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

    Gene ID: 114609, updated on 2-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (126283093..126294933)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (126314493..126326362)
    RS_2024_09 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 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. Role of S180L polymorphism in etiology of malaria caused by Plasmodium falciparum in a small group of Pakistani population. Nawaz SK, et al. Bosn J Basic Med Sci, 2015 Aug 19. PMID 26614847, Free PMC Article
    2. Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy. Hamann L, et al. BMC Med Genet, 2009 Jul 14. PMID 19602285, Free PMC Article
    3. Solution structure of the TLR adaptor MAL/TIRAP reveals an intact BB loop and supports MAL Cys91 glutathionylation for signaling. Hughes MM, et al. Proc Natl Acad Sci U S A, 2017 Aug 8. PMID 28739909, Free PMC Article
    4. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Ferwerda B, et al. Proc Natl Acad Sci U S A, 2009 Jun 23. PMID 19509334, Free PMC Article
    5. Membrane targeting of TIRAP is negatively regulated by phosphorylation in its phosphoinositide-binding motif. Zhao X, et al. Sci Rep, 2017 Feb 22. PMID 28225045, Free PMC Article

    See all (152) 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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    NEW Try the new Transcript table

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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