ID S26A3_HUMAN Reviewed; 764 AA. AC P40879; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 29-MAY-2013, entry version 127. DE RecName: Full=Chloride anion exchanger; DE AltName: Full=Down-regulated in adenoma; DE Short=Protein DRA; DE AltName: Full=Solute carrier family 26 member 3; GN Name=SLC26A3; Synonyms=DRA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Colon; RX PubMed=7683425; DOI=10.1073/pnas.90.9.4166; RA Schweinfest C.W., Henderson K.W., Suster S., Kondoh N., Papas T.S.; RT "Identification of a colon mucosa gene that is down-regulated in colon RT adenomas and adenocarcinomas."; RL Proc. Natl. Acad. Sci. U.S.A. 90:4166-4170(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP SIMILARITY TO SULFATE PERMEASES. RX PubMed=8140616; DOI=10.1016/0968-0004(94)90168-6; RA Sandal N.N., Marcker K.A.; RT "Similarities between a soybean nodulin, Neurospora crassa sulphate RT permease II and a putative human tumour suppressor."; RL Trends Biochem. Sci. 19:19-19(1994). RN [4] RP INTERACTION WITH PDZK1. RX PubMed=15766278; DOI=10.1021/bi048828b; RA Rossmann H., Jacob P., Baisch S., Hassoun R., Meier J., Natour D., RA Yahya K., Yun C., Biber J., Lackner K.J., Fiehn W., Gregor M., RA Seidler U., Lamprecht G.; RT "The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3- RT exchanger DRA in rabbit small intestinal mucosa."; RL Biochemistry 44:4477-4487(2005). RN [5] RP GLYCOSYLATION AT ASN-153; ASN-161 AND ASN-165, AND SUBCELLULAR RP LOCATION. RX PubMed=22159084; DOI=10.1152/ajpcell.00165.2011; RA Hayashi H., Yamashita Y.; RT "Role of N-glycosylation in cell surface expression and protection RT against proteolysis of the intestinal anion exchanger SLC26A3."; RL Am. J. Physiol. 302:C781-C795(2012). RN [6] RP VARIANTS DIAR1 LEU-124 AND VAL-317 DEL, AND VARIANT TRP-307. RX PubMed=8896562; DOI=10.1038/ng1196-316; RA Hoeglund P., Haila S., Socha J., Tomaszewski L., Saarialho-Kere U., RA Karjalainen-Lindsberg M.-L., Airola K., Holmberg C., RA de la Chapelle A., Kere J.; RT "Mutations of the Down-regulated in adenoma (DRA) gene cause RT congenital chloride diarrhoea."; RL Nat. Genet. 14:316-319(1996). RN [7] RP VARIANTS DIAR1 SER-120; LEU-124; ARG-131 AND ARG-496. RX PubMed=9718329; DOI=10.1086/301998; RA Hoglund P., Auranen M., Socha J., Popinska K., Nazer H., Rajaram U., RA Al Sanie A., Al-Ghanim M., Holmberg C., de la Chapelle A., Kere J.; RT "Genetic background of congenital chloride diarrhea in high-incidence RT populations: Finland, Poland, and Saudi Arabia and Kuwait."; RL Am. J. Hum. Genet. 63:760-768(1998). RN [8] RP VARIANTS DIAR1 SER-120; ARG-131; VAL-317 DEL AND TYR-527 DEL. RX PubMed=9554749; RX DOI=10.1002/(SICI)1098-1004(1998)11:4<321::AID-HUMU10>3.3.CO;2-1; RA Hoeglund P., Haila S., Gustavson K.