Molecule Information

General Information of the Molecule (ID: Mol00186)

• Name: TNF receptor-associated factor 6 (TRAF6) ,Homo sapiens
• Synonyms: E3 ubiquitin-protein ligase TRAF6; Interleukin-1 signal transducer; RING finger protein 85; RING-type E3 ubiquitin transferase TRAF6; RNF85
• Molecule Type: Protein
• Gene Name: TRAF6
• Gene ID: 7189
• Location: chr11:36483769-36510272[-]
• Sequence:
  MSLLNCENSCGSSQSESDCCVAMASSCSAVTKDDSVGGTASTGNLSSSFMEEIQGYDVEF
  DPPLESKYECPICLMALREAVQTPCGHRFCKACIIKSIRDAGHKCPVDNEILLENQLFPD
  NFAKREILSLMVKCPNEGCLHKMELRHLEDHQAHCEFALMDCPQCQRPFQKFHINIHILK
  DCPRRQVSCDNCAASMAFEDKEIHDQNCPLANVICEYCNTILIREQMPNHYDLDCPTAPI
  PCTFSTFGCHEKMQRNHLARHLQENTQSHMRMLAQAVHSLSVIPDSGYISEVRNFQETIH
  QLEGRLVRQDHQIRELTAKMETQSMYVSELKRTIRTLEDKVAEIEAQQCNGIYIWKIGNF
  GMHLKCQEEEKPVVIHSPGFYTGKPGYKLCMRLHLQLPTAQRCANYISLFVHTMQGEYDS
  HLPWPFQGTIRLTILDQSEAPVRQNHEEIMDAKPELLAFQRPTIPRNPKGFGYVTFMHLE
  ALRQRTFIKDDTLLVRCEVSTRFDMGSLRREGFQPRSTDAGV
• Function: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as 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.
• Uniprot ID: TRAF6_HUMAN
• Ensembl ID: ENSG00000175104
• HGNC ID: HGNC:12036

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Dezocine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pain [1]

• Resistant Disease: Pain [ICD-11: MG30.0]
• Resistant Drug: Dezocine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Western blot analysis; Quantitative reverse-transcription PCR assay
• Mechanism Description: miR-124-3p alleviates the dezocine tolerance against pain by regulating TRAF6 in a rat model. miR-124-3p expression was highly downregulated in a dezocine-resistant model. miR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. miR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

Temozolomide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioblastoma [2]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/NF-kappaB signaling pathway; Inhibition; hsa05135
• In Vitro Model: U251-MG cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR 146b 5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Overexpression of miR 146b 5p or TRAF6 knockdown significantly decreased the level of p AkT and p p65.

Clinical Trial Drug(s) 1 drug(s) in total

Calycosin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Nasopharyngeal carcinoma [3]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Sensitive Drug: Calycosin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: TRAF6-related signaling pathway; Regulation; hsa05206
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: C666-1 cells; Throat; Homo sapiens (Human); CVCL_7949
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; BrdU assay
• Mechanism Description: Calycosin inhibits nasopharyngeal carcinoma cells by downregulating EWSAT1 expression to regulate the TRAF6-related pathways.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.88E-04; Fold-change: 1.00E-01; Z-score: 3.74E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.53E-01; Fold-change: -2.33E-01; Z-score: -3.01E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.59E-03; Fold-change: 8.42E-01; Z-score: 1.47E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.62E-04; Fold-change: 1.77E-01; Z-score: 1.59E+00

References

• Ref 1: MiR-124-3p alleviates the dezocine tolerance against pain by regulating TRAF6 in a rat model .Neuroreport. 2021 Jan 6;32(1):44-51. doi: 10.1097/WNR.0000000000001559. 10.1097/WNR.0000000000001559
• Ref 2: miR 146b 5p suppresses glioblastoma cell resistance to temozolomide through targeting TRAF6. Oncol Rep. 2017 Nov;38(5):2941-2950. doi: 10.3892/or.2017.5970. Epub 2017 Sep 19.
• Ref 3: Calycosin inhibits nasopharyngeal carcinoma cells by influencing EWSAT1 expression to regulate the TRAF6-related pathways. Biomed Pharmacother. 2018 Oct;106:342-348. doi: 10.1016/j.biopha.2018.06.143. Epub 2018 Jul 11.