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 03-AUG-2022, entry version 177.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DOMAIN, INTERACTION WITH
RP TRAF6; IL1R1; IL1RAP; IRAK1; IRAK2; IRAK3; IRAK4; TIRAP AND TICAM1, AND
RP 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 adapter
RT protein involved in TIR signaling.";
RL J. Biol. Chem. 278:24526-24532(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, INTERACTION WITH
RP TICAM1 AND TLR4, TISSUE SPECIFICITY, AND MUTAGENESIS OF PRO-116 AND
RP 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 recruiting
RT to toll-like receptor 4 TICAM-1 that induces interferon-beta.";
RL J. Biol. Chem. 278:49751-49762(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH TICAM1;
RP TIRAP; TLR4; IRF3 AND IRF7, AND MUTAGENESIS OF PRO-116 AND 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 adapters
RT TRAM and TRIF.";
RL J. Exp. Med. 198:1043-1055(2003).
RN [4]
RP ERRATUM OF PUBMED:14517278.
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., 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., Husebye H.,
RA Banahan K., Gong M., Golenbock D., Espevik T., 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., 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 [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., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., 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., 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 (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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, AND MUTAGENESIS OF
RP 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., Yamamoto M.,
RA Akira S., O'Neill L.A., Fitzgerald K.A., Golenbock D.T.;
RT "The myristoylation of TRIF-related adaptor molecule is essential for Toll-
RT 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 MUTAGENESIS
RP 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 Toll-
RT 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., Kondo N.;
RT "TRAM is involved in IL-18 signaling and functions as a sorting adaptor for
RT MyD88.";
RL PLoS ONE 7:E38423-E38423(2012).
RN [14]
RP FUNCTION, INTERACTION WITH TLR2 AND MYD88, AND MUTAGENESIS OF GLY-2.
RX PubMed=25385819; DOI=10.4049/jimmunol.1401605;
RA Stack J., Doyle S.L., Connolly D.J., Reinert L.S., O'Keeffe K.M.,
RA McLoughlin R.M., Paludan S.R., Bowie A.G.;
RT "TRAM is required for TLR2 endosomal signaling to type I IFN induction.";
RL J. Immunol. 193:6090-6102(2014).
RN [15]
RP PHOSPHORYLATION AT TYR-167, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-154
RP AND TYR-167, AND FUNCTION.
RX PubMed=25825441; DOI=10.4049/jimmunol.1402183;
RA Huai W., Song H., Wang L., Li B., Zhao J., Han L., Gao C., Jiang G.,
RA Zhang L., Zhao W.;
RT "Phosphatase PTPN4 preferentially inhibits TRIF-dependent TLR4 pathway by
RT dephosphorylating TRAM.";
RL J. Immunol. 194:4458-4465(2015).
RN [16]
RP FUNCTION, INTERACTION WITH RAB11FIP2, AND SUBCELLULAR LOCATION.
RX PubMed=30883606; DOI=10.1371/journal.ppat.1007684;
RA Skjesol A., Yurchenko M., Boesl K., Gravastrand C., Nilsen K.E.,
RA Groevdal L.M., Agliano F., Patane F., Lentini G., Kim H., Teti G.,
RA Kumar Sharma A., Kandasamy R.K., Sporsheim B., Starheim K.K.,
RA Golenbock D.T., Stenmark H., McCaffrey M., Espevik T., Husebye H.;
RT "The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria
RT by interacting with the Rab11-family interacting protein 2.";
RL PLoS Pathog. 15:E1007684-E1007684(2019).
CC -!- FUNCTION: Functions as sorting adapter in different signaling pathways
CC to facilitate downstream signaling leading to type I interferon
CC induction (PubMed:16603631, PubMed:16757566, PubMed:25385819,
CC PubMed:25825441). In TLR4 signaling, physically bridges TLR4 and TICAM1
CC and functionally transmits signal to TICAM1 in early endosomes after
CC endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and
CC MYD88 and is required for the TLR2-dependent movement of MYD88 to
CC endosomes following ligand engagement (PubMed:25385819). Involved in
CC IL-18 signaling and is proposed to function as a sorting adapter for
CC MYD88 in IL-18 signaling during adaptive immune response
CC (PubMed:22685567). Forms a complex with RAB11FIP2 that is recruited to
CC the phagosomes to promote the activation of the actin-regulatory
CC GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative
CC bacteria (PubMed:30883606). {ECO:0000269|PubMed:16603631,
CC ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:22685567,
CC ECO:0000269|PubMed:25385819, ECO:0000269|PubMed:25825441,
CC ECO:0000269|PubMed:30883606}.
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 TRAF6.
CC Interacts with protein kinase-inactive mutants of IRAK1 and IRAK4.
