Target Information
Target General Information | Top | |||||
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Target ID |
T44190
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Target Name |
TIR domain-containing adapter molecule 1 (TICAM1)
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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
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Gene Name |
TICAM1
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Target Type |
Patented-recorded target
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[1] | ||||
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.
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UniProt ID | ||||||
Sequence |
MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARIS
LEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQE AVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPR PIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVP EPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNY PVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSP PPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALG VPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQ GSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMW RKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTG APYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQS PAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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TIR domain-containing adapter molecule 2 (TICAM2) | 33.333 (54/162) | 6.44E-13 |
KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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NF-kappa B signaling pathway | hsa04064 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Necroptosis | hsa04217 | Affiliated Target |
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Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
Toll-like receptor signaling pathway | hsa04620 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
NOD-like receptor signaling pathway | hsa04621 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 1.98E-05 |
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Closeness centrality | 2.25E-01 | Radiality | 1.40E+01 | Clustering coefficient | 4.44E-01 |
Neighborhood connectivity | 4.04E+01 | Topological coefficient | 1.80E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 14 KEGG Pathways | + | ||||
1 | NF-kappa B signaling pathway | |||||
2 | Necroptosis | |||||
3 | Toll-like receptor signaling pathway | |||||
4 | NOD-like receptor signaling pathway | |||||
5 | Pertussis | |||||
6 | Yersinia infection | |||||
7 | Chagas disease (American trypanosomiasis) | |||||
8 | Hepatitis C | |||||
9 | Hepatitis B | |||||
10 | Influenza A | |||||
11 | Human papillomavirus infection | |||||
12 | Kaposi sarcoma-associated herpesvirus infection | |||||
13 | Herpes simplex virus 1 infection | |||||
14 | PD-L1 expression and PD-1 checkpoint pathway in cancer |
References | Top | |||||
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REF 1 | TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation. Brain Behav Immun. 2018 Jan;67:65-76. |
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