ID TCAM1_HUMAN Reviewed; 712 AA.
AC Q8IUC6; B3Y691; O75532; Q86XP8; Q96GA0;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 27-MAR-2024, entry version 177.
DE RecName: Full=TIR domain-containing adapter molecule 1;
DE Short=TICAM-1;
DE AltName: Full=Proline-rich, vinculin and TIR domain-containing protein B;
DE AltName: Full=Putative NF-kappa-B-activating protein 502H;
DE AltName: Full=Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta;
DE Short=MyD88-3;
DE Short=TIR domain-containing adapter protein inducing IFN-beta;
GN Name=TICAM1; Synonyms=PRVTIRB, TRIF;
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, TISSUE SPECIFICITY, DOMAIN, AND
RP INTERACTION WITH IRF3; TLR2 AND TLR3.
RX PubMed=12471095; DOI=10.4049/jimmunol.169.12.6668;
RA Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K.,
RA Akira S.;
RT "A novel Toll/IL-1 receptor domain-containing adapter that preferentially
RT activates the IFN-beta promoter in the Toll-like receptor signaling.";
RL J. Immunol. 169:6668-6672(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH TLR3, SUBUNIT,
RP TISSUE SPECIFICITY, DOMAIN, AND MUTAGENESIS OF PRO-434.
RC TISSUE=Lung;
RX PubMed=12539043; DOI=10.1038/ni886;
RA Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.;
RT "TICAM-1, an adapter molecule that participates in Toll-like receptor 3
RT mediated interferon-beta induction.";
RL Nat. Immunol. 4:161-167(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT "Natural selection in the TLR-related genes in the course of primate
RT evolution.";
RL Immunogenetics 60:727-735(2008).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 137-712.
RA Begum N.A.;
RT "PRVTIRB is a differentially expressed gene.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 297-712.
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH TICAM2.
RX PubMed=12721283; DOI=10.1074/jbc.m303451200;
RA Bin L.-H., Xu L.-G., Shu H.-B.;
RT "TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter
RT protein involved in TIR signaling.";
RL J. Biol. Chem. 278:24526-24532(2003).
RN [9]
RP INTERACTION WITH TRAF6 AND TBK1, PHOSPHORYLATION BY TBK1, MOTIF, AND
RP MUTAGENESIS OF GLU-88; GLU-252 AND GLU-303.
RX PubMed=14530355; DOI=10.4049/jimmunol.171.8.4304;
RA Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K.,
RA Akira S.;
RT "Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF)
RT associates with TNF receptor-associated factor 6 and TANK-binding kinase 1,
RT and activates two distinct transcription factors, NF-kappa B and IFN-
RT regulatory factor-3, in the Toll-like receptor signaling.";
RL J. Immunol. 171:4304-4310(2003).
RN [10]
RP INTERACTION WITH PIAS4.
RX PubMed=15251447; DOI=10.1016/j.febslet.2004.05.081;
RA Zhang J., Xu L.G., Han K.J., Wei X., Shu H.B.;
RT "PIASy represses TRIF-induced ISRE and NF-kappaB activation but not
RT apoptosis.";
RL FEBS Lett. 570:97-101(2004).
RN [11]
RP FUNCTION, INTERACTION WITH IKBKB; IKBKE; IRF3; IRF7; TBK1 AND TRAF6, AND
RP DOMAIN.
RX PubMed=14739303; DOI=10.1074/jbc.m311629200;
RA Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.;
RT "Mechanisms of the TRIF-induced interferon-stimulated response element and
RT NF-kappaB activation and apoptosis pathways.";
RL J. Biol. Chem. 279:15652-15661(2004).
RN [12]
RP INTERACTION WITH TRAF6, AND MUTAGENESIS OF GLU-252 AND GLU-493.
RX PubMed=14982987; DOI=10.1073/pnas.0308496101;
RA Jiang Z., Mak T.W., Sen G., Li X.;
RT "Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at
RT Toll-IL-1 receptor domain-containing adapter inducing IFN-beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:3533-3538(2004).
RN [13]
RP INTERACTION WITH AZI2.
RX PubMed=15611223; DOI=10.4049/jimmunol.174.1.27;
RA Sasai M., Oshiumi H., Matsumoto M., Inoue N., Fujita F., Nakanishi M.,
RA Seya T.;
RT "NF-kappaB-activating kinase-associated protein 1 participates in
RT TLR3/Toll-IL-1 homology domain-containing adapter molecule-1-mediated IFN
RT regulatory factor 3 activation.";
RL J. Immunol. 174:27-30(2005).
RN [14]
RP INTERACTION WITH HCV NS3/4A PROTEASE (MICROBIAL INFECTION), MUTAGENESIS OF
RP CYS-372, AND PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION).
RX PubMed=15710891; DOI=10.1073/pnas.0408824102;
RA Li K., Foy E., Ferreon J.C., Nakamura M., Ferreon A.C., Ikeda M., Ray S.C.,
RA Gale M. Jr., Lemon S.M.;
RT "Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of
RT the Toll-like receptor 3 adaptor protein TRIF.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:2992-2997(2005).
RN [15]
RP INTERACTION WITH SARM1.
RX PubMed=16964262; DOI=10.1038/ni1382;
RA Carty M., Goodbody R., Schroeder M., Stack J., Moynagh P.N., Bowie A.G.;
RT "The human adaptor SARM negatively regulates adaptor protein TRIF-dependent
RT Toll-like receptor signaling.";
RL Nat. Immunol. 7:1074-1081(2006).
RN [16]
RP REVIEW.
