Chloride anion exchanger

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

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) Band 7q22.3-q31.1 Start 107,765,467 bp End 107,803,225 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12 A2|12 13.45 cM Start 31,440,870 bp End 31,523,916 bp
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
Wikidata
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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.

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.

Clinical significance

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

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

See also

• Solute carrier family

Further reading

• 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.