TRAF2
gene geneOn this page
Also known as TRAP3RNF117
Summary
TRAF2 (TNF receptor associated factor 2, HGNC:12032) is a protein-coding gene on chromosome 9q34.3, encoding TNF receptor-associated factor 2 (Q12933). E3 ubiquitin-protein ligase that regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis.
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.
Source: NCBI Gene 7186 — RefSeq curated summary.
At a glance
- Clinical variants (ClinVar): 85 total
- Druggable target: yes
- MANE Select transcript:
NM_021138
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:12032 |
| Approved symbol | TRAF2 |
| Name | TNF receptor associated factor 2 |
| Location | 9q34.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | TRAP3, RNF117 |
| Ensembl gene | ENSG00000127191 |
| Ensembl biotype | protein_coding |
| OMIM | 601895 |
| Entrez | 7186 |
Gene structure
Transcript identifiers
Ensembl transcripts: 61 — 57 protein_coding, 4 protein_coding_CDS_not_defined
ENST00000247668, ENST00000414589, ENST00000419057, ENST00000429509, ENST00000466107, ENST00000469701, ENST00000474950, ENST00000482854, ENST00000850853, ENST00000882552, ENST00000882553, ENST00000882554, ENST00000882555, ENST00000882556, ENST00000882557, ENST00000882558, ENST00000882559, ENST00000882560, ENST00000882561, ENST00000882562, ENST00000882563, ENST00000882564, ENST00000882565, ENST00000882566, ENST00000882567, ENST00000882568, ENST00000882569, ENST00000882570, ENST00000882571, ENST00000882572, ENST00000882573, ENST00000882574, ENST00000882575, ENST00000882576, ENST00000882577, ENST00000882578, ENST00000936013, ENST00000936014, ENST00000936015, ENST00000936016, ENST00000936017, ENST00000936018, ENST00000936019, ENST00000936020, ENST00000936021, ENST00000936022, ENST00000936023, ENST00000936024, ENST00000936025, ENST00000936026, ENST00000943528, ENST00000943529, ENST00000943530, ENST00000943531, ENST00000943532, ENST00000943533, ENST00000943534, ENST00000943535, ENST00000943536, ENST00000943537, ENST00000943538
RefSeq mRNA: 1 — MANE Select: NM_021138
NM_021138
CCDS: CCDS7013
Canonical transcript exons
ENST00000247668 — 11 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000870770 | 136920234 | 136920515 |
| ENSE00000870771 | 136921038 | 136921215 |
| ENSE00000985052 | 136923852 | 136924000 |
| ENSE00001042880 | 136899594 | 136899672 |
| ENSE00001095643 | 136900422 | 136900520 |
| ENSE00001307288 | 136886516 | 136886541 |
| ENSE00001556395 | 136925683 | 136926607 |
| ENSE00002394952 | 136898713 | 136898928 |
| ENSE00003461184 | 136909920 | 136909994 |
| ENSE00003570672 | 136916541 | 136916615 |
| ENSE00003628449 | 136908070 | 136908231 |
Expression profiles
Bgee: expression breadth ubiquitous, 191 present calls, max score 90.38.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4597 / max 73.7123, expressed in 1748 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 99580 | 7.4597 | 1748 |
Top tissues by expression
273 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| lower esophagus mucosa | UBERON:0035834 | 90.38 | gold quality |
| endometrium epithelium | UBERON:0004811 | 89.14 | silver quality |
| mucosa of transverse colon | UBERON:0004991 | 87.43 | gold quality |
| olfactory bulb | UBERON:0002264 | 86.60 | gold quality |
| type B pancreatic cell | CL:0000169 | 86.21 | gold quality |
| lymph node | UBERON:0000029 | 85.96 | gold quality |
| right testis | UBERON:0004534 | 85.33 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 85.29 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 85.24 | gold quality |
| cerebellar cortex | UBERON:0002129 | 85.20 | gold quality |
| granulocyte | CL:0000094 | 84.95 | gold quality |
| left testis | UBERON:0004533 | 84.88 | gold quality |
| ganglionic eminence | UBERON:0004023 | 84.08 | gold quality |
| cerebellum | UBERON:0002037 | 83.92 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 83.91 | gold quality |
| spleen | UBERON:0002106 | 83.56 | gold quality |
| apex of heart | UBERON:0002098 | 83.52 | gold quality |
| esophagus mucosa | UBERON:0002469 | 83.51 | gold quality |
| popliteal artery | UBERON:0002250 | 83.23 | gold quality |
| tibial artery | UBERON:0007610 | 83.22 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 83.10 | gold quality |
| triceps brachii | UBERON:0001509 | 82.94 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 82.68 | gold quality |
| ventricular zone | UBERON:0003053 | 82.26 | gold quality |
| right lobe of liver | UBERON:0001114 | 82.22 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 82.21 | gold quality |
