CPLM-016312

Genbank Nucleotide ID

TIR domain-containing adapter molecule 2

Protein Synonyms/Alias

TICAM-2; Putative NF-kappa-B-activating protein 502; TRIF-related adapter molecule; Toll-like receptor adaptor protein 3; Toll/interleukin-1 receptor domain-containing protein; MyD88-4

Homo sapiens (Human)

Position	Peptide	Type	References
83	RLEDPDGKVLYKEMK	ubiquitination	[1, 2, 3]
87	PDGKVLYKEMKKQYD	ubiquitination	[1]
91	VLYKEMKKQYDSFTF	ubiquitination	[1]
204	GYHESDSKKSEDLSL	acetylation	[4]
205	YHESDSKKSEDLSLC	acetylation	[4]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[4] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]

Functional Description

Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.

DOMAIN 73 232 TIR.
MOD_RES 16 16 Phosphoserine; by PKC/PRKCE.
LIPID 2 2 N-myristoyl glycine.

Alternative splicing; Cell membrane; Complete proteome; Cytoplasm; Endoplasmic reticulum; Endosome; Golgi apparatus; Immunity; Inflammatory response; Innate immunity; Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005769; C:early endosome; IDA:UniProtKB.
GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
GO:0010008; C:endosome membrane; TAS:Reactome.
GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
GO:0005770; C:late endosome; IDA:UniProtKB.
GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO:0004871; F:signal transducer activity; IMP:UniProtKB.
GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
GO:2000494; P:positive regulation of interleukin-18-mediated signaling pathway; IMP:UniProtKB.
GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; IDA:UniProtKB.
GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.