RX PubMed=17457343; DOI=10.1038/nri2079;
RA O'Neill L.A., Bowie A.G.;
RT "The family of five: TIR-domain-containing adaptors in Toll-like receptor
RT signalling.";
RL Nat. Rev. Immunol. 7:353-364(2007).
RN [17]
RP FUNCTION, AND INTERACTION WITH TLR5.
RX PubMed=20855887; DOI=10.1074/jbc.m110.158394;
RA Choi Y.J., Im E., Chung H.K., Pothoulakis C., Rhee S.H.;
RT "TRIF mediates Toll-like receptor 5-induced signaling in intestinal
RT epithelial cells.";
RL J. Biol. Chem. 285:37570-37578(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH UBQLN1.
RX PubMed=21695056; DOI=10.1371/journal.pone.0021153;
RA Biswas N., Liu S., Ronni T., Aussenberg S.E., Liu W., Fujita T., Wang T.;
RT "The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif
RT signaling.";
RL PLoS ONE 6:E21153-E21153(2011).
RN [20]
RP CLEAVAGE BY HAV PROTEIN 3CD (MICROBIAL INFECTION), CLEAVAGE SITES, AND
RP MUTAGENESIS OF GLN-190 AND GLN-554.
RX PubMed=21931545; DOI=10.1371/journal.ppat.1002169;
RA Qu L., Feng Z., Yamane D., Liang Y., Lanford R.E., Li K., Lemon S.M.;
RT "Disruption of TLR3 signaling due to cleavage of TRIF by the hepatitis A
RT virus protease-polymerase processing intermediate, 3CD.";
RL PLoS Pathog. 7:E1002169-E1002169(2011).
RN [21]
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), MUTAGENESIS OF GLN-653;
RP GLN-659; GLN-672 AND GLN-702, AND INTERACTION WITH CVB3 PROTEASE 3C.
RX PubMed=21436888; DOI=10.1371/journal.ppat.1001311;
RA Mukherjee A., Morosky S.A., Delorme-Axford E., Dybdahl-Sissoko N.,
RA Oberste M.S., Wang T., Coyne C.B.;
RT "The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host
RT type I interferon and apoptotic signaling.";
RL PLoS Pathog. 7:E1001311-E1001311(2011).
RN [22]
RP INTERACTION WITH TRIM56.
RX PubMed=22948160; DOI=10.1074/jbc.m112.397075;
RA Shen Y., Li N.L., Wang J., Liu B., Lester S., Li K.;
RT "TRIM56 is an essential component of the TLR3 antiviral signaling
RT pathway.";
RL J. Biol. Chem. 287:36404-36413(2012).
RN [23]
RP UBIQUITINATION BY TRIM38, AND MUTAGENESIS OF ASP-281 AND ASP-289.
RX PubMed=23056470; DOI=10.1371/journal.pone.0046825;
RA Xue Q., Zhou Z., Lei X., Liu X., He B., Wang J., Hung T.;
RT "TRIM38 negatively regulates TLR3-mediated IFN-beta signaling by targeting
RT TRIF for degradation.";
RL PLoS ONE 7:E46825-E46825(2012).
RN [24]
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION).
RX PubMed=24672048; DOI=10.1128/jvi.03138-13;
RA Xiang Z., Li L., Lei X., Zhou H., Zhou Z., He B., Wang J.;
RT "Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses
RT mediated by Toll-like receptor 3.";
RL J. Virol. 88:6650-6659(2014).
RN [25]
RP INTERACTION WITH TLR3; TICAM2; RIPK1; TRAF6 AND TBK1.
RX PubMed=25736436; DOI=10.15252/embr.201439637;
RA Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B.,
RA Liu Y.;
RT "WDFY1 mediates TLR3/4 signaling by recruiting TRIF.";
RL EMBO Rep. 16:447-455(2015).
RN [26]
RP FUNCTION, DOMAIN, INTERACTION WITH IRF3, PHOSPHORYLATION AT SER-210, AND
RP MUTAGENESIS OF 210-SER--THR-214.
RX PubMed=25636800; DOI=10.1126/science.aaa2630;
RA Liu S., Cai X., Wu J., Cong Q., Chen X., Li T., Du F., Ren J., Wu Y.T.,
RA Grishin N.V., Chen Z.J.;
RT "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF
RT induces IRF3 activation.";
RL Science 347:AAA2630-AAA2630(2015).
RN [27]
RP INTERACTION WITH SENECA VALLEY VIRUS PROTEASE 3C (MICROBIAL INFECTION),
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), AND MUTAGENESIS OF GLN-159 AND
RP GLN-190.
RX PubMed=28566380; DOI=10.1128/jvi.00823-17;
RA Qian S., Fan W., Liu T., Wu M., Zhang H., Cui X., Zhou Y., Hu J., Wei S.,
RA Chen H., Li X., Qian P.;
RT "Seneca Valley virus suppresses host type I interferon production by
RT targeting adaptor proteins MAVS, TRIF, and TANK for cleavage.";
RL J. Virol. 91:0-0(2017).
RN [28]
RP INTERACTION WITH TAX1BP1 AND TRIM32.
RX PubMed=28898289; DOI=10.1371/journal.ppat.1006600;
RA Yang Q., Liu T.T., Lin H., Zhang M., Wei J., Luo W.W., Hu Y.H., Zhong B.,
RA Hu M.M., Shu H.B.;
RT "TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF
RT negatively regulates TLR3/4-mediated innate immune responses.";
RL PLoS Pathog. 13:e1006600-e1006600(2017).
RN [29]
RP FUNCTION, INTERACTION WITH TRIM8, AND UBIQUITINATION BY TRIM8.