| thyroid gland | UBERON:0002046 | 82.07 | gold quality |
| testis | UBERON:0000473 | 81.93 | gold quality |
| endocervix | UBERON:0000458 | 81.91 | gold quality |
| transverse colon | UBERON:0001157 | 81.81 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 2.94 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
24 targeting TRAF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-4487 | 99.96 | 64.58 | 1252 |
| HSA-MIR-4756-3P | 99.62 | 66.30 | 1319 |
| HSA-MIR-4753-5P | 99.54 | 68.51 | 1356 |
| HSA-MIR-532-3P | 99.34 | 65.76 | 1195 |
| HSA-MIR-7974 | 99.24 | 65.48 | 1137 |
| HSA-MIR-593-3P | 99.22 | 67.28 | 1327 |
| HSA-MIR-361-3P | 99.19 | 66.45 | 1381 |
| HSA-MIR-146A-3P | 99.13 | 68.99 | 1881 |
| HSA-MIR-140-3P | 99.04 | 67.69 | 1324 |
| HSA-MIR-320A-5P | 98.88 | 66.75 | 1248 |
| HSA-MIR-3190-5P | 98.87 | 64.89 | 1345 |
| HSA-MIR-5088-3P | 98.29 | 66.63 | 1310 |
| HSA-MIR-4436B-3P | 98.25 | 65.26 | 1494 |
| HSA-MIR-6735-5P | 98.24 | 65.36 | 1488 |
| HSA-MIR-6867-3P | 98.12 | 66.07 | 1305 |
| HSA-MIR-7843-5P | 98.12 | 65.26 | 1421 |
| HSA-MIR-4632-5P | 97.82 | 65.38 | 1470 |
| HSA-MIR-6879-5P | 97.77 | 65.52 | 1521 |
| HSA-MIR-4287 | 97.55 | 67.24 | 1247 |
| HSA-MIR-4685-3P | 97.55 | 67.35 | 1255 |
| HSA-MIR-15A-3P | 97.47 | 65.08 | 527 |
| HSA-MIR-214-5P | 97.34 | 66.50 | 617 |
| HSA-MIR-4790-3P | 96.63 | 67.08 | 806 |
| HSA-MIR-342-3P | 96.44 | 67.48 | 1344 |
Literature-anchored findings (GeneRIF, showing 40)
- These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis. (PMID:11777919)
- TNF-RII and c-IAP1 mediate its ubiquination (PMID:11907583)
- TRAF2, TRAF3, cIAP1, Smac, and lymphotoxin beta receptor associate and are involved in apoptosis (PMID:12571250)
- TNF signaling leads to oligomerization, ubiquitination, and activation of GCKR and activation of the SAPK pathway in a manner that depends upon TRAF2 polyubiquitination and oligomerization and Ubc13 function (PMID:12591926)
- TRAF2 has a role in TNF-alpha induced IKK phosphorylation of NF-kappaB p65 (PMID:12842894)
- stoichiometry of TRAF1-TRAF2 heteromeric complexes ((TRAF2)2-TRAF1 versus TRAF2-(TRAF1)2) determines their capability to mediate CD40 signaling but has no major effect on TNF signaling (PMID:14557256)
- TRAF2 plays an important role as regulator of IAP nucleocytoplasmic localization, by preventing nuclear translocation of cIAP1 and cIAP2. (PMID:15265700)
- AIP1 is a novel transducer in TNF-induced TRAF2-dependent activation of ASK1 that mediates a balance between JNK versus NF-kappaB signaling (PMID:15310755)
- there is a novel association between TRAF2 and TRAF3 that is mediated by unique portions of each protein and that specifically regulates activation of NF-kappaB, but not AP-1 (PMID:15383523)
- TNF receptor-associated factor 2 (TRAF2) overexpression does not only block apoptosis induction by CD95 antigen but also converts this death receptor into a mediator of invasiveness in pancreatic adenocarcinoma (PMID:15670977)
- TRAF3 specifically blocked the NF-kappaB activation via TRAF2/5. (PMID:15708970)
- TRAF2 colocalizes with eIF4GI in insoluble stress granules during cellular exposure to stress conditions. (PMID:15743837)
- In contrast with its effects on signaling triggered by other TNF receptors, functional studies reveal that TRAF2 plays a novel inhibitory role in glucocorticoid-induced TNF receptor (GITR)-triggered NF-kappa B activation. (PMID:15944293)
- Results for the first time place tumor necrosis factor receptor-associated factor-2 (TRAF2), previously shown to function in TNF signaling, within the interferon signal transduction pathway (PMID:16009713)
- TRAF2-dependent CD40 signal transduction requires TRAF6 in nonhemopoietic cells (PMID:16260598)
- a single cIAP can direct its E3 ligase activity toward different substrates and can alter the cellular functions of different protein targets, including TRAF2 and SMAC, in accordance with differences in the specificity of individual BIR domains (PMID:16282325)
- A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented (PMID:16304992)
- These data indicate that vFLIP uses TRAF2 and TRAF3 for signalling to NF-kappaB, which is crucial for KSHV-associated lymphomagenesis (PMID:16311516)
- an LMP1-associated complex containing TRAF6, TAB2, and TAK1 plays an essential role in the activation of JNK (PMID:16446357)
- GSTP1-1 plays an important regulatory role in TNF-alpha-induced signaling by forming ligand-binding interactions with TRAF2, which provides insight for analysing the protective effects of GSTP1-1 in tumor cells. (PMID:16636664)
