TICAM1 (toll like receptor adaptor molecule 1)

Gene

• Entrez ID: 148022
• Gene name: Toll like receptor adaptor molecule 1
• Gene symbol: TICAM1
• Synonyms: IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF
• Chromosome: 19
• Chromosome location: 19p13.3
• Summary: This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. This protein is involved in native immunity against invading pathogens. It specifically interacts with toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B, during an antiviral immune response. Mutations in this gene are associated with encephalopathy, acute, infection-induced. [provided by RefSeq, Jul 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143679494	C>A,T	Likely-benign, risk-factor	Missense variant, coding sequence variant
rs387907307	G>A,C	Risk-factor	Stop gained, coding sequence variant, missense variant
rs1555730283	G>A	Risk-factor	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005475	hsa-miR-221-3p	Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	21236259
MIRT041391	hsa-miR-193b-3p	CLASH	23622248

Transcription factors

Transcription factor	Regulation	Reference
SP1	Repression	14960149
TRAF6	Unknown	14530355;20047764

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002281	Process	Macrophage activation involved in immune response	IEA
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	IBA	21873635
GO:0002735	Process	Positive regulation of myeloid dendritic cell cytokine production	ISS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	TAS
GO:0005515	Function	Protein binding	IPI	14982987, 15142865, 15841462, 19416887, 21903422, 22948160, 25736436
GO:0005739	Component	Mitochondrion	ISS
GO:0005776	Component	Autophagosome	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006954	Process	Inflammatory response	IEA
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0010008	Component	Endosome membrane	TAS
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0016032	Process	Viral process	IEA
GO:0019901	Function	Protein kinase binding	IBA	21873635
GO:0019901	Function	Protein kinase binding	IPI	14530355
GO:0030890	Process	Positive regulation of B cell proliferation	IEA
GO:0031398	Process	Positive regulation of protein ubiquitination	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IBA	21873635
GO:0032092	Process	Positive regulation of protein binding	IEA
GO:0032722	Process	Positive regulation of chemokine production	IEA
GO:0032728	Process	Positive regulation of interferon-beta production	IEA
GO:0032755	Process	Positive regulation of interleukin-6 production	IEA
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IEA
GO:0032816	Process	Positive regulation of natural killer cell activation	IBA	21873635
GO:0034128	Process	Negative regulation of MyD88-independent toll-like receptor signaling pathway	TAS
GO:0034138	Process	Toll-like receptor 3 signaling pathway	TAS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IBA	21873635
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IMP	25636800
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	ISS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	HMP	12761501
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	14982987
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	ISS
GO:0043254	Process	Regulation of protein-containing complex assembly	IEA
GO:0043330	Process	Response to exogenous dsRNA	IBA	21873635
GO:0043330	Process	Response to exogenous dsRNA	IMP	21266579
GO:0043330	Process	Response to exogenous dsRNA	ISS
GO:0045087	Process	Innate immune response	IEA
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IEA
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051607	Process	Defense response to virus	IEA
GO:0070266	Process	Necroptotic process	TAS
GO:0071222	Process	Cellular response to lipopolysaccharide	ISS
GO:0097190	Process	Apoptotic signaling pathway	TAS
GO:0097342	Component	Ripoptosome	IDA	21737330
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	ISS
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IBA	21873635
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	ISS

Other IDs

• MIM: 607601
• HGNC: 18348
• e!Ensembl: ENSG00000127666

Protein

• UniProt ID: Q8IUC6
• 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)
• Protein 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).
• PDB: 2M1X, 2M63, 3RC4, 4BSX, 4C0M, 5JEL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17798	TRIF-NTD	1 → 148	TRIF N-terminal domain	Domain
  PF12721	RHIM	642 → 697	RIP homotypic interaction motif	Family

• Sequence:

  MACTGPSLPSAFDILGAAGQDKLLYLKHKLKTPRPGCQGQDLLHAMVLLKLGQETEARIS
  LEALKADAVARLVARQWAGVDSTEDPEEPPDVSWAVARLYHLLAEEKLCPASLRDVAYQE
  AVRTLSSRDDHRLGELQDEARNRCGWDIAGDPGSIRTLQSNLGCLPPSSALPSGTRSLPR
  PIDGVSDWSQGCSLRSTGSPASLASNLEISQSPTMPFLSLHRSPHGPSKLCDDPQASLVP
  EPVPGGCQEPEEMSWPPSGEIASPPELPSSPPPGLPEVAPDATSTGLPDTPAAPETSTNY
  PVECTEGSAGPQSLPLPILEPVKNPCSVKDQTPLQLSVEDTTSPNTKPCPPTPTTPETSP
  PPPPPPPSSTPCSAHLTPSSLFPSSLESSSEQKFYNFVILHARADEHIALRVREKLEALG
  VPDGATFCEDFQVPGRGELSCLQDAIDHSAFIILLLTSNFDCRLSLHQVNQAMMSNLTRQ
  GSPDCVIPFLPLESSPAQLSSDTASLLSGLVRLDEHSQIFARKVANTFKPHRLQARKAMW
  RKEQDTRALREQSQHLDGERMQAAALNAAYSAYLQSYLSYQAQMEQLQVAFGSHMSFGTG
  APYGARMPFGGQVPLGAPPPFPTWPGCPQPPPLHAWQAGTPPPPSPQPAAFPQSLPFPQS
  PAFPTASPAPPQSPGLQPLIIHHAQMVQLGLNNHMWNQRGSQAPEDKTQEAE

• Sequence length: 712