TIRP is a Toll/interleukin-1 receptor (IL1R; MIM 147810) (TIR) domain-containing adaptor protein involved in Toll receptor signaling (see TLR4; MIM 603030).[supplied by OMIM, Apr 2004] See more...

Aliases for TICAM2 Gene

Aliases for TICAM2 Gene

  • Toll Like Receptor Adaptor Molecule 2 2 3 5
  • TICAM-2 2 3 4
  • TIRP 2 3 4
  • TRAM 2 3 4
  • Putative NF-Kappa-B-Activating Protein 502 3 4
  • TIR Domain-Containing Adapter Molecule 2 3 4
  • Toll-Like Receptor Adaptor Protein 3 3 4
  • MyD88-4 3 4
  • TIRAP3 3 4
  • Toll/Interleukin-1 Receptor (TIR) Domain-Containing Adapter Protein 3
  • Toll/Interleukin-1 Receptor Domain-Containing Protein 4
  • Toll-Like Receptor Adaptor Molecule 2 2
  • NF-Kappa-B-Activating Protein 502 3
  • TRIF-Related Adaptor Molecule 3
  • TRIF-Related Adapter Molecule 4
  • Cytoplasmic Adaptor 3
  • TICAM2 5

External Ids for TICAM2 Gene

Previous GeneCards Identifiers for TICAM2 Gene

  • GC00U917008
  • GC05M114942
  • GC05M110096

Summaries for TICAM2 Gene

Entrez Gene Summary for TICAM2 Gene

  • TIRP is a Toll/interleukin-1 receptor (IL1R; MIM 147810) (TIR) domain-containing adaptor protein involved in Toll receptor signaling (see TLR4; MIM 603030).[supplied by OMIM, Apr 2004]

GeneCards Summary for TICAM2 Gene

TICAM2 (Toll Like Receptor Adaptor Molecule 2) is a Protein Coding gene. Among its related pathways are Activated TLR4 signalling and IKK complex recruitment mediated by RIP1. Gene Ontology (GO) annotations related to this gene include obsolete signal transducer activity and phospholipid binding.

UniProtKB/Swiss-Prot Summary for TICAM2 Gene

  • Functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction (PubMed:16603631, PubMed:16757566, PubMed:25385819, PubMed:25825441). In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement (PubMed:25385819). Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response (PubMed:22685567). Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria (PubMed:30883606).
  • [Isoform 2]: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

Gene Wiki entry for TICAM2 Gene

Additional gene information for TICAM2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TICAM2 Gene

Genomics for TICAM2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TICAM2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TICAM2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TICAM2

Top Transcription factor binding sites by QIAGEN in the TICAM2 gene promoter:
  • AML1a
  • AREB6
  • FOXO4
  • GCNF
  • GCNF-1
  • GCNF-2
  • HOXA3
  • STAT1
  • ZID

Genomic Locations for TICAM2 Gene

Genomic Locations for TICAM2 Gene
chr5:115,578,496-115,602,479
(GRCh38/hg38)
Size:
23,984 bases
Orientation:
Minus strand
chr5:114,914,339-114,961,876
(GRCh37/hg19)
Size:
47,538 bases
Orientation:
Minus strand

Genomic View for TICAM2 Gene

Genes around TICAM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TICAM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TICAM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TICAM2 Gene

Proteins for TICAM2 Gene

  • Protein details for TICAM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q86XR7-TCAM2_HUMAN
    Recommended name:
    TIR domain-containing adapter molecule 2
    Protein Accession:
    Q86XR7
    Secondary Accessions:
    • B3Y698
    • Q6JUT2

    Protein attributes for TICAM2 Gene

    Size:
    235 amino acids
    Molecular mass:
    26916 Da
    Quaternary structure:
    • Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and TRAF6. Interacts with protein kinase-inactive mutants of IRAK1 and IRAK4. Isoform 1 interacts with isoform 2; the interaction occurs in late endosomes and disrupts the interaction between isoform 1 and TICAM1. Interacts with MYD88; the interaction decreases after IL-18 stimulation in a time-dependent manner. Interacts with IL18R1 and IL18RAP. Interacts with TLR2 (PubMed:25385819). Interacts with RAB11FIP2 (PubMed:30883606).

    Three dimensional structures from OCA and Proteopedia for TICAM2 Gene

    Alternative splice isoforms for TICAM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TICAM2 Gene

Post-translational modifications for TICAM2 Gene

  • Phosphorylated by PRKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation. Tyrosine phosphorylation is inhibited by phosphatase PTPN4.
  • Isoform 1 is myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TICAM2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TICAM2 Gene

Domains & Families for TICAM2 Gene

Gene Families for TICAM2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for TICAM2 Gene

Suggested Antigen Peptide Sequences for TICAM2 Gene

GenScript: Design optimal peptide antigens:
  • Toll/interleukin-1 receptor domain-containing protein (TCAM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q86XR7

UniProtKB/Swiss-Prot:

TCAM2_HUMAN :
  • The TIR domain mediates the interaction with TRAF6 and MYD88.
Domain:
  • The TIR domain mediates the interaction with TRAF6 and MYD88.
genes like me logo Genes that share domains with TICAM2: view

Function for TICAM2 Gene

Molecular function for TICAM2 Gene

UniProtKB/Swiss-Prot Function:
Functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction (PubMed:16603631, PubMed:16757566, PubMed:25385819, PubMed:25825441). In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement (PubMed:25385819). Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response (PubMed:22685567). Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria (PubMed:30883606).
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