- the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB independently of TRAF1 AND TRAF2 and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity (PMID:16891304)
- JAB1 regulates ubiquitination of TRAF2 (PMID:16936264)
- IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappaB-mediated signaling and is partially responsible for the apoptotic activity of IHPK2. (PMID:17379600)
- TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling. (PMID:17389591)
- These data together uncovers a new signaling pathway regulating APE/Ref-1 nuclear translocation involving CD40-crosslinking, TRAF2 and p38. (PMID:17599408)
- Dominant-negative forms of TRAF2 and TRAF3 inhibited but did not fully block LMP1-mediated transformation. (PMID:17626074)
- These findings demonstrate that Trx, TRAF2, and TRAF6 regulate ASK1 activity by modulating N-terminal homophilic interaction of ASK1. (PMID:17724081)
- There was a positive correlation between TRAF2 and cyclin D1 expressions and the expression NF-kappaBp65 in the epithelial cells and lymphocytes in oral lichen planus. (PMID:18024283)
- Our findings suggest that the TRAF-2 pathway is involved Alzheimer disease. The mechanisms are currently unclear and need further examination. (PMID:18069092)
- LMP2A protein controls the expression of TRAF2 mRNA, which in turn is necessary for signaling by LMP1. (PMID:18230756)
- TNF-R2 mediates TNF-alpha signaling in chromaffin cells via activation of nuclear factor (NF)-kappaB. (PMID:18292192)
- TRAF2 might be involved in activation of NF-kappaB in a subset of ABC-like primary nodal diffuse large B-cell lymphomas indicating a poor outcome. (PMID:18312353)
- place TRAF2 directly in the signaling pathway transduced through the IFNAR1 subunit of the IFN receptor (PMID:18362156)
- These results suggest an important role for Smurf2 binding to TRAF2 in determining specific signalling outputs of TNF-R2. (PMID:18671942)
- TRAF2 expression and subsequent degradation are required for the differentiation of monocytes into fully functional macrophages (PMID:18827186)
- results unveil a new, finely tuned mechanism for TNF-alpha-induced IKK activation modulated by TRAF2 phosphorylation and suggest that TRAF2 phosphorylation contributes to elevated levels of basal NF-kappaB activity in certain human cancers (PMID:18981220)
- TRAF2 plays a critical role in TNF signaling by directing the IKK complex to the membrane, promoting TRAF2 K63-linked ubiquitination, and positioning the IKKalpha and IKKbeta chains with the TAK1/TAB kinase. (PMID:19150425)
- glomerular and tubular expression of TNF-alpha, (TNF receptor-associated death domain protein)TRADD, RIP(receptor-interacting protein) and TRAF-2 (TNF receptor-associated factor-) was significantly up-regulated in Lupus nephritis (PMID:19151112)
- TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes and resistance to apoptosis. (PMID:19234489)
- c-IAP1 can be targeted for degradation by two distinct processes,through degradation of the TRAF2-c-IAP1 heterodimer or through induced autoubiquitination of c-IAP1 by IAP antagonists, releasing TRAF2 (PMID:19243308)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | traf2a | ENSDARG00000030173 |
| danio_rerio | unm_sa808 | ENSDARG00000078378 |
| mus_musculus | Traf2 | ENSMUSG00000026942 |
| rattus_norvegicus | Traf2 | ENSRNOG00000006238 |
| caenorhabditis_elegans | WBGENE00006612 | |
| caenorhabditis_elegans | trf-2 | WBGENE00022454 |
Paralogs (5): TRAF1 (ENSG00000056558), TRAF4 (ENSG00000076604), TRAF5 (ENSG00000082512), TRAF3 (ENSG00000131323), TRAF6 (ENSG00000175104)
Protein
Protein identifiers
TNF receptor-associated factor 2 — Q12933 (reviewed: Q12933)
Alternative names: E3 ubiquitin-protein ligase TRAF2, RING-type E3 ubiquitin transferase TRAF2, Tumor necrosis factor type 2 receptor-associated protein 3
All UniProt accessions (4): Q12933, B1AMX7, B1AMX8, B1AMY1
UniProt curated annotations — full annotation on UniProt →
Function. E3 ubiquitin-protein ligase that regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Catalyzes ‘Lys-63’-linked ubiquitination of target proteins, such as BIRC3, IKBKE, MLST8, 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. Acts as a regulator of mTORC1 and mTORC2 assembly by mediating ‘Lys-63’-linked ubiquitination of MLST8, thereby inhibiting formation of the mTORC2 complex, while facilitating assembly of the mTORC1 complex. Required for normal antibody isotype switching from IgM to IgG.
