Toll/interleukin-1 receptor domain-containing adapter protein; TIR domain-containing adapter protein; adaptor protein Wyatt; MyD88 adapter-like protein (TIRAP, MAL)

Function

• adapter involved in TLR4 signaling
• innate immune response
• acts via IRAK2 & TRAF-6
• activation of NF-kappa-B, MAPK1, MAPK3 & JNK
• cytokine secretion
• inflammatory response
• positively regulates production of TNF-alpha & IL-6
• phosphorylated by IRAK1 & IRAK4
• also phosphorylated by BTK
• polyubiquitination follows phosphorylation by BTK & leads to TIRAP degradation
• forms homodimers & heterodimers with MyD88
• binds to TLR4 via their TIR domain
• binds to BMX, PKR & TBK1
• does not interact with IRAK1, nor TLR9

Structure

• homodimer
• contains 1 TIR domain

Compartment

cytoplasm

Alternative splicing

named isoforms=3

Expression

• expressed in liver, kidney, spleen, skeletal muscle, heart > peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon, brain

Polymorphism

• genetic variations in TIRAP may influence susceptibility or resistance to invasive pneumococcal disease, malaria, & tuberculosis
• genetic variations in TIRAP influence susceptibility or resistance to bacterial invasion of the blood & define the bacteremia susceptibility locus 1 (BACTS1)

More general terms

• secreted protein
• glycoprotein

Additional terms

• interleukin-1 receptor (IL1R)
• Toll-like receptor 4; hToll; CD284 (TLR4)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=114609
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:114609
• OMIM: https://mirror.omim.org/entry/606252
• OMIM: https://mirror.omim.org/entry/607948
• OMIM: https://mirror.omim.org/entry/610799
• OMIM: https://mirror.omim.org/entry/611162
• OMIM: https://mirror.omim.org/entry/614382
• UniProt: http://www.uniprot.org/uniprot/P58753.html