-H., Taipale M., Hannula K., RA Popinska K., Holmberg C., Socha J., de la Chapelle A., Kere J.; RT "Clustering of private mutations in the congenital chloride RT diarrhea/down-regulated in adenoma gene."; RL Hum. Mutat. 11:321-327(1998). RN [9] RP VARIANTS DIAR1 PRO-206 AND VAL-468. RX PubMed=11524734; DOI=10.1002/humu.1179; RA Hoeglund P., Sormaala M., Haila S., Socha J., Rajaram U., RA Scheurlen W., Sinaasappel M., de Jonge H., Holmberg C., Yoshikawa H., RA Kere J.; RT "Identification of seven novel mutations including the first two RT genomic rearrangements in SLC26A3 mutated in congenital chloride RT diarrhea."; RL Hum. Mutat. 18:233-242(2001). RN [10] RP VARIANTS DIAR1 CYS-520 AND ASN-652. RX PubMed=19861545; DOI=10.1073/pnas.0910672106; RA Choi M., Scholl U.I., Ji W., Liu T., Tikhonova I.R., Zumbo P., RA Nayir A., Bakkaloglu A., Ozen S., Sanjad S., Nelson-Williams C., RA Farhi A., Mane S., Lifton R.P.; RT "Genetic diagnosis by whole exome capture and massively parallel DNA RT sequencing."; RL Proc. Natl. Acad. Sci. U.S.A. 106:19096-19101(2009). RN [11] RP VARIANTS DIAR1 LEU-129; LEU-131; ILE-136; ASP-204; PRO-220; TYR-343; RP 344-PHE--VAL-349 DELINS ASP-ALA; ALA-379; PHE-398; ASN-521 AND RP ASN-544. RX PubMed=21394828; DOI=10.1002/humu.21498; RA Wedenoja S., Pekansaari E., Hoglund P., Makela S., Holmberg C., RA Kere J.; RT "Update on SLC26A3 mutations in congenital chloride diarrhea."; RL Hum. Mutat. 32:715-722(2011). RN [12] RP VARIANT DIAR1 PRO-220. RX PubMed=21150650; DOI=10.1097/MPG.0b013e3181f28d1a; RA Rodriguez-Herrera A., Navas-Lopez V.M., Redondo-Nevado J., RA Gutierrez G.; RT "Compound heterozygous mutations in the SLC26A3 gene in 2 Spanish RT siblings with congenital chloride diarrhea."; RL J. Pediatr. Gastroenterol. Nutr. 52:106-110(2011). CC -!- FUNCTION: Chloride/bicarbonate exchanger. Mediates the efficient CC absorbtion of chloride ions in the colon, participating in fluid CC homeostasis. CC -!- SUBUNIT: Interacts with PDZK1. CC -!- SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane CC protein. CC -!- DEVELOPMENTAL STAGE: Expression is significantly decreased in CC adenomas (polyps) and adenocarcinomas of the colon. CC -!- PTM: N-glycosylation is required for efficient cell surface CC expression, and protection from proteolytic degradation. CC -!- DISEASE: Diarrhea 1, secretory chloride, congenital (DIAR1) CC [MIM:214700]: A disease characterized by voluminous watery stools CC containing an excess of chloride. The children with this disease CC are often premature. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SLC26A/SulP transporter (TC 2.A.53) CC family. CC -!