Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000142
UniProt IDQ92974
Primary gene name(s)ARHGEF2
Synonym gene name(s)KIAA0651, LFP40
Protein nameRho guanine nucleotide exchange factor 2
Protein functionActivates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan, PGN-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins, IpgB2 and OspB which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. {ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:9857026}.
Subcellular locationCytoplasm. Cell junction, tight junction. Golgi apparatus. Cytoplasm, cytoskeleton, spindle. Cell projection, ruffle membrane. Cytoplasmic vesicle. Note=Localizes to the tips of cortical microtubules of the mitotic spindle during cell division, and is further released upon microtubule depolymerization. Recruited into membrane ruffles induced by S.flexneri at tight junctions of polarized epithelial cells. Colocalized with NOD2 and RIPK2 in vesicles and with the cytoskeleton.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q92974
Gene Ontology
(Biological Process)
Complete annatation
actin filament organization [GO:0007015];
cell division [GO:0051301];
cell morphogenesis [GO:0000902];
cellular hyperosmotic response [GO:0071474];
cellular response to muramyl dipeptide [GO:0071225];
cellular response to tumor necrosis factor [GO:0071356];
establishment of mitotic spindle orientation [GO:0000132];
innate immune response [GO:0045087];
intracellular protein transport [GO:0006886];
intracellular signal transduction [GO:0035556];
mitotic nuclear division [GO:0007067];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress [GO:1902219];
negative regulation of microtubule depolymerization [GO:0007026];
negative regulation of necroptotic process [GO:0060546];
negative regulation of neurogenesis [GO:0050768];
positive regulation of apoptotic process [GO:0043065];
positive regulation of interleukin-6 production [GO:0032755];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tumor necrosis factor production [GO:0032760];
regulation of cell proliferation [GO:0042127];
regulation of Rho protein signal transduction [GO:0035023];
regulation of small GTPase mediated signal transduction [GO:0051056]
Gene Ontology
(Molecular Function)
Complete annatation
guanyl-nucleotide exchange factor activity [GO:0005085];
microtubule binding [GO:0008017];
Rac GTPase binding [GO:0048365];
Rac guanyl-nucleotide exchange factor activity [GO:0030676];
Rho GTPase binding [GO:0017048];
Rho guanyl-nucleotide exchange factor activity [GO:0005089];
transcription factor binding [GO:0008134];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
bicellular tight junction [GO:0005923];
cytoplasm [GO:0005737];
cytoplasmic, membrane-bounded vesicle [GO:0016023];
cytoskeleton [GO:0005856];
cytosol [GO:0005829];
dendritic shaft [GO:0043198];
focal adhesion [GO:0005925];
Golgi apparatus [GO:0005794];
microtubule [GO:0005874];
neuronal cell body [GO:0043025];
neuronal postsynaptic density [GO:0097481];
protein complex [GO:0043234];
ruffle membrane [GO:0032587];
spindle [GO:0005819];
vesicle [GO:0031982]
Protein-protein interaction114618
Phylogenetic treeQ92974
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.025704469693270.001934083564497310.00643347581131391
AZA vs. DISU-0.03815191379885450.8800571231659220.991771899371402
AZA vs. IL7-0.09786743040217430.6109516820621120.999311006273513
AZA vs. SAHA-0.07691352789191190.7524728131733760.932620099138933
DISU vs. CD3-1.076263263927480.003372294292643740.0116994163791281
DISU vs. IL7-0.06886142306425190.784460200827940.950659278010737
DISU vs. SAHA-0.03725261296784240.8982421109096630.974691865488595
DMSO vs. AZA0.02623006238139240.8756250431686111
DMSO vs. CD3-1.012528406232420.001737175370779220.00550726998333101
DMSO vs. DISU0.0620353156293580.7991650175937940.976440474715297
DMSO vs. IL7-0.1165224365758990.517106084538710.889301967358611
DMSO vs. SAHA-0.1092242844463720.6431323709503880.885232443666716
HIV vs. Mock in Activation0.2732639415517480.6603455322923470.999983755607037
HIV vs. Mock in Latency-0.2118707699032320.1990206920086820.999834320637052
IL7 vs. CD3-1.116456755500880.0006164713343435050.00280642477274529
SAHA vs. CD3-1.127207276663790.001612497786924740.00539049282363705
SAHA vs. IL70.01730410799777030.9433936490055490.978040981094199
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.102725 0.547042
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.953 1.036 1.139 1.16 1.116
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
5EFX X-ray 2.4Å A=439-582.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04530 Tight junction - Homo sapiens (human)
hsa05130 Pathogenic Escherichia coli infection - Homo sapiens (human)