TRAF6

Summary

TRAF6 (TNF receptor associated factor 6, HGNC:12036) is a protein-coding gene on chromosome 11p12, encoding TNF receptor-associated factor 6 (Q9Y4K3). E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ‘Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2.

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain and mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. The protein encoded by this gene is a key molecule in antiviral innate and antigen-specific immune responses.

Source: NCBI Gene 7189 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant hypohidrotic ectodermal dysplasia (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 43 total
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_004620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12036
Approved symbol	TRAF6
Name	TNF receptor associated factor 6
Location	11p12
Locus type	gene with protein product
Status	Approved
Aliases	RNF85
Ensembl gene	ENSG00000175104
Ensembl biotype	protein_coding
OMIM	602355
Entrez	7189

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000348124, ENST00000526995, ENST00000529150, ENST00000876418, ENST00000876419, ENST00000876420

RefSeq mRNA: 2 — MANE Select: NM_004620 NM_004620, NM_145803

CCDS: CCDS7901

Canonical transcript exons

ENST00000526995 — 7 exons

Exon	Start	End
ENSE00001185246	36497108	36497266
ENSE00001185250	36498490	36498640
ENSE00001250977	36501220	36501537
ENSE00001335744	36510048	36510272
ENSE00002178885	36483769	36490650
ENSE00003518904	36492551	36492628
ENSE00003623792	36494976	36495047

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 89.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5807 / max 148.7481, expressed in 1789 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119393	9.5807	1789

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	89.03	gold quality
endothelial cell	CL:0000115	86.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.33	gold quality
oocyte	CL:0000023	85.15	gold quality
adrenal tissue	UBERON:0018303	83.12	gold quality
islet of Langerhans	UBERON:0000006	82.63	gold quality
calcaneal tendon	UBERON:0003701	82.43	gold quality
middle temporal gyrus	UBERON:0002771	82.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.79	gold quality
tendon	UBERON:0000043	81.35	gold quality
lower esophagus mucosa	UBERON:0035834	80.91	gold quality
ascending aorta	UBERON:0001496	80.08	gold quality
monocyte	CL:0000576	80.05	gold quality
thoracic aorta	UBERON:0001515	80.01	gold quality
leukocyte	CL:0000738	79.94	gold quality
mononuclear cell	CL:0000842	79.72	gold quality
aorta	UBERON:0000947	79.60	gold quality
popliteal artery	UBERON:0002250	79.44	gold quality
tibial artery	UBERON:0007610	79.42	gold quality
descending thoracic aorta	UBERON:0002345	79.24	gold quality
gastrocnemius	UBERON:0001388	79.15	gold quality
rectum	UBERON:0001052	79.10	gold quality
cortical plate	UBERON:0005343	79.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.98	gold quality
stromal cell of endometrium	CL:0002255	78.95	gold quality
granulocyte	CL:0000094	78.80	gold quality
muscle of leg	UBERON:0001383	78.78	gold quality
ventricular zone	UBERON:0003053	78.12	gold quality
amniotic fluid	UBERON:0000173	78.08	gold quality
left coronary artery	UBERON:0001626	78.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CD40	Unknown
IL12B	Activation
TICAM1	Unknown
VEGFA	Repression

Upstream regulators (CollecTRI, top): AP1, CUX1, FOS, FOXO1, IRF6, MYC, NFATC1, NR2C2, RELA, RUNX1, RUNX3, STAT1

miRNA regulators (miRDB)

264 targeting TRAF6, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 40)

• the novel zinc finger protein TIZ may play a role during osteoclast differentiation by modulating TRAF6 signaling activity. (PMID:11751921)
• The C-terminal fragment of TRAF6 inhibits lipopolysaccharide-induced NF-kappa B nuclear translocation and c-Jun NH2-terminal kinase activation in endothelial cells. (PMID:12193732)
• Results establish a major role of TRAF3 and -6 in X-linked ectodermal dysplasia receptor (XEDAR) signaling and in the process of ectodermal differentiation. (PMID:12270937)
• Pellino 1 is required for interleukin-1-mediated signaling through its interaction with the interleukin-1 receptor-associated kinase 4-IRAK-tumor necrosis factor receptor-associated factor 6 complex (PMID:12496252)
• direct endothelial-stimulatory role of lipopolysaccharides in initiating angiogenesis through activation of TRAF6-dependent signaling pathways. (PMID:12714497)
• Pellino2 interacts with TRAF6 and activates the MAP kinase pathway. (PMID:12804775)
• TRAF6 interacts with TIR domain-containing adaptor inducing IFN-beta (TRIF) through the TRAF domain of TRAF6 and TRAF6-binding motifs found in the N-terminal portion of TRIF. (PMID:14530355)
• In liver cells, IL-1 stimulates TRAF6 poly-ubiquitination (PMID:14550571)
• STAT3/NF-kappaB p65 cross-talk activated by IL-1 via TRAF6. (PMID:14593105)
• TRAF6 acts as a bifurcation point of the lipopolysaccharide-initiated death and survival signals in endothelial cells. (PMID:14996708)
• TRAF6 ubiquitin ligase kinase mediates IKK activation by BCL10 and MALT1. RNAi-mediated silencing of TRAF6 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells. (PMID:15125833)
• identified a putative TRAF6 interaction site in Mal but not in MyD88 and we demonstrate that Mal can be co-immunoprecipitated with TRAF6 (PMID:15247281)
• TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination. (PMID:15361868)
• Data show that endogenous germinal center kinase is activated by agonists that require TRAF6 for c-Jun N-terminal kinase activation. (PMID:15456887)
• oligomerization and polyubiquitination of TRAF6 induced by TIFA leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PMID:15492226)
• IL-8-induced NF-kappaB activation proceeds through a TRAF2-independent but TRAF6-dependent pathway, followed by recruitment of IRAK and activation of IKK (PMID:15591054)
• TRAF6 acts as a critical adapter of both the Src/ERK1/2 kinases and IkappaB kinase/NF-kappaB proinflammatory signaling pathways in monocytes and macrophages. (PMID:15634933)
• p62 regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination (PMID:16079148)
• Involvement of the TAB2/TRAF6/TAK1 signalling complex in the Edar signal transduction pathway has important implications for understanding of NF-kappaB activation and anhidrotic ectodermal dysplasia in human. (PMID:16251197)
• TRAF2-dependent CD40 signal transduction requires TRAF6 in nonhemopoietic cells (PMID:16260598)
• LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway) (PMID:16280329)
• Rac1 facilitated the recruitment of Nox2 into the endosomal compartment and subsequent redox-dependent recruitment of TRAF6 to the MyD88/IL-1R1 complex. (PMID:16354686)
• TRAF6 regulates cell fate decisions by inducing caspase 8-dependent apoptosis and the activation of NF-kappaB (PMID:16436380)
• an LMP1-associated complex containing TRAF6, TAB2, and TAK1 plays an essential role in the activation of JNK (PMID:16446357)
• NF-kappa B signaling is induced by the oncoprotein Tio through direct interaction with TRAF6. (PMID:16452479)
• the interaction of IRF-8 with TRAF6 modulates TLR signaling and may contribute to the cross-talk between IFN-gamma and TLR signal pathways (PMID:16484229)
• TGF-beta-activated kinase 1, TNF receptor-associated factor 6, and myeloid differentiation primary response gene (88) are important signal transducers in H. pylori-infected human epithelial cells (PMID:16517750)
• A candidate gene in ectodermal dysplasia. (PMID:16527194)
• TRAF6 is a critical adaptor linking two convergent signaling events; PKCtheta control of CARMA1 phosphorylation, and BCL10-dependent caspase-8 activation. (PMID:16920630)
• knockdown of UL144, TRAF6 or NFkappaB by specific siRNA in infections with UL144-encoding HCMV prevents the activation of CCL22 expression (PMID:16932746)
• An intact RING domain of TRAF6 is required for NF-kappaB activation and biological signaling. (PMID:17135271)
• This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. (PMID:17346928)
• Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-gamma (PMID:17363736)
• Sequencing of the promoter region and exons of the TRAF6 gene revealed three sequence variants, one of which was found in three affected members within one family with osteoporosis. (PMID:17377523)
• These data establish a signaling cascade in which regulated Lys63-linked TRAF6 auto-ubiquitination is the critical upstream mediator of osteoclast differentiation. (PMID:17572386)
• Results show that decrease in the ubiquitination of TRAF6 is YopJ-dependent and to prevent or is to remove the K63-polymerized ubiquitin conjugates required for signal transduction. (PMID:17608743)
• These findings demonstrate that Trx, TRAF2, and TRAF6 regulate ASK1 activity by modulating N-terminal homophilic interaction of ASK1. (PMID:17724081)
• IRAK-2 plays a more central role than IRAK-1 in TLR signaling to NFkappaB through TRAF6 ubiquitination (PMID:17878161)
• MyD88, IRAK1 and TRAF6 proteins are crucial early mediators for the IL-1-induced MMP-13 regulation through MAPK pathways and AP-1 activity. (PMID:17905570)
• two independent and indispensable signaling pathways-1) JAK1-associated PI3K signaling and 2) Act1/TRAF6/TAK1-mediated NF-kappaB activation-are stimulated by IL-17A to regulate gene induction in human airway epithelial cells. (PMID:17982039)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	traf6	ENSDARG00000028058
mus_musculus	Traf6	ENSMUSG00000027164
rattus_norvegicus	Traf6	ENSRNOG00000004639
drosophila_melanogaster	Traf6	FBGN0265464

