Chloride anion exchanger

Protein-coding gene in the species Homo sapiens

SLC26A3

Identifiers

Aliases

SLC26A3, CLD, DRA, solute carrier family 26 member 3

External IDs

OMIM: 126650; MGI: 107181; HomoloGene: 55435; GeneCards: SLC26A3; OMA:SLC26A3 - orthologs

Gene location (Human)

Chr.	Chromosome 7 (human)^[1]

Band	7q22.3-q31.1	Start	107,765,467 bp^[1]
Band	7q22.3-q31.1	End	107,803,225 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 12 (mouse)^[2]

Band	12 A2\|12 13.45 cM	Start	31,440,870 bp^[2]
Band	12 A2\|12 13.45 cM	End	31,523,916 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

mucosa of colon

mucosa of sigmoid colon

rectum

mucosa of transverse colon

seminal vesicula

mucosa of ileum

jejunal mucosa

duodenum

appendix

corpus epididymis

Top expressed in

left colon

epithelium of small intestine

duodenum

seminal vesicula

ileum

jejunum

Paneth cell

efferent ductule

migratory enteric neural crest cell

cecum

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	chloride transmembrane transporter activity transporter activity DNA-binding transcription factor activity transcription coregulator activity sulfate transmembrane transporter activity secondary active sulfate transmembrane transporter activity bicarbonate transmembrane transporter activity oxalate transmembrane transporter activity protein binding antiporter activity chloride channel activity inorganic anion exchanger activity
Cellular component	integral component of membrane membrane plasma membrane integral component of plasma membrane brush border membrane apical plasma membrane sperm midpiece
Biological process	excretion intracellular pH elevation membrane hyperpolarization sulfate transport regulation of membrane potential regulation of intracellular pH ion transport anion transport bicarbonate transport sperm capacitation chloride transport cellular response to cAMP regulation of transcription, DNA-templated chloride transmembrane transport oxalate transport sulfate transmembrane transport transmembrane transport regulation of nucleic acid-templated transcription anion transmembrane transport
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


1811


13487

Ensembl


ENSG00000091138


ENSMUSG00000001225

UniProt


P40879


Q9WVC8

RefSeq (mRNA)


NM_000111


NM_021353

RefSeq (protein)


NP_000102


NP_067328

Location (UCSC)

Chr 7: 107.77 – 107.8 Mb

Chr 12: 31.44 – 31.52 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Chloride anion exchanger, also known as down-regulated in adenoma (protein DRA), is a protein that in humans is encoded by the SLC26A3 gene.^[5]

Function

Protein DRA is a membrane protein in intestinal cells. It is an anion exchanger and a member of the sulfate anion transporter (SAT) family. It mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is different from the anion exchanger that present in erythrocytes, renal tubule, and several other tissues.^[6]

The protein encoded by this gene is a transmembrane glycoprotein that functions as a sulfate transporter. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells, and is instrumental in chloride reuptake, aiding in the creation of an osmotic gradient for resorption of fluid from the lumen of the intestine.^[7]

Clinical significance

Mutations in this gene have been associated with congenital chloride diarrhoea,^[5] a treatable disease.

The congenital absence of this membrane protein results in an autosomal recessive disorder called congenital chloridorrhea or congenital chloride diarrhea (CLD).^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000091138 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000001225 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: SLC26A3 solute carrier family 26, member 3".
^ Sterling D, Brown NJ, Supuran CT, Casey JR (November 2002). "The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II". American Journal of Physiology. Cell Physiology. 283 (5): C1522-9. doi:10.1152/ajpcell.00115.2002. PMID 12372813.
^ Singla A, Kumar A, Priyamvada S, Tahniyath M, Saksena S, Gill RK, Alrefai WA, Dudeja PK (March 2012). "LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and c-Fos-dependent pathway". American Journal of Physiology. Gastrointestinal and Liver Physiology. 302 (6): G618-27. doi:10.1152/ajpgi.00172.2011. PMC 3311307. PMID 22159277.
^ Alrefai WA, Wen X, Jiang W, Katz JP, Steinbrecher KA, Cohen MB, Williams IR, Dudeja PK, Wu GD (November 2007). "Molecular cloning and promoter analysis of downregulated in adenoma (DRA)". American Journal of Physiology. Gastrointestinal and Liver Physiology. 293 (5): G923-34. doi:10.1152/ajpgi.00029.2007. PMID 17761837.

