InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TICAM2

Summary

InnateDB Protein

IDBP-374890.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TICAM2

Protein Name

toll-like receptor adaptor molecule 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000415139

InnateDB Gene

IDBG-406966 (TICAM2)

Protein Structure

UniProt Annotation

Function

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.Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

Subcellular Localization

Isoform 1: Cytoplasm. Golgi apparatus. Cell membrane. Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Note=Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the membrane. Upon LPS stimulation colcoalizes with isoform 2 in late endosomes.Isoform 2: Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Note=Translocates to late endosomes upon LPS stimulation where it colcoalizes with isoform 1.

Disease Associations

Tissue Specificity

Expressed in spleen, prostate, testis, uterus, small intestine, colon, peripheral blood leukocytes, heart, placenta, lung, liver, skeletal muscle, and pancreas Isoform 2 is ubiquitously expressed (at lower levels than isoform 1). {ECO:0000269PubMed:12721283, ECO:0000269PubMed:14519765, ECO:0000269PubMed:19412184}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.

Experimentally validated
Total	23 [view]
Protein-Protein	23 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0005543	phospholipid binding

Biological Process

GO:0001817	regulation of cytokine production
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0032729	positive regulation of interferon-gamma production
GO:0032755	positive regulation of interleukin-6 production
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034144	negative regulation of toll-like receptor 4 signaling pathway
GO:0034145	positive regulation of toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035669	TRAM-dependent toll-like receptor 4 signaling pathway
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0070671	response to interleukin-12
GO:0071222	cellular response to lipopolysaccharide
GO:0071650	negative regulation of chemokine (C-C motif) ligand 5 production
GO:0071651	positive regulation of chemokine (C-C motif) ligand 5 production
GO:2000494	positive regulation of interleukin-18-mediated signaling pathway

Cellular Component

GO:0005768	endosome
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0031901	early endosome membrane
GO:0031902	late endosome membrane