TICAM2 TIR domain containing adaptor molecule 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TICAM2provided by HGNC
Official Full Name: TIR domain containing adaptor molecule 2provided by HGNC
Primary source: HGNC:HGNC:21354
See related: Ensembl:ENSG00000243414 MIM:608321; AllianceGenome:HGNC:21354
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TIRP; TRAM; TIRAP3; MyD88-4; TICAM-2
Summary: Enables molecular adaptor activity. Involved in several processes, including positive regulation of interleukin-18-mediated signaling pathway; regulation of cytokine production; and regulation of innate immune response. Located in endoplasmic reticulum; endosome; and phagocytic cup. Is active in endosome membrane. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in appendix (RPKM 4.0), spleen (RPKM 3.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q22.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (115578496..115602479, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (116091278..116115262, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (114914193..114938176, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

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.
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 show that Toll/IL-1R domain-containing adaptor molecule (TICAM)-2 possesses two conserved acidic amino acids, D91 and E92, which regulate TICAM-2 self-activation and signaling.
Title: Identification of a Regulatory Acidic Motif as the Determinant of Membrane Localization of TICAM-2.
Findings were SNPs in TICAM2 (P = 3.6 x 10(-6)) and IL1B (P = 4.3 x 10(-5)) associated with TB.
Title: Polymorphisms in TICAM2 and IL1B are associated with TB.
TRAM plays a role in TLR7 signaling through a novel signaling axis towards the activation of anti-viral immunity.
Title: The TIR-domain containing adaptor TRAM is required for TLR7 mediated RANTES production.
TRAM acts as a sorting adaptor not only for TLR4, but also for TLR2, to facilitate signaling to IRF7 at the endosome, which explains how TLR2 is capable of causing type I IFN induction.
Title: TRAM is required for TLR2 endosomal signaling to type I IFN induction.
A putative TRAF6-binding motif in TRAM may mediate a new TRAM function in TLR4 signaling in regulating inflammatory responses, distinct from its bridging TLR4 and TRIF. A TRAM E183A mutation abolished this.
Title: The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4.
results suggest TLR adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8 mRNA and increase CXCL12 mRNA expression in HGF and HPDLF.
Title: MyD88 or TRAM knockdown regulates interleukin (IL)-6, IL-8, and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts.
The homotypic interaction between TICAM-2 TIR is indispensable to present a scaffold for recruiting the monomeric moiety of the TICAM-1 TIR dimer.
Title: Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling.
induction of both IL-6 and IL-8 is associated with elevated TIRAP and reduced TRAM mRNA expression
Title: Human cytomegalovirus induces TLR4 signaling components in monocytes altering TIRAP, TRAM and downstream interferon-beta and TNF-alpha expression.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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

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

G60385 (e-PCR)
- UniSTS:137491

NoName (e-PCR)
- UniSTS:484667

AB055258 (e-PCR)
- UniSTS:479895

WI-11806 (e-PCR)
- UniSTS:184

TIRP__5265 (e-PCR)
- UniSTS:463322

Readthrough TMED7-TICAM2

Readthrough gene: TMED7-TICAM2, Included gene: TMED7

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in TRAM-dependent toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in TRAM-dependent toll-like receptor 4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in TRIF-dependent toll-like receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of chemokine (C-C motif) ligand 5 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	HMP more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of chemokine (C-C motif) ligand 5 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-18-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of toll-like receptor 4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type I interferon production	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of type I interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in endosome	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in phagocytic cup	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in secretory granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: TIR domain-containing adapter molecule 2

Names: NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmic adaptor; putative NF-kappa-B-activating protein 502; toll like receptor adaptor molecule 2; toll-like receptor adaptor protein 3; toll/interleukin-1 receptor (TIR) domain-containing adapter protein

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.