Details for: TRAF6

Gene ID: 7189

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TRAF6

Ensembl ID: ENSG00000175104

Description: TNF receptor associated factor 6

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.75
    rCSI 6.63%
    PRS 76.52
  • plasmablast CL0000980
    CSI 3.56
    rCSI 2.8%
    PRS 92.47
  • pro-B cell CL0000826
    CSI 3.56
    rCSI 2.95%
    PRS 91.52
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.89
    rCSI 1.94%
    PRS 97.54
  • small pre-B-II cell CL0000954
    CSI 2.78
    rCSI 2.67%
    PRS 96.38
  • colon epithelial cell CL0011108
    CSI 2.7
    rCSI 2.83%
    PRS 87.91
  • melanocyte CL0000148
    CSI 2.69
    rCSI 1.99%
    PRS 86.46
  • blood vessel endothelial cell CL0000071
    CSI 2.41
    rCSI 5%
    PRS 88.41
  • cerebral cortex endothelial cell CL1001602
    CSI 2.3
    rCSI 3.97%
    PRS 84.74
  • ependymal cell CL0000065
    CSI 2.13
    rCSI 4.32%
    PRS 72.59
  • alpha-beta T cell CL0000789
    CSI 2.08
    rCSI 2.44%
    PRS 97.05
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.92
    rCSI 1.48%
    PRS 93.06
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.79
    rCSI 3%
    PRS 77.07
  • cardiac endothelial cell CL0010008
    CSI 1.77
    rCSI 7.16%
    PRS 90.79
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.57
    rCSI 3.51%
    PRS 77.54
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.37
    rCSI 3.47%
    PRS 83.86
  • basal cell of epidermis CL0002187
    CSI 1.32
    rCSI 2.34%
    PRS 61.3
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.2
    rCSI 2.92%
    PRS 74.91
  • neural progenitor cell CL0011020
    CSI 1.11
    rCSI 4.9%
    PRS 79.85
  • helper T cell CL0000912
    CSI 1.02
    rCSI 1.44%
    PRS 86.25
  • melanocyte of skin CL1000458
    CSI 1.01
    rCSI 1.38%
    PRS 60.85
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.93
    rCSI 5.47%
    PRS 77.56
  • large pre-B-II cell CL0000957
    CSI 0.88
    rCSI 2.5%
    PRS 90.69
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.84
    rCSI 1.02%
    PRS 71.08
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.71
    rCSI 2.56%
    PRS 75.03
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.67
    rCSI 2.53%
    PRS 77.3
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.59
    rCSI 1.86%
    PRS 80.1
  • direct pathway medium spiny neuron CL4023026
    CSI 0.28
    rCSI 6.69%
    PRS 74.78
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.26
    rCSI 6.23%
    PRS 74.94