Subunit / interactions. Homotrimer. Heterotrimer with TRAF1. Heterotrimer with TRAF3 (via TRAF domain). The domain containing the RING-type and the first TRAF-type zinc finger can also form homodimers (in vitro). Interacts with TNFRSF1B/TNFR2. Interacts with TNFRSF5/CD40. Interacts with TNFRSF4, TNFRSF7/CD27, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF16/NGFR, TNFRSF17/BCMA, TNFRSF18/AITR, TNFRSF19/TROY, TNFRSF19L/RELT and EDAR. Stimulation of TNF receptor TNFRSF1A leads to the formation of two distinct signaling complexes. Plasma membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival. Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis. Interacts with TRADD. Identified in a complex with TNFRSF1A, RIPK1 and IKBKB/IKK-beta. Interacts with RIPK2. Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2, or a TRAF2 homotrimer. Identified in a complex composed of TRAF2, TRAF3, BIRC2 and BIRC3. Interacts with BIRC2; the interaction promotes BIRC2 stability. Interaction with BIRC2 and/or BIRC3 is essential for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Within complex I, phosphorylated TRAF2 interacts (via ‘Lys-63’-linked polyubiquitin chains) with CHUCK/IKK-alpha, IKBKB/IKK-beta, IKBKG/IKK-gamma TAB2, TAB3 and TAK1 in response to TNF stimulation. Within complex I, interacts with UXT isoform 1 (via TPQE motif); the interaction prevents the recruitment of FADD and CASP8/caspase 8 to complex I. Forms a complex composed of TNFRSF8/CD30 or TNFRSF1B/TNFR2, and TRAF1, TRAF2 and E3 ligase TRAIP. Within the complex, interacts with TRAIP; the interaction inhibits TRAF2-mediated NF-kappa B activation. Component of a complex composed of TANK and TBK1. Interacts with TRPC4AP. Interacts with MAP3K1/MEKK1, MAP3K5/ASK1 and MAP3K11/MLK3 in response to TNF stimulation; the interaction leads to JNK activation and interaction with MAP3K5 is inhibited by PRMT1. Component of a complex composed of MAP3K14/NIK BIRC3 and TRAF3; the interaction leads to BIRC2/3-mediated ubiquitination of TRAF3 upon CD40 engagement in a TRAF2-dependent manner. Interacts with MAP3K14/NIK in response to TNF stimulation; the interaction leads to NF-kappa B activation. Interacts with PEG3; the interaction may promote TRAF2-mediated NF-kappa B activation. Interacts with HIVEP3; the interaction may inhibit TNF-TRAF2-mediated NF-kappa B and JNK activation. Interacts with TANK/ITRAF; the interaction prevents interaction between TNFRSF1B/TNFR2 and TRAF2. Interacts with deubiquitinating enzyme CYLD; the interaction results in the deubiquitination and inactivation of TRAF2. Interacts with SIAH2; the interaction leads to TRAF2 ubiquitination and degradation. Interacts with E2 conjugating enzyme UBE2N/Ubc13, E3 ligase ITCH and RNF11 in response to TNF stimulation. Interacts with ubiquitin-editing enzyme TNFAIP3/A20 in response to TNF stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13, ITCH, RNF11 and TAX1BP1 and prevents prolonged TRAF-2 ubiquitination. Interacts with TAX1BP1 in response to TNF stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13 and TNFAIP3/A20, and prevents prolonged TRAF-2 ubiquitination. Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with deubiquitinating enzyme USP48. Interacts with PTPN2; probably involved in TNF-mediated signaling. Interacts with Toll-like receptor TLR4/3 adapter TICAM1/TRIF; the interaction may promote TICAM1 ubiquitination. Interacts with kinase/endoribonuclease ERN1/IRE1 and DAB2IP in response to ER stress; the interaction requires DAB2IP. Interacts with ERN1/IRE1 and TAOK3 in response to ER stress; the interaction may promote TRAF2 phosphorylation. Interacts (via zinc fingers) with DAB2IP (via C-terminus PER domain)in response to TNF stimulation. Interacts with CASP8AP2/FLASH. Interacts with NFATC2IP; the interaction may repress IL-4 production in T cells. Interacts with kinase CDK9. Interacts with sphingosine kinase 1 SPHK1. Interacts with kinase TNIK. Interacts with TRAFD1. Interacts with DNA phosphodiesterase TDP2. Interacts with MAVS/IPS1. Interacts with CARD14. Interacts with Epstein-Barr virus LMP1/BNFL1. Interacts with GPS2. Interacts with XPNPEP3. Interacts with RIPK3. Interacts with RELL2. Interacts with LRRC19. Interacts with GAPDH; promoting TRAF2 ubiquitination.
Subcellular location. Cytoplasm.
Post-translational modifications. Phosphorylated at several serine residues within the first 128 amino acid residues. Phosphorylated at Thr-117 in response to signaling via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for ‘Lys-63’-linked polyubiquitination, but not for ‘Lys-48’-linked polyubiquitination. Phosphorylation at Thr-117 is important for interaction with IKKA and IKKB, activation of IKK and subsequent activation of NF-kappa-B. Undergoes both ‘Lys-48’-linked and ‘Lys-63’-linked polyubiquitination. Polyubiquitinated via ‘Lys-63’-linked ubiquitin in response to TNF signaling; this requires prior phosphorylation at Thr-117. ‘Lys-63’-linked polyubiquitination promotes TRAF2-mediated activation of NF-kappa-B. Can be polyubiquitinated at several Lys residues via ‘Lys-48’-linked ubiquitin chains in response to TNF signaling, leading to proteasomal degradation. Autoubiquitinated, leading to its subsequent proteasomal degradation. Polyubiquitinated by BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. Deubiquitinated by CYLD, a protease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains. Ubiquitination is inhibited by LRRC19; inhibits proteasomal degradation. Ubiquitinated at Lys-320 by the SCF(FBXL2) complex, leading to its degradation by the proteasome. Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to repression of NF-kappa-B signaling.
Activity regulation. Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate.
Domain organisation. The coiled coil domain mediates homo- and hetero-oligomerization. The MATH/TRAF domain binds to receptor cytoplasmic domains. The RING-type zinc finger domain is essential for E3 ubiquitin-protein ligase activity. It is not essential for the stabilization of BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 signaling.
Pathway. Protein modification; protein ubiquitination.
Similarity. Belongs to the TNF receptor-associated factor family. A subfamily.
