P40879 (S26A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chloride anion exchanger

Alternative name(s):
Down-regulated in adenoma
Short name=Protein DRA
Solute carrier family 26 member 3

Gene names

Name:	SLC26A3
Synonyms:	DRA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	764 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Chloride/bicarbonate exchanger. Mediates the efficient absorbtion of chloride ions in the colon, participating in fluid homeostasis.
Subunit structure	Interacts with PDZK1. Ref.4
Subcellular location	Apical cell membrane; Multi-pass membrane protein Ref.5.
Developmental stage	Expression is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. N-glycosylation is required for efficient cell surface expression, and protection from proteolytic degradation.
Involvement in disease	Diarrhea 1, secretory chloride, congenital (DIAR1) [MIM:214700]: A disease characterized by voluminous watery stools containing an excess of chloride. The children with this disease are often premature. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Sequence similarities	Belongs to the SLC26A/SulP transporter (TC 2.A.53) family. [View classification] Contains 1 STAS domain.

Ontologies

Keywords
Biological process	Antiport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Chloride
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anion transport Traceable author statement Ref.8. Source: ProtInc excretion Traceable author statement Ref.6. Source: ProtInc sulfate transport Inferred from electronic annotation. Source: InterPro transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell brush border membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	anion:anion antiporter activity Inferred from electronic annotation. Source: Compara secondary active sulfate transmembrane transporter activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription cofactor activity Traceable author statement Ref.1. Source: ProtInc transporter activity Traceable author statement Ref.6. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 764	764	Chloride anion exchanger		PRO_0000080161
Regions
	Transmembrane	77 – 97	21	Helical; Potential
	Transmembrane	100 – 120	21	Helical; Potential
	Transmembrane	125 – 145	21	Helical; Potential
	Topological domain	146 – 175	30	Extracellular Potential
	Transmembrane	176 – 196	21	Helical; Potential
	Transmembrane	198 – 218	21	Helical; Potential
	Transmembrane	259 – 279	21	Helical; Potential
	Transmembrane	286 – 306	21	Helical; Potential
	Transmembrane	343 – 363	21	Helical; Potential
	Transmembrane	375 – 395	21	Helical; Potential
	Transmembrane	412 – 432	21	Helical; Potential
	Transmembrane	439 – 459	21	Helical; Potential
	Transmembrane	470 – 490	21	Helical; Potential
	Transmembrane	644 – 664	21	Helical; Potential
	Transmembrane	702 – 722	21	Helical; Potential
	Domain	525 – 720	196	STAS
Amino acid modifications
	Glycosylation	153	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	161	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	165	1	N-linked (GlcNAc...) Ref.5
Natural variations
	Natural variant	68	1	R → Q. Corresponds to variant rs10280704 [ dbSNP | Ensembl ].		VAR_053660
	Natural variant	120	1	G → S in DIAR1. Ref.7 Ref.8		VAR_007428
	Natural variant	124	1	H → L in DIAR1. Ref.6 Ref.7		VAR_007429
	Natural variant	129	1	P → L in DIAR1. Ref.11		VAR_066062
	Natural variant	131	1	P → L in DIAR1. Ref.11		VAR_066063
	Natural variant	131	1	P → R in DIAR1. Ref.7 Ref.8		VAR_007430
	Natural variant	136	1	M → I in DIAR1. Ref.11		VAR_066064
	Natural variant	204	1	Y → D in DIAR1. Ref.11		VAR_066065
	Natural variant	206	1	S → P in DIAR1. Ref.9		VAR_012777
	Natural variant	220	1	H → P in DIAR1. Ref.11 Ref.12		VAR_066066
	Natural variant	307	1	C → W. Ref.6 Corresponds to variant rs34407351 [ dbSNP | Ensembl ].		VAR_007431
	Natural variant	317	1	Missing in DIAR1. Ref.6 Ref.8		VAR_007432
	Natural variant	343	1	C → Y in DIAR1. Ref.11		VAR_066067
	Natural variant	344 – 349	6	FGIAMV → DA in DIAR1.		VAR_066068
	Natural variant	379	1	G → A in DIAR1. Ref.11		VAR_066069
	Natural variant	398	1	S → F in DIAR1. Ref.11		VAR_066070
	Natural variant	468	1	D → V in DIAR1. Ref.9		VAR_012778
	Natural variant	496	1	L → R in DIAR1. Ref.7		VAR_066071
	Natural variant	520	1	Y → C in DIAR1. Ref.10		VAR_066072
	Natural variant	521	1	K → N in DIAR1. Ref.11		VAR_066073
	Natural variant	527	1	Missing in DIAR1. Ref.8		VAR_007433
	Natural variant	544	1	I → N in DIAR1. Ref.11		VAR_066074
	Natural variant	554	1	R → Q. Corresponds to variant rs2301635 [ dbSNP | Ensembl ].		VAR_053661
	Natural variant	652	1	D → N in DIAR1. Ref.10		VAR_066075
	Natural variant	753	1	N → S. Corresponds to variant rs35342296 [ dbSNP | Ensembl ].		VAR_053662