Paralogs (5): TRAF1 (ENSG00000056558), TRAF4 (ENSG00000076604), TRAF5 (ENSG00000082512), TRAF2 (ENSG00000127191), TRAF3 (ENSG00000131323)

Protein

Protein identifiers

TNF receptor-associated factor 6 — Q9Y4K3 (reviewed: Q9Y4K3)

Alternative names: E3 ubiquitin-protein ligase TRAF6, Interleukin-1 signal transducer, RING finger protein 85, RING-type E3 ubiquitin transferase TRAF6

All UniProt accessions (1): Q9Y4K3

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ‘Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. Acts as a regulator of the JNK and NF-kappa-B signaling pathways by initiating assembly of heterotypic ‘Lys-63’-/‘Lys-48’-linked branched ubiquitin chains that are then recognized by TAB2: TRAF6 catalyzes initial ‘Lys-63’-linked-polyubiquitin chains that are then branched via ‘Lys-48’-linked polyubiquitin by HUWE1. ‘Lys-63’-/‘Lys-48’-linked branched ubiquitin chains protect ‘Lys-63’-linkages from CYLD deubiquitination. Participates also in the TCR signaling by ubiquitinating LAT.

Subunit / interactions. Homotrimer. Homooligomer. N-terminal region is dimeric while C-terminal region is trimeric; maybe providing a mode of oligomerization. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK. Associates with NGFR, TNFRSF17, IRAK2, IRAK3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with PELI2 and PELI3. Binds UBE2V1. Interacts with TAX1BP1; this interaction mediates deubiquitination of TRAF6 and inhibition of NF-kappa-B activation. Interacts with ZNF675. Interacts with ARRB1 and ARRB2. Interacts with MAP3K7 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF domains) with NUMBL (via C-terminal). Interacts with RBCK1. Interacts with LIMD1 (via LIM domains). Interacts with RSAD2/viperin. Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with ZFAND5. Interacts with IL1RL1. Interacts with TRAFD1. Interacts with AJUBA. Interacts with MAVS/IPS1. Interacts (via TRAF domains) with DYNC2I2 (via WD domains). Interacts with IFIT3 (via N-terminus). Interacts with TICAM2. Interacts with CARD14. Interacts with CD40 and MAP3K8; the interaction is required for ERK activation. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1. Interacts with TANK; this interaction increases in response to DNA damage. Interacts with USP10; this interaction increases in response to DNA damage. Interacts with ZC3H12A; this interaction increases in response to DNA damage and is stimulated by TANK. Interacts with WDFY3. Interacts with TRIM13. Interacts with GPS2. Interacts (via C-terminus) with SASH1. Interacts with LRRC19. Interacts with IL17RA and TRAF3IP2. Interacts with TOMM70. Interacts with AMBRA1; interaction is required to mediate ‘Lys-63’-linked ubiquitination of ULK1. Interacts with CRBN; this interaction inhibits TLR4-mediated signaling by preventing TRAF6-mediated ubiquitination of ECSIT.