RX PubMed=28747347; DOI=10.4049/jimmunol.1601647;
RA Ye W., Hu M.M., Lei C.Q., Zhou Q., Lin H., Sun M.S., Shu H.B.;
RT "TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by
RT Blocking TRIF-TBK1 Interaction.";
RL J. Immunol. 199:1856-1864(2017).
RN [30]
RP INTERACTION WITH TLR4.
RX PubMed=36232715; DOI=10.3390/ijms231911414;
RA Youn S.E., Jiang F., Won H.Y., Hong D.E., Kang T.H., Park Y.Y., Koh S.S.;
RT "PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via
RT the TLR4/MyD88/NF-kappaB Signaling Pathway.";
RL Int. J. Mol. Sci. 23:0-0(2022).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 1-153, AND TRIF-NTD REGION.
RX PubMed=24311583; DOI=10.1107/s0907444913022385;
RA Ullah M.O., Ve T., Mangan M., Alaidarous M., Sweet M.J., Mansell A.,
RA Kobe B.;
RT "The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain
RT with structural similarity to IFIT proteins.";
RL Acta Crystallogr. D 69:2420-2430(2013).
RN [32] {ECO:0007744|PDB:5JEL}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 199-219 IN COMPLEX WITH IRF3,
RP INTERACTION WITH IRF3, PHOSPHORYLATION AT SER-210, AND MUTAGENESIS OF
RP SER-202 AND SER-210.
RX PubMed=27302953; DOI=10.1073/pnas.1603269113;
RA Zhao B., Shu C., Gao X., Sankaran B., Du F., Shelton C.L., Herr A.B.,
RA Ji J.Y., Li P.;
RT "Structural basis for concerted recruitment and activation of IRF-3 by
RT innate immune adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E3403-E3412(2016).
RN [33]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-46.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [34]
RP VARIANT IIAE6 LEU-186.
RX PubMed=22105173; DOI=10.1172/jci59259;
RA Sancho-Shimizu V., Perez de Diego R., Lorenzo L., Halwani R., Alangari A.,
RA Israelsson E., Fabrega S., Cardon A., Maluenda J., Tatematsu M.,
RA Mahvelati F., Herman M., Ciancanelli M., Guo Y., AlSum Z., Alkhamis N.,
RA Al-Makadma A.S., Ghadiri A., Boucherit S., Plancoulaine S., Picard C.,
RA Rozenberg F., Tardieu M., Lebon P., Jouanguy E., Rezaei N., Seya T.,
RA Matsumoto M., Chaussabel D., Puel A., Zhang S.Y., Abel L., Al-Muhsen S.,
RA Casanova J.L.;
RT "Herpes simplex encephalitis in children with autosomal recessive and
RT dominant TRIF deficiency.";
RL J. Clin. Invest. 121:4889-4902(2011).
RN [35]
RP VARIANTS ILE-4; CYS-60; GLN-71; MET-80; THR-111; ARG-141 DEL; MET-157;
RP LEU-186; LEU-302; ILE-377; PRO-386; LYS-392; ASN-465; ASN-557; LEU-595;
RP TRP-598 AND ARG-702, AND CHARACTERIZATION OF VARIANTS ILE-4; CYS-60;
RP GLN-71; MET-80; THR-111; ARG-141 DEL; MET-157; LEU-186; LEU-302; ILE-377;
RP PRO-386; LYS-392; ASN-465; ASN-557; LEU-595; TRP-598 AND ARG-702.
RX PubMed=32972995; DOI=10.1126/science.abd4570;
RG COVID-STORM Clinicians;
RG COVID Clinicians;
RG Imagine COVID Group;
RG French COVID Cohort Study Group;
RG CoV-Contact Cohort;
RG Amsterdam UMC Covid-19 Biobank;
RG COVID Human Genetic Effort;
RG NIAID-USUHS/TAGC COVID Immunity Group;
RA Zhang Q., Bastard P., Liu Z., Le Pen J., Moncada-Velez M., Chen J.,
RA Ogishi M., Sabli I.K.D., Hodeib S., Korol C., Rosain J., Bilguvar K.,
RA Ye J., Bolze A., Bigio B., Yang R., Arias A.A., Zhou Q., Zhang Y.,
RA Onodi F., Korniotis S., Karpf L., Philippot Q., Chbihi M., Bonnet-Madin L.,
RA Dorgham K., Smith N., Schneider W.M., Razooky B.S., Hoffmann H.H.,
RA Michailidis E., Moens L., Han J.E., Lorenzo L., Bizien L., Meade P.,
RA Neehus A.L., Ugurbil A.C., Corneau A., Kerner G., Zhang P., Rapaport F.,
RA Seeleuthner Y., Manry J., Masson C., Schmitt Y., Schlueter A., Le Voyer T.,
RA Khan T., Li J., Fellay J., Roussel L., Shahrooei M., Alosaimi M.F.,
RA Mansouri D., Al-Saud H., Al-Mulla F., Almourfi F., Al-Muhsen S.Z.,
RA Alsohime F., Al Turki S., Hasanato R., van de Beek D., Biondi A.,
RA Bettini L.R., D'Angio' M., Bonfanti P., Imberti L., Sottini A., Paghera S.,
RA Quiros-Roldan E., Rossi C., Oler A.J., Tompkins M.F., Alba C.,
RA Vandernoot I., Goffard J.C., Smits G., Migeotte I., Haerynck F.,
RA Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P.E., Keles S.,
RA Coelkesen F., Ozcelik T., Yasar K.K., Senoglu S., Karabela S.N.,
RA Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y.,
RA Duval X., Laouenan C., Snow A.L., Dalgard C.L., Milner J.D., Vinh D.C.,
RA Mogensen T.H., Marr N., Spaan A.N., Boisson B., Boisson-Dupuis S.,
RA Bustamante J., Puel A., Ciancanelli M.J., Meyts I., Maniatis T.,
RA Soumelis V., Amara A., Nussenzweig M., Garcia-Sastre A., Krammer F.,
RA Pujol A., Duffy D., Lifton R.P., Zhang S.Y., Gorochov G., Beziat V.,
RA Jouanguy E., Sancho-Shimizu V., Rice C.M., Abel L., Notarangelo L.D.,
RA Cobat A., Su H.C., Casanova J.L.;
RT "Inborn errors of type I IFN immunity in patients with life-threatening
RT COVID-19.";
RL Science 370:0-0(2020).