- SIMILARITY: Contains 1 STAS domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC26A3"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L02785; AAA58443.1; -; mRNA. DR EMBL; BC025671; AAH25671.1; -; mRNA. DR IPI; IPI00031036; -. DR PIR; A47456; A47456. DR RefSeq; NP_000102.1; NM_000111.2. DR UniGene; Hs.1650; -. DR ProteinModelPortal; P40879; -. DR MINT; MINT-1787198; -. DR STRING; 9606.ENSP00000345873; -. DR PhosphoSite; P40879; -. DR DMDM; 729367; -. DR PaxDb; P40879; -. DR PRIDE; P40879; -. DR DNASU; 1811; -. DR Ensembl; ENST00000340010; ENSP00000345873; ENSG00000091138. DR GeneID; 1811; -. DR KEGG; hsa:1811; -. DR UCSC; uc003ver.2; human. DR CTD; 1811; -. DR GeneCards; GC07M107405; -. DR HGNC; HGNC:3018; SLC26A3. DR HPA; HPA036055; -. DR MIM; 126650; gene. DR MIM; 214700; phenotype. DR neXtProt; NX_P40879; -. DR Orphanet; 53689; Congenital chloride diarrhea. DR PharmGKB; PA35044; -. DR eggNOG; COG0659; -. DR HOGENOM; HOG000006546; -. DR HOVERGEN; HBG000639; -. DR InParanoid; P40879; -. DR KO; K14078; -. DR OMA; YIVARPV; -. DR OrthoDB; EOG415GCZ; -. DR PhylomeDB; P40879; -. DR Reactome; REACT_15518; Transmembrane transport of small molecules. DR GenomeRNAi; 1811; -. DR NextBio; 7381; -. DR ArrayExpress; P40879; -. DR Bgee; P40879; -. DR CleanEx; HS_SLC26A3; -. DR Genevestigator; P40879; -. DR GermOnline; ENSG00000091138; Homo sapiens. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031526; C:brush border membrane; IEA:Compara. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0015301; F:anion:anion antiporter activity; IEA:Compara. DR GO; GO:0008271; F:secondary active sulfate transmembrane transporter activity; IEA:InterPro. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc. DR GO; GO:0003712; F:transcription cofactor activity; TAS:ProtInc. DR GO; GO:0005215; F:transporter activity; TAS:ProtInc. DR GO; GO:0006820; P:anion transport; TAS:ProtInc. DR GO; GO:0007588; P:excretion; TAS:ProtInc. DR GO; GO:0008272; P:sulfate transport; IEA:InterPro. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. DR Gene3D; 3.30.750.24; -; 2. DR InterPro; IPR018045; S04_transporter_CS. DR InterPro; IPR002645; STAS_dom. DR InterPro; IPR001902; SulP_transpt. DR InterPro; IPR011547; Sulph_transpt. DR Pfam; PF01740; STAS; 1. DR Pfam; PF00916; Sulfate_transp; 1. DR SUPFAM; SSF52091; STAS; 1. DR TIGRFAMs; TIGR00815; sulP; 1. DR PROSITE; PS01130; SLC26A; 1. DR PROSITE; PS50801; STAS; 1. PE 1: Evidence at protein level; KW Antiport; Cell membrane; Chloride; Complete proteome; KW Disease mutation; Glycoprotein; Membrane; Polymorphism; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1 764 Chloride anion exchanger. FT /FTId=PRO_0000080161. FT TRANSMEM 77 97 Helical; (Potential). FT TRANSMEM 100 120 Helical; (Potential). FT TRANSMEM 125 145 Helical; (Potential). FT TOPO_DOM 146 175 Extracellular (Potential). FT TRANSMEM 176 196 Helical; (Potential). FT TRANSMEM 198 218 Helical; (Potential). FT TRANSMEM 259 279 Helical; (Potential). FT TRANSMEM 286 306 Helical; (Potential). FT TRANSMEM 343 363 Helical; (Potential). FT