Entry euk:TCAM2_HUMAN

ID   TCAM2_HUMAN             Reviewed;         235 AA.
AC   Q86XR7; B3Y698; Q6JUT2;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   15-MAR-2017, entry version 143.
DE   RecName: Full=TIR domain-containing adapter molecule 2;
DE            Short=TICAM-2;
DE   AltName: Full=Putative NF-kappa-B-activating protein 502;
DE   AltName: Full=TRIF-related adapter molecule;
DE   AltName: Full=Toll-like receptor adaptor protein 3;
DE   AltName: Full=Toll/interleukin-1 receptor domain-containing protein;
DE            Short=MyD88-4;
GN   Name=TICAM2; Synonyms=TIRAP3, TIRP, TRAM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DOMAIN, INTERACTION
RP   WITH TRAF6; IL1R1; IL1RAP; IRAK1; IRAK2; IRAK3; IRAK4; TIRAP AND
RP   TICAM1, AND TISSUE SPECIFICITY.
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
RT   adapter protein involved in TIR signaling.";
RL   J. Biol. Chem. 278:24526-24532(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, INTERACTION
RP   WITH TICAM1 AND TLR4, TISSUE SPECIFICITY, AND MUTAGENESIS OF PRO-116
RP   AND CYS-117.
RX   PubMed=14519765; DOI=10.1074/jbc.M305820200;
RA   Oshiumi H., Sasai M., Shida K., Fujita T., Matsumoto M., Seya T.;
RT   "TIR-containing adapter molecule (TICAM)-2, a bridging adapter
RT   recruiting to toll-like receptor 4 TICAM-1 that induces interferon-
RT   beta.";
RL   J. Biol. Chem. 278:49751-49762(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH
RP   TICAM1; TIRAP; TLR4; IRF3 AND IRF7, AND MUTAGENESIS OF PRO-116 AND
RP   CYS-117.
RX   PubMed=14517278; DOI=10.1084/jem.20031023;
RA   Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A.,
RA   Latz E., Monks B., Pitha P.M., Golenbock D.T.;
RT   "LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll
RT   adapters TRAM and TRIF.";
RL   J. Exp. Med. 198:1043-1055(2003).
RN   [4]
RP   ERRATUM.
RA   Fitzgerald K.A., Rowe D.C., Barnes B.J., Caffrey D.R., Visintin A.,
RA   Latz E., Monks B., Pitha P.M., Golenbock D.T.;
RL   J. Exp. Med. 198:1451-1451(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA   Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T.,
RA   Kimura A.;
RT   "Natural selection in the TLR-related genes in the course of primate
RT   evolution.";
RL   Immunogenetics 60:727-735(2008).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION (ISOFORM 2),
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19412184; DOI=10.1038/ni.1727;
RA   Palsson-McDermott E.M., Doyle S.L., McGettrick A.F., Hardy M.,
RA   Husebye H., Banahan K., Gong M., Golenbock D., Espevik T.,
RA   O'Neill L.A.;
RT   "TAG, a splice variant of the adaptor TRAM, negatively regulates the
RT   adaptor MyD88-independent TLR4 pathway.";
RL   Nat. Immunol. 10:579-586(2009).
RN   [7]
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.,
RA   Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H.,
RA   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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, AND
RP   MUTAGENESIS OF GLY-2.
RX   PubMed=16603631; DOI=10.1073/pnas.0510041103;
RA   Rowe D.C., McGettrick A.F., Latz E., Monks B.G., Gay N.J.,
RA   Yamamoto M., Akira S., O'Neill L.A., Fitzgerald K.A., Golenbock D.T.;
RT   "The myristoylation of TRIF-related adaptor molecule is essential for
RT   Toll-like receptor 4 signal transduction.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:6299-6304(2006).
RN   [12]
RP   FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-16, AND
RP   MUTAGENESIS OF SER-6; SER-10; SER-14 AND SER-16.
RX   PubMed=16757566; DOI=10.1073/pnas.0600462103;
RA   McGettrick A.F., Brint E.K., Palsson-McDermott E.M., Rowe D.C.,
RA   Golenbock D.T., Gay N.J., Fitzgerald K.A., O'Neill L.A.J.;
RT   "Trif-related adapter molecule is phosphorylated by PKCepsilon during
RT   Toll-like receptor 4 signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:9196-9201(2006).
RN   [13]
RP   FUNCTION, AND INTERACTION WITH MYD88; IL18R1 AND IL18RAP.
RX   PubMed=22685567; DOI=10.1371/journal.pone.0038423;
RA   Ohnishi H., Tochio H., Kato Z., Kawamoto N., Kimura T., Kubota K.,
RA   Yamamoto T., Funasaka T., Nakano H., Wong R.W., Shirakawa M.,
RA   Kondo N.;
RT   "TRAM is involved in IL-18 signaling and functions as a sorting
RT   adaptor for MyD88.";
RL   PLoS ONE 7:E38423-E38423(2012).
CC   -!- FUNCTION: Functions as sorting adapter in LPS-TLR4 signaling to
CC       regulate the MYD88-independent pathway during the innate immune
CC       response to LPS. Physically bridges TLR4 and TICAM1 and
CC       functionally transmits LPS-TRL4 signal to TICAM1; signaling is
CC       proposed to occur in early endosomes after endocytosis of TLR4.
CC       May also be involved in IL1-triggered NF-kappa-B activation,
CC       functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however,
CC       reports are controversial. Involved in IL-18 signaling and is
CC       proposed to function as a sorting adaptor for MYD88 in IL-18
CC       signaling during adaptive immune response.
CC   -!- FUNCTION: Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the
CC       late endosome by interaction with isoform 1 thereby disrupting the
CC       association of isoform 1 with TICAM1. May be involved in TLR4
CC       degradation in late endosomes.
CC   -!- SUBUNIT: Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in
CC       response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and
CC       TRAF6. Interacts with protein kinase-inactive mutants of IRAK1 and
CC       IRAK4. Isoform 1 interacts with isoform 2; the interaction occurs
CC       in late endosomes and disrupts the interaction between isoform 1
CC       and TICAM1. Interacts with MYD88; the interaction decreases after
CC       IL-18 stimulation in a time-dependent manner. Interacts with
CC       IL18R1 and IL18RAP. {ECO:0000269|PubMed:12721283,
CC       ECO:0000269|PubMed:14517278, ECO:0000269|PubMed:14519765,
CC       ECO:0000269|PubMed:22685567}.
CC   -!- INTERACTION:
CC       A4D127:MEOX2; NbExp=3; IntAct=EBI-525927, EBI-10172134;
CC       Q6SZW1:SARM1; NbExp=2; IntAct=EBI-525927, EBI-11693532;
CC       O00206:TLR4; NbExp=2; IntAct=EBI-525927, EBI-528701;
CC   -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Golgi apparatus. Cell
CC       membrane. Endoplasmic reticulum. Early endosome membrane. Late
CC       endosome membrane. Note=Localized to the plasma membrane as a
CC       result of myristoylation. Phosphorylation on Ser-16 leads to its
CC       depletion from the membrane. Upon LPS stimulation colcoalizes with
CC       isoform 2 in late endosomes.
CC   -!- SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum. Early
CC       endosome membrane. Late endosome membrane. Note=Translocates to
CC       late endosomes upon LPS stimulation where it colcoalizes with
CC       isoform 1.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=TRAM;
CC         IsoId=Q86XR7-1; Sequence=Displayed;
CC       Name=2; Synonyms=TAG, TRAM adaptor with GOLD domain;
CC         IsoId=Q86XR7-2; Sequence=VSP_047437;
CC   -!- TISSUE SPECIFICITY: Expressed in spleen, prostate, testis, uterus,
CC       small intestine, colon, peripheral blood leukocytes, heart,
CC       placenta, lung, liver, skeletal muscle, and pancreas Isoform 2 is
CC       ubiquitously expressed (at lower levels than isoform 1).
CC       {ECO:0000269|PubMed:12721283, ECO:0000269|PubMed:14519765,
CC       ECO:0000269|PubMed:19412184}.
CC   -!- DOMAIN: The TIR domain mediates the interaction with TRAF6 and
CC       MYD88. {ECO:0000269|PubMed:12721283}.
CC   -!- PTM: Phosphorylated by PRKCE in response to LPS. Phosphorylation
CC       is essential for its function. It is depleted from the membrane
CC       upon phosphorylation. {ECO:0000269|PubMed:16757566}.
CC   -!- PTM: Isoform 1 is myristoylated. Required for membrane association
CC       which is critical for its ability to initiate efficient signaling.
CC       {ECO:0000269|PubMed:16603631}.
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DR   EMBL; AY275836; AAP81748.1; -; mRNA.
DR   EMBL; AB109098; BAC98399.1; -; mRNA.
DR   EMBL; AB091054; BAC98397.1; -; mRNA.
DR   EMBL; AY232653; AAO74498.1; -; mRNA.
DR   EMBL; AY304581; AAQ97430.1; -; mRNA.
DR   EMBL; AY304582; AAQ97431.1; -; mRNA.
DR   EMBL; AY304583; AAQ97432.1; -; mRNA.
DR   EMBL; AY304584; AAQ97433.1; -; mRNA.
DR   EMBL; AB446491; BAG55268.1; -; mRNA.
DR   EMBL; AB097022; BAC77375.1; -; mRNA.
DR   EMBL; AC010226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471086; EAW48960.1; -; Genomic_DNA.
DR   EMBL; CH471086; EAW48961.1; -; Genomic_DNA.
DR   EMBL; BC109265; AAI09266.1; -; mRNA.
DR   EMBL; BC109266; AAI09267.1; -; mRNA.
DR   CCDS; CCDS4119.1; -. [Q86XR7-1]
DR   RefSeq; NP_001157940.1; NM_001164468.3. [Q86XR7-2]
DR   RefSeq; NP_001157941.1; NM_001164469.3.
DR   RefSeq; NP_067681.1; NM_021649.7. [Q86XR7-1]
DR   UniGene; Hs.718838; -.
DR   PDB; 2M1W; NMR; -; A=75-235.
DR   PDBsum; 2M1W; -.
DR   ProteinModelPortal; Q86XR7; -.
DR   SMR; Q86XR7; -.
DR   BioGrid; 131694; 10.
DR   DIP; DIP-33488N; -.
DR   IntAct; Q86XR7; 14.
DR   STRING; 9606.ENSP00000386341; -.
DR   iPTMnet; Q86XR7; -.
DR   PhosphoSitePlus; Q86XR7; -.
DR   SwissPalm; Q86XR7; -.
DR   BioMuta; TICAM2; -.
DR   DMDM; 74727858; -.
DR   MaxQB; Q86XR7; -.
DR   PaxDb; Q86XR7; -.
DR   PeptideAtlas; Q86XR7; -.
DR   PRIDE; Q86XR7; -.
DR   Ensembl; ENST00000427199; ENSP00000415139; ENSG00000243414. [Q86XR7-1]
DR   GeneID; 100302736; -.
DR   GeneID; 353376; -.
DR   KEGG; hsa:100302736; -.
DR   KEGG; hsa:353376; -.
DR   UCSC; uc003krc.4; human. [Q86XR7-1]
DR   CTD; 100302736; -.
DR   CTD; 353376; -.
DR   DisGeNET; 353376; -.
DR   DisGeNET; 51014; -.
DR   GeneCards; TICAM2; -.
DR   HGNC; HGNC:21354; TICAM2.
DR   HPA; HPA008960; -.
DR   MIM; 608321; gene.
DR   neXtProt; NX_Q86XR7; -.
DR   OpenTargets; ENSG00000243414; -.
DR   OpenTargets; ENSG00000251201; -.
DR   PharmGKB; PA134881157; -.
DR   PharmGKB; PA165660570; -.
DR   eggNOG; KOG1693; Eukaryota.
DR   eggNOG; ENOG4111JPD; LUCA.
DR   GeneTree; ENSGT00670000097656; -.
DR   HOGENOM; HOG000068974; -.
DR   HOVERGEN; HBG102133; -.
DR   InParanoid; Q86XR7; -.
DR   KO; K05409; -.
DR   OMA; TRVAYCH; -.
DR   OrthoDB; EOG091G0LX8; -.
DR   PhylomeDB; Q86XR7; -.
DR   TreeFam; TF313000; -.
DR   Reactome; R-HSA-140534; Ligand-dependent caspase activation.
DR   Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR   Reactome; R-HSA-166166; MyD88-independent TLR3/TLR4 cascade.
DR   Reactome; R-HSA-2562578; TRIF-mediated programmed cell death.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR   Reactome; R-HSA-937072; TRAF6 mediated induction of TAK1 complex.
DR   Reactome; R-HSA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR   SignaLink; Q86XR7; -.
DR   SIGNOR; Q86XR7; -.
DR   GeneWiki; TICAM2; -.
DR   PRO; PR:Q86XR7; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000243414; -.
DR   CleanEx; HS_TICAM2; -.
DR   Genevisible; Q86XR7; HS.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR   GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR   GO; GO:0004871; F:signal transducer activity; IMP:UniProtKB.
DR   GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0070266; P:necroptotic process; TAS:Reactome.
DR   GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
DR   GO; GO:0034128; P:negative regulation of MyD88-independent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR   GO; GO:2000494; P:positive regulation of interleukin-18-mediated signaling pathway; IMP:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0070671; P:response to interleukin-12; IEA:Ensembl.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR   GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR   Gene3D; 3.40.50.10140; -; 1.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR015720; TMP21-related.
DR   PANTHER; PTHR22811; PTHR22811; 1.
DR   Pfam; PF13676; TIR_2; 1.
DR   SUPFAM; SSF52200; SSF52200; 1.
DR   PROSITE; PS50104; TIR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW   Cytoplasm; Endoplasmic reticulum; Endosome; Golgi apparatus; Immunity;
KW   Inflammatory response; Innate immunity; Lipoprotein; Membrane;
KW   Myristate; Phosphoprotein; Reference proteome.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    235       TIR domain-containing adapter molecule 2.
FT                                /FTId=PRO_0000317689.
FT   DOMAIN       73    232       TIR. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00204}.
FT   MOD_RES      16     16       Phosphoserine; by PKC/PRKCE.
FT                                {ECO:0000269|PubMed:16757566}.
FT   LIPID         2      2       N-myristoyl glycine.
FT                                {ECO:0000269|PubMed:16603631}.
FT   VAR_SEQ       1     20       MGIGKSKINSCPLSLSWGKR -> MPRPGSAQRWAAVAGRW
FT                                GCRLLALLLLVPGPGGASEITFELPDNAKQCFYEDIAQGTK
FT                                CTLEFQVITGGHYDVDCRLEDPDGKVLYKEMKKQYDSFTFT
FT                                ASKNGTYKFCFSNEFSTFTHKTVYFDFQVGEDPPLFPSENR
FT                                VSALTQMESACVSIHEALKSVIDYQTHFRLREAQGRSRAED
FT                                LNTRVAYW (in isoform 2).
FT                                {ECO:0000303|PubMed:19412184}.
FT                                /FTId=VSP_047437.
FT   MUTAGEN       2      2       G->A: Results in relocalization from
FT                                membrane to cytosol; Loss of ability to
FT                                transduce TLR4-signal.
FT                                {ECO:0000269|PubMed:16603631}.
FT   MUTAGEN       6      6       S->A: Loss of phosphorylation.
FT                                Significant reduction in the ability to
FT                                activate IRF3 or NF-kappa-B.
