TICAM1 toll like receptor adaptor molecule 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TICAM1provided by HGNC
Official Full Name: toll like receptor adaptor molecule 1provided by HGNC
Primary source: HGNC:HGNC:18348
See related: Ensembl:ENSG00000127666 MIM:607601
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TRIF; IIAE6; MyD88-3; PRVTIRB; TICAM-1
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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in esophagus (RPKM 10.4), duodenum (RPKM 6.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (4815932..4831712, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (4815936..4831754, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.
Title: New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.
TIR-domain-containing adapter-inducing interferon-beta contributes to TLR3/TLR4 triggered apoptosis and inflammation in nucleus pulposus cells.
Title: TIR-domain-containing adapter-inducing interferon-β contributes to TLR3/TLR4 triggered apoptosis and inflammation in nucleus pulposus cells.
Phosphorylation of TRIF at Serine 210 is required for IRF-3 recruitment and subsequent IRF-3 activation.Kinase activity of TBK1 is required for the association of TRIF and IRF-3.
Title: Priming Phosphorylation of TANK-Binding Kinase 1 by IκB Kinase β Is Essential in Toll-Like Receptor 3/4 Signaling.
SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.
Title: SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.
These data indicate a novel role of the TLR3-TICAM-1 pathway in controlling miR-21 levels in extracellular vesicles.
Title: Activation of TLR3 and its adaptor TICAM-1 increases miR-21 levels in extracellular vesicles released from human cells.
Findings suggest that Toll/IL-1R domain-containing adapter-inducing IFN-beta may be involved in the epileptogenesis of temporal lobe epilepsy, which would make it a potential therapeutic target for the treatment of epilepsy.
Title: TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation.
The down regulation of TRIF, TLR3, and mitochondrial antiviral signaling protein (MAVS) expressions in chronic hepatitis C correlates with the disease severity and the outcome of hepatitis C virus infection
Title: Down regulation of TRIF, TLR3, and MAVS in HCV infected liver correlates with the outcome of infection.
TRIM56 may act as a tumor suppressor in multiple myeloma through activation of TLR3/TRIF signaling pathway.
Title: TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling.
Data suggest that endosomal localization of TICAM2 is essential for TLR4-mediated type I interferon-inducing signaling from endosomes; TICAM2 acts as scaffold protein and activates TICAM1; N-terminal myristoylation allows TICAM2 to anchor to endosomal membrane. (TICAM2 = toll like receptor adaptor molecule-2; TICAM1 = toll like receptor adaptor molecule-1; TLR4 = toll-like receptor 4) [REVIEW]
Title: Functional interfaces between TICAM-2/TRAM and TICAM-1/TRIF in TLR4 signaling.
Data suggest that pro-death signals through TIR-domain-containing adapter-inducing interferon-beta (TRIF) are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms.
Title: TIR-domain-containing adapter-inducing interferon-β (TRIF) forms filamentous structures, whose pro-apoptotic signalling is terminated by autophagy.

Submit: New GeneRIF Correction See all GeneRIFs (84)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. GeneReviews: Not available
Herpes simplex encephalitis, susceptibility to, 4 MedGen: C3553869 OMIM: 614850 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC34257 (e-PCR)
- UniSTS:9241

STS-R73446 (e-PCR)
- UniSTS:35071

Homology

Homologs of the TICAM1 gene: The TICAM1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 258 organisms have orthologs with human gene TICAM1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
I-kappaB kinase/NF-kappaB signaling	TAS Traceable Author Statement more info
MyD88-independent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
TRIF-dependent toll-like receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
TRIF-dependent toll-like receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
TRIF-dependent toll-like receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
apoptotic signaling pathway	TAS Traceable Author Statement more info
cellular response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info
cellular response to oxidised low-density lipoprotein particle stimulus	ISS Inferred from Sequence or Structural Similarity more info
defense response to virus	IEA Inferred from Electronic Annotation more info
inflammatory response	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
lipopolysaccharide-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
macrophage activation involved in immune response	IEA Inferred from Electronic Annotation more info
necroptotic process	TAS Traceable Author Statement more info
negative regulation of MyD88-independent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
positive regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of I-kappaB kinase/NF-kappaB signaling	HMP more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of NF-kappaB transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of autophagy	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of chemokine production	IEA Inferred from Electronic Annotation more info
positive regulation of cytokine production involved in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of cytokine production involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interferon-beta production	IEA Inferred from Electronic Annotation more info
positive regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
positive regulation of myeloid dendritic cell cytokine production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of myeloid dendritic cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of natural killer cell activation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of nitric oxide biosynthetic process	IEA Inferred from Electronic Annotation more info
positive regulation of protein binding	IEA Inferred from Electronic Annotation more info
positive regulation of protein ubiquitination	IEA Inferred from Electronic Annotation more info
positive regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
regulation of protein-containing complex assembly	IEA Inferred from Electronic Annotation more info
response to exogenous dsRNA	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to exogenous dsRNA	IMP Inferred from Mutant Phenotype more info	PubMed
response to exogenous dsRNA	ISS Inferred from Sequence or Structural Similarity more info
toll-like receptor 3 signaling pathway	TAS Traceable Author Statement more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
autophagosome	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
endosome membrane	TAS Traceable Author Statement more info
mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
ripoptosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: TIR domain-containing adapter molecule 1

Names: TIR domain containing adaptor inducing interferon-beta; TIR domain-containing adapter protein inducing IFN-beta; 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

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_031998.1 RefSeqGene

Range

5001..20819

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_358

mRNA and Protein(s)

NM_001385678.1 → NP_001372607.1 TIR domain-containing adapter molecule 1 isoform 2

Status: REVIEWED

Source sequence(s)

AC027319
NM_001385679.1 → NP_001372608.1 TIR domain-containing adapter molecule 1 isoform 3

Status: REVIEWED

Source sequence(s)

AC027319
NM_001385680.1 → NP_001372609.1 TIR domain-containing adapter molecule 1 isoform 4

Status: REVIEWED

Source sequence(s)

AC027319
NM_182919.4 → NP_891549.1 TIR domain-containing adapter molecule 1 isoform 1

See identical proteins and their annotated locations for NP_891549.1

Status: REVIEWED

Source sequence(s)

AB086380, BC035331, BX349282, DR000002

Consensus CDS

CCDS12136.1

UniProtKB/Swiss-Prot

Q8IUC6

Related

ENSP00000248244.4, ENST00000248244.5

Conserved Domains (2) summary

pfam12721
Location:654 → 696

RHIM; RIP homotypic interaction motif

cl23749
Location:399 → 527

TIR_2; TIR domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p13 Primary Assembly

Range

4815932..4831712 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_014261.1: Suppressed sequence

Description

NM_014261.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.