TCAM2_MOUSE
ID TCAM2_MOUSE Reviewed; 232 AA.
AC Q8BJQ4; Q3U996;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=TIR domain-containing adapter molecule 2;
DE Short=TICAM-2;
DE AltName: Full=TRIF-related adapter molecule;
DE AltName: Full=Toll/interleukin-1 receptor domain-containing protein;
GN Name=Ticam2; Synonyms=Tirp, Tram;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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].
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].
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, Bone marrow, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 FUNCTION.
RX PubMed=14556004; DOI=10.1038/ni986;
RA Yamamoto M., Sato S., Hemmi H., Uematsu S., Hoshino K., Kaisho T.,
RA Takeuchi O., Takeda K., Akira S.;
RT "TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-
RT independent signaling pathway.";
RL Nat. Immunol. 4:1144-1150(2003).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-2; LYS-7; TRP-15 AND
RP LYS-17.
RX PubMed=18297073; DOI=10.1038/ni1569;
RA Kagan J.C., Su T., Horng T., Chow A., Akira S., Medzhitov R.;
RT "TRAM couples endocytosis of Toll-like receptor 4 to the induction of
RT interferon-beta.";
RL Nat. Immunol. 9:361-368(2008).
RN [9]
RP FUNCTION.
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).
CC -!- FUNCTION: Functions as sorting adapter in different signaling pathways
CC to facilitate downstream signaling leading to type I interferon
CC induction. In TLR4 signaling, physically bridges TLR4 and TICAM1 and
CC 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. Involved in IL-18 signaling and
CC is proposed to function as a sorting adapter for MYD88 in IL-18
CC signaling during adaptive immune response. Forms a complex with
CC RAB11FIP2 that is recruited to the phagosomes to promote the activation
CC of the actin-regulatory GTPases RAC1 and CDC42 and subsequent
CC phagocytosis of Gram-negative bacteria. {ECO:0000250|UniProtKB:Q86XR7,
CC ECO:0000269|PubMed:14556004, ECO:0000269|PubMed:18297073,
CC ECO:0000269|PubMed:22685567}.
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. Interacts with RAB11FIP2.
CC {ECO:0000250|UniProtKB:Q86XR7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Golgi apparatus
CC {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:18297073}. Early
CC endosome {ECO:0000269|PubMed:18297073}. Late endosome {ECO:0000250}.
CC Endoplasmic reticulum {ECO:0000250}. Cell projection, phagocytic cup
CC {ECO:0000250|UniProtKB:Q86XR7}. Note=Localized to the plasma membrane
CC as a result of myristoylation. {ECO:0000250}.
CC -!- DOMAIN: The TIR domain mediates the interaction with TRAF6 and MYD88.
CC {ECO:0000250|UniProtKB:Q86XR7}.
CC -!- PTM: Myristoylated. Required for membrane association which is critical
CC for its ability to initiate efficient signaling.
CC {ECO:0000250|UniProtKB:Q86XR7}.
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:0000250|UniProtKB:Q86XR7}.
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DR EMBL; AB100441; BAC98398.1; -; mRNA.
DR EMBL; AY275837; AAP81749.1; -; mRNA.
DR EMBL; AY268050; AAP29979.1; -; mRNA.
DR EMBL; AK080873; BAC38055.1; -; mRNA.
DR EMBL; AK151885; BAE30771.1; -; mRNA.
DR EMBL; AK134103; BAE22014.1; -; mRNA.
DR EMBL; BC099933; AAH99933.1; -; mRNA.
DR CCDS; CCDS29232.1; -.
DR RefSeq; NP_775570.1; NM_173394.3.
DR AlphaFoldDB; Q8BJQ4; -.
DR SMR; Q8BJQ4; -.
DR BioGRID; 230399; 7.
DR IntAct; Q8BJQ4; 1.
DR STRING; 10090.ENSMUSP00000066239; -.
DR iPTMnet; Q8BJQ4; -.