CC -!- FUNCTION: Involved in innate immunity against invading pathogens.
CC Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-
CC kappa-B and interferon-regulatory factor (IRF) activation, and to
CC induce apoptosis (PubMed:12471095, PubMed:12539043, PubMed:14739303,
CC PubMed:28747347). Ligand binding to these receptors results in TRIF
CC recruitment through its TIR domain (PubMed:12471095, PubMed:12539043,
CC PubMed:14739303). Distinct protein-interaction motifs allow recruitment
CC of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to
CC the activation of transcription factors IRF3 and IRF7, NF-kappa-B and
CC FADD respectively (PubMed:12471095, PubMed:12539043, PubMed:14739303).
CC Phosphorylation by TBK1 on the pLxIS motif leads to recruitment and
CC subsequent activation of the transcription factor IRF3 to induce
CC expression of type I interferon and exert a potent immunity against
CC invading pathogens (PubMed:25636800). Component of a multi-helicase-
CC TICAM1 complex that acts as a cytoplasmic sensor of viral double-
CC stranded RNA (dsRNA) and plays a role in the activation of a cascade of
CC antiviral responses including the induction of pro-inflammatory
CC cytokines (By similarity). {ECO:0000250|UniProtKB:Q80UF7,
CC ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043,
CC ECO:0000269|PubMed:14739303, ECO:0000269|PubMed:25636800}.
CC -!- SUBUNIT: Homodimer (PubMed:12539043). Found in a multi-helicase-TICAM1
CC complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this
CC complex exists in resting cells with or without poly(I:C) RNA ligand
CC stimulation. Interacts (via TIR domain) with DDX21 (via C-terminus).
CC Interacts (via TIR domain) with DHX36 (via C-terminus) (By similarity).
CC Interacts with AZI2 and IRF7 (PubMed:12471095, PubMed:15611223).
CC Interacts with TICAM2 in TLR4 recruitment (PubMed:12721283,
CC PubMed:25736436). Interaction with PIAS4 inhibits the TICAM1-induced
CC NF-kappa-B, IRF and IFNB1 activation (PubMed:15251447). Interacts with
CC IKBKB and IKBKE. Interaction with SARM1 blocks TICAM1-dependent
CC transcription factor activation (PubMed:16964262). Interacts with TRAF3
CC (By similarity). Interacts (when phosphorylated) with IRF3; following
CC activation and phosphorylation on the pLxIS motif by TBK1, recruits
CC IRF3 (PubMed:12471095, PubMed:14739303, PubMed:25636800,
CC PubMed:27302953). Interacts with TBK1, TRAF6 and RIPK1 and these
CC interactions are enhanced in the presence of WDFY1 (PubMed:14982987,
CC PubMed:25736436). Interacts with TRAFD1 (By similarity). Interacts with
CC UBQLN1 (via UBA domain) (PubMed:21695056). Interacts with TLR4
CC (PubMed:36232715). Interacts with WDFY1 in response to poly(I:C) (By
CC similarity). Interacts (via the TIR domain) with TLR3 in response to
CC poly(I:C) and this interaction is enhanced in the presence of WDFY1
CC (PubMed:25736436). Interacts with TRIM56 (PubMed:22948160). Component
CC of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of
CC viral double-stranded RNA (dsRNA) and plays a role in the activation of
CC a cascade of antiviral responses including the induction of pro-
CC inflammatory cytokines (By similarity). Interacts (via the TIR domain)
CC with TLR5 (PubMed:20855887). Interacts with TRIM8 (PubMed:28747347).
CC Interacts with TAX1BP1 and TRIM32; these interactions target TICAM1 to
CC TAX1BP1-mediated selective autophagic degradation (PubMed:28898289).
CC {ECO:0000250|UniProtKB:Q80UF7, ECO:0000269|PubMed:12471095,
CC ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:12721283,
CC ECO:0000269|PubMed:14739303, ECO:0000269|PubMed:14982987,
CC ECO:0000269|PubMed:15251447, ECO:0000269|PubMed:15611223,
CC ECO:0000269|PubMed:16964262, ECO:0000269|PubMed:20855887,
CC ECO:0000269|PubMed:21695056, ECO:0000269|PubMed:22948160,
CC ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:25736436,
CC ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:28898289,
CC ECO:0000269|PubMed:36232715}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus (HCV)
CC NS3/4A protease; this interaction leads to TICAM1 cleavage, thereby
CC disrupting TLR3 signaling and preventing the establishment of an
CC antiviral state. {ECO:0000269|PubMed:15710891}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Seneca Valley virus
CC protease 3C; this interaction allows the cleavage of TICAM1/TRIF and
CC subsequent suppression of host innate immunity.
