Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003103
UniProt IDQ13114
Primary gene name(s)TRAF3
Synonym gene name(s)CAP1, CRAF1
Protein nameTNF receptor-associated factor 3
Protein functionRegulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819}.
Subcellular locationCytoplasm {ECO:0000305}. Endosome {ECO:0000250}. Mitochondrion. Note=Undergoes endocytosis together with TLR4 upon LPS signaling, By similarity. Associated with mitochondria in response to virus. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13114
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
innate immune response [GO:0045087];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
negative regulation of type I interferon production [GO:0032480];
regulation of apoptotic process [GO:0042981];
regulation of cytokine production [GO:0001817];
regulation of defense response to virus [GO:0050688];
regulation of interferon-beta production [GO:0032648];
regulation of proteolysis [GO:0030162];
signal transduction [GO:0007165];
toll-like receptor signaling pathway [GO:0002224];
Toll signaling pathway [GO:0008063];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
protein phosphatase binding [GO:0019903];
signal transducer activity [GO:0004871];
thioesterase binding [GO:0031996];
tumor necrosis factor receptor binding [GO:0005164];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
CD40 receptor complex [GO:0035631];
cytoplasmic side of plasma membrane [GO:0009898];
cytosol [GO:0005829];
endosome [GO:0005768];
mitochondrion [GO:0005739]
Protein-protein interaction113039
Phylogenetic treeQ13114
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. CD30.8750290015772060.02633570501627980.058406672455175
AZA vs. DISU0.2643732981304430.2963349076912330.859528450507179
AZA vs. IL70.1609313766521140.4033031911048850.999311006273513
AZA vs. SAHA-0.1222430826198930.6166289381450790.875360859609696
DISU vs. CD3-0.6233149058342170.1190578278416590.213906757674037
DISU vs. IL7-0.1125130062209770.6551059250170170.901215099517406
DISU vs. SAHA-0.3847771774383250.1872735474155780.553737420659246
DMSO vs. AZA0.04972603809144660.7672200413885211
DMSO vs. CD3-0.8390961858800130.03172716177578060.0657726286159536
DMSO vs. DISU-0.2171789444483410.3735368620604250.853038416616246
DMSO vs. IL70.1188642209425410.5092164188542370.88780433692056
DMSO vs. SAHA-0.1776772535503070.4515817924924840.782003654288608
HIV vs. Mock in Activation0.2590182239180520.7638834447639710.999983755607037
HIV vs. Mock in Latency-0.06258093070374450.7049772443267710.999834320637052
IL7 vs. CD3-0.7070867556312070.07080130647326670.144762356547958
SAHA vs. CD3-1.021766933375330.009309215815418880.0241398200569181
SAHA vs. IL7-0.2864032039288850.2401398061730750.482153879825261
(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
-1.2 0.059403807 -1.3 0.003831196 -1.8 0.001563737
(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 -0.641067 0.00420274
(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
1FLK X-ray 2.8Å A/B=341-568.
1FLL X-ray 3.5Å A/B=341-568.
1KZZ X-ray 3.5Å A=377-568.
1L0A X-ray 2.9Å A=377-568.
1RF3 X-ray 3.5Å A=377-568.
1ZMS X-ray 2.8Å A=377-568.
2ECY NMR - A=43-101.
2GKW X-ray 2.7Å A=377-568.

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

HIV Partner Interaction Type PubMed
Tat downregulates 22709905

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)