FT                                {ECO:0000269|PubMed:16757566}.
FT   MUTAGEN      10     10       S->A: No effect on phosphorylation and on
FT                                the ability to activate IRF3 or NF-kappa-
FT                                B. {ECO:0000269|PubMed:16757566}.
FT   MUTAGEN      14     14       S->A: No effect on phosphorylation and on
FT                                the ability to activate IRF3 or NF-kappa-
FT                                B. {ECO:0000269|PubMed:16757566}.
FT   MUTAGEN      16     16       S->A: Loss of phosphorylation. Abolishes
FT                                ability to activate IRF3 or NF-kappa-B
FT                                and to transduce TLR4 signal.
FT                                {ECO:0000269|PubMed:16757566}.
FT   MUTAGEN      16     16       S->E: Significant decrease of
FT                                localization in the membrane.
FT                                {ECO:0000269|PubMed:16757566}.
FT   MUTAGEN     116    116       P->H: Loss of ability to dimerize.
FT                                Significant loss of RANTES-inducing
FT                                activity. Loss of ability to induce NF-
FT                                kappa-B activation.
FT                                {ECO:0000269|PubMed:14517278,
FT                                ECO:0000269|PubMed:14519765}.
FT   MUTAGEN     117    117       C->H: Loss of ability to dimerize. Loss
FT                                of RANTES-inducing activity and ability
FT                                to induce NF-kappa-B activation.
FT                                Inhibition of TLR4-dependent activation
FT                                of IRF3 and IRF7. Loss of interaction
FT                                with TLR4. {ECO:0000269|PubMed:14517278,
FT                                ECO:0000269|PubMed:14519765}.
FT   STRAND       80     84       {ECO:0000244|PDB:2M1W}.
FT   STRAND       87     89       {ECO:0000244|PDB:2M1W}.
FT   HELIX        90    100       {ECO:0000244|PDB:2M1W}.
FT   TURN        101    104       {ECO:0000244|PDB:2M1W}.
FT   STRAND      108    111       {ECO:0000244|PDB:2M1W}.
FT   TURN        112    114       {ECO:0000244|PDB:2M1W}.
FT   STRAND      118    120       {ECO:0000244|PDB:2M1W}.
FT   HELIX       125    128       {ECO:0000244|PDB:2M1W}.
FT   STRAND      130    133       {ECO:0000244|PDB:2M1W}.
FT   STRAND      135    137       {ECO:0000244|PDB:2M1W}.
FT   HELIX       141    153       {ECO:0000244|PDB:2M1W}.
FT   HELIX       155    160       {ECO:0000244|PDB:2M1W}.
FT   STRAND      166    168       {ECO:0000244|PDB:2M1W}.
FT   STRAND      176    178       {ECO:0000244|PDB:2M1W}.
FT   HELIX       182    184       {ECO:0000244|PDB:2M1W}.
FT   TURN        187    191       {ECO:0000244|PDB:2M1W}.
FT   STRAND      196    199       {ECO:0000244|PDB:2M1W}.
FT   HELIX       202    209       {ECO:0000244|PDB:2M1W}.
FT   HELIX       212    232       {ECO:0000244|PDB:2M1W}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT        82    182       ipfam:TIR_2 [T]
FT   MYHIT        73    232       iprf:TIR [T]
SQ   SEQUENCE   235 AA;  26916 MW;  2D1171F9B04D9C4C CRC64;
     MGIGKSKINS CPLSLSWGKR HSVDTSPGYH ESDSKKSEDL SLCNVAEHSN TTEGPTGKQE
     GAQSVEEMFE EEAEEEVFLK FVILHAEDDT DEALRVQNLL QDDFGIKPGI IFAEMPCGRQ
     HLQNLDDAVN GSAWTILLLT ENFLRDTWCN FQFYTSLMNS VNRQHKYNSV IPMRPLNNPL
     PRERTPFALQ TINALEEESR GFPTQVERIF QESVYKTQQT IWKETRNMVQ RQFIA
//