CC {ECO:0000269|PubMed:28566380}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with
CC coxsackievirus B3 (CVB3) protease 3C. {ECO:0000269|PubMed:21436888}.
CC -!- INTERACTION:
CC Q8IUC6; Q9UHD2: TBK1; NbExp=3; IntAct=EBI-525995, EBI-356402;
CC Q8IUC6; Q9BRZ2: TRIM56; NbExp=2; IntAct=EBI-525995, EBI-1048636;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:21695056}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q80UF7}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q80UF7}. Note=Colocalizes with UBQLN1 in the
CC autophagosome (PubMed:21695056). Colocalizes in the cytosol with DDX1,
CC DDX21 and DHX36. Colocalizes in the mitochondria with DDX1 and
CC poly(I:C) RNA ligand. The multi-helicase-TICAM1 complex may translocate
CC to the mitochondria upon poly(I:C) RNA ligand stimulation (By
CC similarity). {ECO:0000250|UniProtKB:Q80UF7,
CC ECO:0000269|PubMed:21695056}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed but with higher levels in
CC liver. {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043}.
CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following
CC phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1
CC recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and
CC activated by TBK1 to induce type-I interferons and other cytokines
CC (PubMed:25636800). {ECO:0000269|PubMed:25636800}.
CC -!- DOMAIN: The N-terminal region is essential for activation of the IFNB
CC promoter activity. {ECO:0000269|PubMed:12471095,
CC ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:14739303}.
CC -!- DOMAIN: The N-terminal domain (TRIF-NTD) is globular and consists of
CC two alpha-helical subdomains connected by a 14-residue linker. It
CC shares structural similarity with IFIT family members N-terminal
CC regions. {ECO:0000269|PubMed:24311583}.
CC -!- PTM: Phosphorylated by TBK1 (PubMed:14530355, PubMed:25636800).
CC Following activation, phosphorylated by TBK1 at Ser-210 in the pLxIS
CC motif (PubMed:25636800). The phosphorylated pLxIS motif constitutes an
CC IRF3-binding motif, leading to recruitment of the transcription factor
CC IRF3 to induce type-I interferons and other cytokines (PubMed:25636800,
CC PubMed:27302953). {ECO:0000269|PubMed:14530355,
CC ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953}.
CC -!- PTM: Polyubiquitinated at Lys-229 by TRIM38 with 'Lys-48'-linked
CC chains, leading to proteasomal degradation (PubMed:23056470).
CC Polyubiquitinated with 'Lys-6'- and 'Lys-33'-linked chains in a TRIM8-
CC dependent manner; ubiquitination disrupts the interaction with TBK1 and
CC subsequent interferon production (PubMed:28747347).
CC {ECO:0000269|PubMed:23056470, ECO:0000269|PubMed:28747347}.
CC -!- PTM: (Microbial infection) Cleaved and degraded by hepatitis A virus
CC (HAV) protein 3CD allowing the virus to disrupt host TLR3 signaling.
CC {ECO:0000269|PubMed:21931545}.
CC -!- PTM: (Microbial infection) Cleaved by CVB3 protease 3C allowing the
CC virus to disrupt host TLR3 signaling. {ECO:0000269|PubMed:21436888}.
CC -!- PTM: (Microbial infection) Cleaved by Seneca Valley virus protease 3C
CC allowing the virus to disrupt host TLR3 signaling.
CC {ECO:0000269|PubMed:28566380}.
CC -!- PTM: (Microbial infection) Cleaved by protease 3C of human enterovirus
CC D68 (EV68) allowing the virus to disrupt host TLR3 signaling.
CC {ECO:0000269|PubMed:24672048}.
CC -!- PTM: (Microbial infection) Cleaved by HCV protease NS3/4A, thereby
CC disrupting TLR3 signaling and preventing the establishment of an
CC antiviral state. {ECO:0000269|PubMed:15710891}.
CC -!- DISEASE: Encephalopathy, acute, infection-induced, 6, herpes-specific
CC (IIAE6) [MIM:614850]: A rare complication of human herpesvirus 1 (HHV-
CC 1) infection, occurring in only a small minority of HHV-1 infected
CC individuals. It is characterized by hemorrhagic necrosis of parts of
CC the temporal and frontal lobes. Onset is over several days and involves
CC fever, headache, seizures, stupor, and often coma, frequently with a
CC fatal outcome. {ECO:0000269|PubMed:22105173}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO85488.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB093555; BAC44839.1; -; mRNA.
DR EMBL; AB086380; BAC55579.1; -; mRNA.
DR EMBL; AB446484; BAG55261.1; -; mRNA.
DR EMBL; AB097023; BAC77376.1; -; mRNA.
DR EMBL; BC009860; AAH09860.2; -; mRNA.
DR EMBL; BC136556; AAI36557.1; -; mRNA.
DR EMBL; BC136557; AAI36558.1; -; mRNA.
DR EMBL; AF492646; AAO85488.1; ALT_FRAME; mRNA.
DR EMBL; AF070530; AAC28630.1; -; mRNA.
DR CCDS; CCDS12136.1; -.
DR RefSeq; NP_891549.1; NM_182919.3.
DR PDB; 2M1X; NMR; -; A=387-545.
DR PDB; 2M63; NMR; -; A=1-156.
DR PDB; 3RC4; X-ray; 1.50 A; B=360-372.
DR PDB; 4BSX; X-ray; 2.23 A; A/B/C/D=1-153.
DR PDB; 4C0M; X-ray; 2.80 A; A/B/C/D=1-153.
DR PDB; 5JEL; X-ray; 1.60 A; B=199-217.
DR PDBsum; 2M1X; -.
DR PDBsum; 2M63; -.
DR PDBsum; 3RC4; -.
DR PDBsum; 4BSX; -.
DR PDBsum; 4C0M; -.
DR PDBsum; 5JEL; -.
DR AlphaFoldDB; Q8IUC6; -.
DR BMRB; Q8IUC6; -.
DR SMR; Q8IUC6; -.
DR BioGRID; 127114; 50.
DR CORUM; Q8IUC6; -.
DR DIP; DIP-33490N; -.
DR IntAct; Q8IUC6; 13.
DR MINT; Q8IUC6; -.
DR STRING; 9606.ENSP00000248244; -.
DR iPTMnet; Q8IUC6; -.
DR PhosphoSitePlus; Q8IUC6; -.
DR BioMuta; TICAM1; -.
DR DMDM; 74727957; -.
DR EPD; Q8IUC6; -.
DR jPOST; Q8IUC6; -.
DR MassIVE; Q8IUC6; -.
DR MaxQB; Q8IUC6; -.
DR PaxDb; 9606-ENSP00000248244; -.
DR PeptideAtlas; Q8IUC6; -.
DR ProteomicsDB; 70544; -.
DR Pumba; Q8IUC6; -.
DR Antibodypedia; 11536; 411 antibodies from 42 providers.
DR DNASU; 148022; -.
DR Ensembl; ENST00000248244.6; ENSP00000248244.4; ENSG00000127666.11.
DR GeneID; 148022; -.
DR KEGG; hsa:148022; -.
DR MANE-Select; ENST00000248244.6; ENSP00000248244.4; NM_182919.4; NP_891549.1.
DR UCSC; uc002mbi.5; human.
DR AGR; HGNC:18348; -.
DR CTD; 148022; -.
DR DisGeNET; 148022; -.
DR GeneCards; TICAM1; -.
DR HGNC; HGNC:18348; TICAM1.
DR HPA; ENSG00000127666; Tissue enhanced (esophagus).
DR MalaCards; TICAM1; -.
DR MIM; 607601; gene.
DR MIM; 614850; phenotype.
DR neXtProt; NX_Q8IUC6; -.
DR OpenTargets; ENSG00000127666; -.
DR Orphanet; 1930; Herpes simplex virus encephalitis.
DR PharmGKB; PA142670812; -.
DR VEuPathDB; HostDB:ENSG00000127666; -.
DR eggNOG; ENOG502RXF3; Eukaryota.
DR GeneTree; ENSGT00940000162411; -.
DR HOGENOM; CLU_022539_0_0_1; -.
DR InParanoid; Q8IUC6; -.
DR OMA; TRHGWQD; -.
DR OrthoDB; 4640439at2759; -.
DR PhylomeDB; Q8IUC6; -.
DR TreeFam; TF336953; -.
DR PathwayCommons; Q8IUC6; -.
DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-HSA-166166; MyD88-independent TLR4 cascade.
DR Reactome; R-HSA-168164; Toll Like Receptor 3 (TLR3) Cascade.
DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-HSA-2562578; TRIF-mediated programmed cell death.
DR Reactome; R-HSA-5602566; TICAM1 deficiency - HSE.
DR Reactome; R-HSA-5602571; TRAF3 deficiency - HSE.
DR Reactome; R-HSA-9013957; TLR3-mediated TICAM1-dependent programmed cell death.
DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7.
DR Reactome; R-HSA-9014325; TICAM1,TRAF6-dependent induction of TAK1 complex.
DR Reactome; R-HSA-936964; Activation of IRF3, IRF7 mediated by TBK1, IKBKE.
DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-HSA-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-HSA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR SignaLink; Q8IUC6; -.
DR SIGNOR; Q8IUC6; -.
DR BioGRID-ORCS; 148022; 16 hits in 1159 CRISPR screens.
DR ChiTaRS; TICAM1; human.
DR EvolutionaryTrace; Q8IUC6; -.
DR GenomeRNAi; 148022; -.
DR Pharos; Q8IUC6; Tbio.
DR PRO; PR:Q8IUC6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IUC6; Protein.
DR Bgee; ENSG00000127666; Expressed in lower esophagus mucosa and 152 other cell types or tissues.
DR ExpressionAtlas; Q8IUC6; baseline and differential.
DR Genevisible; Q8IUC6; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IDA:UniProt.
DR GO; GO:0005768; C:endosome; IDA:UniProt.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProt.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; IEA:Ensembl.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ParkinsonsUK-UCL.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISS:ARUK-UCL.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IBA:GO_Central.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProt.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IDA:UniProt.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProt.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IDA:UniProt.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IMP:CACAO.
DR Gene3D; 1.25.40.780; -; 1.
DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR InterPro; IPR025735; RHIM_dom.
DR InterPro; IPR046946; TCAM1/2.
DR InterPro; IPR017278; TICAM1.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR InterPro; IPR040886; TRIF_N.
DR PANTHER; PTHR47230; TIR DOMAIN-CONTAINING ADAPTER MOLECULE 1; 1.
DR PANTHER; PTHR47230:SF1; TIR DOMAIN-CONTAINING ADAPTER MOLECULE 1; 1.
DR Pfam; PF12721; RHIM; 1.
DR Pfam; PF17798; TRIF-NTD; 1.
DR PIRSF; PIRSF037744; TIR_Ticam; 1.
DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Apoptosis; Cytoplasm; Cytoplasmic vesicle;
KW Disease variant; Host-virus interaction; Immunity; Inflammatory response;
KW Innate immunity; Isopeptide bond; Mitochondrion; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..712
FT /note="TIR domain-containing adapter molecule 1"
FT /id="PRO_0000317663"
FT DOMAIN 393..553
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 1..153
FT /note="TRIF-NTD"
FT /evidence="ECO:0000269|PubMed:24311583"
FT REGION 216..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 512..712
FT /note="Sufficient to induce apoptosis"
FT REGION 620..677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 84..91
FT /note="TRAF6-binding"
FT MOTIF 207..210
FT /note="pLxIS motif"
FT /evidence="ECO:0000269|PubMed:25636800"
FT MOTIF 248..255
FT /note="TRAF6-binding"
FT MOTIF 299..309
FT /note="TRAF6-binding"
FT COMPBIAS 261..278
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..372
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..675
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 148
FT /note="(Microbial infection) Cleavage by CV3B"
FT /evidence="ECO:0000269|PubMed:21436888"
FT SITE 159..160
FT /note="(Microbial infection) Cleavage; by viral Seneca
FT Valley virus protease 3C"
FT /evidence="ECO:0000269|PubMed:28566380"
FT SITE 190
FT /note="(Microbial infection) Cleavage; by viral HAV 3CD"
FT /evidence="ECO:0000269|PubMed:21931545"
FT SITE 312..313
FT /note="(Microbial infection) Cleavage; by viral EV68
FT protease C"
FT /evidence="ECO:0000269|PubMed:24672048"
FT SITE 372..373
FT /note="(Microbial infection) Cleavage; by viral HCV NS3/4A"
FT /evidence="ECO:0000269|PubMed:15710891"
FT SITE 554
FT /note="(Microbial infection) Cleavage; by viral HAV 3CD"
FT /evidence="ECO:0000269|PubMed:21931545"
FT SITE 653..654
FT /note="(Microbial infection) Cleavage; by viral EV68
FT protease C"
FT /evidence="ECO:0000269|PubMed:24672048"
FT MOD_RES 210
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000269|PubMed:25636800,
FT ECO:0000269|PubMed:27302953"
FT CROSSLNK 229
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q80UF7"
FT VARIANT 4
FT /note="T -> I (inhibition of IFNB induction;
FT dbSNP:rs114566317)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084053"
FT VARIANT 46
FT /note="M -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_038789"
FT VARIANT 60
FT /note="S -> C (inhibition of IFNB induction;
FT dbSNP:rs201782115)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084054"
FT VARIANT 71
FT /note="R -> Q (no effect on IFNB induction;
FT dbSNP:rs372818181)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084055"
FT VARIANT 75
FT /note="R -> C (in dbSNP:rs11466719)"
FT /id="VAR_051416"
FT VARIANT 80
FT /note="V -> M (no effect on IFNB induction;
FT dbSNP:rs199816697)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084056"
FT VARIANT 111
FT /note="A -> T (no effect on IFNB induction;
FT dbSNP:rs201291933)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084057"
FT VARIANT 141
FT /note="Missing (inhibition of IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084058"
FT VARIANT 157
FT /note="T -> M (no effect on IFNB induction;
FT dbSNP:rs770166865)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084059"
FT VARIANT 186
FT /note="S -> L (in IIAE6; no effect on IFNB induction;
FT dbSNP:rs146550489)"
FT /evidence="ECO:0000269|PubMed:22105173,
FT ECO:0000269|PubMed:32972995"
FT /id="VAR_069082"
FT VARIANT 275
FT /note="L -> V (in dbSNP:rs11466721)"
FT /id="VAR_051417"
FT VARIANT 302
FT /note="V -> L (no effect on IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084060"
FT VARIANT 377
FT /note="T -> I (no effect on IFNB induction;
FT dbSNP:rs147816959)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084061"
FT VARIANT 386
FT /note="L -> P (no effect on IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084062"
FT VARIANT 392
FT /note="Q -> K (inhibition of IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084063"
FT VARIANT 465
FT /note="S -> N (no effect on IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084064"
FT VARIANT 557
FT /note="D -> N (no effect on IFNB induction;
FT dbSNP:rs143066432)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084065"
FT VARIANT 595
FT /note="M -> L (no effect on IFNB induction;
FT dbSNP:rs561021962)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084066"
FT VARIANT 598
FT /note="G -> W (no effect on IFNB induction;
FT dbSNP:rs150224968)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084067"
FT VARIANT 666
FT /note="A -> T (in dbSNP:rs11466724)"
FT /id="VAR_051418"
FT VARIANT 702
FT /note="Q -> R (no effect on IFNB induction)"
FT /evidence="ECO:0000269|PubMed:32972995"
FT /id="VAR_084068"
FT MUTAGEN 88
FT /note="E->A: Reduces binding to TRAF6 and activation of
FT NFKB signaling pathway; when associated with A-252 and A-
FT 303."
FT /evidence="ECO:0000269|PubMed:14530355"
FT MUTAGEN 159
FT /note="Q->A: Complete loss of cleavage by Seneca Valley
FT virus protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 190
FT /note="Q->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 190
FT /note="Q->R: No cleavage by HAV 3CD."
FT /evidence="ECO:0000269|PubMed:21931545"
FT MUTAGEN 202
FT /note="S->A: Decreased interaction with IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 210..214
FT /note="SQSPT->AQAPA: Abolished ability to activate IRF3."
FT /evidence="ECO:0000269|PubMed:25636800"
FT MUTAGEN 210
FT /note="S->A: Abolished interaction with IRF3."
