Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002755
UniProt IDO14745
Primary gene name(s)SLC9A3R1
Synonym gene name(s)NHERF, NHERF1
Protein nameNa(+/H(+ exchange regulatory cofactor NHE-RF1
Protein functionScaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli, By similarity. Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}.
Subcellular locationCytoplasm {ECO:0000250}. Apical cell membrane {ECO:0000250}. Endomembrane system;
Peripheral membrane protein. Cell projection, filopodium. Cell projection, ruffle. Cell projection, microvillus. Note=Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm tail, By similarity. Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast. Found in microvilli, ruffling membrane and filopodia of HeLa cells. Present in lipid rafts of T-cells. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14745
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton organization [GO:0030036];
adenylate cyclase-activating dopamine receptor signaling pathway [GO:0007191];
auditory receptor cell stereocilium organization [GO:0060088];
bile acid secretion [GO:0032782];
cAMP-mediated signaling [GO:0019933];
cellular phosphate ion homeostasis [GO:0030643];
establishment of epithelial cell apical/basal polarity [GO:0045198];
establishment of Golgi localization [GO:0051683];
establishment of nucleus localization [GO:0040023];
establishment of protein localization to plasma membrane [GO:0090002];
gland morphogenesis [GO:0022612];
glutathione transport [GO:0034635];
microvillus assembly [GO:0030033];
negative regulation of catenin import into nucleus [GO:0035414];
negative regulation of cell migration [GO:0030336];
negative regulation of cell proliferation [GO:0008285];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of mitotic cell cycle [GO:0045930];
negative regulation of phosphatidylinositol 3-kinase signaling [GO:0014067];
negative regulation of platelet-derived growth factor receptor signaling pathway [GO:0010642];
negative regulation of protein kinase B signaling [GO:0051898];
negative regulation of sodium:proton antiporter activity [GO:0032416];
phospholipase C-activating dopamine receptor signaling pathway [GO:0060158];
positive regulation of intrinsic apoptotic signaling pathway [GO:2001244];
protein complex assembly [GO:0006461];
regulation of cell shape [GO:0008360];
regulation of cell size [GO:0008361];
regulation of excretion [GO:0044062];
regulation of protein kinase activity [GO:0045859];
regulation of sodium:proton antiporter activity [GO:0032415];
renal absorption [GO:0070293];
renal phosphate ion absorption [GO:0097291];
renal sodium ion transport [GO:0003096];
sensory perception of sound [GO:0007605];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
beta-2 adrenergic receptor binding [GO:0031698];
beta-catenin binding [GO:0008013];
chloride channel regulator activity [GO:0017081];
growth factor receptor binding [GO:0070851];
PDZ domain binding [GO:0030165];
phosphatase binding [GO:0019902];
protein self-association [GO:0043621];
receptor binding [GO:0005102]
Gene Ontology
(Cellular Component)
Complete annatation
actin cytoskeleton [GO:0015629];
apical plasma membrane [GO:0016324];
brush border membrane [GO:0031526];
cell periphery [GO:0071944];
centrosome [GO:0005813];
cytoplasm [GO:0005737];
endomembrane system [GO:0012505];
extracellular exosome [GO:0070062];
filopodium [GO:0030175];
intracellular membrane-bounded organelle [GO:0043231];
membrane [GO:0016020];
membrane raft [GO:0045121];
microvillus [GO:0005902];
microvillus membrane [GO:0031528];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
ruffle [GO:0001726];
sperm midpiece [GO:0097225];
stereocilium tip [GO:0032426];
vesicle [GO:0031982]
Protein-protein interaction114769
Phylogenetic treeO14745
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. CD3-2.053677697680652.37845032557971e-093.16398970054169e-08
AZA vs. DISU-0.626789677993320.02966993097022150.409954380045785
AZA vs. IL7-0.1362281928660340.4806351842435760.999311006273513
AZA vs. SAHA-0.3116852704721990.2139627125222660.581996326760701
DISU vs. CD31.416233657486620.0001595527411323290.000853779914742184
DISU vs. IL70.4805570171426640.07852123606815890.372611956113327
DISU vs. SAHA0.317871479767280.3119113016186170.694271084930758
DMSO vs. AZA-0.0002112791689050640.9991101576028351
DMSO vs. CD32.044891360323011.04377984033732e-091.3451277412046e-08
DMSO vs. DISU0.625482153740040.02218297771631480.306719538054511
DMSO vs. IL7-0.1289128882470950.4726125769544120.879173864245188
DMSO vs. SAHA-0.3168511839542790.1789336670832450.51131545166975
HIV vs. Mock in Activation0.2080740420157350.7391554633912230.999983755607037
HIV vs. Mock in Latency0.1310601135430690.4261119012547280.999834320637052
IL7 vs. CD31.92237722995339.02305374861356e-091.35462638598458e-07
SAHA vs. CD31.720098453320313.06376065328795e-062.21443036187287e-05
SAHA vs. IL7-0.1768788463039570.4678542437248060.702522296282726
(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 -0.143272 0.334227
(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
1.016 0.94 0.872 0.863 0.908
(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
1G9O X-ray 1.5Å A=11-99.
1GQ4 X-ray 1.9Å A=11-94.
1GQ5 X-ray 2.2Å A=11-94.
1I92 X-ray 1.7Å A=11-94.
1SGH X-ray 3.5Å B=321-358.
2D10 X-ray 2.5Å E/F/G/H=331-358.
2JXO NMR - A=150-240.
2KJD NMR - A=150-270.
2KRG NMR - A=150-358.
2M0T NMR - A=11-120.
2M0U NMR - A=11-120.
2M0V NMR - A=150-270.
2OZF X-ray 1.5Å A=150-235.
4JL7 X-ray 1.1Å A=11-95.
4LMM X-ray 1.1Å A=11-94.
4MPA X-ray 1.1Å A=11-94.
4N6X X-ray 1.0Å A=11-94.
4PQW X-ray 1.4Å A=11-94.
4Q3H X-ray 1.4Å A/B=150-234.

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

HIV Partner Interaction Type PubMed
reverse transcriptase interacts with 22190034
Envelope surface glycoprotein gp120 interacts with 22028271
Envelope surface glycoprotein gp120 upregulates 22028271
Envelope surface glycoprotein gp120 requires 22028271

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04530 Tight junction - Homo sapiens (human)