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TRAF6](/details-gene/7189) (TNF receptor associated factor 6) is a protein-coding gene located on chromosome 11 that encodes a critical E3 ubiquitin ligase and signaling adaptor. It functions as a central node in numerous signal transduction pathways, most notably those mediating innate and adaptive immunity, inflammation, and tissue homeostasis. As a key transducer for the TNF receptor superfamily and the Interleukin-1/Toll-like receptor superfamily, [TRAF6](/details-gene/7189) is essential for activating downstream signaling cascades, including the canonical NF-kappaB and MAP kinase pathways ([Link](https://doi.org/10.1038/383443a0)). Its expression profile is broad, with high significance observed in various immune cell lineages, such as developing B-cells and memory T-cells, as well as in non-immune cell types including specific neuronal and endothelial populations, suggesting pleiotropic physiological roles. ## Cellular Roles and Expression Landscape The expression pattern of [TRAF6](/details-gene/7189) underscores its widespread importance as a fundamental signaling molecule across diverse cellular systems. **Overall**, the gene shows high significance in both hematopoietic and non-hematopoietic lineages. Within the immune system, [TRAF6](/details-gene/7189) is a key component of lymphocyte function. It exhibits high significance scores in both early and late stages of B-cell development, including [pro-B cell](/details-cell/CL0000826) (CSI: 3.56) and terminally differentiated [plasmablast](/details-cell/CL0000980) (CSI: 3.56). This suggests a sustained role for the gene throughout B-cell maturation, from initial development to antibody production. Similarly, its prominence in [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 2.89) and [alpha-beta T cell](/details-cell/CL0000789) (CSI: 2.08) populations is consistent with its established function in T-cell activation and memory formation. Beyond the adaptive immune system, [TRAF6](/details-gene/7189) is also significant in certain myeloid cells, such as the [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 1.92), reflecting its role in innate immune responses. Notably, the gene displays high significance in several non-immune cell types. Its top-ranking expression is in a neuronal subtype, the [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 3.75), with notable significance in other neural cells like [ependymal cell](/details-cell/CL0000065) and [astrocyte of the cerebral cortex](/details-cell/CL0002605). Furthermore, its high CSI in various endothelial cells, including [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 2.41) and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.30), points to a critical role in vascular biology and inflammation. ## Pathways and Molecular Function The functional annotations for [TRAF6](/details-gene/7189) confirm its identity as a master regulator of immune and inflammatory signaling. Its core molecular function is that of a [ubiquitin-protein transferase activity](/details-go/GO:0004842), specifically mediating K63-linked polyubiquitination ([GO:0070534](https://www.ebi.ac.uk/QuickGO/term/GO:0070534)), a non-degradative signal that facilitates the assembly of signaling complexes. [TRAF6](/details-gene/7189) is a central component of the [Innate Immune System](/details-reactome/R-HSA-168249), acting as a downstream effector for nearly all Toll-like receptors via the [MyD88-dependent toll-like receptor signaling pathway](/details-go/GO:0002755). It is also integral to signaling from other pattern recognition receptors, such as C-type lectins ([R-HSA-5621481](https://reactome.org/content/detail/R-HSA-5621481)). Upon activation, [TRAF6](/details-gene/7189) triggers cascades leading to the activation of key transcription factors, most prominently through [canonical NF-kappaB signal transduction](/details-go/GO:0007249) and MAP kinase pathways like JNK ([GO:0043507](https://www.ebi.ac.uk/QuickGO/term/GO:0043507)). In the context of the [Adaptive Immune System](/details-reactome/R-HSA-1280218), [TRAF6](/details-gene/7189) is indispensable for lymphocyte activation. It is a key mediator of the [CD40 signaling pathway](/details-go/GO:0023035) in B-cells and is involved in the [T cell receptor signaling pathway](/details-go/GO:0050852). These roles align with its high expression in lymphocytes and are critical for orchestrating immune responses, including cytokine production ([GO:0002726](https://www.ebi.ac.uk/QuickGO/term/GO:0002726)) and proliferation ([GO:0042102](https://www.ebi.ac.uk/QuickGO/term/GO:0042102)). Furthermore, it integrates signals from numerous cytokines, including the [Interleukin-1-mediated signaling pathway](/details-go/GO:0070498) and the [Interleukin-17-mediated signaling pathway](/details-go/GO:0097400). Its involvement extends to other biological processes, including [osteoclast differentiation](/details-go/GO:0030316) and bone resorption, as well as roles in developmental processes such as [neural tube closure](/details-go/GO:0001843). Its annotated function in the [regulation of neurotransmitter receptor localization to postsynaptic specialization membrane](/details-go/GO:0098696) provides a molecular basis for its high significance in specific neuronal populations. ## Research Directions The widespread significance of [TRAF6](/details-gene/7189) across diverse cell types, particularly its prominent role in both immune and nervous systems, presents several avenues for future investigation. **Proposed Hypotheses:** 1. Given its top significance score in [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) and its annotated role in regulating neurotransmitter receptors, [TRAF6](/details-gene/7189) may function as a key regulator of inhibitory synapse formation or plasticity in the cerebral cortex, a role distinct from its canonical immune signaling functions. 2. The high significance of [TRAF6](/details-gene/7189) in endothelial cells, coupled with its central role in inflammatory cytokine signaling ([R-HSA-1280215](https://reactome.org/content/detail/R-HSA-1280215)), suggests it is a primary driver of endothelial activation during inflammation, mediating processes such as leukocyte adhesion and vascular permeability. **Experimental Approach:** To test the first hypothesis regarding the neurological function of [TRAF6](/details-gene/7189), a conditional knockout mouse model could be employed. By crossing a mouse with floxed *Traf6* alleles to a line expressing Cre recombinase under the control of a specific cortical interneuron promoter (e.g., Dlx5/6-Cre), one could selectively delete [TRAF6](/details-gene/7189) in this cell population. Subsequent analysis using slice electrophysiology could assess changes in synaptic transmission and plasticity, while immunofluorescence and electron microscopy could be used to quantify synaptic density and morphology. **Therapeutic Potential:** [TRAF6](/details-gene/7189) represents a compelling therapeutic target for a wide range of inflammatory and autoimmune diseases due to its central role as an E3 ligase in pro-inflammatory signaling. As an intracellular protein, it is not targetable by conventional antibodies, making small molecule inhibitors the most viable strategy. Development of compounds that specifically block its E3 ligase activity or its interaction with upstream adaptors or downstream kinases could potently suppress aberrant NF-kappaB and MAP kinase activation. However, the pleiotropic functions of [TRAF6](/details-gene/7189) present a significant challenge, as systemic inhibition could lead to broad immunosuppression and other off-target effects. Therefore, therapeutic strategies might require targeted delivery systems or the development of highly specific inhibitors that modulate, rather than completely ablate, its function.

