TIFA_HUMAN
ID TIFA_HUMAN Reviewed; 184 AA.
AC Q96CG3;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=TRAF-interacting protein with FHA domain-containing protein A {ECO:0000303|PubMed:12566447};
DE AltName: Full=Putative MAPK-activating protein PM14;
DE AltName: Full=Putative NF-kappa-B-activating protein 20 {ECO:0000303|PubMed:12761501};
DE AltName: Full=TRAF2-binding protein {ECO:0000250|UniProtKB:Q793I8};
GN Name=TIFA {ECO:0000303|PubMed:12566447, ECO:0000312|HGNC:HGNC:19075};
GN Synonyms=T2BP {ECO:0000250|UniProtKB:Q793I8};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH TRAF6 AND
RP IRAK1, AND MUTAGENESIS OF GLY-50; SER-66 AND GLU-178.
RC TISSUE=B-cell;
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 TISSUE=Lung;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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 [7]
RP INTERACTION WITH TIFAB.
RX PubMed=15047173; DOI=10.1016/j.bbrc.2004.03.030;
RA Matsumura T., Semba K., Azuma S., Ikawa S., Gohda J., Akiyama T., Inoue J.;
RT "TIFAB inhibits TIFA, TRAF-interacting protein with a forkhead-associated
RT domain.";
RL Biochem. Biophys. Res. Commun. 317:230-234(2004).
RN [8]
RP FUNCTION.
RX PubMed=15492226; DOI=10.1073/pnas.0404132101;
RA Ea C.-K., Sun L., Inoue J., Chen Z.J.;
RT "TIFA activates IkappaB kinase (IKK) by promoting oligomerization and
RT ubiquitination of TRAF6.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15318-15323(2004).
RN [9]
RP INTERACTION WITH ZCCHC11.
RX PubMed=16643855; DOI=10.1016/j.bbrc.2006.04.006;
RA Minoda Y., Saeki K., Aki D., Takaki H., Sanada T., Koga K., Kobayashi T.,
RA Takaesu G., Yoshimura A.;
RT "A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates
RT TLR signaling.";
RL Biochem. Biophys. Res. Commun. 344:1023-1030(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, PHOSPHORYLATION AT THR-9, AND
RP MUTAGENESIS OF THR-9; ARG-51; 88-LYS-ASN-89 AND GLU-178.
RX PubMed=22566686; DOI=10.1128/mcb.00438-12;
RA Huang C.C., Weng J.H., Wei T.Y., Wu P.Y., Hsu P.H., Chen Y.H., Wang S.C.,
RA Qin D., Hung C.C., Chen S.T., Wang A.H., Shyy J.Y., Tsai M.D.;
RT "Intermolecular binding between TIFA-FHA and TIFA-pT mediates tumor
RT necrosis factor alpha stimulation and NF-kappaB activation.";
RL Mol. Cell. Biol. 32:2664-2673(2012).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT THR-9, AND
RP MUTAGENESIS OF THR-9; GLY-50; SER-66 AND GLU-178.
RX PubMed=26068852; DOI=10.1126/science.aaa4921;
RA Gaudet R.G., Sintsova A., Buckwalter C.M., Leung N., Cochrane A., Li J.,
RA Cox A.D., Moffat J., Gray-Owen S.D.;
RT "INNATE IMMUNITY. Cytosolic detection of the bacterial metabolite HBP
RT activates TIFA-dependent innate immunity.";
RL Science 348:1251-1255(2015).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF THR-9.
RX PubMed=28877472; DOI=10.1016/j.celrep.2017.08.039;
RA Zimmermann S., Pfannkuch L., Al-Zeer M.A., Bartfeld S., Koch M., Liu J.,
RA Rechner C., Soerensen M., Sokolova O., Zamyatina A., Kosma P.,
RA Maeurer A.P., Glowinski F., Pleissner K.P., Schmid M., Brinkmann V.,
RA Karlas A., Naumann M., Rother M., Machuy N., Meyer T.F.;
RT "ALPK1- and TIFA-dependent innate immune response triggered by the
RT Helicobacter pylori type IV secretion system.";
RL Cell Rep. 20:2384-2395(2017).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF THR-9; ARG-51; 88-LYS-ASN-89 AND GLU-178.
RX PubMed=28222186; DOI=10.1371/journal.ppat.1006224;
RA Milivojevic M., Dangeard A.S., Kasper C.A., Tschon T., Emmenlauer M.,
RA Pique C., Schnupf P., Guignot J., Arrieumerlou C.;
RT "ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-
RT bisphosphate of gram-negative bacteria.";
RL PLoS Pathog. 13:E1006224-E1006224(2017).
RN [15]
RP FUNCTION, PHOSPHORYLATION AT THR-9, AND MUTAGENESIS OF THR-9.
RX PubMed=30111836; DOI=10.1038/s41586-018-0433-3;
RA Zhou P., She Y., Dong N., Li P., He H., Borio A., Wu Q., Lu S., Ding X.,
RA Cao Y., Xu Y., Gao W., Dong M., Ding J., Wang D.C., Zamyatina A., Shao F.;
RT "Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-
RT heptose.";
RL Nature 561:122-126(2018).
RN [16] {ECO:0007744|PDB:4YM4, ECO:0007744|PDB:4ZGI}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 10-149, SUBUNIT, AND
RP PHOSPHORYLATION AT THR-9.
RX PubMed=26389808; DOI=10.1021/acs.biochem.5b00500;
RA Weng J.H., Hsieh Y.C., Huang C.C., Wei T.Y., Lim L.H., Chen Y.H., Ho M.R.,
RA Wang I., Huang K.F., Chen C.J., Tsai M.D.;
RT "Uncovering the mechanism of forkhead-associated domain-mediated TIFA
RT oligomerization that plays a central role in immune responses.";
RL Biochemistry 54:6219-6229(2015).
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:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472,
CC PubMed:28222186, PubMed:30111836). Promotes activation of an innate
CC immune response by inducing the oligomerization and polyubiquitination
CC of TRAF6, which leads to the activation of TAK1 and IKK through a
CC proteasome-independent mechanism (PubMed:15492226, PubMed:26068852).
CC TIFA-dependent innate immune response is triggered by ADP-D-glycero-
CC beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-
CC negative and some Gram-positive bacteria: ADP-Heptose is recognized by
CC ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA
CC homooligomerization and subsequent activation of pro-inflammatory NF-
CC kappa-B signaling (PubMed:30111836). {ECO:0000269|PubMed:12566447,
CC ECO:0000269|PubMed:15492226, ECO:0000269|PubMed:26068852,
CC ECO:0000269|PubMed:28222186, ECO:0000269|PubMed:28877472,
CC ECO:0000269|PubMed:30111836}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes following phosphorylation at
CC Thr-9 (PubMed:12566447, PubMed:22566686, PubMed:26068852,
CC PubMed:26389808). Interacts with IRAK1, TRAF2 and TRAF6
CC (PubMed:12566447). Interacts with TIFAB; binding to TIFAB inhibits
CC TRAF6 activation, possibly by inducing a conformational change in TIFA
CC (PubMed:15047173). Interacts with ZCCHC11; binding to ZCCHC11
CC suppresses the TRAF6-dependent activation of NF-kappa-B
CC (PubMed:16643855). {ECO:0000269|PubMed:12566447,
CC ECO:0000269|PubMed:15047173, ECO:0000269|PubMed:16643855,
CC ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26068852,
CC ECO:0000269|PubMed:26389808}.
CC -!- INTERACTION:
CC Q96CG3; Q9BXS5: AP1M1; NbExp=7; IntAct=EBI-740711, EBI-541426;
CC Q96CG3; Q8N4T4: ARHGEF39; NbExp=4; IntAct=EBI-740711, EBI-745468;
CC Q96CG3; O14641: DVL2; NbExp=3; IntAct=EBI-740711, EBI-740850;
CC Q96CG3; O60443: GSDME; NbExp=3; IntAct=EBI-740711, EBI-719315;
CC Q96CG3; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-740711, EBI-2556193;
CC Q96CG3; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-740711, EBI-741158;
CC Q96CG3; Q9UBU9: NXF1; NbExp=6; IntAct=EBI-740711, EBI-398874;
CC Q96CG3; P54646: PRKAA2; NbExp=3; IntAct=EBI-740711, EBI-1383852;
CC Q96CG3; P57055: RIPPLY3; NbExp=3; IntAct=EBI-740711, EBI-12092053;
CC Q96CG3; P32969: RPL9P9; NbExp=6; IntAct=EBI-740711, EBI-358122;
CC Q96CG3; O00560: SDCBP; NbExp=8; IntAct=EBI-740711, EBI-727004;
CC Q96CG3; Q9H190: SDCBP2; NbExp=6; IntAct=EBI-740711, EBI-742426;
CC Q96CG3; Q6ZNK6: TIFAB; NbExp=3; IntAct=EBI-740711, EBI-26453465;
CC Q96CG3; O95379: TNFAIP8; NbExp=3; IntAct=EBI-740711, EBI-1049336;
CC Q96CG3; Q12933: TRAF2; NbExp=12; IntAct=EBI-740711, EBI-355744;
CC Q96CG3; Q9Y4K3: TRAF6; NbExp=6; IntAct=EBI-740711, EBI-359276;
CC Q96CG3; Q5TAX3-1: TUT4; NbExp=2; IntAct=EBI-740711, EBI-1606425;
CC Q96CG3; Q99757: TXN2; NbExp=3; IntAct=EBI-740711, EBI-2932492;
CC Q96CG3; P70196: Traf6; Xeno; NbExp=4; IntAct=EBI-740711, EBI-448028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22566686,
CC ECO:0000305|PubMed:26068852}. Note=Colocalizes with lysosomal marker
CC LAMP2 following homooligomerization and subsequent activation.
