Gene Report

Basic Information

Approved Symbol	TOLLIP
Approved Name	toll interacting protein
Symbol Alias	IL-1RAcPIP
Location	11p
Position	chr11:1295598-1330892 (-)
External Links	Entrez Gene: 54472 Ensembl: ENSG00000078902 UCSC: uc001lte.3 HGNC ID: 16476
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between TOLLIP and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
TOLLIP	Sequeira A, 2009	patients and nomal controls	Group: P-value=0.001, F=10.9; Substance: P-value=0.007, F=8.9	Genes differentially expressed after an ANCOVA analysis betw...... Genes differentially expressed after an ANCOVA analysis between the three groups(C = control, S = suicide, SMD = suicide with major depression). More...

Positive relationships between TOLLIP and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
TOLLIP		Suicide(suicide)	symptoms	Sequeira A, 2009	patients and nomal controls	Group: P-value=0.001, F=10.9; Substance: P-value=0.007, F=8.9	Genes differentially expressed after an ANCOVA analysis betw...... Genes differentially expressed after an ANCOVA analysis between the three groups(C = control, S = suicide, SMD = suicide with major depression). More...

Positive relationship network of TOLLIP in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between TOLLIP and MDD (count: 0)

Negative relationships between TOLLIP and other components at different levels (count: 0)

TOLLIP related SNPs in MK4MDD (count: 0)

TOLLIP related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Toll-interacting protein	Q9H0E2	0(0/0)	Gene mapped

TOLLIP related GO terms (count: 22)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006954	inflammatory response	biological process	NAS[10854325]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0031625	ubiquitin protein ligase binding	molecular function	IEA
GO:0005829	cytosol	cellular component	TAS
GO:0007267	cell-cell signaling	biological process	TAS[10854325]
GO:0031624	ubiquitin conjugating enzyme binding	molecular function	IEA
GO:0019900	kinase binding	molecular function	IPI[10854325]
GO:0035325	Toll-like receptor binding	molecular function	IPI[11441107]
GO:0045087	innate immune response	biological process	IEA
GO:0004871	signal transducer activity	molecular function	NAS[11441107]
GO:0016604	nuclear body	cellular component	IEA
GO:0033235	positive regulation of protein sumoylation	biological process	IEA
GO:0005737	cytoplasm	cellular component	IC[11441107]
GO:0045321	leukocyte activation	biological process	NAS[11441107]
GO:0007165	signal transduction	biological process	IPI[11441107]
GO:0048471	perinuclear region of cytoplasm	cellular component	IEA
GO:0045323	interleukin-1 receptor complex	cellular component	NAS[10854325]
GO:0032183	SUMO binding	molecular function	IEA
GO:0035556	intracellular signal transduction	biological process	NAS[10854325]
GO:0016310	phosphorylation	biological process	IDA[1085432]
GO:0005150	interleukin-1, Type I receptor binding	molecular function	IEA
GO:0045092	interleukin-18 receptor complex	cellular component	NAS[10854325]
GO:0005515	protein binding	molecular function	IPI

TOLLIP related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04620	toll like_receptor_signaling_pathway	Toll-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK. More...