FT /evidence="ECO:0000269|PubMed:27302953"
FT MUTAGEN 252
FT /note="E->A: Loss of TCAM1-induced NF-kappa-B activation.
FT Reduces interaction with TRAF6 and activation of NF-kappa-B
FT signaling pathway; when associated with A-88 and A-303."
FT /evidence="ECO:0000269|PubMed:14530355,
FT ECO:0000269|PubMed:14982987"
FT MUTAGEN 281
FT /note="D->E: Resistant to caspase cleavage, no effect on
FT TRIM38-mediated degradation; when associated with E-289."
FT /evidence="ECO:0000269|PubMed:23056470"
FT MUTAGEN 289
FT /note="D->E: Resistant to caspase cleavage, no effect on
FT TRIM38-mediated degradation; when associated with E-281."
FT /evidence="ECO:0000269|PubMed:23056470"
FT MUTAGEN 303
FT /note="E->A: Reduces binding to TRAF6 and activation of
FT NFKB signaling pathway; when associated with A-88 and A-
FT 252."
FT /evidence="ECO:0000269|PubMed:14530355"
FT MUTAGEN 372
FT /note="C->R: Complete loss of cleavage by HCV NS3/4A
FT protease."
FT /evidence="ECO:0000269|PubMed:15710891"
FT MUTAGEN 434
FT /note="P->H: Abolishes interaction with TLR3."
FT /evidence="ECO:0000269|PubMed:12539043"
FT MUTAGEN 493
FT /note="E->A: Loss of TCAM1-induced NF-kappa-B and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:14982987"
FT MUTAGEN 554
FT /note="Q->R: No cleavage by HAV 3CD."
FT /evidence="ECO:0000269|PubMed:21931545"
FT MUTAGEN 653
FT /note="Q->A: Complete loss of cleavage by CV3B; when
FT associated with A-659; A-671 and A-702."
FT /evidence="ECO:0000269|PubMed:21436888"
FT MUTAGEN 659
FT /note="Q->A: Complete loss of cleavage by CV3B; when
FT associated with A-653; A-671 and A-702."
FT /evidence="ECO:0000269|PubMed:21436888"
FT MUTAGEN 672
FT /note="Q->A: Complete loss of cleavage by CV3B; when
FT associated with A-653; A-659 and A-702."
FT /evidence="ECO:0000269|PubMed:21436888"
FT MUTAGEN 702
FT /note="Q->A: Complete loss of cleavage by CV3B; when
FT associated with A-653; A-659 and A-671."
FT /evidence="ECO:0000269|PubMed:21436888"
FT CONFLICT 147
FT /note="D -> T (in Ref. 6; AAO85488)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="G -> W (in Ref. 6; AAO85488)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="L -> S (in Ref. 6; AAO85488)"
FT /evidence="ECO:0000305"
FT CONFLICT 633..659
FT /note="Missing (in Ref. 6; AAO85488)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="S -> P (in Ref. 6; AAO85488)"
FT /evidence="ECO:0000305"
FT HELIX 8..16
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 20..30
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 40..50
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 54..62
FT /evidence="ECO:0007829|PDB:4BSX"
FT TURN 63..66
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 68..76
FT /evidence="ECO:0007829|PDB:4BSX"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 93..105
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 111..127
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 133..144
FT /evidence="ECO:0007829|PDB:4BSX"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:5JEL"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:3RC4"
FT HELIX 406..417
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 444..447
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 448..455
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 462..475
FT /evidence="ECO:0007829|PDB:2M1X"
FT TURN 477..480
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 486..490
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 503..506
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:2M1X"
FT STRAND 513..516
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 520..527
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 530..535
FT /evidence="ECO:0007829|PDB:2M1X"
FT TURN 536..540
FT /evidence="ECO:0007829|PDB:2M1X"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:2M1X"
SQ SEQUENCE 712 AA; 76422 MW; 5D071E3BE9240D9A CRC64;
MACTGPSLPS AFDILGAAGQ DKLLYLKHKL KTPRPGCQGQ DLLHAMVLLK LGQETEARIS
LEALKADAVA RLVARQWAGV DSTEDPEEPP DVSWAVARLY HLLAEEKLCP ASLRDVAYQE
AVRTLSSRDD HRLGELQDEA RNRCGWDIAG DPGSIRTLQS NLGCLPPSSA LPSGTRSLPR
PIDGVSDWSQ GCSLRSTGSP ASLASNLEIS QSPTMPFLSL HRSPHGPSKL CDDPQASLVP
EPVPGGCQEP EEMSWPPSGE IASPPELPSS PPPGLPEVAP DATSTGLPDT PAAPETSTNY
PVECTEGSAG PQSLPLPILE PVKNPCSVKD QTPLQLSVED TTSPNTKPCP PTPTTPETSP
PPPPPPPSST PCSAHLTPSS LFPSSLESSS EQKFYNFVIL HARADEHIAL RVREKLEALG
VPDGATFCED FQVPGRGELS CLQDAIDHSA FIILLLTSNF DCRLSLHQVN QAMMSNLTRQ
GSPDCVIPFL PLESSPAQLS SDTASLLSGL VRLDEHSQIF ARKVANTFKP HRLQARKAMW
RKEQDTRALR EQSQHLDGER MQAAALNAAY SAYLQSYLSY QAQMEQLQVA FGSHMSFGTG
APYGARMPFG GQVPLGAPPP FPTWPGCPQP PPLHAWQAGT PPPPSPQPAA FPQSLPFPQS
PAFPTASPAP PQSPGLQPLI IHHAQMVQLG LNNHMWNQRG SQAPEDKTQE AE
//