CC Isoform 1 interacts with isoform 2; the interaction occurs in late
CC endosomes and disrupts the interaction between isoform 1 and TICAM1.
CC Interacts with MYD88; the interaction decreases after IL-18 stimulation
CC in a time-dependent manner. Interacts with IL18R1 and IL18RAP.
CC Interacts with TLR2 (PubMed:25385819). Interacts with RAB11FIP2
CC (PubMed:30883606). {ECO:0000269|PubMed:12721283,
CC ECO:0000269|PubMed:14517278, ECO:0000269|PubMed:14519765,
CC ECO:0000269|PubMed:22685567, ECO:0000269|PubMed:25385819,
CC ECO:0000269|PubMed:30883606}.
CC -!- INTERACTION:
CC Q86XR7; P50222: MEOX2; NbExp=3; IntAct=EBI-525927, EBI-748397;
CC Q86XR7; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-525927, EBI-741158;
CC Q86XR7; Q6SZW1: SARM1; NbExp=2; IntAct=EBI-525927, EBI-11693532;
CC Q86XR7; O00206: TLR4; NbExp=3; IntAct=EBI-525927, EBI-528701;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:25825441}. Golgi apparatus. Cell membrane
CC {ECO:0000269|PubMed:25825441}. Endoplasmic reticulum. Early endosome
CC membrane. Late endosome membrane. Cell projection, phagocytic cup
CC {ECO:0000269|PubMed:30883606}. Note=Localized to the plasma membrane as
CC a 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 late
CC endosomes upon LPS stimulation where it colcoalizes with 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, placenta,
CC lung, liver, skeletal muscle, and pancreas Isoform 2 is ubiquitously
CC 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 MYD88.
CC {ECO:0000269|PubMed:12721283}.
CC -!- PTM: Phosphorylated by PRKCE in response to LPS. Phosphorylation is
CC essential for its function. It is depleted from the membrane upon
CC phosphorylation. Tyrosine phosphorylation is inhibited by phosphatase
CC PTPN4. {ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:25825441}.
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 PDB; 2M1W; NMR; -; A=75-235.
DR PDBsum; 2M1W; -.
DR AlphaFoldDB; Q86XR7; -.
DR BMRB; Q86XR7; -.
DR SMR; Q86XR7; -.
DR BioGRID; 131694; 20.
DR BioGRID; 970651; 5.
DR CORUM; Q86XR7; -.
DR DIP; DIP-33488N; -.
DR ELM; Q86XR7; -.
DR IntAct; Q86XR7; 15.
DR MINT; Q86XR7; -.
DR STRING; 9606.ENSP00000415139; -.
DR GlyGen; Q86XR7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86XR7; -.
DR PhosphoSitePlus; Q86XR7; -.
DR SwissPalm; Q86XR7; -.
DR BioMuta; TICAM2; -.
DR DMDM; 74727858; -.
DR EPD; Q86XR7; -.
DR jPOST; Q86XR7; -.
DR MassIVE; Q86XR7; -.
DR MaxQB; Q86XR7; -.
DR PaxDb; Q86XR7; -.
DR PeptideAtlas; Q86XR7; -.
DR PRIDE; Q86XR7; -.
DR ProteomicsDB; 66519; -.
DR ProteomicsDB; 70323; -. [Q86XR7-1]
DR Antibodypedia; 34833; 336 antibodies from 36 providers.
DR DNASU; 353376; -.
DR Ensembl; ENST00000427199.3; ENSP00000415139.3; ENSG00000243414.6. [Q86XR7-1]
DR GeneID; 100302736; -.
DR GeneID; 353376; -.
DR KEGG; hsa:100302736; -.
DR KEGG; hsa:353376; -.
DR MANE-Select; ENST00000427199.3; ENSP00000415139.3; NM_021649.7; NP_067681.1.
DR UCSC; uc003krc.4; human. [Q86XR7-1]
DR CTD; 100302736; -.
DR CTD; 353376; -.
DR DisGeNET; 100302736; -.
DR DisGeNET; 353376; -.
DR GeneCards; TICAM2; -.
DR HGNC; HGNC:21354; TICAM2.
DR HPA; ENSG00000243414; Low tissue specificity.
DR MIM; 608321; gene.
DR neXtProt; NX_Q86XR7; -.
DR OpenTargets; ENSG00000243414; -.
DR OpenTargets; ENSG00000251201; -.
DR PharmGKB; PA134881157; -.
DR PharmGKB; PA165660570; -.
DR VEuPathDB; HostDB:ENSG00000243414; -.
DR eggNOG; ENOG502S2I6; Eukaryota.
DR GeneTree; ENSGT00940000158463; -.
DR GeneTree; ENSGT00940000163706; -.
DR HOGENOM; CLU_094608_0_0_1; -.
