Gene Report

Basic Information

Approved Symbol	ARHGEF2
Approved Name	Rho/Rac guanine nucleotide exchange factor (GEF) 2
Previous Name	rho/rac guanine nucleotide exchange factor (GEF) 2
Symbol Alias	LFP40, GEF-H1, KIAA0651, P40
Location	1q21-q22
Position	chr1:155916630-155948336 (-)
External Links	Entrez Gene: 9181 Ensembl: ENSG00000116584 UCSC: uc001fmt.2 HGNC ID: 682
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between ARHGEF2 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
ARHGEF2	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder

Positive relationships between ARHGEF2 and other components at different levels (count: 0)

Positive relationship network of ARHGEF2 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 ARHGEF2 and MDD (count: 0)

Negative relationships between ARHGEF2 and other components at different levels (count: 0)

ARHGEF2 related SNPs in MK4MDD (count: 0)

ARHGEF2 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Rho guanine nucleotide exchange factor 2	Q92974	0(0/0)	Gene mapped

ARHGEF2 related GO terms (count: 36)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006915	apoptotic process	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0071474	cellular hyperosmotic response	biological process	ISS
GO:0000132	establishment of mitotic spindle orientation	biological process	IEA
GO:0007015	actin filament organization	biological process	IMP[9857026]
GO:0006886	intracellular protein transport	biological process	NAS[9857026]
GO:0008270	zinc ion binding	molecular function	NAS[11912491]
GO:0043025	neuronal cell body	cellular component	IEA
GO:0005089	Rho guanyl-nucleotide exchange factor activity	molecular function	IDA[9857026]
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological process	IDA[19043560]
GO:0032587	ruffle membrane	cellular component	IDA[19043560]
GO:0051301	cell division	biological process	IEA
GO:0007264	small GTPase mediated signal transduction	biological process	TAS
GO:0005819	spindle	cellular component	IEA
GO:0030676	Rac guanyl-nucleotide exchange factor activity	molecular function	IDA[9857026]
GO:0017048	Rho GTPase binding	molecular function	IDA[9857026]
GO:0005923	tight junction	cellular component	IEA
GO:0060547	negative regulation of necrotic cell death	biological process	ISS
GO:0005829	cytosol	cellular component	TAS
GO:0050768	negative regulation of neurogenesis	biological process	IEA
GO:0007067	mitosis	biological process	IEA
GO:0007026	negative regulation of microtubule depolymerization	biological process	IMP[11912491]
GO:0000902	cell morphogenesis	biological process	IMP[11912491]
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0008134	transcription factor binding	molecular function	ISS
GO:0005794	Golgi apparatus	cellular component	IEA
GO:0008017	microtubule binding	molecular function	IDA[9857026]
GO:0043066	negative regulation of apoptotic process	biological process	ISS
GO:0005543	phospholipid binding	molecular function	IEA
GO:0051056	regulation of small GTPase mediated signal transduction	biological process	TAS
GO:0035023	regulation of Rho protein signal transduction	biological process	NAS[11912491]
GO:0048365	Rac GTPase binding	molecular function	IDA[9857026]
GO:0071356	cellular response to tumor necrosis factor	biological process	ISS
GO:0042127	regulation of cell proliferation	biological process	TAS[9857026]
GO:0005515	protein binding	molecular function	IPI[19043560]
GO:0005874	microtubule	cellular component	IDA
GO:0043198	dendritic shaft	cellular component	IEA

ARHGEF2 related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05130	pathogenic escherichia_coli_infection	Pathogenic Escherichia coli infection	Eenteropathogenic E. coli (EPEC) and enterohemorrhagic E. co...... Eenteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections is induction of attaching and effacing (A/E) lesions that damage intestinal epithelial cells. The capacity to form A/E lesions is encoded mainly by the locus of enterocyte effacement (LEE) pathogenicity island. Tir, Map, EspF, EspG are known LEE-encoded effector proteins secreted via the type III secretion system, which is also LEE-encoded, into the host cell. EPEC and EHEC Tir's link the extracellular bacterium to the cell cytoskeleton. Map and EspF are involved in mitochondrion membrane permeabilization. EspG interacts with tubulins and stimulates microtubule destabilization. LEE-encoded adhesin or intimin (Eae) is exported via the general secretory pathway to the periplasm, where it is inserted into the outer membrane. In addition to Tir, two potential host cell-carried intimin receptors, beta1 integrin (ITGB1) and nucleolin (NCL), have so far been identified. The distinguishing feature of EHEC is the elaboration of Shiga-like toxin (Stx). Stx cleaves ribosomal RNA, thereby disrupting protein synthesis and killing the intoxicated epithelial or endothelial cells. More...