TRANSMEM 375 395 Helical; (Potential). FT TRANSMEM 412 432 Helical; (Potential). FT TRANSMEM 439 459 Helical; (Potential). FT TRANSMEM 470 490 Helical; (Potential). FT TRANSMEM 644 664 Helical; (Potential). FT TRANSMEM 702 722 Helical; (Potential). FT DOMAIN 525 720 STAS. FT CARBOHYD 153 153 N-linked (GlcNAc...). FT CARBOHYD 161 161 N-linked (GlcNAc...). FT CARBOHYD 165 165 N-linked (GlcNAc...). FT VARIANT 68 68 R -> Q (in dbSNP:rs10280704). FT /FTId=VAR_053660. FT VARIANT 120 120 G -> S (in DIAR1). FT /FTId=VAR_007428. FT VARIANT 124 124 H -> L (in DIAR1). FT /FTId=VAR_007429. FT VARIANT 129 129 P -> L (in DIAR1). FT /FTId=VAR_066062. FT VARIANT 131 131 P -> L (in DIAR1). FT /FTId=VAR_066063. FT VARIANT 131 131 P -> R (in DIAR1). FT /FTId=VAR_007430. FT VARIANT 136 136 M -> I (in DIAR1). FT /FTId=VAR_066064. FT VARIANT 204 204 Y -> D (in DIAR1). FT /FTId=VAR_066065. FT VARIANT 206 206 S -> P (in DIAR1). FT /FTId=VAR_012777. FT VARIANT 220 220 H -> P (in DIAR1). FT /FTId=VAR_066066. FT VARIANT 307 307 C -> W (in dbSNP:rs34407351). FT /FTId=VAR_007431. FT VARIANT 317 317 Missing (in DIAR1). FT /FTId=VAR_007432. FT VARIANT 343 343 C -> Y (in DIAR1). FT /FTId=VAR_066067. FT VARIANT 344 349 FGIAMV -> DA (in DIAR1). FT /FTId=VAR_066068. FT VARIANT 379 379 G -> A (in DIAR1). FT /FTId=VAR_066069. FT VARIANT 398 398 S -> F (in DIAR1). FT /FTId=VAR_066070. FT VARIANT 468 468 D -> V (in DIAR1). FT /FTId=VAR_012778. FT VARIANT 496 496 L -> R (in DIAR1). FT /FTId=VAR_066071. FT VARIANT 520 520 Y -> C (in DIAR1). FT /FTId=VAR_066072. FT VARIANT 521 521 K -> N (in DIAR1). FT /FTId=VAR_066073. FT VARIANT 527 527 Missing (in DIAR1). FT /FTId=VAR_007433. FT VARIANT 544 544 I -> N (in DIAR1). FT /FTId=VAR_066074. FT VARIANT 554 554 R -> Q (in dbSNP:rs2301635). FT /FTId=VAR_053661. FT VARIANT 652 652 D -> N (in DIAR1). FT /FTId=VAR_066075. FT VARIANT 753 753 N -> S (in dbSNP:rs35342296). FT /FTId=VAR_053662. SQ SEQUENCE 764 AA; 84505 MW; 694C5BC2D4121F6D CRC64; MIEPFGNQYI VARPVYSTNA FEENHKKTGR HHKTFLDHLK VCCSCSPQKA KRIVLSLFPI ASWLPAYRLK EWLLSDIVSG ISTGIVAVLQ GLAFALLVDI PPVYGLYASF FPAIIYLFFG TSRHISVGPF PILSMMVGLA VSGAVSKAVP DRNATTLGLP NNSNNSSLLD DERVRVAAAA SVTVLSGIIQ LAFGILRIGF VVIYLSESLI SGFTTAAAVH VLVSQLKFIF QLTVPSHTDP VSIFKVLYSV FSQIEKTNIA DLVTALIVLL VVSIVKEINQ RFKDKLPVPI PIEFIMTVIA AGVSYGCDFK NRFKVAVVGD MNPGFQPPIT PDVETFQNTV GDCFGIAMVA FAVAFSVASV YSLKYDYPLD GNQELIALGL GNIVCGVFRG FAGSTALSRS AVQESTGGKT QIAGLIGAII VLIVVLAIGF LLAPLQKSVL AALALGNLKG MLMQFAEIGR LWRKDKYDCL IWIMTFIFTI VLGLGLGLAA SVAFQLLTIV FRTQFPKCST LANIGRTNIY KNKKDYYDMY EPEGVKIFRC PSPIYFANIG FFRRKLIDAV GFSPLRILRK RNKALRKIRK LQKQGLLQVT PKGFICTVDT IKDSDEELDN NQIEVLDQPI NTTDLPFHID WNDDLPLNIE VPKISLHSLI LDFSAVSFLD VSSVRGLKSI LQEFIRIKVD VYIVGTDDDF IEKLNRYEFF DGEVKSSIFF LTIHDAVLHI LMKKDYSTSK FNPSQEKDGK IDFTINTNGG LRNRVYEVPV ETKF //