TIFA_MOUSE
ID TIFA_MOUSE Reviewed; 184 AA.
AC Q793I8; Q3TLY9;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=TRAF-interacting protein with FHA domain-containing protein A {ECO:0000303|PubMed:12566447};
DE AltName: Full=TRAF2-binding protein {ECO:0000303|PubMed:11798190};
GN Name=Tifa {ECO:0000303|PubMed:12566447, ECO:0000312|MGI:MGI:2182965};
GN Synonyms=T2bp {ECO:0000303|PubMed:11798190};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12566447; DOI=10.1074/jbc.m300720200;
RA Takatsuna H., Kato H., Gohda J., Akiyama T., Moriya A., Okamoto Y.,
RA Yamagata Y., Otsuka M., Umezawa K., Semba K., Inoue J.;
RT "Identification of TIFA as an adapter protein that links tumor necrosis
RT factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1)
RT receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling.";
RL J. Biol. Chem. 278:12144-12150(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow, Liver, Mammary gland, Retina, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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).
RN [4]
RP FUNCTION, INTERACTION WITH TRAF2, AND TISSUE SPECIFICITY.
RX PubMed=11798190; DOI=10.1006/bbrc.2001.6315;
RA Kanamori M., Suzuki H., Saito R., Muramatsu M., Hayashizaki Y.;
RT "T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1
RT without TNF stimulation.";
RL Biochem. Biophys. Res. Commun. 290:1108-1113(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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)
CC (PubMed:11798190). Promotes activation of an innate immune response by
CC inducing the oligomerization and polyubiquitination of TRAF6, which
CC leads to the activation of TAK1 and IKK through a proteasome-
CC independent mechanism (By similarity). TIFA-dependent innate immune
CC response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-
CC Heptose), a potent PAMP present in all Gram-negative and some Gram-
CC 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q96CG3,
CC ECO:0000269|PubMed:11798190}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes following phosphorylation at
CC Thr-9 (By similarity). Interacts with IRAK1, TRAF2 and TRAF6
CC (PubMed:11798190). Interacts with TIFAB; binding to TIFAB inhibits
CC TRAF6 activation, possibly by inducing a conformational change in TIFA
CC (By similarity). Interacts with ZCCHC11; binding to ZCCHC11 suppresses
CC the TRAF6-dependent activation of NF-kappa-B (By similarity).
CC {ECO:0000250|UniProtKB:Q96CG3, ECO:0000269|PubMed:11798190}.
CC -!- INTERACTION:
CC Q793I8; Q62406: Irak1; NbExp=2; IntAct=EBI-524817, EBI-448533;
CC Q793I8; P70196: Traf6; NbExp=2; IntAct=EBI-524817, EBI-448028;
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 -!- TISSUE SPECIFICITY: Highly expressed in the spleen and at lower levels
CC in heart, brain, lung, liver, kidney and testes.
CC {ECO:0000269|PubMed:11798190, ECO:0000269|PubMed:12566447}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB062111; BAB86903.1; -; mRNA.
DR EMBL; AK041891; BAE43315.1; -; mRNA.
DR EMBL; AK044221; BAC31825.1; -; mRNA.
DR EMBL; AK149408; BAE28856.1; -; mRNA.
DR EMBL; AK149864; BAE29133.1; -; mRNA.
DR EMBL; AK151651; BAE30580.1; -; mRNA.
DR EMBL; AK166239; BAE38653.1; -; mRNA.
DR EMBL; BC065775; AAH65775.1; -; mRNA.
DR CCDS; CCDS38628.1; -.
DR RefSeq; NP_660115.1; NM_145133.3.
DR RefSeq; XP_006501299.1; XM_006501236.3.
DR RefSeq; XP_006501300.1; XM_006501237.3.
DR RefSeq; XP_006501301.1; XM_006501238.3.
DR RefSeq; XP_006501302.1; XM_006501239.3.
