Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002714
UniProt IDQ9BXS9
Primary gene name(s)SLC26A6
Synonym gene name(s)unknown
Protein nameSolute carrier family 26 member 6
Protein functionApical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Function in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.; FUNCTION: Isoform 4: Apical membrane chloride-bicarbonate exchanger. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site.
Subcellular locationCell membrane;
Multi-pass membrane protein. Membrane;
Multi-pass membrane protein. Apical cell membrane {ECO:0000250};
Multi-pass membrane protein {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250};
Multi-pass membrane protein {ECO:0000250}. Microsome {ECO:0000250}. Note=Localized in sperm membranes. Colocalizes with CFTR at the midpiece of sperm tail. Localizes to the apical membrane brush border of epithelial cells in the proximal tubules of kidney, of enterocytes of the small intestine and of gastric parietal cells in the stomach. May be translocated from the cytosolic surface of the cell membrane to the intracellular space by PKC in phorbol myristate acetate, PMA-induced cells, By similarity. Colocalized with CA2 at the surface of the cell membrane in order to form a bicarbonate transport metabolon;
colocalization is reduced in phorbol myristate acetate, PMA-induced cells. {ECO:0000250}.;
SUBCELLULAR LOCATION: Isoform 4: Cell membrane;
Multi-pass membrane protein. Apical cell membrane;
Multi-pass membrane protein. Basolateral cell membrane;
Multi-pass membrane protein. Note=Localizes to the apical and basolateral surfaces of tubular wall cells in kidney and in the brush border of pancreatic duct cells.;
SUBCELLULAR LOCATION: Isoform 5: Cell membrane;
Multi-pass membrane protein.;
SUBCELLULAR LOCATION: Isoform 6: Cell membrane;
Multi-pass membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9BXS9
Gene Ontology
(Biological Process)
Complete annatation
angiotensin-activated signaling pathway [GO:0038166];
bicarbonate transport [GO:0015701];
cellular response to cAMP [GO:0071320];
cellular response to fructose stimulus [GO:0071332];
cellular response to interferon-gamma [GO:0071346];
chloride transport [GO:0006821];
epithelial fluid transport [GO:0042045];
formate transport [GO:0015724];
intestinal absorption [GO:0050892];
intracellular pH elevation [GO:0051454];
ion transport [GO:0006811];
mannitol transport [GO:0015797];
oxalate transport [GO:0019532];
oxalic acid secretion [GO:0046724];
positive regulation of dipeptide transmembrane transport [GO:2001150];
protein kinase C signaling [GO:0070528];
regulation of intracellular pH [GO:0051453];
regulation of membrane potential [GO:0042391];
sperm capacitation [GO:0048240];
sulfate transport [GO:0008272];
transepithelial chloride transport [GO:0030321];
transepithelial transport [GO:0070633]
Gene Ontology
(Molecular Function)
Complete annatation
anion:anion antiporter activity [GO:0015301];
bicarbonate transmembrane transporter activity [GO:0015106];
chloride channel activity [GO:0005254];
chloride transmembrane transporter activity [GO:0015108];
efflux transmembrane transporter activity [GO:0015562];
formate efflux transmembrane transporter activity [GO:0015660];
formate transmembrane transporter activity [GO:0015499];
formate uptake transmembrane transporter activity [GO:0015659];
inorganic anion exchanger activity [GO:0005452];
oxalate transmembrane transporter activity [GO:0019531];
PDZ domain binding [GO:0030165];
secondary active sulfate transmembrane transporter activity [GO:0008271];
sulfate transmembrane transporter activity [GO:0015116]
Gene Ontology
(Cellular Component)
Complete annatation
apical plasma membrane [GO:0016324];
basolateral plasma membrane [GO:0016323];
brush border membrane [GO:0031526];
chloride channel complex [GO:0034707];
cytoplasmic vesicle membrane [GO:0030659];
endoplasmic reticulum [GO:0005783];
integral component of membrane [GO:0016021];
integral component of plasma membrane [GO:0005887];
intracellular [GO:0005622];
membrane [GO:0016020];
membrane-bounded vesicle [GO:0031988];
plasma membrane [GO:0005886];
sperm midpiece [GO:0097225];
vesicle membrane [GO:0012506]
Protein-protein interaction122373
Phylogenetic treeQ9BXS9
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. CD3-0.1580390515435680.6305546168688840.730437259660888
AZA vs. DISU0.1467546570752380.5638266066351320.951925020821155
AZA vs. IL7-0.1307278886900570.5007524567612950.999311006273513
AZA vs. SAHA0.6614287697942950.007313636662917730.0795423947018917
DISU vs. CD30.2918510513617680.423779357235130.555724230618734
DISU vs. IL7-0.2873213105685310.2569201537194430.642760497037037
DISU vs. SAHA0.517574529563190.0791235132772690.357134012758826
DMSO vs. AZA0.1236861306164260.4657981625185911
DMSO vs. CD30.2689361427701970.4016945994011710.516253978841378
DMSO vs. DISU-0.0250500623430150.9186736354625830.988899823982894
DMSO vs. IL7-0.2470240365161510.1737840134905320.683904150417244
DMSO vs. SAHA0.5331693531512280.02480256636969060.163088777381155
HIV vs. Mock in Activation0.3258476212818080.6024147927985650.999983755607037
HIV vs. Mock in Latency0.09251786745909670.5794021208380350.999834320637052
IL7 vs. CD30.03185429466850440.9212656466298160.950461128792007
SAHA vs. CD30.7963205448124790.02522069667619450.055951111277823
SAHA vs. IL70.7901186970298910.001348816849622620.0147120587490676
(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) TRUE
(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 0.327559 0.0726683
(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
1.093 1.318 2.069 2.542 1.485
(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

not found

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
hsa04978 Mineral absorption - Homo sapiens (human)