Search
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 [2], malaria [3], & tuberculosis [4]
- genetic variations in TIRAP influence susceptibility or resistance to bacterial invasion of the blood & define the bacteremia susceptibility locus 1 (BACTS1) [5]
Related
interleukin-1 receptor (IL1R)
Toll-like receptor 4; hToll; CD284 (TLR4)
General
glycoprotein
secreted protein
Properties
SIZE: entity length = 221 aa
MW = 24 kD
COMPARTMENT: cytoplasm
MOTIF: glycosylation site
TIR domain {84-221}
MOTIF: cysteine residue {C89}
MODIFICATION: cysteine residue {C134}
cysteine residue {C134}
MODIFICATION: cysteine residue {C89}
cysteine residue {C142}
MODIFICATION: cysteine residue {C174}
cysteine residue {C174}
MODIFICATION: cysteine residue {C142}
Database Correlations
OMIM correlations
MORBIDMAP 606252
UniProt P58753
Pfam PF13676
Entrez Gene 114609
Kegg hsa:114609
References
- UniProt :accession P58753
- OMIM :accession 610799
- OMIM :accession 611162
- OMIM :accession 607948
- OMIM :accession 614382
- SeattleSNPs
http://pga.gs.washington.edu/data/tirap/