Genular Protein ID: 1370190705

Symbol: TRAF6_HUMAN

Name: TNF receptor-associated factor 6

UniProtKB Accession Codes:

Q9Y4K3 A6NKI7 A8KAB3 D3DR16 Q8NEH5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 ELM 1 EMBL 9 Ensembl 2 EvolutionaryTrace 1 GO 80 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 MoonDB 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 13 PDBsum 13 PIR 1 PIRSF 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 35 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8837778

Title: TRAF6 is a signal transducer for interleukin-1.

PubMed ID: 8837778

DOI: 10.1038/383443a0

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9020361

Title: MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1.

PubMed ID: 9020361

DOI: 10.1038/385540a0

PubMed ID: 9374458

Title: IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.

PubMed ID: 9374458

DOI: 10.1126/science.278.5343.1612

PubMed ID: 9642260

Title: RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase.

PubMed ID: 9642260

DOI: 10.1074/jbc.273.27.16968

PubMed ID: 9774460

Title: The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor.

PubMed ID: 9774460

DOI: 10.1074/jbc.273.43.28355

PubMed ID: 9432981

Title: Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates extracellular signal-regulated kinase (ERK) activity in CD40 signaling along a ras-independent pathway.

PubMed ID: 9432981

DOI: 10.1084/jem.187.2.237

PubMed ID: 9774977

Title: ASK1 is essential for JNK/SAPK activation by TRAF2.

PubMed ID: 9774977

DOI: 10.1016/s1097-2765(00)80283-x

PubMed ID: 10346818

Title: Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain.

PubMed ID: 10346818

DOI: 10.1101/gad.13.10.1297

PubMed ID: 9915784

Title: Association of the p75 neurotrophin receptor with TRAF6.

PubMed ID: 9915784

DOI: 10.1074/jbc.274.5.2597

PubMed ID: 10383454

Title: IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family.

PubMed ID: 10383454

DOI: 10.1074/jbc.274.27.19403

PubMed ID: 10514511

Title: TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction.

PubMed ID: 10514511

DOI: 10.1074/jbc.274.42.30202

PubMed ID: 10635328

Title: TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src.

PubMed ID: 10635328

DOI: 10.1016/s1097-2765(00)80232-4

PubMed ID: 10094049

Title: The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway.

PubMed ID: 10094049

DOI: 10.1038/18465

PubMed ID: 10523862

Title: Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1).

PubMed ID: 10523862

DOI: 10.1038/sj.onc.1202975

PubMed ID: 11057907

Title: Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain.

PubMed ID: 11057907

DOI: 10.1016/s0092-8674(00)00126-4

PubMed ID: 10764746

Title: TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation.

PubMed ID: 10764746

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PubMed ID: 10908663

Title: B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1.

PubMed ID: 10908663

DOI: 10.1073/pnas.160213497

PubMed ID: 10920205

Title: T6BP, a TRAF6-interacting protein involved in IL-1 signaling.

PubMed ID: 10920205

DOI: 10.1073/pnas.170279097

PubMed ID: 11460167

Title: TAK1 is a ubiquitin-dependent kinase of MKK and IKK.