Isoforms (4)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q12933-1 | 1 | yes |
| Q12933-2 | 2 | |
| Q12933-3 | 3 | |
| Q12933-4 | 4 |
RefSeq proteins (1): NP_066961* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001293 | Znf_TRAF | Domain |
| IPR001841 | Znf_RING | Domain |
| IPR002083 | MATH/TRAF_dom | Domain |
| IPR008974 | TRAF-like | Homologous_superfamily |
| IPR012227 | TNF_rcpt-assoc_TRAF_met | Family |
| IPR013083 | Znf_RING/FYVE/PHD | Homologous_superfamily |
| IPR017907 | Znf_RING_CS | Conserved_site |
| IPR018957 | Znf_C3HC4_RING-type | Domain |
| IPR027133 | TRAF2_RING-HC | Domain |
| IPR032070 | TRAF_BIRC3-bd | Domain |
| IPR037305 | TRAF2_MATH | Domain |
| IPR049342 | TRAF1-6_MATH_dom | Domain |
| IPR049441 | TRAF2_Znf | Domain |
Pfam: PF00097, PF02176, PF16673, PF21341, PF21355
UniProt features (64 total): helix 17, strand 15, mutagenesis site 7, modified residue 6, turn 4, splice variant 3, zinc finger region 3, cross-link 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1, region of interest 1, coiled-coil region 1
Structure
Experimental structures (PDB)
15 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 3KNV | X-RAY DIFFRACTION | 1.9 |
| 8T5Q | X-RAY DIFFRACTION | 1.9 |
| 1CZY | X-RAY DIFFRACTION | 2 |
| 1D00 | X-RAY DIFFRACTION | 2 |
| 1D01 | X-RAY DIFFRACTION | 2 |
| 1D0A | X-RAY DIFFRACTION | 2 |
| 1F3V | X-RAY DIFFRACTION | 2 |
| 1CA4 | X-RAY DIFFRACTION | 2.2 |
| 1CA9 | X-RAY DIFFRACTION | 2.3 |
| 1QSC | X-RAY DIFFRACTION | 2.4 |
| 1D0J | X-RAY DIFFRACTION | 2.5 |
| 3M0A | X-RAY DIFFRACTION | 2.61 |
| 3M06 | X-RAY DIFFRACTION | 2.67 |
| 1CZZ | X-RAY DIFFRACTION | 2.7 |
| 3M0D | X-RAY DIFFRACTION | 2.8 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q12933-F1 | 90.73 | 0.76 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (8): 7, 11, 22, 117, 31, 320, 2, 5
Mutagenesis-validated functional residues (7):
| Position | Phenotype |
|---|---|
| 11 | reduces global phosphorylation. partial reduction of tnf-dependent activation of nf-kappa-b and activation of jnk. |
| 11 | slight increase of tnf-dependent activation of nf-kappa-b and activation of jnk. |
| 31 | abolishes ’lys-63’-linked polyubiquitination. |
| 117 | loss of phosphorylation site. abolishes activation of nf-kappa-b. |
| 285 | strongly reduced interaction with birc3. |
| 288 | strongly reduced interaction with birc3. |
| 292 | strongly reduced interaction with birc3. |
Function
Pathways and Gene Ontology
Reactome pathways
17 pathways
| ID | Pathway |
|---|---|
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand |
| R-HSA-3371378 | Regulation by c-FLIP |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis |
| R-HSA-5218900 | CASP8 activity is inhibited |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling |
| R-HSA-5357905 | Regulation of TNFR1 signaling |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway |
| R-HSA-5675482 | Regulation of necroptotic cell death |
| R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
| R-HSA-5689880 | Ub-specific processing proteases |
| R-HSA-69416 | Dimerization of procaspase-8 |
| R-HSA-75893 | TNF signaling |
| R-HSA-933541 | TRAF6 mediated IRF7 activation |
| R-HSA-933542 | TRAF6 mediated NF-kB activation |
| R-HSA-9693928 | Defective RIPK1-mediated regulated necrosis |
| R-HSA-9758274 | Regulation of NF-kappa B signaling |
MSigDB gene sets: 420 (showing top):
REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, BIOCARTA_TNFR2_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS
GO Biological Process (45): toll-like receptor signaling pathway (GO:0002224), regulation of immunoglobulin production (GO:0002637), positive regulation of T cell cytokine production (GO:0002726), signal transduction (GO:0007165), canonical NF-kappaB signal transduction (GO:0007249), signal transduction involved in regulation of gene expression (GO:0023019), CD40 signaling pathway (GO:0023035), protein catabolic process (GO:0030163), positive regulation of interleukin-2 production (GO:0032743), tumor necrosis factor-mediated signaling pathway (GO:0033209), negative regulation of glial cell apoptotic process (GO:0034351), response to endoplasmic reticulum stress (GO:0034976), non-canonical NF-kappaB signal transduction (GO:0038061), T cell activation (GO:0042110), regulation of apoptotic process (GO:0042981), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), regulation of protein-containing complex assembly (GO:0043254), positive regulation of JUN kinase activity (GO:0043507), regulation of JNK cascade (GO:0046328), mRNA stabilization (GO:0048255), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein autoubiquitination (GO:0051865), protein-containing complex assembly (GO:0065003), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), protein K63-linked ubiquitination (GO:0070534), cellular response to nitric oxide (GO:0071732), programmed necrotic cell death (GO:0097300), interleukin-17-mediated signaling pathway (GO:0097400), CD27 signaling pathway (GO:0160162), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), TORC1 complex assembly (GO:1905669), TORC2 complex disassembly (GO:1905670), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), protein polyubiquitination (GO:0000209), regulation of production of molecular mediator of immune response (GO:0002700), apoptotic process (GO:0006915), activation of NF-kappaB-inducing kinase activity (GO:0007250), positive regulation of gene expression (GO:0010628), programmed cell death (GO:0012501)
