TICAM1
entrez
148022
canonical
uniprot
Q8IUC6
canonical
ensembl
ENSG00000127666
resolver
ensp
ENSP00000248244
resolver
ensp
ENSP00000538594
resolver
enst
ENST00000248244
resolver
enst
ENST00000868535
resolver
genesymbol
TICAM1
resolver
genesymbol_syn
PRVTIRB
resolver
genesymbol_syn
TRIF
resolver
hgnc
HGNC:18348
resolver
uniprot
B3Y691
resolver
uniprot
O75532
resolver
uniprot
Q86XP8
resolver
uniprot
Q96GA0
resolver
uniprot_entry
TCAM1_HUMAN
resolver
uniprot_sec
B3Y691
resolver
uniprot_sec
O75532
resolver
uniprot_sec
Q86XP8
resolver
uniprot_sec
Q96GA0
resolver
amino_acid_sequence
MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARISLEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQEAVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPRPIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVPEPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNYPVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSPPPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALGVPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQGSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMWRKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTGAPYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQSPAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE
uniprot
proteins
disease_involvement
DISEASE: Encephalopathy, acute, infection-induced, 6, herpes-specific (IIAE6) [MIM:614850]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:22105173}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
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, PubMed:35215908, PubMed:31511519). 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 pro-inflammatory cytokines (By similarity). {ECO:0000250|UniProtKB:Q80UF7, ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:14739303, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:31511519, ECO:0000269|PubMed:35215908}.
uniprot
proteins
mass_dalton
76422
uniprot
proteins
mutagenesis
MUTAGEN 88; /note="E->A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-252 and A-303."; /evidence="ECO:0000269|PubMed:14530355"; MUTAGEN 159; /note="Q->A: Complete loss of cleavage by Seneca Valley virus protease 3C."; /evidence="ECO:0000269|PubMed:28566380"; MUTAGEN 190; /note="Q->A: No effect on cleavage by Seneca Valley virus protease 3C."; /evidence="ECO:0000269|PubMed:28566380"; MUTAGEN 190; /note="Q->R: No cleavage by HAV 3CD."; /evidence="ECO:0000269|PubMed:21931545"; MUTAGEN 202; /note="S->A: Decreased interaction with IRF3."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 210..214; /note="SQSPT->AQAPA: Abolished ability to activate IRF3."; /evidence="ECO:0000269|PubMed:25636800"; MUTAGEN 210; /note="S->A: Abolished interaction with IRF3."; /evidence="ECO:0000269|PubMed:27302953"; MUTAGEN 252; /note="E->A: Loss of TCAM1-induced NF-kappa-B activation. Reduces interaction with TRAF6 and activation of NF-kappa-B signaling pathway; when associated with A-88 and A-303."; /evidence="ECO:0000269|PubMed:14530355, ECO:0000269|PubMed:14982987"; MUTAGEN 281; /note="D->E: Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-289."; /evidence="ECO:0000269|PubMed:23056470"; MUTAGEN 289; /note="D->E: Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-281."; /evidence="ECO:0000269|PubMed:23056470"; MUTAGEN 303; /note="E->A: Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-88 and A-252."; /evidence="ECO:0000269|PubMed:14530355"; MUTAGEN 372; /note="C->R: Complete loss of cleavage by HCVNS3/4A protease."; /evidence="ECO:0000269|PubMed:15710891"; MUTAGEN 434; /note="P->H: Abolishes interaction with TLR3."; /evidence="ECO:0000269|PubMed:12539043"; MUTAGEN 493; /note="E->A: Loss of TCAM1-induced NF-kappa-B and IRF3 activation."; /evidence="ECO:0000269|PubMed:14982987"; MUTAGEN 554; /note="Q->R: No cleavage by HAV 3CD."; /evidence="ECO:0000269|PubMed:21931545"; MUTAGEN 653; /note="Q->A: Complete loss of cleavage by CV3B; when associated with A-659; A-671 and A-702."; /evidence="ECO:0000269|PubMed:21436888"; MUTAGEN 659; /note="Q->A: Complete loss of cleavage by CV3B; when associated with A-653; A-671 and A-702."; /evidence="ECO:0000269|PubMed:21436888"; MUTAGEN 672; /note="Q->A: Complete loss of cleavage by CV3B; when associated with A-653; A-659 and A-702."; /evidence="ECO:0000269|PubMed:21436888"; MUTAGEN 702; /note="Q->A: Complete loss of cleavage by CV3B; when associated with A-653; A-659 and A-671."; /evidence="ECO:0000269|PubMed:21436888
uniprot
proteins
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). Polyubiquitinated with 'Lys-27'-linked chains at Lys-523, promoting TLR3/4-mediated innate immune signaling (PubMed:31511519). {ECO:0000269|PubMed:23056470, ECO:0000269|PubMed:28747347, ECO:0000269|PubMed:31511519}.; 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}.
uniprot
proteins
pubmed
12471095
uniprot
proteins
pubmed
12539043
uniprot
proteins
pubmed
12721283
uniprot
proteins
pubmed
12761501
uniprot
proteins
pubmed
14530355
uniprot
proteins
pubmed
14739303
uniprot
proteins
pubmed
14982987
uniprot
proteins
pubmed
15251447
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15611223
uniprot
proteins
pubmed
15710891
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16964262
uniprot
proteins
pubmed
17457343
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18810425
uniprot
proteins
pubmed
20855887
uniprot
proteins
pubmed
21436888
uniprot
proteins
pubmed
21695056
uniprot
proteins
pubmed
21931545
uniprot
proteins
pubmed
22105173
uniprot
proteins
pubmed
22948160
uniprot
proteins
pubmed
23056470
uniprot
proteins
pubmed
24311583
uniprot
proteins
pubmed
24672048
uniprot
proteins
pubmed
25636800
uniprot
proteins
pubmed
25736436
uniprot
proteins
pubmed
27302953
uniprot
proteins
pubmed
28566380
uniprot
proteins
pubmed
28747347
uniprot
proteins
pubmed
28898289
uniprot
proteins
pubmed
31511519
uniprot
proteins
pubmed
32972995
uniprot
proteins
pubmed
35215908
uniprot
proteins
pubmed
36232715
uniprot
proteins
sequence_length
712
uniprot
proteins
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}.
uniprot
proteins