InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SLC26A6

Summary

InnateDB Protein

IDBP-376302.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SLC26A6

Protein Name

solute carrier family 26, member 6

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000404684

InnateDB Gene

IDBG-304554 (SLC26A6)

Protein Structure

UniProt Annotation

Function

Apical 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.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 Localization

Cell 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}.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.Isoform 5: Cell membrane; Multi-pass membrane protein.Isoform 6: Cell membrane; Multi-pass membrane protein.

Disease Associations

Tissue Specificity

Ubiquitous. Highest levels in kidney and pancreas. Lower expression in heart, skeletal muscle, liver and placenta. Also found in lung and brain. Isoform 4 is ubiquitously expressed. Isoform 6 is expressed in heart, brain, placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis and ovary. Isoform 5 is expressed weakly in placenta, lung, liver and pancreas. {ECO:0000269PubMed:11087667, ECO:0000269PubMed:11247665}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005254	chloride channel activity
GO:0005515	protein binding
GO:0008271	secondary active sulfate transmembrane transporter activity
GO:0015106	bicarbonate transmembrane transporter activity
GO:0015108	chloride transmembrane transporter activity
GO:0015116	sulfate transmembrane transporter activity
GO:0015301	anion:anion antiporter activity
GO:0015499	formate transmembrane transporter activity
GO:0015562	efflux transmembrane transporter activity
GO:0015659	formate uptake transmembrane transporter activity
GO:0015660	formate efflux transmembrane transporter activity
GO:0019531	oxalate transmembrane transporter activity
GO:0030165	PDZ domain binding

Biological Process

GO:0006811	ion transport
GO:0006820	anion transport
GO:0006821	chloride transport
GO:0008272	sulfate transport
GO:0015701	bicarbonate transport
GO:0015724	formate transport
GO:0015797	mannitol transport
GO:0019532	oxalate transport
GO:0030321	transepithelial chloride transport
GO:0038166	angiotensin-activated signaling pathway
GO:0042045	epithelial fluid transport
GO:0046724	oxalic acid secretion
GO:0048240	sperm capacitation
GO:0050892	intestinal absorption
GO:0051453	regulation of intracellular pH
GO:0051454	intracellular pH elevation
GO:0055085	transmembrane transport
GO:0070528	protein kinase C signaling
GO:0070633	transepithelial transport
GO:0071320	cellular response to cAMP
GO:0071332	cellular response to fructose stimulus
GO:0071346	cellular response to interferon-gamma
GO:1902358	sulfate transmembrane transport
GO:1902476	chloride transmembrane transport
GO:2001150	positive regulation of dipeptide transmembrane transport

Cellular Component

GO:0005783	endoplasmic reticulum
GO:0005886	plasma membrane
GO:0012506	vesicle membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016323	basolateral plasma membrane
GO:0016324	apical plasma membrane
GO:0030659	cytoplasmic vesicle membrane
GO:0031526	brush border membrane
GO:0031988	membrane-bounded vesicle
GO:0034707	chloride channel complex
GO:0097225	sperm midpiece