GO Molecular Function (22): ubiquitin-protein transferase activity (GO:0004842), tumor necrosis factor receptor binding (GO:0005164), CD40 receptor binding (GO:0005174), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), protein-macromolecule adaptor activity (GO:0030674), mitogen-activated protein kinase kinase kinase binding (GO:0031435), ubiquitin protein ligase binding (GO:0031625), thioesterase binding (GO:0031996), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), tumor necrosis factor binding (GO:0043120), protein-containing complex binding (GO:0044877), sphingolipid binding (GO:0046625), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), lipid binding (GO:0008289), transferase activity (GO:0016740), tumor necrosis factor receptor superfamily binding (GO:0032813), metal ion binding (GO:0046872)
GO Cellular Component (14): ubiquitin ligase complex (GO:0000151), tumor necrosis factor receptor superfamily complex (GO:0002947), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cell cortex (GO:0005938), cytoplasmic side of plasma membrane (GO:0009898), vesicle membrane (GO:0012506), CD40 receptor complex (GO:0035631), membrane raft (GO:0045121), TRAF2-GSTP1 complex (GO:0097057), IRE1-TRAF2-ASK1 complex (GO:1990604), protein-containing complex (GO:0032991), signaling receptor complex (GO:0043235)
Reactome top-level categories
Rollup of top-13 pathways:
| Category | Pathways |
|---|---|
| TNF signaling | 3 |
| Caspase activation via Death Receptors in the presence of ligand | 2 |
| DDX58/IFIH1-mediated induction of interferon-alpha/beta | 2 |
| Caspase activation via extrinsic apoptotic signalling pathway | 1 |
| Regulated Necrosis | 1 |
| Regulation of necroptotic cell death | 1 |
| Cytokine Signaling in Immune system | 1 |
| RIPK1-mediated regulated necrosis | 1 |
| TNFR2 non-canonical NF-kB pathway | 1 |
| Deubiquitination | 1 |
| Death Receptor Signaling | 1 |
| Diseases of programmed cell death | 1 |
| TAK1-dependent IKK and NF-kappa-B activation | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| protein binding | 3 |
| binding | 3 |
| cellular anatomical structure | 3 |
| intracellular signaling cassette | 2 |
| canonical NF-kappaB signal transduction | 2 |
| regulation of canonical NF-kappaB signal transduction | 2 |
| tumor necrosis factor receptor superfamily binding | 2 |
| cytoplasm | 2 |
| protein-containing complex | 2 |
| pattern recognition receptor signaling pathway | 1 |
| immunoglobulin production | 1 |
| regulation of production of molecular mediator of immune response | 1 |
| T cell cytokine production | 1 |
| positive regulation of T cell mediated immunity | 1 |
| positive regulation of cytokine production involved in immune response | 1 |
| regulation of T cell cytokine production | 1 |
| cell communication | 1 |
| cellular process | 1 |
| signaling | 1 |
| regulation of cellular process | 1 |
| cellular response to stimulus | 1 |
| signal transduction | 1 |
| regulation of gene expression | 1 |
| cell surface receptor signaling pathway | 1 |
| macromolecule catabolic process | 1 |
| protein metabolic process | 1 |
| positive regulation of cytokine production | 1 |
| interleukin-2 production | 1 |
| regulation of interleukin-2 production | 1 |
| cytokine-mediated signaling pathway | 1 |
| cellular response to tumor necrosis factor | 1 |
| glial cell apoptotic process | 1 |
| regulation of glial cell apoptotic process | 1 |
| negative regulation of apoptotic process | 1 |
| cellular response to stress | 1 |
| lymphocyte activation | 1 |
| apoptotic process | 1 |
| regulation of programmed cell death | 1 |
| positive regulation of intracellular signal transduction | 1 |
| negative regulation of intracellular signal transduction | 1 |
Protein interactions and networks
STRING
2016 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| TRAF2 | TRADD | Q15628 | 996 |
| TRAF2 | RIPK1 | Q13546 | 994 |
| TRAF2 | MAP3K5 | Q99683 | 994 |
| TRAF2 | ERN1 | O75460 | 993 |
| TRAF2 | BIRC2 | Q13490 | 993 |
| TRAF2 | TNFRSF1A | P19438 | 992 |
| TRAF2 | BIRC3 | Q13489 | 990 |
| TRAF2 | FADD | Q13158 | 982 |
| TRAF2 | TRAF5 | O00463 | 970 |
| TRAF2 | IKBKG | Q9Y6K9 | 958 |
| TRAF2 | CASP8 | Q14790 | 941 |
| TRAF2 | SPHK1 | Q9NYA1 | 941 |
| TRAF2 | TRAF3 | Q13114 | 921 |