Phenotypes From GWAS Catalog for TICAM2 Gene

Gene Ontology (GO) - Molecular Function for TICAM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 17258210
genes like me logo Genes that share ontologies with TICAM2: view
genes like me logo Genes that share phenotypes with TICAM2: view

Animal Models for TICAM2 Gene

MGI Knock Outs for TICAM2:

Animal Model Products

CRISPR Products

miRNA for TICAM2 Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TICAM2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TICAM2 Gene

Localization for TICAM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TICAM2 Gene

[Isoform 1]: Cytoplasm. Golgi apparatus. Cell membrane. Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Cell projection, phagocytic cup. Note=Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the membrane. Upon LPS stimulation colcoalizes with isoform 2 in late endosomes.
[Isoform 2]: Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Note=Translocates to late endosomes upon LPS stimulation where it colcoalizes with isoform 1.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TICAM2 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
endosome 5
golgi apparatus 3
extracellular 2
nucleus 2
cytosol 2
cytoskeleton 1
mitochondrion 1
lysosome 1

Gene Ontology (GO) - Cellular Components for TICAM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001891 phagocytic cup IEA,IDA 30883606
GO:0005737 cytoplasm IEA --
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IBA 21873635
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment IBA 21873635
genes like me logo Genes that share ontologies with TICAM2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TICAM2 Gene

Pathways & Interactions for TICAM2 Gene

genes like me logo Genes that share pathways with TICAM2: view

Pathways by source for TICAM2 Gene

SIGNOR curated interactions for TICAM2 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for TICAM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
GO:0006886 intracellular protein transport IBA 21873635
GO:0006888 ER to Golgi vesicle-mediated transport IBA 21873635
GO:0006909 phagocytosis IMP 30883606
genes like me logo Genes that share ontologies with TICAM2: view

Drugs & Compounds for TICAM2 Gene

No Compound Related Data Available

Transcripts for TICAM2 Gene

mRNA/cDNA for TICAM2 Gene

1 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TICAM2

Alternative Splicing Database (ASD) splice patterns (SP) for TICAM2 Gene

No ASD Table

Relevant External Links for TICAM2 Gene

GeneLoc Exon Structure for
TICAM2

Expression for TICAM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TICAM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TICAM2 Gene

This gene is overexpressed in Bone (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TICAM2 Gene



Protein tissue co-expression partners for TICAM2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TICAM2

SOURCE GeneReport for Unigene cluster for TICAM2 Gene:

Hs.718838

mRNA Expression by UniProt/SwissProt for TICAM2 Gene:

Q86XR7-TCAM2_HUMAN
Tissue specificity: Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas Isoform 2 is ubiquitously expressed (at lower levels than isoform 1).

Evidence on tissue expression from TISSUES for TICAM2 Gene

  • Lung(4.2)
genes like me logo Genes that share expression patterns with TICAM2: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TICAM2 Gene

Orthologs for TICAM2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TICAM2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TICAM2 30 31
  • 99.43 (n)
OneToMany
Dog
(Canis familiaris)
Mammalia TMED7 31
  • 85 (a)
OneToMany
TICAM2 30
  • 75.04 (n)
Cow
(Bos Taurus)
Mammalia TICAM2 30 31
  • 83.76 (n)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 79 (a)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Ticam2 30
  • 78.59 (n)
Mouse
(Mus musculus)
Mammalia Ticam2 30 17 31
  • 78.59 (n)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 38 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves -- 31
  • 76 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 40 (a)
OneToMany
Zebrafish
(Danio rerio)
Actinopterygii tmed7 31
  • 69 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta p24-1 31
  • 43 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea F57B10.5 31
  • 49 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes EMP24 31
  • 21 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9127 31
  • 48 (a)
OneToMany
Species where no ortholog for TICAM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for TICAM2 Gene

ENSEMBL:
Gene Tree for TICAM2 (if available)
TreeFam:
Gene Tree for TICAM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TICAM2: view image

Paralogs for TICAM2 Gene

No data available for Paralogs for TICAM2 Gene

Variants for TICAM2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TICAM2 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
790566 Benign: not provided 115,580,654(-) T/G SYNONYMOUS_VARIANT,THREE_PRIME_UTR_VARIANT
790567 Benign: not provided 115,581,066(-) C/T MISSENSE_VARIANT,THREE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for TICAM2 Gene

Structural Variations from Database of Genomic Variants (DGV) for TICAM2 Gene

Variant ID Type Subtype PubMed ID
nsv830455 CNV gain 17160897

Variation tolerance for TICAM2 Gene

Residual Variation Intolerance Score: 75.6% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TICAM2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TICAM2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TICAM2 Gene

Disorders for TICAM2 Gene

Additional Disease Information for TICAM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for TICAM2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for TICAM2 Gene

Publications for TICAM2 Gene

  1. TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling. (PMID: 12721283) Bin LH … Shu HB (The Journal of biological chemistry 2003) 3 4 23
  2. The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. (PMID: 30883606) Skjesol A … Husebye H (PLoS pathogens 2019) 3 4
  3. TRAM is required for TLR2 endosomal signaling to type I IFN induction. (PMID: 25385819) Stack J … Bowie AG (Journal of immunology (Baltimore, Md. : 1950) 2014) 3 4
  4. TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88. (PMID: 22685567) Ohnishi H … Kondo N (PloS one 2012) 3 4
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41

Products for TICAM2 Gene

Sources for TICAM2 Gene