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Protein

Toll/interleukin-1 receptor domain-containing adapter protein

Gene

Tirap

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter involved in the TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response (By similarity). Positively regulates the production of TNF-alpha and interleukin-6 (By similarity).By similarity

GO - Molecular functioni

  • phosphatidylinositol-4,5-bisphosphate binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase C binding Source: BHF-UCL
  • Toll-like receptor 2 binding Source: BHF-UCL
  • Toll-like receptor 4 binding Source: MGI

GO - Biological processi

  • 3'-UTR-mediated mRNA stabilization Source: BHF-UCL
  • activation of JUN kinase activity Source: MGI
  • cell surface receptor signaling pathway Source: MGI
  • cellular response to bacterial lipopeptide Source: MGI
  • cellular response to lipoteichoic acid Source: MGI
  • defense response to Gram-positive bacterium Source: MGI
  • I-kappaB kinase/NF-kappaB signaling Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • myeloid cell differentiation Source: MGI
  • negative regulation of growth of symbiont in host Source: MGI
  • positive regulation of B cell proliferation Source: BHF-UCL
  • positive regulation of chemokine (C-X-C motif) ligand 1 production Source: BHF-UCL
  • positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of innate immune response Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-15 production Source: MGI
  • positive regulation of interleukin-6 biosynthetic process Source: BHF-UCL
  • positive regulation of interleukin-8 production Source: BHF-UCL
  • positive regulation of JNK cascade Source: BHF-UCL
  • positive regulation of neutrophil chemotaxis Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • positive regulation of protein homodimerization activity Source: MGI
  • positive regulation of toll-like receptor 2 signaling pathway Source: BHF-UCL
  • positive regulation of toll-like receptor 3 signaling pathway Source: BHF-UCL
  • positive regulation of toll-like receptor 4 signaling pathway Source: BHF-UCL
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • regulation of innate immune response Source: BHF-UCL
  • regulation of interferon-beta production Source: BHF-UCL
  • regulation of interleukin-15 production Source: BHF-UCL
  • response to bacterium Source: MGI
  • response to lipopolysaccharide Source: BHF-UCL
  • TIRAP-dependent toll-like receptor 4 signaling pathway Source: MGI
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Toll/interleukin-1 receptor domain-containing adapter protein
Short name:
TIR domain-containing adapter protein
Alternative name(s):
Adaptor protein Wyatt
MyD88 adapter-like protein
Gene namesi
Name:Tirap
Synonyms:Mal
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2152213. Tirap.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • endocytic vesicle Source: BHF-UCL
  • intercellular bridge Source: MGI
  • nucleoplasm Source: MGI
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 241241Toll/interleukin-1 receptor domain-containing adapter proteinPRO_0000072548Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi109 ↔ 154By similarity
Disulfide bondi162 ↔ 194By similarity

Post-translational modificationi

Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.By similarity
Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ99JY1.
PaxDbiQ99JY1.
PRIDEiQ99JY1.

PTM databases

PhosphoSiteiQ99JY1.

Interactioni

Subunit structurei

Homodimer. Also forms heterodimers with MYD88. Interacts with BMX and TBK1 (By similarity). Interacts with TLR4 and IRAK2 via their respective TIR domains. Interacts with EIF2AK2. Does not interact with IRAK1-1, nor TLR9. May interact with PIK3AP1.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Pik3ap1Q9EQ322EBI-6559589,EBI-643949

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase C binding Source: BHF-UCL
  • Toll-like receptor 2 binding Source: BHF-UCL
  • Toll-like receptor 4 binding Source: MGI

Protein-protein interaction databases

BioGridi228172. 5 interactions.
IntActiQ99JY1. 3 interactions.
STRINGi10090.ENSMUSP00000135224.

Structurei

3D structure databases

ProteinModelPortaliQ99JY1.
SMRiQ99JY1. Positions 99-241.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 241138TIRPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi94 – 996Poly-Ser

Sequence similaritiesi

Contains 1 TIR domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IVIY. Eukaryota.
ENOG411205V. LUCA.
HOGENOMiHOG000068972.
HOVERGENiHBG054203.
InParanoidiQ99JY1.
KOiK05403.
PhylomeDBiQ99JY1.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000157. TIR_dom.
IPR017279. Tol-interleuk_rcpt_adapt_Tirap.
[Graphical view]
PANTHERiPTHR22662. PTHR22662. 1 hit.
PfamiPF13676. TIR_2. 1 hit.
[Graphical view]
PIRSFiPIRSF037750. TIR_Tirap. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99JY1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASSSSVPAS STPSKKPRDK IADWFRQALL KKPKKMPISQ ESHLYDGSQT
60 70 80 90 100
ATQDGLSPSS CSSPPSHSSP ESRSSPSSCS SGMSPTSPPT HVDSSSSSSG
110 120 130 140 150
RWSKDYDVCV CHSEEDLEAA QELVSYLEGS QASLRCFLQL RDAAPGGAIV
160 170 180 190 200
SELCQALSRS HCRALLITPG FLRDPWCKYQ MLQALTEAPA SEGCTIPLLS
210 220 230 240
GLSRAAYPPE LRFMYYVDGR GKDGGFYQVK EAVIHYLETL S
Length:241
Mass (Da):26,035
Last modified:June 1, 2001 - v1
Checksum:iC387D20229E12265
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti164 – 1641A → V in AAL05628 (PubMed:11526399).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF378130 mRNA. Translation: AAL05628.1.
AF410784 mRNA. Translation: AAL05037.1.
BC005584 mRNA. Translation: AAH05584.1.
RefSeqiNP_473437.2. NM_054096.2.
UniGeneiMm.23987.

Genome annotation databases

GeneIDi117149.
KEGGimmu:117149.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF378130 mRNA. Translation: AAL05628.1.
AF410784 mRNA. Translation: AAL05037.1.
BC005584 mRNA. Translation: AAH05584.1.
RefSeqiNP_473437.2. NM_054096.2.
UniGeneiMm.23987.

3D structure databases

ProteinModelPortaliQ99JY1.
SMRiQ99JY1. Positions 99-241.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228172. 5 interactions.
IntActiQ99JY1. 3 interactions.
STRINGi10090.ENSMUSP00000135224.

PTM databases

PhosphoSiteiQ99JY1.

Proteomic databases

MaxQBiQ99JY1.
PaxDbiQ99JY1.
PRIDEiQ99JY1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi117149.
KEGGimmu:117149.

Organism-specific databases

CTDi114609.
MGIiMGI:2152213. Tirap.

Phylogenomic databases

eggNOGiENOG410IVIY. Eukaryota.
ENOG411205V. LUCA.
HOGENOMiHOG000068972.
HOVERGENiHBG054203.
InParanoidiQ99JY1.
KOiK05403.
PhylomeDBiQ99JY1.

Miscellaneous databases

NextBioi369528.
PROiQ99JY1.
SOURCEiSearch...

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000157. TIR_dom.
IPR017279. Tol-interleuk_rcpt_adapt_Tirap.
[Graphical view]
PANTHERiPTHR22662. PTHR22662. 1 hit.
PfamiPF13676. TIR_2. 1 hit.
[Graphical view]
PIRSFiPIRSF037750. TIR_Tirap. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "TIRAP: an adapter molecule in the Toll signaling pathway."
    Horng T., Barton G.M., Medzhitov R.
    Nat. Immunol. 2:835-841(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  2. "Characterization and structural analysis of TIR domain-containing adaptor protein Wyatt."
    Kirk P.B., Pereira J.P., Bazan J.F.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary gland.
  4. "Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt."
    Troutman T.D., Hu W., Fulenchek S., Yamazaki T., Kurosaki T., Bazan J.F., Pasare C.
    Proc. Natl. Acad. Sci. U.S.A. 109:273-278(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PIK3AP1.

Entry informationi

Entry nameiTIRAP_MOUSE
AccessioniPrimary (citable) accession number: Q99JY1
Secondary accession number(s): Q91ZW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: June 1, 2001
Last modified: May 11, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.