| TRAF2 | TNF | P01375 | 918 |
| TRAF2 | TAB2 | Q9NYJ8 | 797 |
IntAct
1573 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CD40 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.960 |
| TRAF2 | CD40 | psi-mi:“MI:0915”(physical association) | 0.960 |
| TRAF2 | TRADD | psi-mi:“MI:0407”(direct interaction) | 0.940 |
| TRAF2 | TRAF6 | psi-mi:“MI:0915”(physical association) | 0.900 |
| RIPK1 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.880 |
| TNFAIP3 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.870 |
| RAD23A | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.870 |
| GORASP2 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.870 |
| TRAF2 | TNFAIP3 | psi-mi:“MI:0915”(physical association) | 0.870 |
| TRAF2 | RAD23A | psi-mi:“MI:0915”(physical association) | 0.870 |
| TRAF2 | GORASP2 | psi-mi:“MI:0915”(physical association) | 0.870 |
| ATXN1 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.860 |
| EFEMP1 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.860 |
| TRAF2 | BCL10 | psi-mi:“MI:0915”(physical association) | 0.850 |
| TIFA | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.840 |
| TRAF2 | TIFA | psi-mi:“MI:0915”(physical association) | 0.840 |
| TRAF2 | PRKAB2 | psi-mi:“MI:0915”(physical association) | 0.830 |
| THAP7 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.830 |
| SPG21 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.830 |
| PRKAB2 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.830 |
| TRAF2 | SPG21 | psi-mi:“MI:0915”(physical association) | 0.830 |
| USP2 | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.780 |
| NEBL | TRAF2 | psi-mi:“MI:0915”(physical association) | 0.780 |
| TRAF2 | GABPB1 | psi-mi:“MI:0915”(physical association) | 0.780 |
| TRAF2 | PIN1 | psi-mi:“MI:0915”(physical association) | 0.780 |
BioGRID (2201): TRAF2 (Co-crystal Structure), TRAF2 (Affinity Capture-Western), PPP4R1 (Two-hybrid), TRAF2 (Affinity Capture-Western), TRAF2 (Affinity Capture-Western), TRAF2 (Affinity Capture-Western), TRAF2 (Affinity Capture-MS), TRAF2 (Affinity Capture-Western), ELAVL1 (Affinity Capture-Western), TRAF2 (Two-hybrid), TRAF2 (Two-hybrid), TRAF2 (Two-hybrid), TRAF2 (Two-hybrid), TRAF2 (Two-hybrid), TRAF2 (Two-hybrid)
ESM2 similar proteins: A0A974CYQ5, A5WW08, A7XUJ6, B5DF45, B6CJY4, B6CJY5, O00463, O15344, O70583, P0DW87, P0DW89, P39429, P53351, P70191, P70196, P82457, P82458, Q08CH8, Q12933, Q13114, Q28DL4, Q29RQ5, Q2TAD9, Q3KPU8, Q3MV19, Q3U9F6, Q3ZCC3, Q5FWP4, Q5R4L1, Q60803, Q61382, Q6DJN2, Q6GNX1, Q6IWL4, Q6J1I7, Q6P256, Q80WG7, Q8N2W9, Q91ZY8, Q969K3
Diamond homologs: O00463, P39428, P39429, P68907, P70191, Q12933, Q13077, Q13114, Q60803, Q69ZS0, Q9UPQ7, A0A0C5PRQ1, A8Q2D1, B3EWZ5, B3EWZ6, C9D7R3, D2KBH9, D5FM34, D5FM37, D5FM38, K7Z9Q9, O16977, O19045, O43897, O57382, O57460, O62243, P07584, P0DJJ2, P0DM61, P0DM62, P13497, P28825, P28826, P31579, P31580, P31581, P42662, P42664, P42674
SIGNOR signaling
48 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| CYLD | “down-regulates activity” | TRAF2 | deubiquitination |
| UBE2N | “up-regulates activity” | TRAF2 | ubiquitination |
| TRAF2 | “up-regulates activity” | MAP3K7 | ubiquitination |
| TRAF2 | up-regulates | BIRC3 | binding |
| BIRC2 | “down-regulates quantity by destabilization” | TRAF2 | ubiquitination |
| TRAF2 | “down-regulates quantity by destabilization” | MAP3K14 | ubiquitination |
| TRAF2 | “up-regulates activity” | BIRC2 | binding |
| TRAF2 | “up-regulates activity” | RIPK1 | ubiquitination |
| CD40 | “up-regulates activity” | TRAF2 | binding |
| TRAF2 | up-regulates | MAP3K1 | binding |
| TRAF2 | “up-regulates activity” | UBE2N | binding |
| BIRC3 | “down-regulates quantity by destabilization” | TRAF2 | ubiquitination |
| PRKCZ | unknown | TRAF2 | phosphorylation |
| TNFRSF1A | up-regulates | TRAF2 | |
| TRAF2 | up-regulates | RIPK1 | |
| Ub:E2 | “up-regulates activity” | TRAF2 | ubiquitination |
| TRAF2 | up-regulates | TICAM1 | polyubiquitination |
| IKBKE | “up-regulates activity” | TRAF2 | phosphorylation |
| MAP4K4 | “down-regulates quantity” | TRAF2 | phosphorylation |
| TNFRSF1B | “up-regulates activity” | TRAF2 | binding |
| TRAF1 | up-regulates | TRAF2 | binding |
| TRAF2 | up-regulates | TRAF1 | binding |
| TRADD | “up-regulates activity” | TRAF2 | binding |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| TNFR1-induced proapoptotic signaling | 5 | 43.1× | 2e-05 |
| Regulation of TNFR1 signaling | 5 | 21.9× | 4e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
85 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 63 |
| Likely benign | 3 |
| Benign | 3 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
0 predictions. Top by Δscore:
AlphaMissense
3299 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 9:136898840:T:C | C34R | 1.000 |
| 9:136898878:G:C | Q46H | 1.000 |
| 9:136898878:G:T | Q46H | 1.000 |
