Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002420
UniProt IDP63000
Primary gene name(s)RAC1
Synonym gene name(s)TC25
Protein nameRas-related C3 botulinum toxin substrate 1
Protein functionPlasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs, ruffled borders in osteoclasts. In glioma cells, promotes cell migration and invasion. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin, CFL1 and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3.; FUNCTION: Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.
Subcellular locationCell membrane {ECO:0000250};
Lipid-anchor {ECO:0000250};
Cytoplasmic side {ECO:0000250}. Melanosome {ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:21693584}. Cytoplasm {ECO:0000250}. Note=Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine, By similarity. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Found in the ruffled border, a late endosomal-like compartment in the plasma membrane of bone-resorbing osteoclasts, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P63000
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton organization [GO:0030036];
actin filament polymerization [GO:0030041];
anatomical structure arrangement [GO:0048532];
anatomical structure morphogenesis [GO:0009653];
auditory receptor cell morphogenesis [GO:0002093];
axon guidance [GO:0007411];
blood coagulation [GO:0007596];
bone resorption [GO:0045453];
cell adhesion [GO:0007155];
cell-cell junction organization [GO:0045216];
cell-matrix adhesion [GO:0007160];
cell motility [GO:0048870];
cell proliferation [GO:0008283];
cellular response to mechanical stimulus [GO:0071260];
cerebral cortex GABAergic interneuron development [GO:0021894];
cerebral cortex radially oriented cell migration [GO:0021799];
cochlea morphogenesis [GO:0090103];
dendrite morphogenesis [GO:0048813];
embryonic olfactory bulb interneuron precursor migration [GO:0021831];
engulfment of apoptotic cell [GO:0043652];
ephrin receptor signaling pathway [GO:0048013];
epithelial cell morphogenesis [GO:0003382];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
G-protein coupled receptor signaling pathway [GO:0007186];
homeostasis of number of cells within a tissue [GO:0048873];
hyperosmotic response [GO:0006972];
inflammatory response [GO:0006954];
intracellular signal transduction [GO:0035556];
lamellipodium assembly [GO:0030032];
localization within membrane [GO:0051668];
mast cell chemotaxis [GO:0002551];
midbrain dopaminergic neuron differentiation [GO:1904948];
movement of cell or subcellular component [GO:0006928];
negative regulation of interleukin-23 production [GO:0032707];
negative regulation of receptor-mediated endocytosis [GO:0048261];
platelet activation [GO:0030168];
positive regulation of actin filament polymerization [GO:0030838];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cell-substrate adhesion [GO:0010811];
positive regulation of dendritic spine development [GO:0060999];
positive regulation of DNA replication [GO:0045740];
positive regulation of focal adhesion assembly [GO:0051894];
positive regulation of GTPase activity [GO:0043547];
positive regulation of lamellipodium assembly [GO:0010592];
positive regulation of neutrophil chemotaxis [GO:0090023];
positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of Rho protein signal transduction [GO:0035025];
positive regulation of stress fiber assembly [GO:0051496];
positive regulation of substrate adhesion-dependent cell spreading [GO:1900026];
protein localization to plasma membrane [GO:0072659];
regulation of cell migration [GO:0030334];
regulation of cell size [GO:0008361];
regulation of defense response to virus by virus [GO:0050690];
regulation of fibroblast migration [GO:0010762];
regulation of hydrogen peroxide metabolic process [GO:0010310];
regulation of neuronal synaptic plasticity [GO:0048168];
regulation of neuron maturation [GO:0014041];
regulation of respiratory burst [GO:0060263];
regulation of small GTPase mediated signal transduction [GO:0051056];
response to wounding [GO:0009611];
ruffle assembly [GO:0097178];
ruffle organization [GO:0031529];
semaphorin-plexin signaling pathway [GO:0071526];
small GTPase mediated signal transduction [GO:0007264];
substrate adhesion-dependent cell spreading [GO:0034446];
synaptic transmission, GABAergic [GO:0051932];
T cell costimulation [GO:0031295];
vascular endothelial growth factor receptor signaling pathway [GO:0048010];
Wnt signaling pathway, planar cell polarity pathway [GO:0060071]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
GTPase activity [GO:0003924];
GTP binding [GO:0005525];
Rho GDP-dissociation inhibitor binding [GO:0051022];
thioesterase binding [GO:0031996]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytoplasmic ribonucleoprotein granule [GO:0036464];
cytosol [GO:0005829];
early endosome membrane [GO:0031901];
endoplasmic reticulum membrane [GO:0005789];
extracellular exosome [GO:0070062];
extrinsic component of plasma membrane [GO:0019897];
focal adhesion [GO:0005925];
Golgi membrane [GO:0000139];
lamellipodium [GO:0030027];
melanosome [GO:0042470];
membrane [GO:0016020];
nucleus [GO:0005634];
phagocytic cup [GO:0001891];
plasma membrane [GO:0005886];
ruffle membrane [GO:0032587];
trans-Golgi network [GO:0005802]
Protein-protein interaction111817
Phylogenetic treeP63000
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. CD30.6155449336679650.06091450351536650.117359503641008
AZA vs. DISU-0.02880354979316690.909305889749090.994271142470137
AZA vs. IL7-0.02335189893026530.9033253007752610.999311006273513
AZA vs. SAHA-0.1628677876021430.5043403038023210.823612773646766
DISU vs. CD3-0.6565159869326850.07086510978804840.142448415114687
DISU vs. IL7-0.004058785808360470.9871373916492180.99841350273619
DISU vs. SAHA-0.1320566863686290.6502507209479960.891919383390081
DMSO vs. AZA-0.02509046428854660.8809908521243871
DMSO vs. CD3-0.6513480572190940.04234960117748390.0836059155731614
DMSO vs. DISU0.002043943328082290.9933130546838870.998391502308472
DMSO vs. IL70.008953158012456420.9602894017040860.993028037500967
DMSO vs. SAHA-0.1435571321547240.5424906562527140.834750181711649
HIV vs. Mock in Activation-0.1360661113815630.8267130465924150.999983755607037
HIV vs. Mock in Latency-0.01661456246169320.9198464735421760.999834320637052
IL7 vs. CD3-0.6323327028217410.04966614499048540.109143869870475
SAHA vs. CD3-0.8022374822308730.02391648982623030.0534784884422552
SAHA vs. IL7-0.1420081108410290.5597056643499770.769703776712027
(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 -0.244744 0.1297
(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
1.021 0.967 0.977 0.969 0.977
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04315 Guanosine-5&,39;-Diphosphate experimental unknown unknown
DB00514 Dextromethorphan approved unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1E96 X-ray 2.4Å A=2-192.
1FOE X-ray 2.8Å B/D/F/H=1-177.
1G4U X-ray 2.3Å R=1-184.
1HE1 X-ray 2.0Å C/D=2-176.
1HH4 X-ray 2.7Å A/B=2-192.
1I4D X-ray 2.5Å D=1-192.
1I4L X-ray 2.7Å D=1-192.
1I4T X-ray 2.6Å D=1-192.
1MH1 X-ray 1.3Å A=2-184.
1RYF X-ray 1.7Å A/B=1-182.
1RYH X-ray 1.7Å A/B=1-182.
2FJU X-ray 2.2Å A=1-177.
2H7V X-ray 2.6Å A/B=1-184.
2NZ8 X-ray 2.0Å A=1-177.
2P2L X-ray 1.9Å A/B/C=1-184.
2RMK NMR - A=1-192.
2VRW X-ray 1.8Å A=1-184.
2WKP X-ray 1.9Å A=4-180.
2WKQ X-ray 1.6Å A=4-180.
2WKR X-ray 2.2Å A=4-180.
2YIN X-ray 2.7Å C/D=1-177.
3B13 X-ray 3.0Å B/D=1-177.
3BJI X-ray 2.6Å C/D=1-177.
3RYT X-ray 3.5Å C=1-177.
3SBD X-ray 2.1Å A/B=2-177.
3SBE X-ray 2.6Å A=2-177.
3SU8 X-ray 3.2Å A=1-177.
3SUA X-ray 4.3Å A/B/C=1-177.
3TH5 X-ray 2.3Å A/B=2-177.
4GZL X-ray 2.0Å A/B=2-177.
4GZM X-ray 2.8Å A/B=2-177.
4YON X-ray 1.9Å B=1-177.
5FI0 X-ray 3.2Å B/D/F/H=1-192.

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

HIV Partner Interaction Type PubMed
Pr55(Gag) localized by 26018170
Nef interacts with 14737186
Tat activates 16436505
Pr55(Gag) required by 26018170
HIV-1 virus replication enhanced by expression of human gene 26018170
Envelope surface glycoprotein gp120 enhanced by 21936715
Envelope surface glycoprotein gp120 induces phosphorylation of 21321123
Pr55(Gag) activates 26018170
HIV-1 virus replication enhannced by expression of human gene 26018170
Nef inhibited by 18005680
Nef enhances 22721673
Envelope surface glycoprotein gp120 activates 18632858
Tat downregulates 16526095
Nef activates 10394361

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04145 Phagosome - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04370 VEGF signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04810 Regulation of actin cytoskeleton - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa04972 Pancreatic secretion - Homo sapiens (human)
hsa05014 Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
hsa05100 Bacterial invasion of epithelial cells - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)