Human Gene TIRAP (ENST00000392679.6_10) from GENCODE V47lift37
  Description: TIR domain containing adaptor protein, transcript variant 5 (from RefSeq NM_001318777.2)
Gencode Transcript: ENST00000392679.6_10
Gencode Gene: ENSG00000150455.15_17
Transcript (Including UTRs)
   Position: hg19 chr11:126,152,988-126,164,828 Size: 11,841 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr11:126,160,790-126,163,582 Size: 2,793 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:126,152,988-126,164,828)mRNA (may differ from genome)Protein (221 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TIRAP_HUMAN
DESCRIPTION: RecName: Full=Toll/interleukin-1 receptor domain-containing adapter protein; Short=TIR domain-containing adapter protein; AltName: Full=Adaptor protein Wyatt; AltName: Full=MyD88 adapter-like protein;
FUNCTION: Adapter involved in 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. Positively regulates the production of TNF-alpha and interleukin-6.
SUBUNIT: Homodimer. Also forms heterodimers with MyD88. Binds to TLR4 and IRAK2 via their respective TIR domains. Binds to BMX, PKR and TBK1. Does not interact with IRAK1, nor TLR9.
INTERACTION: P10398:ARAF; NbExp=2; IntAct=EBI-528644, EBI-365961; Q96A33:CCDC47; NbExp=2; IntAct=EBI-528644, EBI-720151; P51617:IRAK1; NbExp=2; IntAct=EBI-528644, EBI-358664; O43187:IRAK2; NbExp=2; IntAct=EBI-528644, EBI-447733; Q9NWZ3:IRAK4; NbExp=2; IntAct=EBI-528644, EBI-448378; O94822:LTN1; NbExp=2; IntAct=EBI-528644, EBI-1044684; Q99836:MYD88; NbExp=4; IntAct=EBI-528644, EBI-447677; Q9Y3Z3:SAMHD1; NbExp=2; IntAct=EBI-528644, EBI-1054601; O00206:TLR4; NbExp=2; IntAct=EBI-528644, EBI-528701;
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
TISSUE SPECIFICITY: Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.
PTM: Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
PTM: Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.
POLYMORPHISM: Genetic variations in TIRAP may influence susceptibility or resistance to invasive pneumococcal disease [MIM:610799], malaria [MIM:611162], and tuberculosis [MIM:607948].
POLYMORPHISM: Genetic variations in TIRAP influence susceptibility or resistance to bacterial invasion of the blood and define the bacteremia susceptibility locus 1 (BACTS1) [MIM:614382].
SIMILARITY: Contains 1 TIR domain.
CAUTION: Variant Leu-180 has been reported to reduce TLR2 signal transduction (PubMed:17322885). In contrast, PubMed:19509286 reports that this variant is fully active and has no effect on signal transduction pathways and cytokine production.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/tirap/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TIRAP
Diseases sorted by gene-association score: bacteremia, protection against* (550), invasive pneumococcal disease, recurrent isolated, 1* (389), malaria* (160), bacteremia (19), pelvic inflammatory disease (13), tuberculosis (11), epiglottitis (9), bacteriuria (8), irak4 deficiency (6), myd88 deficiency (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.30 RPKM in Ovary
Total median expression: 71.98 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -90.40277-0.326 Picture PostScript Text
3' UTR -411.801246-0.330 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000157 - TIR_dom
IPR017279 - Tol-interleuk_rcpt_adapt_Tirap

Pfam Domains:
PF01582 - TIR domain
PF13676 - TIR domain

SCOP Domains:
52200 - Toll/Interleukin receptor TIR domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2Y92 - X-ray MuPIT 3UB2 - X-ray MuPIT 3UB3 - X-ray MuPIT 3UB4 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P58753
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005080 protein kinase C binding
GO:0005515 protein binding
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
GO:0030674 protein binding, bridging
GO:0035662 Toll-like receptor 4 binding
GO:0035663 Toll-like receptor 2 binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0002376 immune system process
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0030099 myeloid cell differentiation
GO:0030890 positive regulation of B cell proliferation
GO:0032496 response to lipopolysaccharide
GO:0032648 regulation of interferon-beta production
GO:0032735 positive regulation of interleukin-12 production
GO:0032738 positive regulation of interleukin-15 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034137 positive regulation of toll-like receptor 2 signaling pathway
GO:0034141 positive regulation of toll-like receptor 3 signaling pathway
GO:0034145 positive regulation of toll-like receptor 4 signaling pathway
GO:0035665 TIRAP-dependent toll-like receptor 4 signaling pathway
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044130 negative regulation of growth of symbiont in host
GO:0045087 innate immune response
GO:0045088 regulation of innate immune response
GO:0045410 positive regulation of interleukin-6 biosynthetic process
GO:0046330 positive regulation of JNK cascade
GO:0050830 defense response to Gram-positive bacterium
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070935 3'-UTR-mediated mRNA stabilization
GO:0071221 cellular response to bacterial lipopeptide
GO:0071223 cellular response to lipoteichoic acid
GO:0090023 positive regulation of neutrophil chemotaxis
GO:0090073 positive regulation of protein homodimerization activity
GO:2000340 positive regulation of chemokine (C-X-C motif) ligand 1 production
GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0030139 endocytic vesicle
GO:0032587 ruffle membrane


-  Descriptions from all associated GenBank mRNAs
  JB181746 - Sequence 11 from Patent WO2012118911.
AK124298 - Homo sapiens cDNA FLJ42305 fis, clone TRACH2001443, highly similar to Toll-interleukin 1 receptor domain-containing adapter protein.
HW547077 - JP 2014509511-A/12: OLIGONUCLEOTIDE MODULATORS OF THE TOLL-LIKE RECEPTOR PATHWAY.
JB181747 - Sequence 12 from Patent WO2012118911.
LZ187089 - JP 2017148060-A/12: OLIGONUCLEOTIDE MODULATORS OF THE TOLL-LIKE RECEPTOR PATHWAY.
AK313147 - Homo sapiens cDNA, FLJ93639, Homo sapiens toll-interleukin 1 receptor (TIR) domain containingadaptor protein (TIRAP), transcript variant 2, mRNA.
AF378129 - Homo sapiens TIR domain containing adaptor protein TIRAP mRNA, complete cds.
AF410783 - Homo sapiens TIR domain-containing adaptor wyatt mRNA, complete cds.
BC032474 - Homo sapiens toll-interleukin 1 receptor (TIR) domain containing adaptor protein, mRNA (cDNA clone MGC:40573 IMAGE:5216171), complete cds.
JD186217 - Sequence 167241 from Patent EP1572962.
JD500387 - Sequence 481411 from Patent EP1572962.
JD200647 - Sequence 181671 from Patent EP1572962.
JD488133 - Sequence 469157 from Patent EP1572962.
AY576787 - Homo sapiens MyD88 adapter-like protein variant b (TIRAP) mRNA, complete cds, alternatively spliced.
AY576785 - Homo sapiens MyD88 adapter-like protein variant a (TIRAP) mRNA, complete cds, alternatively spliced.
AY576786 - Homo sapiens MyD88 adapter-like protein variant a (TIRAP) mRNA, complete cds, alternatively spliced.
AB590321 - Synthetic construct DNA, clone: pFN21AB9901, Homo sapiens TIRAP gene for toll-interleukin 1 receptor (TIR) domain containing adaptor protein, without stop codon, in Flexi system.
KJ900002 - Synthetic construct Homo sapiens clone ccsbBroadEn_09396 TIRAP gene, encodes complete protein.
KR710835 - Synthetic construct Homo sapiens clone CCSBHm_00017569 TIRAP (TIRAP) mRNA, encodes complete protein.
AF406652 - Homo sapiens MyD88 adapter-like protein mRNA, complete cds.
AB446477 - Homo sapiens TIRAP mRNA for TIR domain-containing adaptor protein, complete cds.
DQ890988 - Synthetic construct clone IMAGE:100003618; FLH168288.01X; RZPDo839E1092D toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP) gene, encodes complete protein.
DQ894164 - Synthetic construct Homo sapiens clone IMAGE:100008624; FLH168284.01L; RZPDo839E1091D toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP) gene, encodes complete protein.
CU689388 - Synthetic construct Homo sapiens gateway clone IMAGE:100018061 5' read TIRAP mRNA.
JD168516 - Sequence 149540 from Patent EP1572962.
JD174165 - Sequence 155189 from Patent EP1572962.
JD231654 - Sequence 212678 from Patent EP1572962.
JD512240 - Sequence 493264 from Patent EP1572962.
JD548564 - Sequence 529588 from Patent EP1572962.
JD521131 - Sequence 502155 from Patent EP1572962.
JD146579 - Sequence 127603 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P58753 (Reactome details) participates in the following event(s):

R-HSA-2559456 MAL(TIRAP) binds PIP2-rich regions in the plasma membrane
R-HSA-2201316 Activated TLR2/4 interacts with MAL(TIRAP)
R-HSA-2201322 MAL is phosphorylated by BTK
R-HSA-2559414 Activated TLR2/4:MAL interacts with BTK
R-HSA-166072 MyD88 forms a complex with MAL:activated TLR2/4
R-HSA-937079 MyD88 oligomerization within the complex of activated TLR:Mal:MyD88
R-HSA-166082 IRAK4 binds to the activated TLR receptor:Mal:MyD88 complex
R-HSA-937022 IRAK4 autophosphorylation in the complex with activated TLR:MyD88:Mal
R-HSA-166091 IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex
R-HSA-166362 Dissociation of hp-IRAK1:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-2262775 Dissociation of p-IRAK2:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-166286 Multiple IRAK1 autophosphorylation steps
R-HSA-166284 Second phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166119 First phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166363 TRAF6 binds to hp- IRAK1
R-HSA-937059 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:Mal:activated TLR complex
R-HSA-2262777 TRAF6 binds to p-IRAK2
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-5602358 Diseases associated with the TLR signaling cascade
R-HSA-168249 Innate Immune System
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5260271 Diseases of Immune System
R-HSA-168256 Immune System
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: B3KW65, ENST00000392679.1, ENST00000392679.2, ENST00000392679.3, ENST00000392679.4, ENST00000392679.5, MAL, NM_001318777, P58753, Q56UH9, Q56UI0, Q8N5E5, TIRAP_HUMAN, uc318vhh.1, uc318vhh.2
UCSC ID: ENST00000392679.6_10
RefSeq Accession: NM_001318777.2
Protein: P58753 (aka TIRAP_HUMAN or TIRA_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.