DR PhosphoSitePlus; Q8BJQ4; -.
DR MaxQB; Q8BJQ4; -.
DR PaxDb; Q8BJQ4; -.
DR PRIDE; Q8BJQ4; -.
DR ProteomicsDB; 263087; -.
DR DNASU; 225471; -.
DR Ensembl; ENSMUST00000070084; ENSMUSP00000066239; ENSMUSG00000056130.
DR GeneID; 225471; -.
DR KEGG; mmu:225471; -.
DR UCSC; uc008evp.2; mouse.
DR CTD; 353376; -.
DR MGI; MGI:3040056; Ticam2.
DR VEuPathDB; HostDB:ENSMUSG00000056130; -.
DR eggNOG; ENOG502S2I6; Eukaryota.
DR GeneTree; ENSGT00940000164712; -.
DR HOGENOM; CLU_094608_0_0_1; -.
DR InParanoid; Q8BJQ4; -.
DR OMA; SAWTIIL; -.
DR OrthoDB; 1351613at2759; -.
DR PhylomeDB; Q8BJQ4; -.
DR TreeFam; TF336953; -.
DR BioGRID-ORCS; 225471; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ticam2; mouse.
DR PRO; PR:Q8BJQ4; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BJQ4; protein.
DR Bgee; ENSMUSG00000056130; Expressed in ureter and 41 other tissues.
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; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0045323; C:interleukin-1 receptor complex; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0001891; C:phagocytic cup; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005149; F:interleukin-1 receptor binding; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:MGI.
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:0006909; P:phagocytosis; IMP:UniProtKB.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; IMP:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0070671; P:response to interleukin-12; IMP:UniProtKB.
DR GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; ISS: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 Cell membrane; Cell projection; Cytoplasm; Endoplasmic reticulum; Endosome;
KW Golgi apparatus; Immunity; Inflammatory response; Innate immunity;
KW Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q86XR7"
FT CHAIN 2..232
FT /note="TIR domain-containing adapter molecule 2"
FT /id="PRO_0000317690"
FT DOMAIN 74..226
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 164
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q86XR7"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q86XR7"
FT MUTAGEN 2
FT /note="G->A: Results in relocalization from membrane to
FT cytosol; impairs ability to promote LPS-induced IL6 and
FT CCL5 production."
FT /evidence="ECO:0000269|PubMed:18297073"
FT MUTAGEN 7
FT /note="K->E: Results in exclusive localization to early
FT endosomes and no effect on ability to promote LPS-induced
FT IL6 and CCL5 production; when associated with E-15 and E-
FT 17."
FT /evidence="ECO:0000269|PubMed:18297073"
FT MUTAGEN 15
FT /note="W->E: Results in exclusive localization to early
FT endosomes and no effect on ability to promote LPS-induced
FT IL6 and CCL5 production; when associated with E-7 and E-
FT 17."
FT /evidence="ECO:0000269|PubMed:18297073"
FT MUTAGEN 17
FT /note="K->E: Results in exclusive localization to early
FT endosomes and no effect on ability to promote LPS-induced
FT IL6 and CCL5 production; when associated with E-7 and E-
FT 15."
FT /evidence="ECO:0000269|PubMed:18297073"
FT CONFLICT 185
FT /note="A -> T (in Ref. 5; BAE30771)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 232 AA; 26362 MW; B41B3B826365D569 CRC64;
MGVGKSKLDK CPLSWHKKDS VDADQDGHES DSKNSEEACL RGFVEQSSGS EPPTGEQDQP
EAKGAGPEEQ DEEEFLKFVI LHAEDDTDEA LRVQDLLQND FGIRPGIVFA EMPCGRLHLQ
NLDDAVNGSA WTILLLTENF LRDTWCNFQF YTSLMNSVSR QHKYNSVIPM RPLNSPLPRE
RTPLALQTIN ALEEESQGFS TQVERIFRES VFERQQSIWK ETRSVSQKQF IA
