UniProt functional annotation for Q96CG3



	UniProt functional annotation for Q96CG3

UniProt code: Q96CG3.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, 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 proinflammatory NF- kappa-B signaling (PubMed:30111836). {ECO:0000269|PubMed:12566447, ECO:0000269|PubMed:15492226, ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:28222186, ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836}.

Subunit: Homooligomer; homooligomerizes following phosphorylation at Thr-9 (PubMed:12566447, PubMed:22566686, PubMed:26068852, PubMed:26389808). Interacts with IRAK1, TRAF2 and TRAF6 (PubMed:12566447). Interacts with TIFAB; binding to TIFAB inhibits TRAF6 activation, possibly by inducing a conformational change in TIFA (PubMed:15047173). Interacts with ZCCHC11; binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B (PubMed:16643855). {ECO:0000269|PubMed:12566447, ECO:0000269|PubMed:15047173, ECO:0000269|PubMed:16643855, ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:26389808}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:22566686, ECO:0000305|PubMed:26068852}. Note=Colocalizes with lysosomal marker LAMP2 following homooligomerization and subsequent activation. {ECO:0000269|PubMed:26068852}.

Domain: The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B. {ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26389808}.

Ptm: 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:30111836, PubMed:26389808). {ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26389808, ECO:0000269|PubMed:30111836}.

Similarity: Belongs to the TIFA family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, 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 proinflammatory NF- kappa-B signaling (PubMed:30111836). {ECO:0000269\|PubMed:12566447, ECO:0000269\|PubMed:15492226, ECO:0000269\|PubMed:26068852, ECO:0000269\|PubMed:28222186, ECO:0000269\|PubMed:28877472, ECO:0000269\|PubMed:30111836}.


Subunit:		Homooligomer; homooligomerizes following phosphorylation at Thr-9 (PubMed:12566447, PubMed:22566686, PubMed:26068852, PubMed:26389808). Interacts with IRAK1, TRAF2 and TRAF6 (PubMed:12566447). Interacts with TIFAB; binding to TIFAB inhibits TRAF6 activation, possibly by inducing a conformational change in TIFA (PubMed:15047173). Interacts with ZCCHC11; binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B (PubMed:16643855). {ECO:0000269\|PubMed:12566447, ECO:0000269\|PubMed:15047173, ECO:0000269\|PubMed:16643855, ECO:0000269\|PubMed:22566686, ECO:0000269\|PubMed:26068852, ECO:0000269\|PubMed:26389808}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:22566686, ECO:0000305\|PubMed:26068852}. Note=Colocalizes with lysosomal marker LAMP2 following homooligomerization and subsequent activation. {ECO:0000269\|PubMed:26068852}.
Domain:		The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B. {ECO:0000269\|PubMed:22566686, ECO:0000269\|PubMed:26389808}.
Ptm:		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:30111836, PubMed:26389808). {ECO:0000269\|PubMed:22566686, ECO:0000269\|PubMed:26389808, ECO:0000269\|PubMed:30111836}.
Similarity:		Belongs to the TIFA family. {ECO:0000305}.