Browse TRAF2

Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm
Domain PF16673 TNF receptor-associated factor BIRC3 binding domain
PF00097 Zinc finger
PF02176 TRAF-type zinc finger
Function

Regulates 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.

> Gene Ontology
 
Biological Process GO:0000209 protein polyubiquitination
GO:0000302 response to reactive oxygen species
GO:0001819 positive regulation of cytokine production
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0001961 positive regulation of cytokine-mediated signaling pathway
GO:0002250 adaptive immune response
GO:0002367 cytokine production involved in immune response
GO:0002369 T cell cytokine production
GO:0002377 immunoglobulin production
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002637 regulation of immunoglobulin production
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002709 regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002718 regulation of cytokine production involved in immune response
GO:0002720 positive regulation of cytokine production involved in immune response
GO:0002724 regulation of T cell cytokine production
GO:0002726 positive regulation of T cell cytokine production
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006979 response to oxidative stress
GO:0007159 leukocyte cell-cell adhesion
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007252 I-kappaB phosphorylation
GO:0007254 JNK cascade
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0009306 protein secretion
GO:0010035 response to inorganic substance
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0010939 regulation of necrotic cell death
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032092 positive regulation of protein binding
GO:0032147 activation of protein kinase activity
GO:0032623 interleukin-2 production
GO:0032663 regulation of interleukin-2 production
GO:0032743 positive regulation of interleukin-2 production
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033674 positive regulation of kinase activity
GO:0034349 glial cell apoptotic process
GO:0034350 regulation of glial cell apoptotic process
GO:0034351 negative regulation of glial cell apoptotic process
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0034614 cellular response to reactive oxygen species
GO:0034976 response to endoplasmic reticulum stress
GO:0038061 NIK/NF-kappaB signaling
GO:0042110 T cell activation
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043393 regulation of protein binding
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043496 regulation of protein homodimerization activity
GO:0043506 regulation of JUN kinase activity
GO:0043507 positive regulation of JUN kinase activity
GO:0045785 positive regulation of cell adhesion
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0048305 immunoglobulin secretion
GO:0050708 regulation of protein secretion
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0051023 regulation of immunoglobulin secretion
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051291 protein heterooligomerization
GO:0051403 stress-activated MAPK cascade
GO:0051865 protein autoubiquitination
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060759 regulation of response to cytokine stimulus
GO:0060760 positive regulation of response to cytokine stimulus
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070206 protein trimerization
GO:0070207 protein homotrimerization
GO:0070265 necrotic cell death
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070534 protein K63-linked ubiquitination
GO:0070997 neuron death
GO:0071241 cellular response to inorganic substance
GO:0071356 cellular response to tumor necrosis factor
GO:0071550 death-inducing signaling complex assembly
GO:0071593 lymphocyte aggregation
GO:0071731 response to nitric oxide
GO:0071732 cellular response to nitric oxide
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090073 positive regulation of protein homodimerization activity
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:0097300 programmed necrotic cell death
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901222 regulation of NIK/NF-kappaB signaling
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902170 cellular response to reactive nitrogen species
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway
GO:1903719 regulation of I-kappaB phosphorylation
GO:1903721 positive regulation of I-kappaB phosphorylation
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001267 regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Molecular Function GO:0004842 ubiquitin-protein transferase activity
GO:0005126 cytokine receptor binding
GO:0005164 tumor necrosis factor receptor binding
GO:0005174 CD40 receptor binding
GO:0016874 ligase activity
GO:0019787 ubiquitin-like protein transferase activity
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0031435 mitogen-activated protein kinase kinase kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0031996 thioesterase binding
GO:0032813 tumor necrosis factor receptor superfamily binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0046625 sphingolipid binding
Cellular Component GO:0000151 ubiquitin ligase complex
GO:0005938 cell cortex
GO:0009898 cytoplasmic side of plasma membrane
GO:0035631 CD40 receptor complex
GO:0043235 receptor complex
GO:0045121 membrane raft
GO:0097057 TRAF2-GSTP1 complex
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
GO:0098589 membrane region
GO:0098802 plasma membrane receptor complex
GO:0098857 membrane microdomain
GO:0099568 cytoplasmic region
GO:1990597 AIP1-IRE1 complex
GO:1990604 IRE1-TRAF2-ASK1 complex
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04064 NF-kappa B signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04210 Apoptosis
hsa04380 Osteoclast differentiation
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04668 TNF signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-109581: Apoptosis
R-HSA-5218900: CASP8 activity is inhibited
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-73887: Death Receptor Signalling
R-HSA-5688426: Deubiquitination
R-HSA-69416: Dimerization of procaspase-8
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-140534: Ligand-dependent caspase activation
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-5357801: Programmed Cell Death
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-5213460: RIPK1-mediated regulated necrosis
R-HSA-5218859: Regulated Necrosis
R-HSA-3371378: Regulation by c-FLIP
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-5675482: Regulation of necroptotic cell death
R-HSA-162582: Signal Transduction
R-HSA-5676594: TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-75893: TNF signaling
R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway
R-HSA-5357786: TNFR1-induced proapoptotic signaling
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TRAF2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TRAF2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
21282461Bladder CarcinomaPromote immunityApoptosis induction requires a TRAF2-interacting CD40 motif but is initiated within a cytosolic death-inducing signaling complex after mobilization of receptor-bound TRAF2 to the cytoplasm.
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TRAF2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -2.98; FDR: 0.00722 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TRAF2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.140.58
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0680.969
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1920.882
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3690.356
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.4360.815
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2930.909
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3120.287
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3670.745
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2240.863
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6970.594
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6620.734
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0910.32
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TRAF2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TRAF2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TRAF2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TRAF2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TRAF2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TRAF2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TRAF2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTRAF2
NameTNF receptor-associated factor 2
Aliases TRAP3; MGC:45012; E3 ubiquitin-protein ligase TRAF2; tumor necrosis factor type 2 receptor associated protei ......
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TRAF2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.