Subcellular location. Cytoplasm. Cell cortex. Nucleus. Lipid droplet.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1. Polyubiquitinated on Lys-124 by TRAF3IP2; after cell stimulation with IL17A. Polyubiquitinated on Lys-124; after cell stimulation with IL1B or TGFB. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This ‘Lys-63’ site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage. LRRC19 induces ‘Lys-63’ ubiquitination. Ubiquitinated at Lys-319 by the SCF(FBXL2) complex, leading to its degradation by the proteasome. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both ‘Lys-48’ and ‘Lys-63’-linked ubiquitin chains; leading to NF-kappa-B signaling inhibition.

Domain organisation. The coiled coil domain mediates homo- and hetero-oligomerization. The MATH/TRAF domain binds to receptor cytoplasmic domains.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TNF receptor-associated factor family. A subfamily.

RefSeq proteins (2): NP_004611, NP_665802 (=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
IPR027139	TRAF6_RING-HC	Domain
IPR037309	TRAF6_MATH	Domain
IPR041310	TRAF6_Z2	Domain
IPR049342	TRAF1-6_MATH_dom	Domain

Pfam: PF02176, PF13923, PF18048, PF21355

UniProt features (70 total): strand 22, helix 15, mutagenesis site 12, turn 7, cross-link 5, zinc finger region 3, region of interest 2, chain 1, domain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1LB6	X-RAY DIFFRACTION	1.8
3HCT	X-RAY DIFFRACTION	2.1
6A33	X-RAY DIFFRACTION	2.1
3HCS	X-RAY DIFFRACTION	2.2
1LB4	X-RAY DIFFRACTION	2.4
1LB5	X-RAY DIFFRACTION	2.4
3HCU	X-RAY DIFFRACTION	2.6
5ZUJ	X-RAY DIFFRACTION	2.6
8HZ2	X-RAY DIFFRACTION	2.6
7L3L	X-RAY DIFFRACTION	2.8
4Z8M	X-RAY DIFFRACTION	2.95
2ECI	SOLUTION NMR
2JMD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4K3-F1	85.30	0.72

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 (5): 142, 319, 453, 124, 124

Mutagenesis-validated functional residues (12):

Position	Phenotype
57	loss of interaction with ube2n.
70	loss of ligase activity, autoubiquitination and signaling capacity.
72	loss of interaction with ube2n. has no effect on traf3ip2-mediated ’lys-63’-linked polyubiquitination.
74	loss of interaction with ube2n.
88	loss of traf6 homodimerization and impaired polyubiquitin synthesis. loss of traf6 homodimerization and impaired polyubi
118	loss of traf6 homodimerization and impaired polyubiquitin synthesis.
118	partially impaired polyubiquitin synthesis.
122	loss of traf6 homodimerization and partially impaired polyubiquitin synthesis. loss of traf6 homodimerization and impair
124	loss of sumo1-modification and c-myb-mediated transcriptional repressive activation. loss of traf3ip2-mediated ’lys-63’-
142	loss of sumo1-modification and c-myb-mediated transcriptional repressive activation.
453	loss of sumo1-modification and c-myb-mediated transcriptional repressive activation.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-193692	Regulated proteolysis of p75NTR
R-HSA-202424	Downstream TCR signaling
R-HSA-205043	NRIF signals cell death from the nucleus
R-HSA-209543	p75NTR recruits signalling complexes
R-HSA-209560	NF-kB is activated and signals survival
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9014325	TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-9020702	Interleukin-1 signaling
R-HSA-933541	TRAF6 mediated IRF7 activation
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-937039	IRAK1 recruits IKK complex
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-937042	IRAK2 mediated activation of TAK1 complex
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-9645460	Alpha-protein kinase 1 signaling pathway
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975110	TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation

MSigDB gene sets: 630 (showing top): PID_BCR_5PATHWAY, REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, BIOCARTA_RELA_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM

GO Biological Process (72): autophagosome assembly (GO:0000045), negative regulation of transcription by RNA polymerase II (GO:0000122), protein polyubiquitination (GO:0000209), ossification (GO:0001503), in utero embryonic development (GO:0001701), neural tube closure (GO:0001843), stimulatory C-type lectin receptor signaling pathway (GO:0002223), regulation of immunoglobulin production (GO:0002637), positive regulation of T cell cytokine production (GO:0002726), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), DNA damage response (GO:0006974), canonical NF-kappaB signal transduction (GO:0007249), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), CD40 signaling pathway (GO:0023035), osteoclast differentiation (GO:0030316), positive regulation of protein ubiquitination (GO:0031398), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), activation of protein kinase activity (GO:0032147), positive regulation of type I interferon production (GO:0032481), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-6 production (GO:0032755), tumor necrosis factor-mediated signaling pathway (GO:0033209), toll-like receptor 3 signaling pathway (GO:0034138), toll-like receptor 4 signaling pathway (GO:0034142), TRIF-dependent toll-like receptor signaling pathway (GO:0035666), non-canonical NF-kappaB signal transduction (GO:0038061), Fc-epsilon receptor signaling pathway (GO:0038095), interleukin-33-mediated signaling pathway (GO:0038172), interleukin-17A-mediated signaling pathway (GO:0038173), T-helper 1 type immune response (GO:0042088), positive regulation of T cell proliferation (GO:0042102), odontogenesis of dentin-containing tooth (GO:0042475), regulation of apoptotic process (GO:0042981), myeloid dendritic cell differentiation (GO:0043011), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of JUN kinase activity (GO:0043507)

GO Molecular Function (15): ubiquitin-protein transferase activity (GO:0004842), tumor necrosis factor receptor binding (GO:0005164), zinc ion binding (GO:0008270), protein-macromolecule adaptor activity (GO:0030674), ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin-ubiquitin ligase activity (GO:0034450), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), histone deacetylase binding (GO:0042826), protein kinase B binding (GO:0043422), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (13): nucleus (GO:0005634), cytoplasm (GO:0005737), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), cytoplasmic side of plasma membrane (GO:0009898), endosome membrane (GO:0010008), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), protein-containing complex (GO:0032991), CD40 receptor complex (GO:0035631), perinuclear region of cytoplasm (GO:0048471), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-22 pathways:

Category	Pathways
Toll Like Receptor 3 (TLR3) Cascade	3
p75NTR signals via NF-kB	2
MAP kinase activation	2
Deubiquitination	2
Intracellular signaling by second messengers	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
p75 NTR receptor-mediated signalling	1
TCR signaling	1
Cell death signalling via NRAGE, NRIF and NADE	1
Fc epsilon receptor (FCERI) signaling	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Interleukin-1 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
cellular anatomical structure	3
cytoplasm	3
protein ubiquitination	2
cell surface receptor signaling pathway	2
cell periphery	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
multicellular organismal process	1
chordate embryonic development	1
primary neural tube formation	1
tube closure	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	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
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
toll-like receptor signaling pathway	1
cellular response to stress	1
intracellular signaling cassette	1
antigen processing and presentation of exogenous peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class II	1
myeloid leukocyte differentiation	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
cellular response to lipopolysaccharide	1

Protein interactions and networks

STRING

4234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAF6	IRAK1	P51617	999
TRAF6	MYD88	P78397	999
TRAF6	TAB1	Q15750	998
TRAF6	IRAK2	O43187	998
TRAF6	TAB2	Q9NYJ8	998
TRAF6	CHUK	O15111	998
TRAF6	IRAK4	Q9NWZ3	998
TRAF6	UBE2N	P61088	997
TRAF6	MAP3K7	O43318	997
TRAF6	TLR4	O00206	997
TRAF6	IKBKG	Q9Y6K9	997
TRAF6	ECSIT	Q9BQ95	996
TRAF6	G3V2F7	G3V2F7	996
TRAF6	CD40	P25942	996
TRAF6	TAB3	Q8N5C8	996
TRAF6	IKBKB	O14920	996

IntAct

656 interactions, top by confidence:

A	B	Type	Score
TRAF1	TRAF6	psi-mi:“MI:0915”(physical association)	0.940
TRAF6	TRAF6	psi-mi:“MI:0915”(physical association)	0.920
TRAF2	TRAF6	psi-mi:“MI:0915”(physical association)	0.900
TRAF6	TRAF2	psi-mi:“MI:0915”(physical association)	0.900
TRAF5	TRAF6	psi-mi:“MI:0915”(physical association)	0.880
TRAF6	TRAF5	psi-mi:“MI:0915”(physical association)	0.880
YES1	TRAF6	psi-mi:“MI:0915”(physical association)	0.720
TRAF6	VPS52	psi-mi:“MI:0915”(physical association)	0.720
TRAF6	YES1	psi-mi:“MI:0915”(physical association)	0.720
VPS52	TRAF6	psi-mi:“MI:0915”(physical association)	0.720
TRAF6	TRAF3IP2	psi-mi:“MI:0915”(physical association)	0.670
TRAF3IP2	TRAF6	psi-mi:“MI:0915”(physical association)	0.670
TRAF6	CD40	psi-mi:“MI:0407”(direct interaction)	0.590
USP2	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
TRAF6	EDARADD	psi-mi:“MI:0915”(physical association)	0.560
PLEKHF2	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
POLI	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
TRAF6	MEOX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1273): TRAF6 (Affinity Capture-Western), PSEN1 (Co-localization), PPP4R1 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), TRAF3IP2 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), UBC (Biochemical Activity), TRAF6 (Biochemical Activity), IKBKG (Biochemical Activity), UBE2V1 (Reconstituted Complex), TRAF6 (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D3 (Reconstituted Complex)

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: A7XUJ6, B5DF45, B6CJY4, B6CJY5, D3YY23, O13033, O70263, P15919, P39428, P43254, P68907, P70196, P93471, Q02084, Q13077, Q17RB8, Q1L5Z9, Q28DL4, Q3MV19, Q3UWA4, Q3ZCC3, Q6CTZ8, Q6DJN2, Q6IWL4, Q6J2U6, Q6MFY8, Q6Q0C0, Q6ZMN7, Q865W2, Q8TBB1, Q91187, Q922B6, Q9D4H7, Q9D9R0, Q9ET26, Q9FNI6, Q9Y4K3, P15918, P39429, Q1XHT8

SIGNOR signaling

71 interactions.

A	Effect	B	Mechanism
CYLD	down-regulates	TRAF6	deubiquitination
TRAF6	up-regulates	MALT1	ubiquitination
TNFAIP3	“down-regulates activity”	TRAF6	deubiquitination
TRAF6	“up-regulates activity”	TRAF6	ubiquitination
TRAF6	“up-regulates activity”	TAB1	binding
TRAF6	“up-regulates activity”	TAB2	binding
TRAF6	“up-regulates activity”	TAB3	binding
RIPK1	“up-regulates activity”	TRAF6	binding
TRAF6	“up-regulates activity”	MAP3K7	ubiquitination
TGFBR1	“up-regulates activity”	TRAF6	binding
TRAF6	“up-regulates activity”	IRAK1	ubiquitination
TRAF6	“up-regulates activity”	MAP3K8
TRAF6	“up-regulates activity”	TNFRSF11A	binding
TRAF6	up-regulates	Osteoclast_differentiation
TRAF6	“up-regulates activity”	MAP3K14	binding
RUNX3	“up-regulates quantity by expression”	TRAF6	“transcriptional regulation”
TRAF6	“down-regulates quantity”	HK2	ubiquitination
MYD88	“up-regulates activity”	TRAF6	binding
9b	“down-regulates quantity by destabilization”	TRAF6
“Papain-like proteinase”	“down-regulates activity”	TRAF6	deubiquitination
NLRX1	“down-regulates activity”	TRAF6	binding
INPP5D	“down-regulates activity”	TRAF6	binding
NOTCH2	“down-regulates activity”	TRAF6	binding
TRIM23	“up-regulates activity”	TRAF6	ubiquitination
BPLF1	“down-regulates activity”	TRAF6	deubiquitination
TRAF6	“down-regulates quantity”	Hexokinase	ubiquitination
Ub:E2	“up-regulates activity”	TRAF6	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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
AUF1 (hnRNP D0) binds and destabilizes mRNA	12	21.6×	4e-11
Regulation of activated PAK-2p34 by proteasome mediated degradation	10	20.2×	3e-09
Regulation of ornithine decarboxylase (ODC)	10	19.7×	3e-09
Hh mutants are degraded by ERAD	11	19.4×	1e-09
Vpu mediated degradation of CD4	10	19.2×	3e-09
Autodegradation of the E3 ubiquitin ligase COP1	10	19.2×	3e-09
Ubiquitin-dependent degradation of Cyclin D	10	19.2×	3e-09
Cross-presentation of soluble exogenous antigens (endosomes)	10	18.4×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	5	11.3×	8e-03
positive regulation of DNA repair	5	11.3×	8e-03
cytoplasmic translation	9	10.6×	1e-04
DNA replication	7	7.3×	8e-03
translation	11	7.2×	1e-04
protein folding	9	5.9×	5e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	15	5.0×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