| 9:136900425:T:C | F91L | 1.000 |
| 9:136900427:C:A | F91L | 1.000 |
| 9:136900427:C:G | F91L | 1.000 |
| 9:136900431:G:C | D93H | 1.000 |
| 9:136923905:G:C | G398R | 1.000 |
| 9:136923906:G:A | G398D | 1.000 |
| 9:136923906:G:T | G398V | 1.000 |
| 9:136923936:C:T | S408F | 1.000 |
| 9:136923941:T:C | F410L | 1.000 |
| 9:136923943:C:A | F410L | 1.000 |
| 9:136923943:C:G | F410L | 1.000 |
| 9:136923983:T:A | W424R | 1.000 |
| 9:136923983:T:C | W424R | 1.000 |
| 9:136923985:G:C | W424C | 1.000 |
| 9:136923985:G:T | W424C | 1.000 |
| 9:136925696:T:C | L434P | 1.000 |
| 9:136925734:T:C | F447L | 1.000 |
| 9:136925735:T:C | F447S | 1.000 |
| 9:136925736:C:A | F447L | 1.000 |
| 9:136925736:C:G | F447L | 1.000 |
| 9:136925761:T:A | F456I | 1.000 |
| 9:136925761:T:C | F456L | 1.000 |
| 9:136925762:T:C | F456S | 1.000 |
| 9:136925763:T:A | F456L | 1.000 |
| 9:136925763:T:G | F456L | 1.000 |
| 9:136925771:C:A | P459Q | 1.000 |
| 9:136925792:C:A | A466E | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000042028 (9:136917399 G>T), RS1000065492 (9:136901904 C>A), RS1000120872 (9:136881044 G>A,C,T), RS1000120925 (9:136887870 TTTTA>T), RS1000127897 (9:136891824 C>T), RS1000158896 (9:136892043 A>G), RS1000220433 (9:136923503 C>G,T), RS1000319904 (9:136897189 C>G,T), RS1000376099 (9:136926223 G>A,T), RS1000399161 (9:136926918 AGGCTCCACCGAGCATCCT>A), RS1000411701 (9:136909291 G>A), RS1000412442 (9:136914230 G>A,C), RS1000462357 (9:136883851 C>T), RS1000462852 (9:136890512 A>G,T), RS1000467458 (9:136914038 C>T)
Disease associations
OMIM: gene MIM:601895 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
0 associations (top):
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL6067211 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.25 | Kd | 565.7 | nM | CHEMBL5653589 |
| 6.17 | ED50 | 680 | nM | CHEMBL5653589 |
| 5.59 | Kd | 2585 | nM | CHEMBL3752910 |
| 5.51 | ED50 | 3107 | nM | CHEMBL3752910 |
PubChem BioAssay actives
2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149651: Binding affinity to human TRAF2 incubated for 45 mins by Kinobead based pull down assay | kd | 0.5657 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149651: Binding affinity to human TRAF2 incubated for 45 mins by Kinobead based pull down assay | kd | 2.5852 | uM |
CTD chemical–gene interactions
72 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | affects methylation, decreases expression, increases expression | 4 |
| Acetaminophen | affects cotreatment, increases expression | 2 |
| Benzo(a)pyrene | decreases methylation, affects methylation | 2 |
| Cisplatin | affects response to substance, decreases expression, increases reaction, affects reaction, increases cleavage (+2 more) | 2 |
| 6-methoxyflavone | decreases expression | 1 |
| parthenolide | decreases reaction, increases expression, decreases expression | 1 |
| 2-anisidine | decreases expression | 1 |
| naringenin | affects cotreatment, increases expression | 1 |
| bisphenol A | affects cotreatment, increases expression | 1 |
| VX-agent | increases expression | 1 |
| coumarin | increases phosphorylation | 1 |
| 1’-acetoxychavicol acetate | decreases reaction, increases expression | 1 |
| harringtonin | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| anacardic acid | decreases activity | 1 |
| zerumbone | affects binding, decreases reaction, increases activity | 1 |
| 2-hydroxyursolic acid | decreases expression | 1 |
| obeticholic acid | decreases expression | 1 |
| abrine | increases expression | 1 |
| xinfeng | increases expression, decreases expression, decreases reaction | 1 |
| jinfukang | decreases expression, increases reaction | 1 |
| ibrutinib | decreases response to substance | 1 |
| NSC 689534 | decreases expression, affects binding | 1 |
| PCI 5002 | affects cotreatment, increases expression | 1 |
| ceritinib | decreases expression | 1 |
| Resveratrol | decreases expression | 1 |
| Zoledronic Acid | increases expression | 1 |
| Arsenic Trioxide | decreases expression | 1 |
| Vorinostat | decreases reaction, increases activity | 1 |
ChEMBL screening assays
1 unique, capped per target: 1 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5652693 | Binding | Binding affinity to human TRAF2 incubated for 45 mins by Kinobead based pull down assay | NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem |
Cellosaurus cell lines
7 cell lines: 6 cancer cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B077 | Z-138 | Cancer cell line | Male |
| CVCL_D8CY | Ubigene A-549 TRAF2 KO | Cancer cell line | Male |
| CVCL_D8XK | Ubigene HCT 116 TRAF2 KO | Cancer cell line | Male |
| CVCL_D9UT | Ubigene HEK293 TRAF2 KO | Transformed cell line | Female |
| CVCL_E0S0 | Ubigene HeLa TRAF2 KO | Cancer cell line | Female |
| CVCL_TT54 | HAP1 TRAF2 (-) 1 | Cancer cell line | Male |
| CVCL_TT55 | HAP1 TRAF2 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.