TOLLIP related BioCarta pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
TOLL_PATHWAY	toll pathway	Toll-Like Receptor Pathway	The innate immune response responds in a general manner to f...... The innate immune response responds in a general manner to factors present in invading pathogens. Bacterial factors such as lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, peptidoglycans and also CpG nucleic acids activate innate immunity as well as stimulating the antigen-specific immune response and triggering the inflammatory response. Members of the toll-like receptor (TLR) gene family convey signals stimulated by these factors, activating signal transduction pathways that result in transcriptional regulation and stimulate immune function. TLR2 is activated by bacterial lipoproteins, TLR4 is activated by LPS, and TLR9 is activated by CpG DNA; peptidoglycan recognition protein (PGRP) is activated by peptidoglycan (PGN). The downstream signaling pathways used by these receptors are similar to that used by the IL-1 receptor, activating the IL-1 receptor associated kinase (IRAK) through the MyD88 adaptor protein, and signaling through TRAF-6 and protein kinase cascades to activate NF-kB and Jun. NF-kB and c-Jun activate transcription of genes such as the proinflammatory cytokines IL-1 and IL-12. Several recent reports have suggested that the functional outcomes of signaling via TLR2, TLR4 and PGRP are not equivalent. For example, while the LPS-induced, p38-dependent response was dependent upon PU.1 binding, the PGN-induced, p38 response was not. The intracelular receptor for PGN, PGRP is conserved from insects to mammals. In insects, PGRP activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown. However, it was suggested that an identical protein Tag7 was a tumor necrosis factor-like (TNF-like) cytokine. PGRP/Tag7 possesses cytotoxicity and triggers intranucleosomal DNA fragmentation in target cells in the same way as many known members of the TNF family. Fragmentation of DNA is one of the characteristics of apoptosis. The possibility that in another system, PGRP/Tag7 would induce NF-kB activation, as observed for TRAIL (TNF-related apoptosis-inducing ligand) receptors canot be ruled out. More...
GSK3_PATHWAY	gsk3 pathway	Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages	Lipopolysaccharide. One of the key actions of AKT is to bloc...... Lipopolysaccharide. One of the key actions of AKT is to block apoptosis. AKT phosphorylation of NF-kB promotes the survival and activation of macrophages responding to LPS. Another substrate of AKT is the protein kinase Gsk3-beta. AKT phosphorylates and deactivates Gsk3-beta. Non-phosphorylated Gsk3-beta is active and phosphorylates beta-catenin, leading to its degradation in the ubiquitin dependent proteosome pathway. Stimulation by LPS causes the accumulation of beta-catenin in the nucleus and the activation of genes in concert with the transcription factor LEF1. This pathway is probably not restricted to alveolar pathway, but leads to the activation of beta-catenin dependent genes by LPS in other cells as well. Other pathways regulate this pathway also, such as the modulation of PI3 kinase activity by ceramide, and the inhibition of Gsk3-beta activity by the Wnt/frizzled/disheveled (DSH) pathway. More...
IL1R_PATHWAY	il1r pathway	Signal transduction through IL1R	Interleukin-1 (IL-1) is a pro-inflammatory cytokine that sig...... Interleukin-1 (IL-1) is a pro-inflammatory cytokine that signals primarily through the type 1 IL-1 receptor (IL-1R1). The activities of IL-1 include induction of fever, expression of vascular adhesion molecules, and roles in arthritis and septic shock. The inflammatory activities of IL-1 are partially derived by transcriptionally inducing expression of cytokines such as TNF-alpha and interferons, as well as inducing the expression of other inflammation-related genes. There are two forms of IL-1 encoded by distinct genes, IL-1 alpha and IL-1 beta. IL-1 beta is produced as a 269 amino acid precursor that is cleaved by IL-1beta converting enzyme (ICE) to the active IL-1 beta form that is secreted. IL-1 signaling is opposed by the naturally occurring peptide IL-1 receptor antagonist which is a therapeutic agent for the treatment of arthritis. The type 1 IL-1 receptor protein binds IL-1 beta but requires the IL-1 receptor accessory protein (IL-1RAcP) to transduce a signal. IL-1 binding causes activation of two kinases, IRAK-1 and IRAK-2, associated with the IL-1 receptor complex. IRAK-1 (IL-1 Receptor Associated Kinase) activates and recruits TRAF6 to the IL-1 receptor complex. TRAF6 activates two pathways, one leading to NF-kB activation and another leading to c-jun activation. The TRAF associated protein ECSIT leads to c-Jun activation through the Map kinase/JNK signaling system. TRAF6 also signals through the TAB1/TAK1 kinases to trigger the degradation of I-kB, and activation of NF-kB. The IL-1 signaling cascade represents a highly conserved response to pathogens through evolution, with homologs in insects and even in plants. The signal transduction cascade utilized by IL-1 receptor is similar to that of TNF, resulting in NF-kB activation, and is most similar to that of the Toll-like receptors that also participate in inflammatory signaling responses to pathogen components like endotoxin. More...

TOLLIP related Reactome pathways (count: 0)

TOLLIP related interactors from protein-protein interaction data in HPRD (count: 18)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
TOLLIP	ZBTB16	Yes	yeast 2-hybrid	16169070
TOLLIP	IRAK1	No	in vivo	10854325
TOLLIP	IL1RAP	No	in vivo;yeast 2-hybrid	10854325
TOLLIP	RHOXF2	No	yeast 2-hybrid	16189514
TOLLIP	SETDB1	Yes	yeast 2-hybrid	16169070
TOLLIP	TOLLIP	Yes	in vitro;in vivo	11751856
TOLLIP	DAZAP2	No	yeast 2-hybrid	16189514
TOLLIP	RBPMS	No	yeast 2-hybrid	16189514
TOLLIP	IL1R1	No	in vivo	10854325
TOLLIP	TOM1	No	in vitro;in vivo;yeast 2-hybrid	14563850
TOLLIP	ZHX1	No	yeast 2-hybrid	16169070
TOLLIP	TLR2	No	in vivo	11751856
TOLLIP	ATXN1	No	yeast 2-hybrid	16713569
TOLLIP	LDB1	No	yeast 2-hybrid	16189514
TOLLIP	XRN2	No	yeast 2-hybrid	15231747
TOLLIP	TLR4	No	in vivo	11751856
TOLLIP	1-Sep	No	yeast 2-hybrid	16189514
TOLLIP	TOM1L1	No	in vitro	15047686

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways