Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2GQT6)

• DTT Name: TIR domain-containing adapter molecule 1 (TICAM1)
• Synonyms: Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta; TRIF; TIR domain-containing adapter protein inducing IFN-beta; TICAM-1; Putative NF-kappa-B-activating protein 502H; Proline-rich, vinculin and TIR domain-containing protein B; PRVTIRB; MyD88-3
• Gene Name: TICAM1
• DTT Type: Patented-recorded target; [1]
• UniProt ID: TCAM1_HUMAN
• TTD ID: T44190
• Sequence:
  MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARIS
  LEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQE
  AVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPR
  PIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVP
  EPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNY
  PVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSP
  PPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALG
  VPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQ
  GSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMW
  RKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTG
  APYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQS
  PAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE
• Function: Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively. Phosphorylation by TBK1 on the pLxIS motif leads to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent immunity against invading pathogens. Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines. Involved in innate immunity against invading pathogens.
• KEGG Pathway:
  NF-kappa B signaling pathway (hsa04064)
  Necroptosis (hsa04217)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
• Reactome Pathway:
  MyD88-independent TLR4 cascade (R-HSA-166166)
  Toll Like Receptor 3 (TLR3) Cascade (R-HSA-168164)
  TICAM1, RIP1-mediated IKK complex recruitment (R-HSA-168927)
  RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476)
  TRIF-mediated programmed cell death (R-HSA-2562578)
  TICAM1 deficiency - HSE (R-HSA-5602566)
  TRAF3 deficiency - HSE (R-HSA-5602571)
  TLR3-mediated TICAM1-dependent programmed cell death (R-HSA-9013957)
  TICAM1-dependent activation of IRF3/IRF7 (R-HSA-9013973)
  TICAM1,TRAF6-dependent induction of TAK1 complex (R-HSA-9014325)
  Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon (R-HSA-936964)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  TRAF6-mediated induction of TAK1 complex within TLR4 complex (R-HSA-937072)
  IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation (R-HSA-975163)
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)

References

• [1] TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation. Brain Behav Immun. 2018 Jan;67:65-76.