Sequences

	Sequence		Length	Mass (Da)
	P40879 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 694C5BC2D4121F6D	FASTA	764	84,505
	10 20 30 40 50 60 MIEPFGNQYI VARPVYSTNA FEENHKKTGR HHKTFLDHLK VCCSCSPQKA KRIVLSLFPI 70 80 90 100 110 120 ASWLPAYRLK EWLLSDIVSG ISTGIVAVLQ GLAFALLVDI PPVYGLYASF FPAIIYLFFG 130 140 150 160 170 180 TSRHISVGPF PILSMMVGLA VSGAVSKAVP DRNATTLGLP NNSNNSSLLD DERVRVAAAA 190 200 210 220 230 240 SVTVLSGIIQ LAFGILRIGF VVIYLSESLI SGFTTAAAVH VLVSQLKFIF QLTVPSHTDP 250 260 270 280 290 300 VSIFKVLYSV FSQIEKTNIA DLVTALIVLL VVSIVKEINQ RFKDKLPVPI PIEFIMTVIA 310 320 330 340 350 360 AGVSYGCDFK NRFKVAVVGD MNPGFQPPIT PDVETFQNTV GDCFGIAMVA FAVAFSVASV 370 380 390 400 410 420 YSLKYDYPLD GNQELIALGL GNIVCGVFRG FAGSTALSRS AVQESTGGKT QIAGLIGAII 430 440 450 460 470 480 VLIVVLAIGF LLAPLQKSVL AALALGNLKG MLMQFAEIGR LWRKDKYDCL IWIMTFIFTI 490 500 510 520 530 540 VLGLGLGLAA SVAFQLLTIV FRTQFPKCST LANIGRTNIY KNKKDYYDMY EPEGVKIFRC 550 560 570 580 590 600 PSPIYFANIG FFRRKLIDAV GFSPLRILRK RNKALRKIRK LQKQGLLQVT PKGFICTVDT 610 620 630 640 650 660 IKDSDEELDN NQIEVLDQPI NTTDLPFHID WNDDLPLNIE VPKISLHSLI LDFSAVSFLD 670 680 690 700 710 720 VSSVRGLKSI LQEFIRIKVD VYIVGTDDDF IEKLNRYEFF DGEVKSSIFF LTIHDAVLHI 730 740 750 760 LMKKDYSTSK FNPSQEKDGK IDFTINTNGG LRNRVYEVPV ETKF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas." Schweinfest C.W., Henderson K.W., Suster S., Kondoh N., Papas T.S. Proc. Natl. Acad. Sci. U.S.A. 90:4166-4170(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[3]	"Similarities between a soybean nodulin, Neurospora crassa sulphate permease II and a putative human tumour suppressor." Sandal N.N., Marcker K.A. Trends Biochem. Sci. 19:19-19(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SIMILARITY TO SULFATE PERMEASES.
[4]	"The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3-exchanger DRA in rabbit small intestinal mucosa." Rossmann H., Jacob P., Baisch S., Hassoun R., Meier J., Natour D., Yahya K., Yun C., Biber J., Lackner K.J., Fiehn W., Gregor M., Seidler U., Lamprecht G. Biochemistry 44:4477-4487(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDZK1.
[5]	"Role of N-glycosylation in cell surface expression and protection against proteolysis of the intestinal anion exchanger SLC26A3." Hayashi H., Yamashita Y. Am. J. Physiol. 302:C781-C795(2012) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-153; ASN-161 AND ASN-165, SUBCELLULAR LOCATION.
[6]	"Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea." Hoeglund P., Haila S., Socha J., Tomaszewski L., Saarialho-Kere U., Karjalainen-Lindsberg M.-L., Airola K., Holmberg C., de la Chapelle A., Kere J. Nat. Genet. 14:316-319(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 LEU-124 AND VAL-317 DEL, VARIANT TRP-307.
[7]	"Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait." Hoglund 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. Am. J. Hum. Genet. 63:760-768(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 SER-120; LEU-124; ARG-131 AND ARG-496.
[8]	"Clustering of private mutations in the congenital chloride diarrhea/down-regulated in adenoma gene." Hoeglund P., Haila S., Gustavson K.-H., Taipale M., Hannula K., Popinska K., Holmberg C., Socha J., de la Chapelle A., Kere J. Hum. Mutat. 11:321-327(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 SER-120; ARG-131; VAL-317 DEL AND TYR-527 DEL.
