TIFA_RAT
ID TIFA_RAT Reviewed; 185 AA.
AC Q5XIB9;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=TRAF-interacting protein with FHA domain-containing protein A {ECO:0000305};
GN Name=Tifa {ECO:0000312|RGD:1359151};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Brown Norway; TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Adapter molecule that plays a key role in the activation of
CC pro-inflammatory NF-kappa-B signaling following detection of bacterial
CC pathogen-associated molecular pattern metabolites (PAMPs). Promotes
CC activation of an innate immune response by inducing the oligomerization
CC and polyubiquitination of TRAF6, which leads to the activation of TAK1
CC and IKK through a proteasome-independent mechanism. TIFA-dependent
CC innate immune response is triggered by ADP-D-glycero-beta-D-manno-
CC heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and
CC some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which
CC phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and
CC subsequent activation of pro-inflammatory NF-kappa-B signaling.
CC {ECO:0000250|UniProtKB:Q96CG3}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes following phosphorylation at
CC Thr-9. Interacts with IRAK1, TRAF2 and TRAF6. Interacts with TIFAB;
CC binding to TIFAB inhibits TRAF6 activation, possibly by inducing a
CC conformational change in TIFA. Interacts with ZCCHC11; binding to
CC ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B.
CC {ECO:0000250|UniProtKB:Q96CG3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96CG3}.
CC Note=Colocalizes with lysosomal marker LAMP2 following
CC homooligomerization and subsequent activation.
CC {ECO:0000250|UniProtKB:Q96CG3}.
CC -!- DOMAIN: The FHA domain recognizes and binds phosphorylated Thr-9,
CC promoting homooligomerization and subsequent activation of NF-kappa-B.
CC {ECO:0000250|UniProtKB:Q96CG3}.
CC -!- PTM: Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-
CC D-manno-heptose (ADP-Heptose) by ALPK1. Phosphorylation at Thr-9 by
CC ALPK1 leads to the formation of an intermolecular binding between the
CC FHA domain and phosphorylated Thr-9, promoting TIFA oligomerization and
CC TIFA-mediated NF-kappa-B activation. {ECO:0000250|UniProtKB:Q96CG3}.
CC -!- SIMILARITY: Belongs to the TIFA family. {ECO:0000305}.
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DR EMBL; BC083765; AAH83765.1; -; mRNA.
DR RefSeq; NP_001014066.1; NM_001014044.1.
DR RefSeq; XP_017446427.1; XM_017590938.1.
DR AlphaFoldDB; Q5XIB9; -.
DR SMR; Q5XIB9; -.
DR STRING; 10116.ENSRNOP00000061870; -.
DR PaxDb; Q5XIB9; -.
DR Ensembl; ENSRNOT00000014533; ENSRNOP00000061870; ENSRNOG00000010941.
DR Ensembl; ENSRNOT00000102851; ENSRNOP00000087830; ENSRNOG00000010941.
DR Ensembl; ENSRNOT00000112612; ENSRNOP00000077082; ENSRNOG00000010941.
DR GeneID; 310877; -.
DR KEGG; rno:310877; -.
DR UCSC; RGD:1359151; rat.
DR CTD; 92610; -.
DR RGD; 1359151; Tifa.
DR eggNOG; ENOG502S0RF; Eukaryota.
DR GeneTree; ENSGT00940000154589; -.
DR HOGENOM; CLU_125520_0_0_1; -.
DR InParanoid; Q5XIB9; -.
DR OrthoDB; 1381983at2759; -.
DR Reactome; R-RNO-9645460; Alpha-protein kinase 1 signaling pathway.
DR PRO; PR:Q5XIB9; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000010941; Expressed in spleen and 18 other tissues.
DR ExpressionAtlas; Q5XIB9; baseline and differential.
DR Genevisible; Q5XIB9; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR033621; TIFA.
DR PANTHER; PTHR31266; PTHR31266; 1.
DR Pfam; PF00498; FHA; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Immunity; Innate immunity; Phosphoprotein; Reference proteome.
FT CHAIN 1..185
FT /note="TRAF-interacting protein with FHA domain-containing
FT protein A"
FT /id="PRO_0000320691"
FT DOMAIN 48..104
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96CG3"
SQ SEQUENCE 185 AA; 21548 MW; D12AE786B7B08756 CRC64;
MSTFEDADTE ETVTCLQMTI YHPGQLQSGI FKSIRFCSKE KFPSIEVVKF GRNSNMCQYT
FQDKQVSRVQ FALQPFKQFN SSVLSFEIKN MSKKTSLMVD NQELGYLNKM DLPYKCMLRF
GEYQFLLQKE DGESVESFET QFILSPRPLL QENNWPTQSP IPEDGVYSSY FTHRSSPAEM
DENEL
