domain:The TIR domain mediates the interaction with TRAF6.,function:Functions in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Also involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1.,PTM:Myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.,PTM:Phosphorylated by PKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation.,similarity:Belongs to the EMP24/GP25L family.,similarity:Contains 1 GOLD domain.,similarity:Contains 1 TIR domain.,subcellular location:Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the membrane.,subunit: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.,tissue specificity:Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas.,
[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.
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).