CC {ECO:0000269|PubMed:26068852}.
CC -!- DOMAIN: The FHA domain recognizes and binds phosphorylated Thr-9,
CC promoting homooligomerization and subsequent activation of NF-kappa-B.
CC {ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26389808}.
CC -!- PTM: Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-
CC D-manno-heptose (ADP-Heptose) by ALPK1 (PubMed:30111836).
CC Phosphorylation at Thr-9 by ALPK1 leads to the formation of an
CC intermolecular binding between the FHA domain and phosphorylated Thr-9,
CC promoting TIFA oligomerization and TIFA-mediated NF-kappa-B activation
CC (PubMed:22566686, PubMed:30111836, PubMed:26389808).
CC {ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26389808,
CC ECO:0000269|PubMed:30111836}.
CC -!- SIMILARITY: Belongs to the TIFA family. {ECO:0000305}.
CC -!- CAUTION: D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) was
CC initially thought to constitute the bacterial pathogen-associated
CC molecular pattern metabolite (PAMP) triggering the ALPK1-TIFA innate
CC immunune response (PubMed:26068852, PubMed:28877472, PubMed:28222186).
CC It was however shown that ADP-D-glycero-beta-D-manno-heptose (ADP-
CC Heptose) constitutes the main PAMP that activates the kinase activity
CC of ALPK1, promoting phosphorylation of TIFA (PubMed:30111836).
CC {ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:28222186,
CC ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836}.
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DR EMBL; AB062110; BAB86902.1; -; mRNA.
DR EMBL; AB097011; BAC77364.1; -; mRNA.
DR EMBL; AB097038; BAC77391.1; -; mRNA.
DR EMBL; AK292900; BAF85589.1; -; mRNA.
DR EMBL; AC109347; AAY40963.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06273.1; -; Genomic_DNA.
DR EMBL; BC014259; AAH14259.1; -; mRNA.
DR CCDS; CCDS34051.1; -.
DR RefSeq; NP_443096.1; NM_052864.2.
DR PDB; 4YM4; X-ray; 3.12 A; A=10-150, B=1-12.
DR PDB; 4ZGI; X-ray; 2.70 A; A=10-149.
DR PDB; 5ZUJ; X-ray; 2.60 A; I=170-184.
DR PDB; 6A33; X-ray; 2.10 A; I=170-184.
DR PDBsum; 4YM4; -.
DR PDBsum; 4ZGI; -.
DR PDBsum; 5ZUJ; -.
DR PDBsum; 6A33; -.
DR AlphaFoldDB; Q96CG3; -.
DR SMR; Q96CG3; -.
DR BioGRID; 124962; 31.
DR DIP; DIP-40185N; -.
DR IntAct; Q96CG3; 27.
DR MINT; Q96CG3; -.
DR STRING; 9606.ENSP00000354911; -.
DR iPTMnet; Q96CG3; -.
DR PhosphoSitePlus; Q96CG3; -.
DR BioMuta; TIFA; -.
DR DMDM; 74751795; -.
DR EPD; Q96CG3; -.
DR jPOST; Q96CG3; -.
DR MassIVE; Q96CG3; -.
DR MaxQB; Q96CG3; -.
DR PaxDb; Q96CG3; -.
DR PeptideAtlas; Q96CG3; -.
DR PRIDE; Q96CG3; -.
DR ProteomicsDB; 76185; -.
DR Antibodypedia; 45213; 117 antibodies from 22 providers.
DR DNASU; 92610; -.
DR Ensembl; ENST00000361717.4; ENSP00000354911.2; ENSG00000145365.11.
DR Ensembl; ENST00000500655.2; ENSP00000424231.1; ENSG00000145365.11.
DR GeneID; 92610; -.
DR KEGG; hsa:92610; -.