890 predictions. Top by Δscore:

Variant	Effect	Δscore
11:36495058:T:TC	acceptor_gain	1.0000
11:36497115:T:C	donor_gain	1.0000
11:36497262:TGATC:T	acceptor_gain	1.0000
11:36497265:TC:T	acceptor_gain	1.0000
11:36497265:TCC:T	acceptor_loss	1.0000
11:36497266:CC:C	acceptor_gain	1.0000
11:36497266:CCTA:C	acceptor_loss	1.0000
11:36497267:C:CC	acceptor_gain	1.0000
11:36497267:CTAT:C	acceptor_loss	1.0000
11:36497268:T:G	acceptor_loss	1.0000
11:36498487:TACC:T	donor_loss	1.0000
11:36498489:C:CA	donor_loss	1.0000
11:36498522:A:AT	donor_gain	1.0000
11:36498636:CATCC:C	acceptor_gain	1.0000
11:36498638:TCC:T	acceptor_gain	1.0000
11:36498639:CC:C	acceptor_gain	1.0000
11:36498639:CCC:C	acceptor_gain	1.0000
11:36498640:CC:C	acceptor_gain	1.0000
11:36498641:C:CC	acceptor_gain	1.0000
11:36498641:C:T	acceptor_gain	1.0000
11:36498645:C:CT	acceptor_gain	1.0000
11:36498646:A:T	acceptor_gain	1.0000
11:36500570:A:AC	donor_gain	1.0000
11:36500571:C:CC	donor_gain	1.0000
11:36500574:A:AC	donor_gain	1.0000
11:36500575:T:C	donor_gain	1.0000
11:36501533:TTGCT:T	acceptor_gain	1.0000
11:36501536:CT:C	acceptor_gain	1.0000
11:36501538:C:CC	acceptor_gain	1.0000
11:36494970:TAATA:T	donor_loss	0.9900

AlphaMissense

3520 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:36489992:C:A	G472V	1.000
11:36489992:C:T	G472D	1.000
11:36489993:C:G	G472R	1.000
11:36489994:A:C	F471L	1.000
11:36489994:A:T	F471L	1.000
11:36489996:A:G	F471L	1.000
11:36489998:C:T	G470D	1.000
11:36489999:C:G	G470R	1.000
11:36490022:G:T	P462H	1.000
11:36490030:G:C	F459L	1.000
11:36490030:G:T	F459L	1.000
11:36490032:A:G	F459L	1.000
11:36490034:G:T	A458D	1.000
11:36490112:A:G	L432P	1.000
11:36490135:C:A	W424C	1.000
11:36490135:C:G	W424C	1.000
11:36490137:A:G	W424R	1.000
11:36490137:A:T	W424R	1.000
11:36490173:G:C	H412D	1.000
11:36490175:A:T	V411D	1.000
11:36490177:A:C	F410L	1.000
11:36490177:A:T	F410L	1.000
11:36490179:A:G	F410L	1.000
11:36490276:G:C	S377R	1.000
11:36490276:G:T	S377R	1.000
11:36490278:T:G	S377R	1.000
11:36490344:A:G	W355R	1.000
11:36490344:A:T	W355R	1.000
11:36498537:A:G	C134R	1.000
11:36498560:T:A	E126V	1.000

dbSNP variants (sampled 300 via entrez): RS1000043685 (11:36495108 T>G), RS1000170608 (11:36508679 A>G), RS1000187526 (11:36508872 A>C,G), RS1000271506 (11:36502393 T>C), RS1000473497 (11:36495766 C>T), RS1000599172 (11:36488847 C>A,G,T), RS1000809630 (11:36483454 G>A), RS1000893055 (11:36500673 G>A,C), RS1000963056 (11:36512106 C>T), RS1001009603 (11:36493913 G>A), RS1001103988 (11:36493594 C>G), RS1001179609 (11:36483598 C>T), RS1001200408 (11:36508035 T>C,G), RS1001240373 (11:36500971 TAAGTAA>T), RS1001362673 (11:36509288 A>G)

Disease associations

OMIM: gene MIM:602355 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant hypohidrotic ectodermal dysplasia	Supportive	Autosomal dominant

Mondo (1): autosomal dominant hypohidrotic ectodermal dysplasia (MONDO:0015884)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000164	Abnormality of the dentition
HP:0000457	Depressed nasal ridge
HP:0000668	Hypodontia
HP:0000963	Thin skin
HP:0000964	Eczematoid dermatitis
HP:0000966	Hypohidrosis
HP:0001000	Abnormality of skin pigmentation
HP:0001231	Abnormal fingernail morphology
HP:0002047	Malignant hyperthermia
HP:0002231	Sparse body hair
HP:0006323	Premature loss of primary teeth
HP:0006482	Abnormal dental morphology
HP:0008070	Sparse hair
HP:0011220	Prominent forehead
HP:0012471	Thick vermilion border

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002318_161	Rheumatoid arthritis	1.000000e-07
GCST002318_35	Rheumatoid arthritis	3.000000e-07
GCST006051_7	Idiopathic inflammatory myopathy	9.000000e-06
GCST006959_89	Rheumatoid arthritis	6.000000e-06
GCST009391_892	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010440	triacylglycerol 58:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3588728 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases expression, decreases reaction, increases expression, affects ubiquitination, increases degradation (+2 more)	5
Benzo(a)pyrene	increases expression, increases methylation, decreases methylation	2
Copper	affects binding, increases expression, decreases expression	2
Estradiol	affects binding, affects cotreatment, increases reaction, increases expression	2
Particulate Matter	decreases reaction, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
CU-CPT22	decreases reaction, increases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
kaempferol	decreases reaction, increases ubiquitination	1
deoxynivalenol	increases expression	1
titanium dioxide	decreases expression	1
sodium arsenite	increases expression	1
nickel chloride	increases expression	1
ochratoxin A	decreases expression	1
zinc sulfide	affects cotreatment, increases expression	1
hydroquinone	decreases expression, increases reaction, affects reaction	1
epigallocatechin gallate	decreases reaction, increases expression	1
cadmium selenide	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
salvianolic acid B	decreases reaction, increases abundance, increases expression	1
lipopolysaccharide, Helicobacter pylori	increases expression, increases reaction	1
anemoside A3	increases expression, increases reaction	1
procyanidin B1	decreases reaction, increases expression	1
clothianidin	decreases expression	1
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate	decreases reaction, increases expression	1
ON 01910	affects localization, affects binding, increases reaction, decreases expression, decreases sumoylation	1
ST2825	decreases reaction, increases abundance, increases expression	1
asparanin A	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3590966	Binding	Binding affinity to human TRAF6 using immobilized biotinylated RANK peptide from by SPR analysis	Structure-Based Development of a Protein-Protein Interaction Inhibitor Targeting Tumor Necrosis Factor Receptor-Associated Factor 6. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2JI	Abcam HeLa TRAF6 KO	Cancer cell line	Female
CVCL_D8D1	Ubigene A-549 TRAF6 KO	Cancer cell line	Male
CVCL_D8XP	Ubigene HCT 116 TRAF6 KO	Cancer cell line	Male
CVCL_D9UW	Ubigene HEK293 TRAF6 KO	Transformed cell line	Female
CVCL_E0S3	Ubigene HeLa TRAF6 KO	Cancer cell line	Female
CVCL_TT63	HAP1 TRAF6 (-) 1	Cancer cell line	Male
CVCL_TT64	HAP1 TRAF6 (-) 2	Cancer cell line	Male
CVCL_ZC30	HT TRAF6 KD	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.