[9]	"Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea." Hoeglund P., Sormaala M., Haila S., Socha J., Rajaram U., Scheurlen W., Sinaasappel M., de Jonge H., Holmberg C., Yoshikawa H., Kere J. Hum. Mutat. 18:233-242(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 PRO-206 AND VAL-468.
[10]	"Genetic diagnosis by whole exome capture and massively parallel DNA sequencing." Choi M., Scholl U.I., Ji W., Liu T., Tikhonova I.R., Zumbo P., Nayir A., Bakkaloglu A., Ozen S., Sanjad S., Nelson-Williams C., Farhi A., Mane S., Lifton R.P. Proc. Natl. Acad. Sci. U.S.A. 106:19096-19101(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 CYS-520 AND ASN-652.
[11]	"Update on SLC26A3 mutations in congenital chloride diarrhea." Wedenoja S., Pekansaari E., Hoglund P., Makela S., Holmberg C., Kere J. Hum. Mutat. 32:715-722(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DIAR1 LEU-129; LEU-131; ILE-136; ASP-204; PRO-220; TYR-343; 344-PHE--VAL-349 DELINS ASP-ALA; ALA-379; PHE-398; ASN-521 AND ASN-544.
[12]	"Compound heterozygous mutations in the SLC26A3 gene in 2 Spanish siblings with congenital chloride diarrhea." Rodriguez-Herrera A., Navas-Lopez V.M., Redondo-Nevado J., Gutierrez G. J. Pediatr. Gastroenterol. Nutr. 52:106-110(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DIAR1 PRO-220.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L02785 mRNA. Translation: AAA58443.1. BC025671 mRNA. Translation: AAH25671.1.
IPI	IPI00031036.
PIR	A47456.
RefSeq	NP_000102.1. NM_000111.2.
UniGene	Hs.1650.
3D structure databases
ProteinModelPortal	P40879.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1787198.
STRING	9606.ENSP00000345873.
PTM databases
PhosphoSite	P40879.
Polymorphism databases
DMDM	729367.
Proteomic databases
PaxDb	P40879.
PRIDE	P40879.
Protocols and materials databases
DNASU	1811.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340010; ENSP00000345873; ENSG00000091138.
GeneID	1811.
KEGG	hsa:1811.
UCSC	uc003ver.2. human.
Organism-specific databases
CTD	1811.
GeneCards	GC07M107405.
HGNC	HGNC:3018. SLC26A3.
HPA	HPA036055.
MIM	126650. gene. 214700. phenotype.
neXtProt	NX_P40879.
Orphanet	53689. Congenital chloride diarrhea.
PharmGKB	PA35044.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0659.
HOGENOM	HOG000006546.
HOVERGEN	HBG000639.
InParanoid	P40879.
KO	K14078.
OMA	YIVARPV.
OrthoDB	EOG415GCZ.
PhylomeDB	P40879.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P40879.
Bgee	P40879.
CleanEx	HS_SLC26A3.
Genevestigator	P40879.
GermOnline	ENSG00000091138. Homo sapiens.
Family and domain databases
Gene3D	3.30.750.24. 2 hits.
InterPro	IPR018045. S04_transporter_CS. IPR002645. STAS_dom. IPR001902. SulP_transpt. IPR011547. Sulph_transpt. [Graphical view]
Pfam	PF01740. STAS. 1 hit. PF00916. Sulfate_transp. 1 hit. [Graphical view]
SUPFAM	SSF52091. STAS. 1 hit.
TIGRFAMs	TIGR00815. sulP. 1 hit.
PROSITE	PS01130. SLC26A. 1 hit. PS50801. STAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1811.
NextBio	7381.
SOURCE	Search...

Entry information

Entry name

S26A3_HUMAN

Accession

Primary (citable) accession number: P40879

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.