ARHGEF2 related BioCarta pathways (count: 3)

ID	Name	Brief Description	Full Description
Literature-origin BioCarta pathway
MYOSIN_PATHWAY	myosin pathway	PKC-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase	The phosphorylation of myosin affects its role in smooth mus...... The phosphorylation of myosin affects its role in smooth muscle contraction, platelet formation and possibly other processes. Phosphorylation by myosin light chain kinase (MLCK) increases myosin activity and dephosphorylation by myosin phosphatase decreases myosin activity. CPI, a factor that binds to and inhibits myosin phosphatase, is a target of phosphorylation by PKC and PKN. The inhibitory activity of CPI is regulated by its own phosphorylation state; when CPI is phosphorylated, its inhibitory activity is increased. The activation of signal transduction cascades such as GPCR pathways can lead to activation of PKC, phosphorylation of CPI, inhibition of myosin phosphatase, increased myosin phosphorylation and increased smooth muscle contraction or platelet release. The action of histamine in vasoconstriction, for example, may be mediated by activation of PKC through the histamine receptor, resulting in phosphorylation of CPI-17, increased inhibition of myosin phosphatase, and increased smooth muscle contraction. More...

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
PAR1_PATHWAY	par1 pathway	Thrombin signaling and protease-activated receptors	Thrombin is an extracellular protease that is involved in th...... Thrombin is an extracellular protease that is involved in the clotting of blood and inflammation through its action on platelets and endothelial cells in the vasculature and that plays a role in thrombosis and myocardial infarction. The protease activated receptors PAR1 and PAR4 are cellular targets of thrombin signaling and members of the G-protein coupled receptor gene family. Both of these receptors are cleaved in their N-terminus by thrombin, unmasking a portion of the receptor sequence that acts itself as a tethered peptide ligand that activates the receptor. The tethered ligand that activates PAR1 is SFLLRN and the tethered ligand that activates PAR4 is GYPGQV. Other members of the family include PAR2 which is activated by trypsin rather than thrombin and PAR3 which seems to play a role in the activation of other PARs but does not itself transduce a signal directly. Addition of peptide agonist exogenously in solution can also activate PAR1, PAR2 and PAR4. PAR1 activation may be involved in the dilation of arteries during inflammation through the action of thrombin on endothelial cells and in platelet activation by thrombin during clotting. PAR1 and PAR2 activation cause bronchodilation in airway and may protect against asthma. PAR 4 activation by thrombin activates platelets during clotting and mice lacking PAR4 have impaired clotting and platelets that do not respond to thrombin signaling. The action of thrombin on PAR1 and PAR4 on platelets and endothelial cells may also contribute to vascular permeability and inflammation. Activated PARs appear to couple primarily through Gq-mediated stimulation of inositol phosphate metabolism and intracellular calcium levels to activate platelets. PAR1 and PAR4 also appear to couple to multiple G-proteins and transduce signals through more than one G-protein mediated pathway in some circumstances. Signaling by PAR1 and PAR4 through Galpha12 pathways couples to Rho signaling and changes in cytoskeletal structure and cell shape. Gi activation does not appear necessary for platelet activation by PAR1 or PAR4, and platelet activation by these receptors requires an ADP signal perhaps acting through the platelet-associated purinergic receptor P2Y12. Gi-coupled signaling may play a role in mitogenic PAR signaling in some settings through Map kinase activation. Activation of Rho by PAR1 can induce cellular transformation through a Galpha12 mediated mechanism and sustained rho-dependent phosphorylation of the myosin light chain by PAR1 contributes to cytoskeletal changes and activation of platelets. Since the activation of PARs by protease cleavage is irreversible the primary mechanism for down-regulation of the PAR signaling cascade appears to be internalization and degradation of PAR receptors. More...
PTDINS_PATHWAY	ptdins pathway	Phosphoinositides and their downstream targets.	Nine currently identified phosphoinositide 3-kinases (PI 3-K...... Nine currently identified phosphoinositide 3-kinases (PI 3-K) constitute a subfamily of lipid kinases that catalyze the addition of a phosphate molecule on the 3-position of the inositol ring of phosphoinositides. Phosphatidylinositol (PtdIns), the precursor of all phosphoinosi-tides (PI), constitutes less than 10% of the total lipid in eukaryotic cell membranes. Approximately 5% of cellular PI is phosphorylated at the 4-position (PtdIns-4-P), and another 5% is phosphorylated at both the 4- and 5-positions (PtdIns-4,5-P2 ). However, less than 0.25% of the total inositol-containing lipids are phosphorylated at the 3-position, consistent with the idea that these lipids exert specific regulatory functions inside the cell, as opposed to a structural function. Here we have chosen to highlight a group of the phosphoinositide targets of the PI3-Ks and their downstream targets. The downstream effects of these PI-3 targets are indicated in the lower band illustrating the important role the PI3Ks have in cell function and survival. More...

ARHGEF2 related Reactome pathways (count: 7)

ID	Name	Description
Gene mapped Reactome pathways
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_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_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_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_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_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_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...

ARHGEF2 related interactors from protein-protein interaction data in HPRD (count: 8)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
ARHGEF2	RRAS2	Yes	in vitro	12384139
ARHGEF2	YWHAE	Yes	in vivo	14970201
ARHGEF2	RHOA	Yes	in vitro	9857026
ARHGEF2	CGN	No	in vitro;in vivo	15866167
ARHGEF2	PAK1	No	in vitro	14970201
ARHGEF2	RAC1	No	in vitro;in vivo	11595749 , 9857026
ARHGEF2	YWHAG	No	in vivo	15324660
ARHGEF2	YWHAZ	No	in vivo	14970201

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Literature-origin BioCarta pathway

Gene mapped BioCarta pathways

Gene mapped Reactome pathways