587006468806740.962938308241404
HIV vs. Mock in Activation-0.001320255084507790.9988382719628670.999983755607037
HIV vs. Mock in Latency0.2559878875389660.1208451715963360.999834320637052
IL7 vs. CD3-1.092311591815610.00796004389195870.0247283061796153
SAHA vs. CD3-0.842361745781030.03925626309011940.0812737855156065
SAHA vs. IL70.2764879367462570.2564729770361320.501046352493863
(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 -0.531217 0.000305467
(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
0.951 1.399 0.956 1.063 1.221
(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
2AK5 X-ray 1.8Å D=904-911.
2BZ8 X-ray 2.0Å C=902-912.
2DO6 NMR - A/B=931-970.
2J6F X-ray 1.7Å C=902-912.
2JNH NMR - A=926-971.
2LDR NMR - A=351-426.
2OOA X-ray 1.5Å A/B=924-973.
2OOB X-ray 1.9Å A=924-973.
3PFV X-ray 2.2Å A/B=38-344.
3VGO X-ray 3.1Å A/B/C=39-426.
3ZNI X-ray 2.2Å A/E/I/M=36-427.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 24162774

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa05100 Bacterial invasion of epithelial cells - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)