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TIRAP TIR domain containing adaptor protein [ Homo sapiens (human) ]

Gene ID: 114609, updated on 11-Apr-2024

Summary

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Official Symbol
TIRAPprovided by HGNC
Official Full Name
TIR domain containing adaptor proteinprovided by HGNC
Primary source
HGNC:HGNC:17192
See related
Ensembl:ENSG00000150455 MIM:606252; AllianceGenome:HGNC:17192
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Mal; wyatt; BACTS1; MyD88-2
Summary
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]
Annotation information
Note: MAL (Gene ID: 4118), TIRAP (Gene ID: 114609), and MKL1 (Gene ID: 57591) share the MAL symbol/alias in common. MAL is a widely used alternative name for TIR domain containing adaptor protein (TIRAP) and megakaryoblastic leukemia (translocation) 1 (MKL1). [23 May 2018]
Expression
Ubiquitous expression in duodenum (RPKM 2.7), ovary (RPKM 2.6) and 25 other tissues See more
Orthologs
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Genomic context

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See TIRAP in Genome Data Viewer
Location:
11q24.2
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (126283093..126294933)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (126314493..126326362)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (126152988..126164828)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902838 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126152727-126153534 Neighboring gene ribosomal protein L35a pseudogene 26 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5706 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:126162703-126163207 Neighboring gene TIRAP antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5707 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5708 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:126185709-126185914 Neighboring gene decapping enzyme, scavenger Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126197556-126198280 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126198281-126199003 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:126203043-126203544 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:126204673-126205174 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126206322-126206884 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126206885-126207448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126207449-126208010 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:126208933-126210132 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:126224473-126225216 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126225217-126225958 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126225959-126226702 Neighboring gene G-quadruplex forming sequence containing lncRNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:126228189-126228930 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:126234481-126234998 Neighboring gene ST3 beta-galactoside alpha-2,3-sialyltransferase 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:126263623-126264550

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. TIRAP Rs8177376, Rs611953, Rs3802814, and Rs8177374 Polymorphisms and Their Association with Cervical Cancer Phenotype and Prognosis. Bekampytė J, et al. Genes (Basel), 2022 Jul 29. PMID 36011276, Free PMC Article
  2. TIRAP in the Mechanism of Inflammation. Rajpoot S, et al. Front Immunol, 2021. PMID 34305934, Free PMC Article
  3. MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients. Saranathan R, et al. Infect Genet Evol, 2020 Jan. PMID 31678649
  4. Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis. Shao JB, et al. Cell Immunol, 2019 Oct. PMID 31196568
  5. TIRAP p.R81C is a novel lymphoma risk variant which enhances cell proliferation via NF-κB mediated signaling in B-cells. Burkhard R, et al. Haematologica, 2019 Apr. PMID 30381301, Free PMC Article

See all (151) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Role of MyD88-Adaptor-Like (MAL) Gene Polymorphism rs8177374 and Cytokine (IFN-gamma, TNF-alpha, IL-10, TGF-beta) Levels in Diverse Malaria Manifestations upon P. falciparum and P. vivax Infections.
    Title: Role of MyD88-Adaptor-Like (MAL) Gene Polymorphism rs8177374 and Cytokine (IFN-γ, TNF-α, IL-10, TGF-β) Levels in Diverse Malaria Manifestations upon P. falciparum and P. vivax Infections.
  2. ALKBH5-mediated m[6] A demethylation of TIRAP mRNA promotes radiation-induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma.
    Title: ALKBH5-mediated m(6) A demethylation of TIRAP mRNA promotes radiation-induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma.
  3. TIRAP Rs8177376, Rs611953, Rs3802814, and Rs8177374 Polymorphisms and Their Association with Cervical Cancer Phenotype and Prognosis.
    Title: TIRAP Rs8177376, Rs611953, Rs3802814, and Rs8177374 Polymorphisms and Their Association with Cervical Cancer Phenotype and Prognosis.
  4. Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19.
    Title: Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19.
  5. Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis.
    Title: Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis.
  6. TIRAP in the Mechanism of Inflammation.
    Title: TIRAP in the Mechanism of Inflammation.
  7. HSV-1/TLR9-Mediated IFNbeta and TNFalpha Induction Is Mal-Dependent in Macrophages.
    Title: HSV-1/TLR9-Mediated IFNβ and TNFα Induction Is Mal-Dependent in Macrophages.
  8. The alphaC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases.
    Title: The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases.
  9. role of Mal signal in the maintenance of DEC205(+) dendritic cell immune tolerogenic function
    Title: Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis.
  10. Results found no association between TIRAP S180L variant and disease severity among human active Tuberculosis (TB) cases.
    Title: MAL adaptor (TIRAP) S180L polymorphism and severity of disease among tuberculosis patients.
Submit: New GeneRIF Correction See all GeneRIFs (94)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Bacteremia, susceptibility to, 1
MedGen: C3280645 OMIM: 614382 GeneReviews: Not available
Compare labs
Malaria, susceptibility to
MedGen: C1970028 OMIM: 611162 GeneReviews: Not available
Compare labs
Mycobacterium tuberculosis, susceptibility to
MedGen: C1834752 OMIM: 607948 GeneReviews: Not available
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat causes proteasomal degradation of TIRAP and NFKBIA in THP-1 cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: DCPS

