Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCDR6M)

• DTT Name: TNF receptor-associated factor 6 (TRAF6)
• Synonyms: RNF85; RING-type E3 ubiquitin transferase TRAF6; RING finger protein 85; Interleukin-1 signal transducer; E3 ubiquitin-protein ligase TRAF6
• Gene Name: TRAF6
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: TRAF6_HUMAN
• TTD ID: T15051
• EC Number: EC 2.3.2.27
• Sequence:
  MSLLNCENSCGSSQSESDCCVAMASSCSAVTKDDSVGGTASTGNLSSSFMEEIQGYDVEF
  DPPLESKYECPICLMALREAVQTPCGHRFCKACIIKSIRDAGHKCPVDNEILLENQLFPD
  NFAKREILSLMVKCPNEGCLHKMELRHLEDHQAHCEFALMDCPQCQRPFQKFHINIHILK
  DCPRRQVSCDNCAASMAFEDKEIHDQNCPLANVICEYCNTILIREQMPNHYDLDCPTAPI
  PCTFSTFGCHEKMQRNHLARHLQENTQSHMRMLAQAVHSLSVIPDSGYISEVRNFQETIH
  QLEGRLVRQDHQIRELTAKMETQSMYVSELKRTIRTLEDKVAEIEAQQCNGIYIWKIGNF
  GMHLKCQEEEKPVVIHSPGFYTGKPGYKLCMRLHLQLPTAQRCANYISLFVHTMQGEYDS
  HLPWPFQGTIRLTILDQSEAPVRQNHEEIMDAKPELLAFQRPTIPRNPKGFGYVTFMHLE
  ALRQRTFIKDDTLLVRCEVSTRFDMGSLRREGFQPRSTDAGV
• Function: Mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. 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. 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.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  NF-kappa B signaling pathway (hsa04064)
  Ubiquitin mediated proteolysis (hsa04120)
  Autophagy - animal (hsa04140)
  Endocytosis (hsa04144)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  RIG-I-like receptor signaling pathway (hsa04622)
  IL-17 signaling pathway (hsa04657)
  Neurotrophin signaling pathway (hsa04722)
  Alcoholic liver disease (hsa04936)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coronavirus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  MyD88 (R-HSA-166058)
  NOD1/2 Signaling Pathway (R-HSA-168638)
  TICAM1, RIP1-mediated IKK complex recruitment (R-HSA-168927)
  Regulated proteolysis of p75NTR (R-HSA-193692)
  Downstream TCR signaling (R-HSA-202424)
  NRIF signals cell death from the nucleus (R-HSA-205043)
  p75NTR recruits signalling complexes (R-HSA-209543)
  NF-kB is activated and signals survival (R-HSA-209560)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989)
  activated TAK1 mediates p38 MAPK activation (R-HSA-450302)
  JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Ub-specific processing proteases (R-HSA-5689880)
  Ovarian tumor domain proteases (R-HSA-5689896)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  TICAM1,TRAF6-dependent induction of TAK1 complex (R-HSA-9014325)
  Interleukin-1 signaling (R-HSA-9020702)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  IRAK1 recruits IKK complex (R-HSA-937039)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  IRAK2 mediated activation of TAK1 complex (R-HSA-937042)
  TRAF6-mediated induction of TAK1 complex within TLR4 complex (R-HSA-937072)
  Alpha-protein kinase 1 signaling pathway (R-HSA-9645460)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling (R-HSA-975110)
  TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (R-HSA-975138)
  IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (R-HSA-975144)
  MyD88 dependent cascade initiated on endosome (R-HSA-975155)
  IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation (R-HSA-975163)
  MyD88 cascade initiated on plasma membrane (R-HSA-975871)
  PIP3 activates AKT signaling (R-HSA-1257604)

References

• [1] Tumor necrosis factor receptor-associated factor 6 as a nuclear factor kappa B-modulating therapeutic target in cardiovascular diseases: at the hea... Transl Res. 2018 May;195:48-61.