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	~~'''~~TIRAP''' (TIR domain-containing adaptor protein), also known as '''Mal''' (MyD88-adapter-like), is a protein that in humans is encoded by the TIRAP gene. TIRAP plays a crucial role in the innate immune response to microbial pathogens. It acts via [[MyD88]], an adapter molecule in the [[Toll-like receptor]] signaling pathway, and plays a role in [[inflammation]] and [[immune response]].		== TIRAP ==

	~~== Function ==~~		[[File:Toll-like_receptor_pathways_revised.jpg\|thumb\|right\|Diagram of Toll-like receptor pathways, including TIRAP involvement.]]

			'''TIRAP''' (Toll-interleukin 1 receptor (TIR) domain-containing adaptor protein), also known as '''MAL''' (MyD88-adapter-like), is a critical adaptor protein involved in the signaling pathways of the [[innate immune system]]. It plays a pivotal role in the [[Toll-like receptor]] (TLR) signaling cascade, which is essential for the recognition of [[pathogen-associated molecular patterns]] (PAMPs) and the subsequent activation of [[immune responses]].

	TIRAP is ~~involved~~ in ~~bridging [[MyD88]] to [[Toll-like receptor]] 4 (TLR4). It is integral to~~ the ~~[[innate immune response]] to [[lipopolysaccharide]] (LPS) from Gram-negative bacteria by acting as a sorting~~ adaptor ~~that mediates TLR4 localization to the [[endosome]]~~. This is ~~necessary~~ for ~~the efficient TLR4~~-~~induced~~ [[~~MAP kinase~~]] activation ~~and subsequent proinflammatory cytokine production~~.		== Structure ==
			TIRAP is characterized by the presence of a TIR domain, which is a conserved region found in all members of the TLR family and their associated adaptor proteins. This domain is crucial for protein-protein interactions that facilitate downstream signaling. The TIR domain of TIRAP allows it to interact with other TIR domain-containing proteins, such as [[MyD88]], to propagate the signal initiated by TLR activation.

	== ~~Clinical significance~~ ==		== Function ==
			TIRAP functions as a bridging adaptor that links specific TLRs to the downstream signaling adaptor MyD88. It is primarily involved in the signaling pathways of TLR2 and TLR4. Upon activation by their respective ligands, TLR2 and TLR4 recruit TIRAP to the plasma membrane, where it facilitates the recruitment of MyD88. This recruitment is essential for the activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and type I [[interferons]].

	Mutations in the TIRAP gene have been associated with ~~increased~~ susceptibility to ~~[[tuberculosis]]~~. ~~A specific polymorphism~~ in TIRAP~~, S180L, has~~ been ~~shown~~ to ~~protect against~~ [[tuberculosis]], [[~~pneumococcal disease~~]], and ~~[[malaria]]~~.		== Role in Disease ==
			Mutations or polymorphisms in the TIRAP gene have been associated with altered susceptibility to various infectious diseases. For example, certain polymorphisms in TIRAP have been linked to increased susceptibility to [[tuberculosis]] and [[malaria]], while others may confer protection against these diseases. The role of TIRAP in inflammatory and autoimmune diseases is also an area of active research, as dysregulation of TLR signaling can contribute to chronic inflammation and autoimmunity.

	== ~~See also~~ ==		== Related Proteins ==
			TIRAP is one of several adaptor proteins involved in TLR signaling. Other key adaptors include MyD88, [[TRIF]] (TIR-domain-containing adapter-inducing interferon-_), and [[TRAM]] (TRIF-related adaptor molecule). Each of these adaptors is involved in distinct TLR signaling pathways, contributing to the specificity and diversity of the immune response.

			== Related Pages ==
	* [[Toll-like receptor]]		* [[Toll-like receptor]]
	* [[MyD88]]		* [[MyD88]]
	* [[Innate immune system]]		* [[Innate immune system]]
	* [[~~Tuberculosis~~]]		* [[Pathogen-associated molecular pattern]]
	* [[Pneumococcal disease]]
	* [[Malaria]]

	~~== References ==~~

	~~<references />~~

	~~== External links ==~~

	* [https://www.ncbi.nlm.nih.gov/gene/114609 NCBI Gene]
	* [https://www.uniprot.org/uniprot/Q6WN34 UniProt]

	[[Category:~~Human proteins]]~~		[[Category:Immunology]]
	~~[[Category:Immune system]]~~
	~~[[Category:Innate immune system~~]]
	[[Category:Signal transduction]]		[[Category:Signal transduction]]
	~~{{stub}}~~

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2024-02-25T21:13:52Z

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'''TIRAP''' (TIR domain-containing adaptor protein), also known as '''Mal''' (MyD88-adapter-like), is a protein that in humans is encoded by the TIRAP gene. TIRAP plays a crucial role in the innate immune response to microbial pathogens. It acts via [[MyD88]], an adapter molecule in the [[Toll-like receptor]] signaling pathway, and plays a role in [[inflammation]] and [[immune response]].

== Function ==

TIRAP is involved in bridging [[MyD88]] to [[Toll-like receptor]] 4 (TLR4). It is integral to the [[innate immune response]] to [[lipopolysaccharide]] (LPS) from Gram-negative bacteria by acting as a sorting adaptor that mediates TLR4 localization to the [[endosome]]. This is necessary for the efficient TLR4-induced [[MAP kinase]] activation and subsequent proinflammatory cytokine production.

== Clinical significance ==

Mutations in the TIRAP gene have been associated with increased susceptibility to [[tuberculosis]]. A specific polymorphism in TIRAP, S180L, has been shown to protect against [[tuberculosis]], [[pneumococcal disease]], and [[malaria]].

== See also ==

* [[Toll-like receptor]]
* [[MyD88]]
* [[Innate immune system]]
* [[Tuberculosis]]
* [[Pneumococcal disease]]
* [[Malaria]]

== References ==

<references />

== External links ==

* [https://www.ncbi.nlm.nih.gov/gene/114609 NCBI Gene]
* [https://www.uniprot.org/uniprot/Q6WN34 UniProt]

[[Category:Human proteins]]
[[Category:Immune system]]
[[Category:Innate immune system]]
[[Category:Signal transduction]]
{{stub}}

TIRAP - Revision history

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