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

Summary

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

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_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
TIRAP in the Mechanism of Inflammation.
Title: TIRAP in the Mechanism of Inflammation.
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.
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.
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.
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	not available
Malaria, susceptibility to MedGen: C1970028 OMIM: 611162 GeneReviews: Not available	not available
Mycobacterium tuberculosis, susceptibility to MedGen: C1834752 OMIM: 607948 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH91927 (e-PCR)
- UniSTS:92517

D1S1423 (e-PCR)
- UniSTS:149619

RH45313 (e-PCR)
- UniSTS:78306

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

NG_011523.1 RefSeqGene

Range

5007..16847

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

126283093..126294933

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

126314493..126326362

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_052887.2: Suppressed sequence

Description

NM_052887.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.