| IED ID | IndEnz0002012879 |
| Enzyme Type ID | protease012879 |
| Protein Name |
TIR domain-containing adapter molecule 1 TICAM-1 Proline-rich, vinculin and TIR domain-containing protein B Putative NF-kappa-B-activating protein 502H Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta MyD88-3 TIR domain-containing adapter protein inducing IFN-beta |
| Gene Name | TICAM1 PRVTIRB TRIF |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARISLEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQEAVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPRPIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVPEPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNYPVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSPPPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALGVPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQGSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMWRKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTGAPYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQSPAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE |
| Enzyme Length | 712 |
| Uniprot Accession Number | Q8IUC6 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis (PubMed:12471095, PubMed:12539043, PubMed:14739303, PubMed:28747347). Ligand binding to these receptors results in TRIF recruitment through its TIR domain (PubMed:12471095, PubMed:12539043, PubMed:14739303). 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 (PubMed:12471095, PubMed:12539043, PubMed:14739303). 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 (PubMed:25636800). 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 (By similarity). {ECO:0000250|UniProtKB:Q80UF7, ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:14739303, ECO:0000269|PubMed:25636800}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (8); Chain (1); Compositional bias (4); Cross-link (1); Domain (1); Frameshift (1); Helix (16); Modified residue (1); Motif (4); Mutagenesis (19); Natural variant (21); Region (5); Sequence conflict (5); Site (7); Turn (3) |
| Keywords | 3D-structure;Antiviral defense;Apoptosis;Cytoplasm;Cytoplasmic vesicle;Disease variant;Host-virus interaction;Immunity;Inflammatory response;Innate immunity;Isopeptide bond;Mitochondrion;Phosphoprotein;Reference proteome;Ubl conjugation |
| Interact With | Q9UHD2; Q9BRZ2 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:21695056}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q80UF7}. Mitochondrion {ECO:0000250|UniProtKB:Q80UF7}. Note=Colocalizes with UBQLN1 in the autophagosome (PubMed:21695056). Colocalizes in the cytosol with DDX1, DDX21 and DHX36. Colocalizes in the mitochondria with DDX1 and poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate to the mitochondria upon poly(I:C) RNA ligand stimulation (By similarity). {ECO:0000250|UniProtKB:Q80UF7, ECO:0000269|PubMed:21695056}. |
| Modified Residue | MOD_RES 210; /note="Phosphoserine; by TBK1"; /evidence="ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953" |
| Post Translational Modification | PTM: Phosphorylated by TBK1 (PubMed:14530355, PubMed:25636800). Following activation, phosphorylated by TBK1 at Ser-210 in the pLxIS motif (PubMed:25636800). The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (PubMed:25636800, PubMed:27302953). {ECO:0000269|PubMed:14530355, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953}.; PTM: Polyubiquitinated at Lys-229 by TRIM38 with 'Lys-48'-linked chains, leading to proteasomal degradation (PubMed:23056470). Polyubiquitinated with 'Lys-6'- and 'Lys-33'-linked chains in a TRIM8-dependent manner; ubiquitination disrupts the interaction with TBK1 and subsequent interferon production (PubMed:28747347). {ECO:0000269|PubMed:23056470, ECO:0000269|PubMed:28747347}.; PTM: (Microbial infection) Cleaved and degraded by hepatitis A virus (HAV) protein 3CD allowing the virus to disrupt host TLR3 signaling. {ECO:0000269|PubMed:21931545}.; PTM: (Microbial infection) Cleaved by CVB3 protease 3C allowing the virus to disrupt host TLR3 signaling. {ECO:0000269|PubMed:21436888}.; PTM: (Microbial infection) Cleaved by Seneca Valley virus protease 3C allowing the virus to disrupt host TLR3 signaling. {ECO:0000269|PubMed:28566380}.; PTM: (Microbial infection) Cleaved by protease 3C of human enterovirus D68 (EV68) allowing the virus to disrupt host TLR3 signaling. {ECO:0000269|PubMed:24672048}.; PTM: (Microbial infection) Cleaved by HCV protease NS3/4A, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state. {ECO:0000269|PubMed:15710891}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (4) |
| Cross Reference PDB | 2M1X; 2M63; 3RC4; 4BSX; 4C0M; 5JEL; |
| Mapped Pubmed ID | 10702308; 10882101; 11057907; 12181749; 12221085; 12242293; 12609980; 12620240; 12692549; 12752666; 12855817; 14517278; 14556004; 14703513; 15064760; 15145317; 15210742; 15327770; 15474016; 15814722; 15841462; 16115877; 16186825; 16260493; 16306936; 16306937; 16547522; 16603398; 17047224; 17135271; 17157040; 17327220; 17496917; 17526488; 17823124; 19112497; 19278658; 19656901; 19666475; 19675569; 19898473; 20047764; 20308068; 20832341; 21507982; 21737329; 21737330; 21903422; 21931591; 21988832; 22123964; 22421964; 23453971; 24255114; 24500696; 26496610; 31818880; 9566918; 9744859; |
| Motif | MOTIF 84..91; /note=TRAF6-binding; MOTIF 207..210; /note=pLxIS motif; /evidence=ECO:0000269|PubMed:25636800; MOTIF 248..255; /note=TRAF6-binding; MOTIF 299..309; /note=TRAF6-binding |
| Gene Encoded By | |
| Mass | 76,422 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |