The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor p... See more...

Aliases for TIRAP Gene

Aliases for TIRAP Gene

  • TIR Domain Containing Adaptor Protein 2 3 5
  • Toll/Interleukin-1 Receptor Domain-Containing Adapter Protein 3 4
  • MyD88 Adapter-Like Protein 3 4
  • Adaptor Protein Wyatt 3 4
  • MyD88-2 3 4
  • Wyatt 2 3
  • Mal 2 3
  • Toll-Interleukin 1 Receptor (TIR) Domain-Containing Adaptor Protein 2
  • Toll-Interleukin 1 Receptor (TIR) Domain Containing Adaptor Protein 3
  • TIR Domain-Containing Adapter Protein 4
  • Toll-Like Receptor Adaptor Protein 3
  • Adapter Protein Wyatt 3
  • MyD88 Adapter-Like 2
  • BACTS1 3
  • TIRAP 5
  • MAL 4

External Ids for TIRAP Gene

Previous GeneCards Identifiers for TIRAP Gene

  • GC11P128153
  • GC11P127665
  • GC11P126186
  • GC11P125690
  • GC11P125658
  • GC11P122098
  • GC11P126153
  • GC11P126282

Summaries for TIRAP Gene

Entrez Gene Summary for TIRAP Gene

  • The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

GeneCards Summary for TIRAP Gene

TIRAP (TIR Domain Containing Adaptor Protein) is a Protein Coding gene. Diseases associated with TIRAP include Bacteremia 1 and Malaria. Among its related pathways are Bacterial infections in CF airways and Diseases associated with the TLR signaling cascade. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein binding, bridging.

UniProtKB/Swiss-Prot Summary for TIRAP Gene

  • 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.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIRAP Gene

Genomics for TIRAP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TIRAP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J126280 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 -0.3 -303 4.8 MXD4 FEZF1 NR2C1 SMAD5 BHLHE40 ELF1 NONO SIN3A GABPA SIN3B NONHSAG009988.2 SNODB566 TIRAP FOXRED1 FAM118B ENSG00000254694 DCPS ENSG00000255062 RPUSD4 RNU4-86P
GH11J126290 Promoter 0.4 EPDnew 250.4 +7.7 7689 0.1 KDM1A TIRAP ENSG00000254905 NONHSAG009988.2 DCPS
GH11J126350 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 42.9 +73.0 73015 11.5 MNT IKZF1 SMAD5 HES1 POLR2A MCM7 ZIC2 ARNT RAD51 SIN3A ST3GAL4 GSEC HSALNG0088028 ENSG00000255062 TIRAP STT3A FOXRED1 DCPS FAM118B KIRREL3
GH11J125624 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas 15.9 -656.8 -656777 3.8 ZSCAN16 TBP ZBTB10 MXD4 MNT IKZF1 SMAD5 ETS1 HES1 ZFP64 CHEK1 HSALNG0087960 MN309420 LOC118567325 lnc-ACRV1-2 MSANTD2 TMEM218 ENSG00000255062 TIRAP STT3A
GH11J126057 Promoter/Enhancer 2.7 VISTA EPDnew Ensembl ENCODE CraniofacialAtlas 10.8 -222.4 -222432 6.9 CHD2 TBP SP1 CEBPA SIX5 NR2C1 MNT MBD2 ZNF217 CTCF CDON STT3A TMEM218 TIRAP HSALNG0087985 piR-54178 VSIG10L2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIRAP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIRAP

Top Transcription factor binding sites by QIAGEN in the TIRAP gene promoter:
  • AREB6
  • c-Ets-1
  • E47
  • FOXI1
  • HFH-3
  • HOXA3
  • HSF1 (long)
  • IRF-7A
  • Tal-1beta

Genomic Locations for TIRAP Gene

Latest Assembly
chr11:126,283,065-126,298,845
(GRCh38/hg38)
Size:
15,781 bases
Orientation:
Plus strand

Previous Assembly
chr11:126,152,988-126,164,828
(GRCh37/hg19 by Entrez Gene)
Size:
11,841 bases
Orientation:
Plus strand

chr11:126,152,960-126,168,740
(GRCh37/hg19 by Ensembl)
Size:
15,781 bases
Orientation:
Plus strand

Genomic View for TIRAP Gene

Genes around TIRAP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIRAP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIRAP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIRAP Gene

Proteins for TIRAP Gene

  • Protein details for TIRAP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P58753-TIRAP_HUMAN
    Recommended name:
    Toll/interleukin-1 receptor domain-containing adapter protein
    Protein Accession:
    P58753
    Secondary Accessions:
    • B3KW65
    • Q56UH9
    • Q56UI0
    • Q8N5E5

    Protein attributes for TIRAP Gene

    Size:
    221 amino acids
    Molecular mass:
    23883 Da
    Quaternary structure:
    • Homodimer. Also forms heterodimers with MYD88. May interact with PIK3AP1 (By similarity). Interacts with TLR4 and IRAK2 via their respective TIR domains. Interacts with BMX and TBK1. Interacts with EIF2AK2. Does not interact with IRAK1, nor TLR9.
    • (Microbial infection) In case of infection, interacts with Brucella protein BtpA.

    Three dimensional structures from OCA and Proteopedia for TIRAP Gene

    Alternative splice isoforms for TIRAP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TIRAP Gene

Post-translational modifications for TIRAP Gene

  • Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
  • Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibodies for research

  • Abcam antibodies for TIRAP

No data available for DME Specific Peptides for TIRAP Gene

Domains & Families for TIRAP Gene

Gene Families for TIRAP Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for TIRAP Gene

Suggested Antigen Peptide Sequences for TIRAP Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ93639, Homo sapiens toll-interleukin 1 receptor (TIR) domain containingadaptor protein (TIRAP), transcript variant 2, mRNA (Q56UH9_HUMAN)
  • MyD88 adapter-like protein (TIRAP_HUMAN)
genes like me logo Genes that share domains with TIRAP: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TIRAP Gene

Function for TIRAP Gene

Molecular function for TIRAP Gene

UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for TIRAP Gene

Gene Ontology (GO) - Molecular Function for TIRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005080 protein kinase C binding IPI 17161867
GO:0005515 protein binding IPI 11544529
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding ISS --
GO:0030674 protein binding, bridging NAS 19509286
GO:0035662 Toll-like receptor 4 binding IPI 19509286
genes like me logo Genes that share ontologies with TIRAP: view
genes like me logo Genes that share phenotypes with TIRAP: view

Animal Models for TIRAP Gene

MGI Knock Outs for TIRAP:

miRNA for TIRAP Gene

miRTarBase miRNAs that target TIRAP

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIRAP

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TIRAP Gene

Localization for TIRAP Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIRAP Gene

Cytoplasm. Cell membrane. Membrane. Note=Colocalizes with DAB2IP at the plasma membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TIRAP gene
Compartment Confidence
plasma membrane 5
cytosol 5
nucleus 4
endosome 3
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytokinetic bridge (2)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TIRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 19948740
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0030139 endocytic vesicle ISS --
genes like me logo Genes that share ontologies with TIRAP: view

Pathways & Interactions for TIRAP Gene

genes like me logo Genes that share pathways with TIRAP: view

Pathways by source for TIRAP Gene

5 GeneGo (Thomson Reuters) pathways for TIRAP Gene
  • Bacterial infections in CF airways
  • Immune response Bacterial infections in normal airways
  • Immune response TLR signaling pathways
  • Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway
  • Mucin expression in CF via TLRs, EGFR signaling pathways
5 Qiagen pathways for TIRAP Gene
  • Tec Kinases Signaling
  • TLR-TRIF Pathway
  • Toll Comparative Pathway
  • Toll-Like Receptors Pathway
  • TRAF Pathway
1 GeneTex pathway for TIRAP Gene

SIGNOR curated interactions for TIRAP Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for TIRAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS 19509286
GO:0006954 inflammatory response IEA --
GO:0007165 signal transduction IEA --
GO:0007166 cell surface receptor signaling pathway ISS --
genes like me logo Genes that share ontologies with TIRAP: view

Drugs & Compounds for TIRAP Gene

(2) Drugs for TIRAP Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ustekinumab Approved, Investigational Pharma 151
genes like me logo Genes that share compounds with TIRAP: view

Transcripts for TIRAP Gene

mRNA/cDNA for TIRAP Gene

5 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIRAP

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for TIRAP Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7 ^ 8a · 8b · 8c · 8d ^ 9a · 9b · 9c
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - - -
SP4: - - - - - - - - -
SP5: - - - - -
SP6: - -
SP7:
SP8: - - - - -
SP9: - - -
SP10: -
SP11: - - - - -

Relevant External Links for TIRAP Gene

GeneLoc Exon Structure for
TIRAP

Expression for TIRAP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIRAP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TIRAP Gene

This gene is overexpressed in Monocytes (34.5), CD4 Tcells (20.5), and Placenta (14.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TIRAP Gene



Protein tissue co-expression partners for TIRAP Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIRAP

SOURCE GeneReport for Unigene cluster for TIRAP Gene:

Hs.537126

mRNA Expression by UniProt/SwissProt for TIRAP Gene:

P58753-TIRAP_HUMAN
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.

Evidence on tissue expression from TISSUES for TIRAP Gene

  • Spleen(4.5)
  • Blood(4.5)
  • Lymph node(4.5)
  • Nervous system(4.4)
  • Heart(2.5)
  • Kidney(2.4)
  • Muscle(2.3)
  • Intestine(2.2)
  • Liver(2.1)
  • Bone marrow(2.1)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with TIRAP: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIRAP Gene

Orthologs for TIRAP Gene

This gene was present in the common ancestor of chordates.

Orthologs for TIRAP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TIRAP 30 31
  • 99.4 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TIRAP 30 31
  • 82.96 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TIRAP 30 31
  • 82.27 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tirap 30
  • 80.24 (n)
Mouse
(Mus musculus)
Mammalia Tirap 30 17 31
  • 79.49 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TIRAP 31
  • 54 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TIRAP 31
  • 51 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TIRAP 30 31
  • 58.96 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TIRAP 31
  • 44 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100491693 30
  • 49.03 (n)
Zebrafish
(Danio rerio)
Actinopterygii tirap 30 31
  • 50.58 (n)
OneToOne
Species where no ortholog for TIRAP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TIRAP Gene

ENSEMBL:
Gene Tree for TIRAP (if available)
TreeFam:
Gene Tree for TIRAP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIRAP: view image

Paralogs for TIRAP Gene

No data available for Paralogs for TIRAP Gene

Variants for TIRAP Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TIRAP Gene

TIRAP_HUMAN-P58753
Genetic variations in TIRAP may influence susceptibility or resistance to invasive pneumococcal disease, malaria [MIM:611162], and tuberculosis [MIM:607948]. It may define the bacteremia susceptibility locus 1 (BACTS1) [MIM:614382].

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIRAP Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs8177374 Protective: Bacteremia, resistance to; Mycobacterium tuberculosis, protection against; Invasive pneumococcal disease, protection against; Malaria, resistance to. - 126,292,948(+) C/Tp.Ser180Leu
NM_148910.2(TIRAP):c.539C>T (p.Ser180Leu)
MISSENSE
rs3802813 - p.Ser55Asn
rs7932976 - p.Val197Ile
rs8177369 - p.Ala9Pro
rs8177399 - p.Arg13Trp

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TIRAP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TIRAP Gene

Variant ID Type Subtype PubMed ID
esv2660319 CNV deletion 23128226
esv2664251 CNV deletion 23128226
esv2762950 CNV loss 21179565
esv3628001 CNV loss 21293372
esv3628002 CNV loss 21293372
nsv556530 CNV loss 21841781
nsv826122 CNV loss 20364138

Variation tolerance for TIRAP Gene

Residual Variation Intolerance Score: 89.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.46; 71.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIRAP Gene

Human Gene Mutation Database (HGMD)
TIRAP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIRAP

SNP Genotyping and Copy Number Assays for research

Disorders for TIRAP Gene

MalaCards: The human disease database

(6) MalaCards diseases for TIRAP Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
bacteremia 1
  • bacteremia, susceptibility to, 1
malaria
  • malaria, susceptibility to
pertussis
  • bordetella infection
bacteriuria
pelvic inflammatory disease
  • pid
- elite association - COSMIC cancer census association via MalaCards
Search TIRAP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TIRAP

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TIRAP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIRAP Gene

Publications for TIRAP Gene

  1. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. (PMID: 16991088) Hawn TR … Aderem A (The Journal of infectious diseases 2006) 3 23 41 74
  2. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. (PMID: 11544529) Fitzgerald KA … O'Neill LA (Nature 2001) 2 3 4 23
  3. AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling. (PMID: 19948740) Wan T … Min W (The Journal of biological chemistry 2010) 3 4 23
  4. A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling. (PMID: 19509286) Nagpal K … Golenbock DT (The Journal of biological chemistry 2009) 3 4 23
  5. Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy. (PMID: 19602285) Hamann L … Schumann RR (BMC medical genetics 2009) 3 4 41

Products for TIRAP Gene

Sources for TIRAP Gene