Sandal NN, Marcker KA (January 1994). "Similarities between a soybean nodulin, Neurospora crassa sulphate permease II and a putative human tumour suppressor". Trends in Biochemical Sciences. 19 (1): 19. doi:10.1016/0968-0004(94)90168-6. PMID 8140616.
Markovich D (October 2001). "Physiological roles and regulation of mammalian sulfate transporters". Physiological Reviews. 81 (4): 1499–533. doi:10.1152/physrev.2001.81.4.1499. PMID 11581495. S2CID 30942862.
Mäkelä S, Kere J, Holmberg C, Höglund P (December 2002). "SLC26A3 mutations in congenital chloride diarrhea". Human Mutation. 20 (6): 425–38. doi:10.1002/humu.10139. PMID 12442266. S2CID 2450225.
Schweinfest CW, Henderson KW, Suster S, Kondoh N, Papas TS (May 1993). "Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas". Proceedings of the National Academy of Sciences of the United States of America. 90 (9): 4166–70. Bibcode:1993PNAS...90.4166S. doi:10.1073/pnas.90.9.4166. PMC 46467. PMID 7683425.
Taguchi T, Testa JR, Papas TS, Schweinfest C (March 1994). "Localization of a candidate colon tumor-suppressor gene (DRA) to 7q22-q31.1 by fluorescence in situ hybridization". Genomics. 20 (1): 146–7. doi:10.1006/geno.1994.1148. PMID 8020951.
Höglund P, Haila S, Socha J, Tomaszewski L, Saarialho-Kere U, Karjalainen-Lindsberg ML, Airola K, Holmberg C, de la Chapelle A, Kere J (November 1996). "Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea". Nature Genetics. 14 (3): 316–9. doi:10.1038/ng1196-316. PMID 8896562. S2CID 1725926.
Byeon MK, Frankel A, Papas TS, Henderson KW, Schweinfest CW (February 1998). "Human DRA functions as a sulfate transporter in Sf9 insect cells". Protein Expression and Purification. 12 (1): 67–74. doi:10.1006/prep.1997.0809. PMID 9473459.
Höglund P, Haila S, Gustavson KH, Taipale M, Hannula K, Popinska K, Holmberg C, Socha J, de la Chapelle A, Kere J (1998). "Clustering of private mutations in the congenital chloride diarrhea/down-regulated in adenoma gene". Human Mutation. 11 (4): 321–7. doi:10.1002/(SICI)1098-1004(1998)11:4<321::AID-HUMU10>3.0.CO;2-A. PMID 9554749. S2CID 39309679.
Antalis TM, Reeder JA, Gotley DC, Byeon MK, Walsh MD, Henderson KW, Papas TS, Schweinfest CW (August 1998). "Down-regulation of the down-regulated in adenoma (DRA) gene correlates with colon tumor progression". Clinical Cancer Research. 4 (8): 1857–63. PMID 9717812.
Höglund P, Auranen M, Socha J, Popinska K, Nazer H, Rajaram U, Al Sanie A, Al-Ghanim M, Holmberg C, de la Chapelle A, Kere J (September 1998). "Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait". American Journal of Human Genetics. 63 (3): 760–8. doi:10.1086/301998. PMC 1377387. PMID 9718329.
Lohi H, Kujala M, Kerkelä E, Saarialho-Kere U, Kestilä M, Kere J (November 2000). "Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger". Genomics. 70 (1): 102–12. doi:10.1006/geno.2000.6355. PMID 11087667.
Höglund P, Sormaala M, Haila S, Socha J, Rajaram U, Scheurlen W, Sinaasappel M, de Jonge H, Holmberg C, Yoshikawa H, Kere J (September 2001). "Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea". Human Mutation. 18 (3): 233–42. doi:10.1002/humu.1179. PMID 11524734. S2CID 19422198.
Lohi H, Kujala M, Makela S, Lehtonen E, Kestila M, Saarialho-Kere U, Markovich D, Kere J (April 2002). "Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9". The Journal of Biological Chemistry. 277 (16): 14246–54. doi:10.1074/jbc.M111802200. PMID 11834742.
Lamprecht G, Heil A, Baisch S, Lin-Wu E, Yun CC, Kalbacher H, Gregor M, Seidler U (October 2002). "The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange". Biochemistry. 41 (41): 12336–42. doi:10.1021/bi0259103. PMID 12369822.
Chernova MN, Jiang L, Shmukler BE, Schweinfest CW, Blanco P, Freedman SD, Stewart AK, Alper SL (May 2003). "Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes". The Journal of Physiology. 549 (Pt 1): 3–19. doi:10.1113/jphysiol.2003.039818. PMC 2342915. PMID 12651923.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7
(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14
