TIRAP_MOUSE
ID TIRAP_MOUSE Reviewed; 241 AA.
AC Q99JY1; Q91ZW0;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Toll/interleukin-1 receptor domain-containing adapter protein;
DE Short=TIR domain-containing adapter protein;
DE AltName: Full=Adaptor protein Wyatt;
DE AltName: Full=MyD88 adapter-like protein;
GN Name=Tirap; Synonyms=Mal;
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].
RC STRAIN=C57BL/6J;
RX PubMed=11526399; DOI=10.1038/ni0901-835;
RA Horng T., Barton G.M., Medzhitov R.;
RT "TIRAP: an adapter molecule in the Toll signaling pathway.";
RL Nat. Immunol. 2:835-841(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kirk P.B., Pereira J.P., Bazan J.F.;
RT "Characterization and structural analysis of TIR domain-containing adaptor
RT protein Wyatt.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [4]
RP INTERACTION WITH PIK3AP1.
RX PubMed=22187460; DOI=10.1073/pnas.1118579109;
RA Troutman T.D., Hu W., Fulenchek S., Yamazaki T., Kurosaki T., Bazan J.F.,
RA Pasare C.;
RT "Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking
RT Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:273-278(2012).
CC -!- FUNCTION: Adapter involved in the TLR2 and TLR4 signaling pathways in
CC the innate immune response. Acts via IRAK2 and TRAF-6, leading to the
CC activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in
CC cytokine secretion and the inflammatory response (By similarity).
CC Positively regulates the production of TNF-alpha and interleukin-6 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Also forms heterodimers with MYD88. Interacts with
CC BMX and TBK1 (By similarity). Interacts with TLR4 and IRAK2 via their
CC respective TIR domains. Interacts with EIF2AK2. Does not interact with
CC IRAK1-1, nor TLR9. May interact with PIK3AP1. {ECO:0000250,
CC ECO:0000269|PubMed:22187460}.
CC -!- INTERACTION:
CC Q99JY1; Q9EQ32: Pik3ap1; NbExp=2; IntAct=EBI-6559589, EBI-643949;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Membrane {ECO:0000250}. Note=Colocalizes with DAB2IP at
CC the plasma membrane. {ECO:0000250}.
CC -!- PTM: Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
CC {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. Polyubiquitination follows phosphorylation by
CC BTK and leads to TIRAP degradation (By similarity). {ECO:0000250}.
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DR EMBL; AF378130; AAL05628.1; -; mRNA.
DR EMBL; AF410784; AAL05037.1; -; mRNA.
DR EMBL; BC005584; AAH05584.1; -; mRNA.
DR RefSeq; NP_473437.2; NM_054096.2.
DR AlphaFoldDB; Q99JY1; -.
DR SMR; Q99JY1; -.
DR BioGRID; 228172; 10.
DR IntAct; Q99JY1; 4.
DR MINT; Q99JY1; -.
DR STRING; 10090.ENSMUSP00000135435; -.
DR iPTMnet; Q99JY1; -.
DR PhosphoSitePlus; Q99JY1; -.
DR MaxQB; Q99JY1; -.
DR PaxDb; Q99JY1; -.
DR PRIDE; Q99JY1; -.
DR ProteomicsDB; 260659; -.
DR DNASU; 117149; -.
DR GeneID; 117149; -.
DR KEGG; mmu:117149; -.
DR CTD; 114609; -.
DR MGI; MGI:2152213; Tirap.
DR eggNOG; ENOG502S07Q; Eukaryota.
DR InParanoid; Q99JY1; -.
DR OrthoDB; 1327598at2759; -.
DR PhylomeDB; Q99JY1; -.
DR Reactome; R-MMU-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR BioGRID-ORCS; 117149; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Tirap; mouse.
DR PRO; PR:Q99JY1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q99JY1; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; ISS:BHF-UCL.
DR GO; GO:0035663; F:Toll-like receptor 2 binding; IPI:BHF-UCL.
DR GO; GO:0035662; F:Toll-like receptor 4 binding; ISO:MGI.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; ISS:BHF-UCL.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IPI:MGI.
DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; IMP:MGI.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:BHF-UCL.
DR GO; GO:2000340; P:positive regulation of chemokine (C-X-C motif) ligand 1 production; IMP:BHF-UCL.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IMP:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:BHF-UCL.
DR GO; GO:0032738; P:positive regulation of interleukin-15 production; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:BHF-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:BHF-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:MGI.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:BHF-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; ISS:BHF-UCL.
DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IDA:BHF-UCL.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; ISS:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:BHF-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; NAS:BHF-UCL.
DR GO; GO:0032648; P:regulation of interferon-beta production; IDA:BHF-UCL.
DR GO; GO:0032658; P:regulation of interleukin-15 production; IMP:BHF-UCL.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:BHF-UCL.
DR GO; GO:0035665; P:TIRAP-dependent toll-like receptor 4 signaling pathway; ISO:MGI.
DR Gene3D; 3.40.50.10140; -; 1.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR017279; Tol-interleuk_rcpt_adapt_Tirap.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR22662; PTHR22662; 1.
DR Pfam; PF13676; TIR_2; 1.
DR PIRSF; PIRSF037750; TIR_Tirap; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Disulfide bond; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..241
FT /note="Toll/interleukin-1 receptor domain-containing
FT adapter protein"
FT /id="PRO_0000072548"
FT DOMAIN 104..233
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 1..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 109..154
FT /evidence="ECO:0000250"
FT DISULFID 162..194
FT /evidence="ECO:0000250"
FT CONFLICT 164
FT /note="A -> V (in Ref. 1; AAL05628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 241 AA; 26035 MW; C387D20229E12265 CRC64;
MASSSSVPAS STPSKKPRDK IADWFRQALL KKPKKMPISQ ESHLYDGSQT ATQDGLSPSS
CSSPPSHSSP ESRSSPSSCS SGMSPTSPPT HVDSSSSSSG RWSKDYDVCV CHSEEDLEAA
QELVSYLEGS QASLRCFLQL RDAAPGGAIV SELCQALSRS HCRALLITPG FLRDPWCKYQ
MLQALTEAPA SEGCTIPLLS GLSRAAYPPE LRFMYYVDGR GKDGGFYQVK EAVIHYLETL
S