PubMed ID: 11460167

DOI: 10.1038/35085597

PubMed ID: 12459498

Title: NF-kappaB activator Act1 associates with IL-1/Toll pathway adapter molecule TRAF6.

PubMed ID: 12459498

DOI: 10.1016/s0014-5793(02)03688-8

PubMed ID: 11751921

Title: A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6.

PubMed ID: 11751921

DOI: 10.1074/jbc.m110964200

PubMed ID: 11960013

Title: IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase.

PubMed ID: 11960013

DOI: 10.1073/pnas.082100399

PubMed ID: 12496252

Title: Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex.

PubMed ID: 12496252

DOI: 10.1074/jbc.m212112200

PubMed ID: 12804775

Title: Pellino2 activates the mitogen activated protein kinase pathway.

PubMed ID: 12804775

DOI: 10.1016/s0014-5793(03)00533-7

PubMed ID: 12721283

Title: TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling.

PubMed ID: 12721283

DOI: 10.1074/jbc.m303451200

PubMed ID: 12874243

Title: Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein.

PubMed ID: 12874243

DOI: 10.4049/jimmunol.171.3.1500

PubMed ID: 14530355

Title: Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling.

PubMed ID: 14530355

DOI: 10.4049/jimmunol.171.8.4304

PubMed ID: 14739303

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PubMed ID: 14739303

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PubMed ID: 14754897

Title: ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor of NFkappaB activation.

PubMed ID: 14754897

DOI: 10.1074/jbc.m309491200

PubMed ID: 15121867

Title: TRAF family proteins link PKR with NF-kappa B activation.

PubMed ID: 15121867

DOI: 10.1128/mcb.24.10.4502-4512.2004

PubMed ID: 14982987

Title: Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta.

PubMed ID: 14982987

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PubMed ID: 16125763

Title: Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.

PubMed ID: 16125763

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PubMed ID: 16286016

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PubMed ID: 16286016

DOI: 10.1016/j.immuni.2005.09.015

PubMed ID: 16221674

Title: FLN29, a novel interferon- and LPS-inducible gene acting as a negative regulator of toll-like receptor signaling.

PubMed ID: 16221674

DOI: 10.1074/jbc.m508221200

PubMed ID: 16153868

Title: VISA is an adapter protein required for virus-triggered IFN-beta Signaling.

PubMed ID: 16153868

DOI: 10.1016/j.molcel.2005.08.014

PubMed ID: 15870274

Title: The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex.

PubMed ID: 15870274

DOI: 10.1128/mcb.25.10.4010-4022.2005

PubMed ID: 16378096

Title: Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling.

PubMed ID: 16378096

DOI: 10.1038/ni1294

PubMed ID: 16951688

Title: Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adapter Pellino-1.

PubMed ID: 16951688

DOI: 10.1038/ni1383

PubMed ID: 17135271

Title: Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation.

PubMed ID: 17135271

DOI: 10.1074/jbc.m609503200

PubMed ID: 17449468

Title: RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation.

PubMed ID: 17449468

DOI: 10.1074/jbc.m701913200

PubMed ID: 17703191

Title: Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPS-mediated NF-kappaB and JNK signaling.

PubMed ID: 17703191

DOI: 10.1038/sj.emboj.7601823

PubMed ID: 18093978

Title: Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification.

PubMed ID: 18093978

DOI: 10.1074/jbc.m706307200

PubMed ID: 18347055

Title: Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation.

PubMed ID: 18347055

DOI: 10.1128/mcb.02098-07

PubMed ID: 18758450

Title: The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner.

PubMed ID: 18758450

DOI: 10.1038/ncb1780

PubMed ID: 19521662

Title: WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway.

PubMed ID: 19521662

DOI: 10.1007/s00018-009-0059-6

PubMed ID: 19675569

Title: Direct activation of protein kinases by unanchored polyubiquitin chains.

PubMed ID: 19675569

DOI: 10.1038/nature08247

PubMed ID: 19713527

Title: The E3 ligase TRAF6 regulates Akt ubiquitination and activation.

PubMed ID: 19713527

DOI: 10.1126/science.1175065

PubMed ID: 19825828

Title: Act1, a U-box E3 ubiquitin ligase for IL-17 signaling.

PubMed ID: 19825828

DOI: 10.1126/scisignal.2000382

PubMed ID: 20079715

Title: NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.

