Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007586
UniProt IDQ12933
Primary gene name(s)TRAF2
Synonym gene name(s)TRAP3
Protein nameTNF receptor-associated factor 2
Protein functionRegulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE. {ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23453969}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:19150425}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q12933
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097296];
activation of NF-kappaB-inducing kinase activity [GO:0007250];
cellular protein complex assembly [GO:0043623];
cellular response to nitric oxide [GO:0071732];
death-inducing signaling complex assembly [GO:0071550];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of glial cell apoptotic process [GO:0034351];
negative regulation of neuron death [GO:1901215];
positive regulation of extrinsic apoptotic signaling pathway [GO:2001238];
positive regulation of I-kappaB phosphorylation [GO:1903721];
positive regulation of interleukin-2 production [GO:0032743];
positive regulation of JUN kinase activity [GO:0043507];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of protein homodimerization activity [GO:0090073];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of T cell activation [GO:0050870];
positive regulation of T cell cytokine production [GO:0002726];
positive regulation of tumor necrosis factor-mediated signaling pathway [GO:1903265];
programmed necrotic cell death [GO:0097300];
protein autoubiquitination [GO:0051865];
protein catabolic process [GO:0030163];
protein complex assembly [GO:0006461];
protein heterooligomerization [GO:0051291];
protein homotrimerization [GO:0070207];
protein K63-linked ubiquitination [GO:0070534];
regulation of apoptotic process [GO:0042981];
regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902041];
regulation of immunoglobulin secretion [GO:0051023];
regulation of necrotic cell death [GO:0010939];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to endoplasmic reticulum stress [GO:0034976];
signal transduction [GO:0007165];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
CD40 receptor binding [GO:0005174];
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
protein kinase binding [GO:0019901];
protein phosphatase binding [GO:0019903];
signal transducer activity [GO:0004871];
sphingolipid binding [GO:0046625];
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
AIP1-IRE1 complex [GO:1990597];
CD40 receptor complex [GO:0035631];
cell cortex [GO:0005938];
cytoplasm [GO:0005737];
cytoplasmic side of plasma membrane [GO:0009898];
cytosol [GO:0005829];
IRE1-TRAF2-ASK1 complex [GO:1990604];
membrane raft [GO:0045121];
TRAF2-GSTP1 complex [GO:0097057];
ubiquitin ligase complex [GO:0000151];
vesicle membrane [GO:0012506]
Protein-protein interaction113038
Phylogenetic treeQ12933
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. CD31.548325467825543.86874210245303e-062.62893061173003e-05
AZA vs. DISU0.5347526361493750.03610673962287070.441601696311484
AZA vs. IL70.1945392576167030.3185721899497640.999311006273513
AZA vs. SAHA-0.01079168238843540.9650427422607370.991180262923937
DISU vs. CD3-1.026006787044320.005075256496375640.0164243058021396
DISU vs. IL7-0.3500456415021710.1671194049414240.529422249344614
DISU vs. SAHA-0.5426642193846010.0644998473602310.321456841858715
DMSO vs. AZA0.04006580351957720.814813810670571
DMSO vs. CD3-1.52085078140293.34466901008579e-062.1448909599064e-05
DMSO vs. DISU-0.4971257651497490.043204797097350.414975329673082
DMSO vs. IL70.1621918842706730.3737828368183530.831519022414553
DMSO vs. SAHA-0.05553850949263470.8155471850055360.950000898532882
HIV vs. Mock in Activation-0.0620354029507140.9209087093289010.999983755607037
HIV vs. Mock in Latency-0.07256576031514740.6649078679098830.999834320637052
IL7 vs. CD3-1.348422163302873.76941188089397e-050.000247673693464319
SAHA vs. CD3-1.582570366969511.23117692836239e-057.50256219588402e-05
SAHA vs. IL7-0.2072091169187380.3992028767494410.646495935122591
(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 0.265858 0.055607
(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
1.043 0.947 0.822 0.768 0.862
(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
1CA4 X-ray 2.2Å A/B/C/D/E/F=334-501.
1CA9 X-ray 2.3Å A/B/C/D/E/F=310-501.
1CZY X-ray 2.0Å A/B/C=334-501.
1CZZ X-ray 2.7Å A/B/C=315-501.
1D00 X-ray 2.0Å A/B/C/D/E/F/G/H=334-501.
1D01 X-ray 2.0Å A/B/C/D/E/F=334-501.
1D0A X-ray 2.0Å A/B/C/D/E/F=334-501.
1D0J X-ray 2.5Å A/B/C/D/E/F=334-501.
1F3V X-ray 2.0Å B=331-501.
1QSC X-ray 2.4Å A/B/C=311-501.
3KNV X-ray 1.9Å A=1-133.
3M06 X-ray 2.6Å A/B/C/D/E/F=266-329.
3M0A X-ray 2.6Å A/B/C=266-329.
3M0D X-ray 2.8Å A/B=266-329.

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

HIV Partner Interaction Type PubMed
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)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - 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)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - 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)