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P40879 (S26A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length764 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Chloride/bicarbonate exchanger. Mediates the efficient absorption of chloride ions in the colon, participating in fluid homeostasis. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.

Subunit structure

Interacts with CFTR, SLC26A6 and SLC9A3R1 By similarity. Interacts with PDZK1. Ref.4

Subcellular location

Apical cell membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein By similarity. Note: Localized in sperm membranes. Midpiece of sperm tail. Colocalizes with CFTR at the midpiece of sperm tail By similarity. Ref.5

Developmental stage

Expression is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon.

Post-translational modification

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 processAntiport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandChloride
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanion transport

Traceable author statement Ref.8. Source: ProtInc

cellular response to cAMP

Inferred from sequence or structural similarity. Source: UniProtKB

chloride transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

excretion

Traceable author statement Ref.6. Source: ProtInc

intracellular pH elevation

Inferred from sequence or structural similarity. Source: UniProtKB

ion transport

Traceable author statement. Source: Reactome

membrane hyperpolarization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of RNA biosynthetic process

Traceable author statement Ref.1. Source: GOC

regulation of transcription, DNA-templated

Traceable author statement Ref.1. Source: GOC

sperm capacitation

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

brush border membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

sperm midpiece

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionanion:anion antiporter activity

Inferred from electronic annotation. Source: Ensembl

bicarbonate transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

chloride transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12369822. Source: IntAct

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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SLC9A3R2Q155995EBI-8542350,EBI-1149760

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 764764Chloride anion exchanger
PRO_0000080161

Regions

Transmembrane77 – 9721Helical; Potential
Transmembrane100 – 12021Helical; Potential
Transmembrane125 – 14521Helical; Potential
Topological domain146 – 17530Extracellular Potential
Transmembrane176 – 19621Helical; Potential
Transmembrane198 – 21821Helical; Potential
Transmembrane259 – 27921Helical; Potential
Transmembrane286 – 30621Helical; Potential
Transmembrane343 – 36321Helical; Potential
Transmembrane375 – 39521Helical; Potential
Transmembrane412 – 43221Helical; Potential
Transmembrane439 – 45921Helical; Potential
Transmembrane470 – 49021Helical; Potential
Transmembrane644 – 66421Helical; Potential
Transmembrane702 – 72221Helical; Potential
Domain525 – 720196STAS

Amino acid modifications

Glycosylation1531N-linked (GlcNAc...) Ref.5
Glycosylation1611N-linked (GlcNAc...) Ref.5
Glycosylation1651N-linked (GlcNAc...) Ref.5

Natural variations

Natural variant681R → Q.
Corresponds to variant rs10280704 [ dbSNP | Ensembl ].
VAR_053660
Natural variant1201G → S in DIAR1. Ref.7 Ref.8
VAR_007428
Natural variant1241H → L in DIAR1. Ref.6 Ref.7
VAR_007429
Natural variant1291P → L in DIAR1. Ref.11
VAR_066062
Natural variant1311P → L in DIAR1. Ref.11
VAR_066063
Natural variant1311P → R in DIAR1. Ref.7 Ref.8
VAR_007430
Natural variant1361M → I in DIAR1. Ref.11
VAR_066064
Natural variant2041Y → D in DIAR1. Ref.11
VAR_066065
Natural variant2061S → P in DIAR1. Ref.9
VAR_012777
Natural variant2201H → P in DIAR1. Ref.11 Ref.12
VAR_066066
Natural variant3071C → W. Ref.6
Corresponds to variant rs34407351 [ dbSNP | Ensembl ].
VAR_007431
Natural variant3171Missing in DIAR1. Ref.6 Ref.8
VAR_007432
Natural variant3431C → Y in DIAR1. Ref.11
VAR_066067
Natural variant344 – 3496FGIAMV → DA in DIAR1.
VAR_066068
Natural variant3791G → A in DIAR1. Ref.11
VAR_066069
Natural variant3981S → F in DIAR1. Ref.11
Corresponds to variant rs143839547 [ dbSNP | Ensembl ].
VAR_066070
Natural variant4681D → V in DIAR1. Ref.9
VAR_012778
Natural variant4961L → R in DIAR1. Ref.7
VAR_066071
Natural variant5201Y → C in DIAR1. Ref.10
VAR_066072
Natural variant5211K → N in DIAR1. Ref.11
VAR_066073
Natural variant5271Missing in DIAR1. Ref.8
VAR_007433
Natural variant5441I → N in DIAR1. Ref.11
VAR_066074
Natural variant5541R → Q.
Corresponds to variant rs2301635 [ dbSNP | Ensembl ].
VAR_053661
Natural variant6521D → N in DIAR1. Ref.10
VAR_066075
Natural variant7531N → S.
Corresponds to variant rs35342296 [ dbSNP | Ensembl ].
VAR_053662

Sequences

Sequence LengthMass (Da)Tools
P40879 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 694C5BC2D4121F6D

FASTA76484,505
        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 

« Hide

References

« Hide '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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L02785 mRNA. Translation: AAA58443.1.
BC025671 mRNA. Translation: AAH25671.1.
CCDSCCDS5748.1.
PIRA47456.
RefSeqNP_000102.1. NM_000111.2.
XP_006715936.1. XM_006715873.1.
UniGeneHs.1650.

3D structure databases

ProteinModelPortalP40879.
SMRP40879. Positions 645-718.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108145. 1 interaction.
IntActP40879. 1 interaction.
MINTMINT-1787198.
STRING9606.ENSP00000345873.

Protein family/group databases

TCDB2.A.53.2.18. the sulfate permease (sulp) family.

PTM databases

PhosphoSiteP40879.

Polymorphism databases

DMDM729367.

Proteomic databases

PaxDbP40879.
PRIDEP40879.

Protocols and materials databases

DNASU1811.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340010; ENSP00000345873; ENSG00000091138.
GeneID1811.
KEGGhsa:1811.
UCSCuc003ver.2. human.

Organism-specific databases

CTD1811.
GeneCardsGC07M107405.
HGNCHGNC:3018. SLC26A3.
HPAHPA036055.
MIM126650. gene.
214700. phenotype.
neXtProtNX_P40879.
Orphanet53689. Congenital chloride diarrhea.
PharmGKBPA35044.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0659.
HOGENOMHOG000006546.
HOVERGENHBG000639.
InParanoidP40879.
KOK14078.
OMAYIVARPV.
OrthoDBEOG76T9QT.
PhylomeDBP40879.
TreeFamTF313784.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP40879.
BgeeP40879.
CleanExHS_SLC26A3.
GenevestigatorP40879.

Family and domain databases

Gene3D3.30.750.24. 2 hits.
InterProIPR018045. S04_transporter_CS.
IPR002645. STAS_dom.
IPR001902. SulP_transpt.
IPR011547. Sulph_transpt.
[Graphical view]
PfamPF01740. STAS. 1 hit.
PF00916. Sulfate_transp. 1 hit.
[Graphical view]
SUPFAMSSF52091. SSF52091. 2 hits.
TIGRFAMsTIGR00815. sulP. 1 hit.
PROSITEPS01130. SLC26A. 1 hit.
PS50801. STAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC26A3.
GenomeRNAi1811.
NextBio7381.
PROP40879.
SOURCESearch...

Entry information

Entry nameS26A3_HUMAN
AccessionPrimary (citable) accession number: P40879
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM