TIFA
Domain
The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B.
Function
Adapter molecule that plays a key role in the activation of pro-inflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28222186, PubMed:28877472, PubMed:30111836). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PubMed:15492226, PubMed:26068852). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of pro-inflammatory NF-kappa-B signaling (PubMed:30111836).
Post-translational modifications
Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) by ALPK1 (PubMed:30111836). Phosphorylation at Thr-9 by ALPK1 leads to the formation of an intermolecular binding between the FHA domain and phosphorylated Thr-9, promoting TIFA oligomerization and TIFA-mediated NF-kappa-B activation (PubMed:22566686, PubMed:26389808, PubMed:30111836).
Sequence Similarities
Belongs to the TIFA family.
Cellular localization
- Cytoplasm
- Colocalizes with lysosomal marker LAMP2 following homooligomerization and subsequent activation.
Alternative names
T2BP, TIFA, TRAF-interacting protein with FHA domain-containing protein A, Putative MAPK-activating protein PM14, Putative NF-kappa-B-activating protein 20, TRAF2-binding protein