Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007589
UniProt IDQ9Y4K3
Primary gene name(s)TRAF6
Synonym gene name(s)RNF85
Protein nameTNF receptor-associated factor 6
Protein functionE3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells, DCs maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1, AP-1 and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. {ECO:0000269|PubMed:11057907, ECO:0000269|PubMed:12140561, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:18347055, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:8837778}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:18093978}. Cytoplasm, cell cortex {ECO:0000269|PubMed:18093978}. Nucleus {ECO:0000269|PubMed:18093978}. Lipid droplet {ECO:0000250}. Note=Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y4K3
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
activation of NF-kappaB-inducing kinase activity [GO:0007250];
activation of protein kinase activity [GO:0032147];
antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886];
bone resorption [GO:0045453];
cell development [GO:0048468];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to lipopolysaccharide [GO:0071222];
Fc-epsilon receptor signaling pathway [GO:0038095];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
interleukin-1-mediated signaling pathway [GO:0070498];
JNK cascade [GO:0007254];
membrane protein intracellular domain proteolysis [GO:0031293];
MyD88-dependent toll-like receptor signaling pathway [GO:0002755];
MyD88-independent toll-like receptor signaling pathway [GO:0002756];
myeloid dendritic cell differentiation [GO:0043011];
negative regulation of apoptotic process [GO:0043066];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
neural tube closure [GO:0001843];
nucleotide-binding oligomerization domain containing signaling pathway [GO:0070423];
odontogenesis of dentin-containing tooth [GO:0042475];
ossification [GO:0001503];
osteoclast differentiation [GO:0030316];
positive regulation of apoptotic process [GO:0043065];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interleukin-12 biosynthetic process [GO:0045084];
positive regulation of interleukin-2 production [GO:0032743];
positive regulation of interleukin-6 biosynthetic process [GO:0045410];
positive regulation of JUN kinase activity [GO:0043507];
positive regulation of lipopolysaccharide-mediated signaling pathway [GO:0031666];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of osteoclast differentiation [GO:0045672];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of T cell activation [GO:0050870];
positive regulation of T cell cytokine production [GO:0002726];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription regulatory region DNA binding [GO:2000679];
protein autoubiquitination [GO:0051865];
protein complex assembly [GO:0006461];
protein K63-linked ubiquitination [GO:0070534];
protein polyubiquitination [GO:0000209];
regulation of immunoglobulin secretion [GO:0051023];
response to interleukin-1 [GO:0070555];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell receptor signaling pathway [GO:0050852];
T-helper 1 type immune response [GO:0042088];
toll-like receptor 9 signaling pathway [GO:0034162];
toll-like receptor signaling pathway [GO:0002224]
Gene Ontology
(Molecular Function)
Complete annatation
histone deacetylase binding [GO:0042826];
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
mitogen-activated protein kinase kinase kinase binding [GO:0031435];
protein kinase B binding [GO:0043422];
protein kinase binding [GO:0019901];
protein N-terminus binding [GO:0047485];
thioesterase binding [GO:0031996];
tumor necrosis factor receptor binding [GO:0005164];
ubiquitin conjugating enzyme binding [GO:0031624];
ubiquitin protein ligase activity [GO:0061630];
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];
cell cortex [GO:0005938];
cytoplasm [GO:0005737];
cytoplasmic side of plasma membrane [GO:0009898];
cytosol [GO:0005829];
endosome membrane [GO:0010008];
lipid particle [GO:0005811];
mitochondrion [GO:0005739];
nucleolus [GO:0005730];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
protein complex [GO:0043234]
Protein-protein interaction113041
Phylogenetic treeQ9Y4K3
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. CD30.1103138923177680.7389188552711930.817633432688307
AZA vs. DISU0.4209992174162640.1006378667514410.641986967165139
AZA vs. IL7-0.09237593526200520.6380709481088980.999311006273513
AZA vs. SAHA0.03823804331100260.8770052199191040.972650433588392
DISU vs. CD30.2971348170358340.4224495071339410.554973020745439
DISU vs. IL7-0.5220487973762660.04113497996500530.267307699875086
DISU vs. SAHA-0.3810104204930080.1967203084400310.568181634438425
DMSO vs. AZA-0.006019991419230180.9721223142593181
DMSO vs. CD3-0.1282704530984810.6914171716716520.772887118144501
DMSO vs. DISU-0.4287922460964570.0829576274780290.534521952451247
DMSO vs. IL7-0.07919481118845250.6665923966677990.931410444032928
DMSO vs. SAHA0.03774592793070660.8743178469808690.968600725657798
HIV vs. Mock in Activation0.1350073617241030.8293991122869730.999983755607037
HIV vs. Mock in Latency0.1059980661712720.5287911095969550.999834320637052
IL7 vs. CD3-0.1956313585078950.5470056388519180.670762772080619
SAHA vs. CD3-0.0968670149483660.7854484973434750.847213844342499
SAHA vs. IL70.1270365006965920.6063476859923020.800708280214451
(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 -0.127964 0.434391
(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
0.995 0.839 0.83 0.834 0.922
(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
1LB4 X-ray 2.4Å A=348-504.
1LB5 X-ray 2.4Å A=347-504.
1LB6 X-ray 1.8Å A=347-504.
2ECI NMR - A=50-128.
2JMD NMR - A=67-124.
3HCS X-ray 2.2Å A/B=50-211.
3HCT X-ray 2.1Å A=50-159.
3HCU X-ray 2.6Å A/C=50-159.
4Z8M X-ray 2.9Å A/B=346-504.

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

HIV Partner Interaction Type PubMed
Vpr interacts with 24912525
Nef interacts with 23774506
Nef binds 21886773
Nef requires 21886773

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - 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)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05162 Measles - 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)
hsa05222 Small cell lung cancer - Homo sapiens (human)