DR MANE-Select; ENST00000361717.4; ENSP00000354911.2; NM_052864.3; NP_443096.1.
DR UCSC; uc003ial.4; human.
DR CTD; 92610; -.
DR DisGeNET; 92610; -.
DR GeneCards; TIFA; -.
DR HGNC; HGNC:19075; TIFA.
DR HPA; ENSG00000145365; Low tissue specificity.
DR MIM; 609028; gene.
DR neXtProt; NX_Q96CG3; -.
DR OpenTargets; ENSG00000145365; -.
DR PharmGKB; PA162405777; -.
DR VEuPathDB; HostDB:ENSG00000145365; -.
DR eggNOG; ENOG502S0RF; Eukaryota.
DR GeneTree; ENSGT00940000154589; -.
DR HOGENOM; CLU_125520_0_0_1; -.
DR InParanoid; Q96CG3; -.
DR OMA; SIRFFNR; -.
DR OrthoDB; 1381983at2759; -.
DR PhylomeDB; Q96CG3; -.
DR TreeFam; TF333218; -.
DR PathwayCommons; Q96CG3; -.
DR Reactome; R-HSA-9645460; Alpha-protein kinase 1 signaling pathway.
DR SignaLink; Q96CG3; -.
DR BioGRID-ORCS; 92610; 10 hits in 1077 CRISPR screens.
DR GenomeRNAi; 92610; -.
DR Pharos; Q96CG3; Tbio.
DR PRO; PR:Q96CG3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96CG3; protein.
DR Bgee; ENSG00000145365; Expressed in secondary oocyte and 165 other tissues.
DR Genevisible; Q96CG3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA: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_0000320689"
FT DOMAIN 47..103
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT REGION 165..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphothreonine; by ALPK1"
FT /evidence="ECO:0000269|PubMed:22566686,
FT ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:26389808,
FT ECO:0000269|PubMed:30111836"
FT VARIANT 19
FT /note="T -> M (in dbSNP:rs6834237)"
FT /id="VAR_051422"
FT MUTAGEN 9
FT /note="T->A: Abolishes phosphorylation by ALPK1 and
FT subsequent TIFA-mediated NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:22566686,
FT ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:28222186,
FT ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836"
FT MUTAGEN 50
FT /note="G->E: Loss of homooligomerization and activation of
FT NF-kappa-B and JNK pathways; when associated with A-66."
FT /evidence="ECO:0000269|PubMed:12566447,
FT ECO:0000269|PubMed:26068852"
FT MUTAGEN 51
FT /note="R->A: In RKN: Loss of homooligomerization and
FT activation of NF-kappa-B and JNK pathways; when associated
FT with 88-A-A-89."
FT /evidence="ECO:0000269|PubMed:22566686,
FT ECO:0000269|PubMed:28222186"
FT MUTAGEN 66
FT /note="S->A: Loss of homooligomerization and activation of
FT NF-kappa-B and JNK pathways; when associated with E-50."
FT /evidence="ECO:0000269|PubMed:12566447,
FT ECO:0000269|PubMed:26068852"
FT MUTAGEN 88..89
FT /note="KN->AA: In RKN: Loss of homooligomerization and
FT activation of NF-kappa-B and JNK pathways; when associated
FT with A-51."
FT /evidence="ECO:0000269|PubMed:22566686,
FT ECO:0000269|PubMed:28222186"
FT MUTAGEN 178
FT /note="E->A: Loss of binding to TRAF6 and activation of NF-
FT kappa-B and JNK pathways."
FT /evidence="ECO:0000269|PubMed:12566447,
FT ECO:0000269|PubMed:22566686, ECO:0000269|PubMed:26068852,
FT ECO:0000269|PubMed:28222186"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:4YM4"
FT STRAND 14..21
FT /evidence="ECO:0007829|PDB:4ZGI"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:4ZGI"
FT TURN 30..33
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:4ZGI"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 81..89
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 134..143
FT /evidence="ECO:0007829|PDB:4ZGI"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:6A33"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:6A33"
SQ SEQUENCE 184 AA; 21445 MW; 2E7FE091A52415B0 CRC64;
MTSFEDADTE ETVTCLQMTV YHPGQLQCGI FQSISFNREK LPSSEVVKFG RNSNICHYTF
QDKQVSRVQF SLQLFKKFNS SVLSFEIKNM SKKTNLIVDS RELGYLNKMD LPYRCMVRFG
EYQFLMEKED GESLEFFETQ FILSPRSLLQ ENNWPPHRPI PEYGTYSLCS SQSSSPTEMD
ENES