PubMed ID: 20079715

DOI: 10.1016/j.bbrc.2010.01.037

PubMed ID: 20628368

Title: Tom70 mediates activation of interferon regulatory factor 3 on mitochondria.

PubMed ID: 20628368

DOI: 10.1038/cr.2010.103

PubMed ID: 21302310

Title: Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-kappaB activation and endoplasmic reticulum stress-induced cell death.

PubMed ID: 21302310

DOI: 10.1002/jcp.22667

PubMed ID: 21813773

Title: IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1.

PubMed ID: 21813773

DOI: 10.4049/jimmunol.1100963

PubMed ID: 23776175

Title: SASH1 is a scaffold molecule in endothelial TLR4 signaling.

PubMed ID: 23776175

DOI: 10.4049/jimmunol.1200583

PubMed ID: 23524951

Title: mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6.

PubMed ID: 23524951

DOI: 10.1038/ncb2708

PubMed ID: 23514740

Title: TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter.

PubMed ID: 23514740

DOI: 10.4049/jimmunol.1202742

PubMed ID: 24586164

Title: Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune evasion through interference with toll-like receptor signaling.

PubMed ID: 24586164

DOI: 10.1371/journal.ppat.1003960

PubMed ID: 25026888

Title: LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria.

PubMed ID: 25026888

DOI: 10.1038/ncomms5434

PubMed ID: 25907557

Title: The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein.

PubMed ID: 25907557

DOI: 10.1074/jbc.m115.646422

PubMed ID: 25736436

Title: WDFY1 mediates TLR3/4 signaling by recruiting TRIF.

PubMed ID: 25736436

DOI: 10.15252/embr.201439637

PubMed ID: 25861989

Title: TRAF family member-associated NF-kappaB activator (TANK) inhibits genotoxic nuclear factor kappaB activation by facilitating deubiquitinase USP10-dependent deubiquitination of TRAF6 ligase.

PubMed ID: 25861989

DOI: 10.1074/jbc.m115.643767

PubMed ID: 28087809

Title: Trim13 potentiates toll-like receptor 2-mediated nuclear factor kappaB activation via K29-linked polyubiquitination of tumor necrosis factor receptor-associated factor 6.

PubMed ID: 28087809

DOI: 10.1124/mol.116.106716

PubMed ID: 31620128

Title: CRBN Is a Negative Regulator of Bactericidal Activity and Autophagy Activation Through Inhibiting the Ubiquitination of ECSIT and BECN1.

PubMed ID: 31620128

DOI: 10.3389/fimmu.2019.02203

PubMed ID: 12140561

Title: Distinct molecular mechanism for initiating TRAF6 signalling.

PubMed ID: 12140561

DOI: 10.1038/nature00888

PubMed ID: 17327397

Title: Structure, interactions, and dynamics of the RING domain from human TRAF6.

PubMed ID: 17327397

DOI: 10.1110/ps.062358007

PubMed ID: 19465916

Title: E2 interaction and dimerization in the crystal structure of TRAF6.

PubMed ID: 19465916

DOI: 10.1038/nsmb.1605

Sequence Information:

  • Length: 522
  • Mass: 59573
  • Checksum: 5AB9C255CCFEE749
  • Sequence:
    • MSLLNCENSC GSSQSESDCC VAMASSCSAV TKDDSVGGTA STGNLSSSFM EEIQGYDVEF 
DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD AGHKCPVDNE ILLENQLFPD 
NFAKREILSL MVKCPNEGCL HKMELRHLED HQAHCEFALM DCPQCQRPFQ KFHINIHILK 
DCPRRQVSCD NCAASMAFED KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI 
PCTFSTFGCH EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SVIPDSGYIS EVRNFQETIH 
QLEGRLVRQD HQIRELTAKM ETQSMYVSEL KRTIRTLEDK VAEIEAQQCN GIYIWKIGNF 
GMHLKCQEEE KPVVIHSPGF YTGKPGYKLC MRLHLQLPTA QRCANYISLF VHTMQGEYDS 
HLPWPFQGTI RLTILDQSEA PVRQNHEEIM DAKPELLAFQ RPTIPRNPKG FGYVTFMHLE 
ALRQRTFIKD DTLLVRCEVS TRFDMGSLRR EGFQPRSTDA GV