Tirap toll-interleukin 1 receptor (TIR) domain-containing adaptor protein [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tirapprovided by MGI
Official Full Name: toll-interleukin 1 receptor (TIR) domain-containing adaptor proteinprovided by MGI
Primary source: MGI:MGI:2152213
See related: Ensembl:ENSMUSG00000032041 AllianceGenome:MGI:2152213
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Mal; Wyatt; Tlr4ap; C130027E04Rik
Summary: Enables Toll-like receptor 2 binding activity; identical protein binding activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including positive regulation of B cell proliferation; positive regulation of NF-kappaB transcription factor activity; and regulation of cytokine production. Acts upstream of or within several processes, including I-kappaB kinase/NF-kappaB signaling; myeloid cell differentiation; and response to bacterium. Located in endocytic vesicle and ruffle membrane. Is expressed in testis. Human ortholog(s) of this gene implicated in malaria and tuberculosis. Orthologous to human TIRAP (TIR domain containing adaptor protein). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in liver adult (RPKM 4.0), bladder adult (RPKM 3.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 A4; 9 19.99 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (35095687..35111587, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (35184391..35200291, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tirap controls Mycobacterium tuberculosis phagosomal acidification.
Title: Tirap controls Mycobacterium tuberculosis phagosomal acidification.
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 drives myelosuppression through an Ifngamma-Hmgb1 axis that disrupts the endothelial niche in mice.
Title: TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the endothelial niche in mice.
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.
mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression.
Title: mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression.
GPR108, an NF-kappaB activator suppressed by TIRAP, negatively regulates TLR-triggered immune responses.
Title: GPR108, an NF-κB activator suppressed by TIRAP, negatively regulates TLR-triggered immune responses.
TIARP independently down-regulated CXCL2 and IL-6 production by fibroblast-like synoviocytes, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, with resultant reduction of neutrophil migration into arthritic joints.
Title: TIARP attenuates autoantibody-mediated arthritis via the suppression of neutrophil migration by reducing CXCL2/CXCR2 and IL-6 expression.
Our key findings provide novel insights into the mechanism of action of heterotrimeric complex (PKCdelta-TIRAP-p38) in proinflammatory cytokine expression, which controls the development of the inflammatory trigger in stimulated macrophages.
Title: Heterotrimeric complex of p38 MAPK, PKCδ, and TIRAP is required for AP1 mediated inflammatory response.
Results suggest that TIR domain-containing adaptor protein positively regulated BV2 microglial M1 polarization through toll-like receptor 4 -mediated Transforming Growth Factor-Beta-Activated Kinase 1/I-Kappa-B Kinase /Nuclear Factor of Kappa Light Polypeptide Gene Enhancer in B-Cells (TAK1/IKK/NF-kappaB), mitogen-activated protein kinases and Akt signalling pathways.
Title: Toll-Interleukin 1 Receptor domain-containing adaptor protein positively regulates BV2 cell M1 polarization.

Submit: New GeneRIF Correction See all GeneRIFs (39)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10Mit157.2 (e-PCR), detects polymorphism
- UniSTS:126061

RH124653 (e-PCR)
- UniSTS:161475

Gene Ontology Provided by MGI

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 2 binding	ISO Inferred from Sequence Orthology more info
enables Toll-like receptor 4 binding	IBA Inferred from Biological aspect of Ancestor more info
enables Toll-like receptor 4 binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables molecular adaptor activity	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-4,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	ISO Inferred from Sequence Orthology more info
enables signaling adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables signaling adaptor activity	ISO Inferred from Sequence Orthology more info	PubMed

Process	Evidence Code	Pubs
involved_in 3'-UTR-mediated mRNA stabilization	ISO Inferred from Sequence Orthology more info
involved_in TIRAP-dependent toll-like receptor 4 signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell surface receptor signaling pathway	IPI Inferred from Physical Interaction more info	PubMed
acts_upstream_of_or_within cell surface receptor signaling pathway	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within cellular response to bacterial lipopeptide	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to lipoteichoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within defense response to Gram-positive bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within immune system process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within inflammatory response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within innate immune response	IEA Inferred from Electronic Annotation more info
NOT involved_in interleukin-1-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in interleukin-1-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of macrophage cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within myeloid cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of JNK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of JUN kinase activity	ISO Inferred from Sequence Orthology 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 NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
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 canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info	PubMed
involved_in positive regulation of chemokine (C-X-C motif) ligand 1 production	IMP Inferred from Mutant Phenotype more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-12 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-15 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-6 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-6 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-8 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-8 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of macrophage cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein-containing complex assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of toll-like receptor 2 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of toll-like receptor 3 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of toll-like receptor 4 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of tumor necrosis factor production	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	ISO Inferred from Sequence Orthology more info
involved_in regulation of innate immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of interleukin-15 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to bacterium	ISO Inferred from Sequence Orthology more info	PubMed
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in toll-like receptor 4 signaling pathway	ISO Inferred from Sequence Orthology more info	PubMed
NOT involved_in toll-like receptor 5 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cell surface	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in endocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in extrinsic component of cytoplasmic side of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
NOT located_in peroxisome	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	ISO Inferred from Sequence Orthology more info
located_in ruffle membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: toll/interleukin-1 receptor domain-containing adapter protein

Names: TIR domain-containing adapter protein; Toll-like receptor 4 adaptor protein; adaptor protein Wyatt; myD88 adapter-like 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.

mRNA and Protein(s)

NM_001177845.1 → NP_001171316.1 toll/interleukin-1 receptor domain-containing adapter protein

See identical proteins and their annotated locations for NP_001171316.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1-4 encode the same protein.

Source sequence(s)

AK080135, AK081514, AK168494, BY507516

Consensus CDS

CCDS40575.2

UniProtKB/TrEMBL

H3BKL1, Q542S6

Related

ENSMUSP00000135435.2, ENSMUST00000175765.8

Conserved Domains (1) summary

pfam13676
Location:116 → 234

TIR_2; TIR domain
NM_001177846.1 → NP_001171317.1 toll/interleukin-1 receptor domain-containing adapter protein

See identical proteins and their annotated locations for NP_001171317.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-4 encode the same protein.

Source sequence(s)

AK036431, AK081514, AK168494, BY507516, BY740695

Consensus CDS

CCDS40575.2

UniProtKB/TrEMBL

H3BKL1, Q542S6

Related

ENSMUSP00000135876.2, ENSMUST00000176685.8

Conserved Domains (1) summary

pfam13676
Location:116 → 234

TIR_2; TIR domain
NM_001177847.1 → NP_001171318.1 toll/interleukin-1 receptor domain-containing adapter protein

See identical proteins and their annotated locations for NP_001171318.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1-4 encode the same protein.

Source sequence(s)

AK081514, AK151117, AK168494, BY507516, BY743490

Consensus CDS

CCDS40575.2

UniProtKB/TrEMBL

H3BKL1, Q542S6

Related

ENSMUSP00000135462.2, ENSMUST00000177129.8

Conserved Domains (1) summary

pfam13676
Location:116 → 234

TIR_2; TIR domain
NM_054096.2 → NP_473437.2 toll/interleukin-1 receptor domain-containing adapter protein

See identical proteins and their annotated locations for NP_473437.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-4 encode the same protein.

Source sequence(s)

AF378130, AK081514, AK168494, BY507516, BY740695

Consensus CDS

CCDS40575.2

UniProtKB/TrEMBL

H3BKL1, Q542S6

Related

ENSMUSP00000135224.2, ENSMUST00000176531.8

Conserved Domains (1) summary

pfam13676
Location:116 → 234

TIR_2; TIR domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

35095687..35111587 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030244028.2 → XP_030099888.1 toll/interleukin-1 receptor domain-containing adapter protein isoform X1

UniProtKB/TrEMBL

H3BKL1, Q542S6

Conserved Domains (1) summary

pfam13676
Location:116 → 234

TIR_2; TIR domain