DR InParanoid; Q86XR7; -.
DR OMA; SAWTIIL; -.
DR OrthoDB; 1328081at2759; -.
DR PhylomeDB; Q86XR7; -.
DR TreeFam; TF313000; -.
DR PathwayCommons; Q86XR7; -.
DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR Reactome; R-HSA-166166; MyD88-independent 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 within TLR4 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 BioGRID-ORCS; 100302736; 7 hits in 922 CRISPR screens.
DR BioGRID-ORCS; 353376; 382 hits in 1007 CRISPR screens.
DR GeneWiki; TICAM2; -.
DR Pharos; Q86XR7; Tbio.
DR PRO; PR:Q86XR7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q86XR7; protein.
DR Bgee; ENSG00000243414; Expressed in monocyte and 92 other tissues.
DR Genevisible; Q86XR7; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central.
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:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001891; C:phagocytic cup; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IMP:UniProtKB.
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; HMP:UniProtKB.
DR GO; GO:2000494; P:positive regulation of interleukin-18-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR015720; Emp24-like.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
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; Cell projection;
KW Cytoplasm; Endoplasmic reticulum; Endosome; Golgi apparatus; Immunity;
KW Inflammatory response; Innate immunity; Lipoprotein; Membrane; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..235
FT /note="TIR domain-containing adapter molecule 2"
FT /id="PRO_0000317689"
FT DOMAIN 73..229
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..39
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 16
FT /note="Phosphoserine; by PKC/PRKCE"
FT /evidence="ECO:0000269|PubMed:16757566"
FT MOD_RES 167
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25825441"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:16603631"
FT VAR_SEQ 1..20
FT /note="MGIGKSKINSCPLSLSWGKR -> MPRPGSAQRWAAVAGRWGCRLLALLLLV
FT PGPGGASEITFELPDNAKQCFYEDIAQGTKCTLEFQVITGGHYDVDCRLEDPDGKVLYK
FT EMKKQYDSFTFTASKNGTYKFCFSNEFSTFTHKTVYFDFQVGEDPPLFPSENRVSALTQ
FT MESACVSIHEALKSVIDYQTHFRLREAQGRSRAEDLNTRVAYW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19412184"
FT /id="VSP_047437"
FT MUTAGEN 2
FT /note="G->A: Results in relocalization from membrane to
FT cytosol; Loss of ability to transduce TLR4-signal. Loss of
FT TLR2-mediated activation of IRF7."
FT /evidence="ECO:0000269|PubMed:16603631,
FT ECO:0000269|PubMed:25385819"
FT MUTAGEN 6
FT /note="S->A: Loss of phosphorylation. Significant reduction
FT in the ability to activate IRF3 or NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:16757566"
FT MUTAGEN 10
FT /note="S->A: No effect on phosphorylation and on the
FT ability to activate IRF3 or NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:16757566"
FT MUTAGEN 14
FT /note="S->A: No effect on phosphorylation and on the
FT ability to activate IRF3 or NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:16757566"
FT MUTAGEN 16
FT /note="S->A: Loss of phosphorylation. Abolishes ability to
FT activate IRF3 or NF-kappa-B and to transduce TLR4 signal."
FT /evidence="ECO:0000269|PubMed:16757566"
FT MUTAGEN 16
FT /note="S->E: Significant decrease of localization in the
FT membrane."
FT /evidence="ECO:0000269|PubMed:16757566"
FT MUTAGEN 116
FT /note="P->H: Loss of ability to dimerize. Significant loss
FT of RANTES-inducing activity. Loss of ability to induce NF-
FT kappa-B activation."
FT /evidence="ECO:0000269|PubMed:14517278,
FT ECO:0000269|PubMed:14519765"
FT MUTAGEN 117
FT /note="C->H: Loss of ability to dimerize. Loss of RANTES-
FT inducing activity and ability to induce NF-kappa-B
FT activation. Inhibition of TLR4-dependent activation of IRF3
FT and IRF7. Loss of interaction with TLR4."
FT /evidence="ECO:0000269|PubMed:14517278,
FT ECO:0000269|PubMed:14519765"
FT MUTAGEN 154
FT /note="Y->F: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:25825441"
FT MUTAGEN 167
FT /note="Y->F: Complete loss of phosphorylation in response
FT to LPS."
FT /evidence="ECO:0000269|PubMed:25825441"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 90..100
FT /evidence="ECO:0007829|PDB:2M1W"
FT TURN 101..104
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2M1W"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 141..153
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 155..160
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:2M1W"
FT TURN 187..191
FT /evidence="ECO:0007829|PDB:2M1W"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:2M1W"
FT HELIX 212..232
FT /evidence="ECO:0007829|PDB:2M1W"
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