(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2
(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11
(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12
(6):	sodium- and chloride- dependent sodium:neurotransmitter symporters SLC6A1 SLC6A2 SLC6A3 SLC6A4 SLC6A5 SLC6A6 SLC6A7 SLC6A8 SLC6A9 SLC6A10 SLC6A11 SLC6A12 SLC6A13 SLC6A14 SLC6A15 SLC6A16 SLC6A17 SLC6A18 SLC6A19 SLC6A20
(7):	cationic amino-acid transporter/glycoprotein-associated SLC7A1 SLC7A2 SLC7A3 SLC7A4 glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters SLC7A5 SLC7A6 SLC7A7 SLC7A8 SLC7A9 SLC7A10 SLC7A11 SLC7A13 SLC7A14
(8):	Na⁺/Ca²⁺ exchanger SLC8A1 SLC8A2 SLC8A3
(9):	Na⁺/H⁺ exchanger SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7 SLC9A8 SLC9A9 SLC9A10 SLC9A11
(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3
(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9
(13):	human Na⁺-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5
(14):	urea transporter SLC14A1 SLC14A2
(15):	proton oligopeptide cotransporter SLC15A1 SLC15A2 SLC15A3 SLC15A4
(16):	monocarboxylate transporter SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8 SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14
(17):	Vesicular glutamate transporter 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9
(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3
(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3
(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide SLCO1A2 SLCO1B1 SLCO1B3 SLCO1B4 SLCO1C1 SLCO2A1 SLCO2B1 SLCO3A1 SLCO4A1 SLCO4C1 SLCO5A1(SLCO6A1)
(22):	organic cation/anion/zwitterion transporter SLC22A1 SLC22A2 SLC22A3 SLC22A4 SLC22A5 SLC22A6 SLC22A7 SLC22A8 SLC22A9 SLC22A10 SLC22A11 SLC22A12 SLC22A13 SLC22A14 SLC22A15 SLC22A16 SLC22A17 SLC22A18 SLC22A19 SLC22A20
(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4
(24):	Na⁺/(Ca²⁺-K⁺) exchanger SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5 SLC24A6
(25):	mitochondrial carrier SLC25A1 SLC25A2 SLC25A3 SLC25A4 SLC25A5 SLC25A6 SLC25A7 SLC25A8 SLC25A9 SLC25A10 SLC25A11 SLC25A12 SLC25A13 SLC25A14 SLC25A15 SLC25A16 SLC25A17 SLC25A18 SLC25A19 SLC25A20 SLC25A21 SLC25A22 SLC25A23 SLC25A24 SLC25A25 SLC25A26 SLC25A27 SLC25A28 SLC25A29 SLC25A30 SLC25A31 SLC25A32 SLC25A33 SLC25A34 SLC25A35 SLC25A36 SLC25A37 SLC25A38 SLC25A39 SLC25A40 SLC25A41 SLC25A42 SLC25A43 SLC25A44 SLC25A45 SLC25A46
(26):	multifunctional anion exchanger SLC26A1 SLC26A2 SLC26A3 SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11
(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6
(28):	Na⁺-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3
(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4
(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1
(32):	Vesicular glutamate transporter 1 SLC32A1
(33):	Acetyl-CoA transporter SLC33A1
(34):	type II Na⁺-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3
(35):	nucleoside-sugar transporter SLC35A1 SLC35A2 SLC35A3 SLC35A4 SLC35A5 SLC35B1 SLC35B2 SLC35B3 SLC35B4 SLC35C1 SLC35C2 SLC35D1 SLC35D2 SLC35D3 SLC35E1 SLC35E2 SLC35E3 SLC35E4
(36):	proton-coupled amino-acid transporter SLC36A1 SLC36A2 SLC36A3 SLC36A436A2
(37):	sugar-phosphate/phosphate exchanger SLC37A1 SLC37A2 SLC37A3 SLC37A4
(38):	System A & N, sodium-coupled neutral amino-acid transporter SLC38A1 SLC38A2 SLC38A3 SLC38A4 SLC38A5 SLC38A6 SLC38A10
(39):	metal ion transporter SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5 SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14
(40):	basolateral iron transporter SLC40A1

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3
(42):	Ammonia transporter RhAG RhBG RhCG
(43):	Na⁺-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3
(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5
(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4
(46):	Folate transporter SLC46A1 SLC46A2
(47):	multidrug and toxin extrusion SLC47A1 SLC47A2
(48):	Heme transporter

SLCO1–4
O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5
Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO⁻ ₃ (Band 3) Cl⁻-formate Cl⁻-oxalate