DR PDB; 6L9U; X-ray; 2.60 A; A=1-184.
DR PDB; 6L9V; X-ray; 3.05 A; A/B/C/D=1-184.
DR PDB; 6L9W; X-ray; 2.90 A; A/B/C/D/E/F=1-184.
DR PDBsum; 6L9U; -.
DR PDBsum; 6L9V; -.
DR PDBsum; 6L9W; -.
DR AlphaFoldDB; Q793I8; -.
DR SASBDB; Q793I8; -.
DR SMR; Q793I8; -.
DR BioGRID; 229244; 4.
DR IntAct; Q793I8; 2.
DR STRING; 10090.ENSMUSP00000054036; -.
DR iPTMnet; Q793I8; -.
DR PhosphoSitePlus; Q793I8; -.
DR MaxQB; Q793I8; -.
DR PaxDb; Q793I8; -.
DR PRIDE; Q793I8; -.
DR ProteomicsDB; 259446; -.
DR Antibodypedia; 45213; 117 antibodies from 22 providers.
DR DNASU; 211550; -.
DR Ensembl; ENSMUST00000054483; ENSMUSP00000054036; ENSMUSG00000046688.
DR Ensembl; ENSMUST00000163775; ENSMUSP00000132309; ENSMUSG00000046688.
DR Ensembl; ENSMUST00000164447; ENSMUSP00000126692; ENSMUSG00000046688.
DR Ensembl; ENSMUST00000171621; ENSMUSP00000127700; ENSMUSG00000046688.
DR GeneID; 211550; -.
DR KEGG; mmu:211550; -.
DR UCSC; uc008rhm.1; mouse.
DR CTD; 92610; -.
DR MGI; MGI:2182965; Tifa.
DR VEuPathDB; HostDB:ENSMUSG00000046688; -.
DR eggNOG; ENOG502S0RF; Eukaryota.
DR GeneTree; ENSGT00940000154589; -.
DR HOGENOM; CLU_125520_0_0_1; -.
DR InParanoid; Q793I8; -.
DR OMA; SIRFFNR; -.
DR OrthoDB; 1381983at2759; -.
DR PhylomeDB; Q793I8; -.
DR TreeFam; TF333218; -.
DR Reactome; R-MMU-9645460; Alpha-protein kinase 1 signaling pathway.
DR BioGRID-ORCS; 211550; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Tifa; mouse.
DR PRO; PR:Q793I8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q793I8; protein.
DR Bgee; ENSMUSG00000046688; Expressed in paneth cell and 166 other tissues.
DR ExpressionAtlas; Q793I8; baseline and differential.
DR Genevisible; Q793I8; MM.
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; IDA:MGI.
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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Immunity; Innate immunity; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..184
FT /note="TRAF-interacting protein with FHA domain-containing
FT protein A"
FT /id="PRO_0000320690"
FT DOMAIN 47..103
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT REGION 152..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..175
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96CG3"
FT CONFLICT 90
FT /note="M -> I (in Ref. 2; BAE38653)"
FT /evidence="ECO:0000305"
FT STRAND 13..21
FT /evidence="ECO:0007829|PDB:6L9U"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:6L9U"
FT TURN 28..32
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:6L9U"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:6L9V"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:6L9U"
FT STRAND 132..143
FT /evidence="ECO:0007829|PDB:6L9U"
SQ SEQUENCE 184 AA; 21560 MW; 1466F2A7307F03E2 CRC64;
MSTFEDADTE ETVTCLQMTI YHPGQQSGIF KSIRFCSKEK FPSIEVVKFG RNSNMCQYTF
QDKQVSRIQF VLQPFKQFNS SVLSFEIKNM SKKTSLMVDN QELGYLNKMD LPYKCMLRFG
EYQFLLQKED GESVESFETQ FIMSSRPLLQ ENNWPTQNPI PEDGMYSSYF THRSSPSEMD
ENEL
