TICAM2

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]

TICAM2 Gene(Protein Coding) Toll Like Receptor Adaptor Molecule 2

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.

Biological Process cellular response to lipopolysaccharideSource:UniProtKB1 Publication
Biological Process endoplasmic reticulum to Golgi vesicle-mediated transportSource:GO_Central1 Publication
Biological Process Golgi organizationSource:GO_Central1 Publication
Biological Process inflammatory responseSource:UniProtKB-KW
Biological Process innate immune responseSource:UniProtKB-KW
Biological Process intracellular protein transportSource:GO_Central1 Publication
Biological Process negative regulation of chemokine (C-C motif) ligand 5 productionSource:UniProtKB
Biological Process negative regulation of toll-like receptor 4 signaling pathwaySource:UniProtKB
Biological Process phagocytosisSource:UniProtKB1 Publication
Biological Process positive regulation of chemokine (C-C motif) ligand 5 productionSource:UniProtKB
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-18-mediated signaling pathwaySource:UniProtKB1 Publication
Biological Process positive regulation of toll-like receptor 4 signaling pathwaySource:UniProtKB1 Publication
Biological Process TRAM-dependent toll-like receptor 4 signaling pathwaySource:UniProtKB1 Publication

Isoform 1
Cytoplasm
Golgi apparatus
Cell membrane
Endoplasmic reticulum
Early endosome membrane
Late endosome membrane
Cell projection, phagocytic cup
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
Translocates to late endosomes upon LPS stimulation where it colcoalizes with isoform 1.

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.