Homology

Clone Names

  • FLJ42305

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables Toll-like receptor 2 binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables Toll-like receptor 2 binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables Toll-like receptor 4 binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables Toll-like receptor 4 binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables molecular adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphatidylinositol-4,5-bisphosphate binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase C binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables signaling adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in 3'-UTR-mediated mRNA stabilization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in MyD88-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in TIRAP-dependent toll-like receptor 4 signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell surface receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to bacterial lipopeptide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to lipoteichoic acid ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in defense response to Gram-positive bacterium ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in myeloid cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of B cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JNK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of canonical NF-kappaB signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of chemokine (C-X-C motif) ligand 1 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of interleukin-12 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of interleukin-15 production IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of interleukin-6 production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of interleukin-8 production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of neutrophil chemotaxis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of protein-containing complex assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of toll-like receptor 2 signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of toll-like receptor 3 signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of toll-like receptor 4 signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of tumor necrosis factor production IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of tumor necrosis factor production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of innate immune response IC
Inferred by Curator
more info
 PubMed 
involved_in regulation of interferon-beta production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in toll-like receptor 4 signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in toll-like receptor 4 signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endocytic vesicle ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in extrinsic component of cytoplasmic side of plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in ruffle membrane ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
toll/interleukin-1 receptor domain-containing adapter protein
Names
MyD88 adapter-like protein
Toll-like receptor adaptor protein
adapter protein wyatt
adaptor protein Wyatt
toll-interleukin 1 receptor (TIR) domain containing adaptor protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011523.1 RefSeqGene

    Range
    5007..16847
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001039661.2 → NP_001034750.1  toll/interleukin-1 receptor domain-containing adapter protein isoform a

    See identical proteins and their annotated locations for NP_001034750.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longer transcript but encodes the shorter isoform (a). Variants 3 and 5 both encode the same isoform (a).
    Source sequence(s)
    AK124298, AP001318, BC032474
    Consensus CDS
    CCDS8472.1
    UniProtKB/Swiss-Prot
    B3KW65, P58753, Q56UH9, Q56UI0, Q8N5E5
    Related
    ENSP00000376447.2, ENST00000392680.6
    Conserved Domains (1) summary
    pfam13676
    Location:88 → 208
    TIR_2; TIR domain

  2. NM_001318776.2 → NP_001305705.1  toll/interleukin-1 receptor domain-containing adapter protein isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 2. Variants 2 and 4 both encode the same isoform (b).
    Source sequence(s)
    AF378129, AK124298, AK313147
    Consensus CDS
    CCDS41731.1
    UniProtKB/Swiss-Prot
    P58753
    Related
    ENSP00000515019.1, ENST00000700491.1
    Conserved Domains (1) summary
    pfam13676
    Location:88 → 208
    TIR_2; TIR domain

  3. NM_001318777.2 → NP_001305706.1  toll/interleukin-1 receptor domain-containing adapter protein isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 3. Variants 3 and 5 both encode the same isoform (a).
    Source sequence(s)
    AK124298, AP001318, AY576785
    Consensus CDS
    CCDS8472.1
    UniProtKB/Swiss-Prot
    B3KW65, P58753, Q56UH9, Q56UI0, Q8N5E5
    Related
    ENSP00000376446.1, ENST00000392679.6
    Conserved Domains (1) summary
    pfam13676
    Location:88 → 208
    TIR_2; TIR domain

  4. NM_148910.3 → NP_683708.1  toll/interleukin-1 receptor domain-containing adapter protein isoform b

    See identical proteins and their annotated locations for NP_683708.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an additional segment within the 5' UTR and differs in the 3' coding region and 3' UTR, compared to variant 3. This results in a longer isoform (b) with a distinct C-terminus, compared to isoform a. Variants 2 and 4 both encode the same isoform (b).
    Source sequence(s)
    AF378129, AK124298
    Consensus CDS
    CCDS41731.1
    UniProtKB/Swiss-Prot
    P58753
    Related
    ENSP00000376445.3, ENST00000392678.7
    Conserved Domains (1) summary
    pfam13676
    Location:88 → 208
    TIR_2; TIR domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    126283093..126294933
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    126314493..126326362
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_052887.2: Suppressed sequence

    Description
    NM_052887.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P58753.2 GenPept UniProtKB/Swiss-Prot:P58753

Gene LinkOut

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