Gene Report

Basic Information

Approved Symbol	TRIO
Approved Name	trio Rho guanine nucleotide exchange factor
Previous Name	triple functional domain (PTPRF interacting)
Symbol Alias	ARHGEF23
Location	5p14-p15.1
Position	chr5:14143829-14509458 (+)
External Links	Entrez Gene: 7204 Ensembl: ENSG00000038382 UCSC: uc003jff.3 HGNC ID: 12303
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between TRIO and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
TRIO	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder

Positive relationships between TRIO and other components at different levels (count: 0)

Positive relationship network of TRIO in MK4MDD

Network loading ...

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 TRIO and MDD (count: 0)

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

TRIO related SNPs in MK4MDD (count: 0)

TRIO related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Triple functional domain protein	O75962	0(0/0)	Gene mapped

TRIO related GO terms (count: 15)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006915	apoptotic process	biological process	TAS
GO:0032553	ribonucleotide binding	molecular function	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005515	protein binding	molecular function	IPI[17043677]
GO:0007264	small GTPase mediated signal transduction	biological process	TAS
GO:0005829	cytosol	cellular component	TAS
GO:0007411	axon guidance	biological process	TAS
GO:0005543	phospholipid binding	molecular function	IEA
GO:0005085	guanyl-nucleotide exchange factor activity	molecular function	TAS[8643598]
GO:0005524	ATP binding	molecular function	IEA
GO:0004674	protein serine/threonine kinase activity	molecular function	IEA
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0035023	regulation of Rho protein signal transduction	biological process	IEA
GO:0005089	Rho guanyl-nucleotide exchange factor activity	molecular function	IEA
GO:0007185	transmembrane receptor protein tyrosine phosphatase signaling pathway	biological process	TAS[8643598]
GO:0051056	regulation of small GTPase mediated signal transduction	biological process	TAS

TRIO related KEGG pathways (count: 0)

TRIO related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
RAC1_PATHWAY	rac1 pathway	Rac 1 cell motility signaling pathway	Rac-1 is a small G-protein in the Rho family that regulates ...... Rac-1 is a small G-protein in the Rho family that regulates cell motility in response to extracellular signals. Several changes in cytoskeletal structure and other aspects of cell structure are involved in cell motility. Rac-1 is activated by GEF factors, and repressed by GAPs. GEFs are guanine nucleotide exchange factors, including Trio and Vav. Sos-1 is involved in Ras signaling and also acts as a GEF for Rac to transduce signals between Ras and Rac. SWAP-70 is a Rac GEF that binds IP3 and transduces signals from tyrosine kinases to Rac to modulate the cytoskeleton and cause membrane ruffling. GAPs are GTPase- activating proteins. Rac stimulates the formation of actin-based structures such as filopodia and lamellopodia, while GAPs such as chimerin oppose the formation of these Rac dependent structures. Several different factors downstream of Rac act on cytoskeletal structure and other aspects of cell motility. Pak1 provides a direct link from Rac to cell motility through phosphorylation of the myosin light chain. Pak1 also phosphorylates and activates LIM kinase, which phosphorylates cofilin as one target. Cofilin stimulates actin depolymerization and changes in cell structure, and phosphorylation of cofilin by LIM kinase represses its activity. In neurons, Rac acts through the protein kinase cdk5 and p35 to phosphorylate and downregulate Pak1, increasing neuronal migration. Rac-1 also interacts with several other factors to regulate a variety of processes. Interaction of Por1 with Rac-1 is involved in membrane ruffling. WAVE is a member of the WASP family of proteins that regulate actin organization and that is involved in Rac signaling to cause membrane ruffling. Interaction of Rac-1 with MEKK1 integrates Rac signaling with pathways signaling through map kinases. More...

TRIO related Reactome pathways (count: 8)

ID	Name	Description
Gene mapped Reactome pathways
REACT_18407	g alpha_12_13_signalling_events	The alpha subunits of G12 and 13 bind RhoGEFs (guanine nucle...... The alpha subunits of G12 and 13 bind RhoGEFs (guanine nucleotide exchange factors, which activate small G proteins) providing a path to Rho-mediated cytoskeletal responses that are likely involved in shape change in platelets. More...
REACT_19184	downstream events_in_gpcr_signaling	G protein-coupled receptors. The beta:gamma G-protein dimer ...... G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK. More...
REACT_18283	g alpha_q_signalling_events	The classic signalling route for G alpha (q) is activation o...... The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets. More...
REACT_11061	signalling by_ngf	Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles i...... Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling. More...
REACT_11051	rho gtpase_cycle	The cycling of Rho GTPases is tightly controlled by three cl...... The cycling of Rho GTPases is tightly controlled by three classes of protein. These are. More...
REACT_13638	nrage signals_death_through_jnk	Once bound by either NGF or proNGF, p75NTR interacts with NR...... Once bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pro-apoptotic genes, and directly activates the cell death machinery. Only NGF-bound p75NTR is shown here. More...
REACT_13776	p75 ntr_receptor_mediated_signalling	Besides signalling through the tyrosine kinase receptors TRK...... Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated. A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus , while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways. More...
REACT_13720	cell death_signalling_via_nrage_nrif_and_nade	p75NTR is a key regulator of neuronal apoptosis, both during...... p75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNGF is at least 10 times more potent than mature NGF in inducing apoptosis. TRKA signalling protects neurons from apoptosis. The molecular mechanisms involved in p75NTR-apoptosis are not well understood. The death signalling requires activation of c-JUN N-terminal Kinase (JNK), as well as transcriptional events. JNK activation appears to involve the receptor interacting proteins TRAF6, NRAGE, and Rac. The transcription events are thought to be regulated by another p75-interacting protein, NRIF. Two other p75-interacting proteins, NADE and Necdin, have been implicated in apoptosis, but their role is less clear. More...

TRIO related interactors from protein-protein interaction data in HPRD (count: 6)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
TRIO	RHOA	Yes	in vitro	10948190
TRIO	PTK2	No	in vitro;in vivo	12551902
TRIO	PTPRF	No	in vitro;in vivo	8643598
TRIO	BLMH	No	yeast 2-hybrid	16169070
TRIO	RAC1	No	in vitro;in vivo	11595749
TRIO	FLNA	No	in vitro;yeast 2-hybrid	11146652

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped BioCarta pathways

Gene mapped Reactome pathways