P40879 · S26A3_HUMAN
- ProteinChloride anion exchanger
- GeneSLC26A3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids764 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia (PubMed:16606687, PubMed:19321737, PubMed:22159084, PubMed:22627094).
Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).
Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).
Catalytic activity
- 2 chloride(out) + hydrogencarbonate(in) = 2 chloride(in) + hydrogencarbonate(out)
2 chloride (out)CHEBI:17996+ hydrogencarbonate (in)CHEBI:17544= 2 chloride (in)CHEBI:17996+ hydrogencarbonate (out)CHEBI:17544
Activity regulation
Inhibited by acidic pH.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | brush border membrane | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Cellular Component | sperm midpiece | |
Molecular Function | bicarbonate transmembrane transporter activity | |
Molecular Function | chloride transmembrane transporter activity | |
Molecular Function | chloride:bicarbonate antiporter activity | |
Molecular Function | oxalate transmembrane transporter activity | |
Molecular Function | secondary active sulfate transmembrane transporter activity | |
Molecular Function | solute:inorganic anion antiporter activity | |
Molecular Function | sulfate transmembrane transporter activity | |
Biological Process | cellular response to cAMP | |
Biological Process | intracellular pH elevation | |
Biological Process | membrane hyperpolarization | |
Biological Process | monoatomic anion transport | |
Biological Process | monoatomic ion transport | |
Biological Process | sperm capacitation |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameChloride anion exchanger
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP40879
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Note: Localized in sperm membranes. Midpiece of sperm tail. Colocalizes with CFTR at the midpiece of sperm tail (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-76 | Cytoplasmic | ||||
Sequence: MIEPFGNQYIVARPVYSTNAFEENHKKTGRHHKTFLDHLKVCCSCSPQKAKRIVLSLFPIASWLPAYRLKEWLLSD | ||||||
Transmembrane | 77-97 | Helical | ||||
Sequence: IVSGISTGIVAVLQGLAFALL | ||||||
Topological domain | 98-99 | Extracellular | ||||
Sequence: VD | ||||||
Transmembrane | 100-120 | Helical | ||||
Sequence: IPPVYGLYASFFPAIIYLFFG | ||||||
Topological domain | 121-124 | Cytoplasmic | ||||
Sequence: TSRH | ||||||
Transmembrane | 125-145 | Helical | ||||
Sequence: ISVGPFPILSMMVGLAVSGAV | ||||||
Topological domain | 146-175 | Extracellular | ||||
Sequence: SKAVPDRNATTLGLPNNSNNSSLLDDERVR | ||||||
Transmembrane | 176-196 | Helical | ||||
Sequence: VAAAASVTVLSGIIQLAFGIL | ||||||
Topological domain | 197 | Cytoplasmic | ||||
Sequence: R | ||||||
Transmembrane | 198-218 | Helical | ||||
Sequence: IGFVVIYLSESLISGFTTAAA | ||||||
Topological domain | 219-257 | Extracellular | ||||
Sequence: VHVLVSQLKFIFQLTVPSHTDPVSIFKVLYSVFSQIEKT | ||||||
Transmembrane | 258-278 | Helical | ||||
Sequence: NIADLVTALIVLLVVSIVKEI | ||||||
Topological domain | 279-342 | Cytoplasmic | ||||
Sequence: NQRFKDKLPVPIPIEFIMTVIAAGVSYGCDFKNRFKVAVVGDMNPGFQPPITPDVETFQNTVGD | ||||||
Transmembrane | 343-363 | Helical | ||||
Sequence: CFGIAMVAFAVAFSVASVYSL | ||||||
Topological domain | 364-374 | Extracellular | ||||
Sequence: KYDYPLDGNQE | ||||||
Transmembrane | 375-395 | Helical | ||||
Sequence: LIALGLGNIVCGVFRGFAGST | ||||||
Topological domain | 396-411 | Cytoplasmic | ||||
Sequence: ALSRSAVQESTGGKTQ | ||||||
Transmembrane | 412-432 | Helical | ||||
Sequence: IAGLIGAIIVLIVVLAIGFLL | ||||||
Topological domain | 433-469 | Extracellular | ||||
Sequence: APLQKSVLAALALGNLKGMLMQFAEIGRLWRKDKYDC | ||||||
Transmembrane | 470-490 | Helical | ||||
Sequence: LIWIMTFIFTIVLGLGLGLAA | ||||||
Topological domain | 491-701 | Cytoplasmic | ||||
Sequence: SVAFQLLTIVFRTQFPKCSTLANIGRTNIYKNKKDYYDMYEPEGVKIFRCPSPIYFANIGFFRRKLIDAVGFSPLRILRKRNKALRKIRKLQKQGLLQVTPKGFICTVDTIKDSDEELDNNQIEVLDQPINTTDLPFHIDWNDDLPLNIEVPKISLHSLILDFSAVSFLDVSSVRGLKSILQEFIRIKVDVYIVGTDDDFIEKLNRYEFFD |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Diarrhea 1, secretory chloride, congenital (DIAR1)
- Note
- DescriptionA disease characterized by voluminous watery stools containing an excess of chloride. The children with this disease are often premature.
- See alsoMIM:214700
Natural variants in DIAR1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_007428 | 120 | G>S | in DIAR1; dbSNP:rs386833479 | |
VAR_007429 | 124 | H>L | in DIAR1; dbSNP:rs121913030 | |
VAR_066062 | 129 | P>L | in DIAR1; dbSNP:rs386833480 | |
VAR_066063 | 131 | P>L | in DIAR1; dbSNP:rs386833481 | |
VAR_007430 | 131 | P>R | in DIAR1; dbSNP:rs386833481 | |
VAR_077354 | 134 | S>N | in DIAR1 | |
VAR_066064 | 136 | M>I | in DIAR1; dbSNP:rs386833483 | |
VAR_077355 | 175 | R>S | in DIAR1; dbSNP:rs386833484 | |
VAR_066065 | 204 | Y>D | in DIAR1; dbSNP:rs386833487 | |
VAR_012777 | 206 | S>P | in DIAR1; dbSNP:rs386833488 | |
VAR_066066 | 220 | H>P | in DIAR1; dbSNP:rs386833489 | |
VAR_007432 | 318 | missing | in DIAR1; dbSNP:rs386833491 | |
VAR_066067 | 343 | C>Y | in DIAR1; dbSNP:rs386833444 | |
VAR_066068 | 344-349 | FGIAMV>DA | in DIAR1 | |
VAR_066069 | 379 | G>A | in DIAR1; dbSNP:rs386833446 | |
VAR_077356 | 394 | S>I | in DIAR1; dbSNP:rs1228273365 | |
VAR_066070 | 398 | S>F | in DIAR1; dbSNP:rs143839547 | |
VAR_077357 | 438 | S>P | in DIAR1; dbSNP:rs763669046 | |
VAR_012778 | 468 | D>V | in DIAR1; dbSNP:rs386833454 | |
VAR_077358 | 495 | Q>P | in DIAR1 | |
VAR_066071 | 496 | L>R | in DIAR1; dbSNP:rs386833457 | |
VAR_077359 | 508 | C>R | in DIAR1 | |
VAR_066072 | 520 | Y>C | in DIAR1; dbSNP:rs386833462 | |
VAR_066073 | 521 | K>N | in DIAR1; dbSNP:rs386833463 | |
VAR_007433 | 527 | missing | in DIAR1; dbSNP:rs386833464 | |
VAR_066074 | 544 | I>N | in DIAR1; dbSNP:rs386833467 | |
VAR_077360 | 547 | A>E | in DIAR1 | |
VAR_066075 | 652 | D>N | in DIAR1; dbSNP:rs140426439 | |
VAR_077361 | 654 | S>P | in DIAR1 | |
VAR_077362 | 675 | I>II | in DIAR1; dbSNP:rs121913031 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_053660 | 68 | in dbSNP:rs10280704 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_007428 | 120 | in DIAR1; dbSNP:rs386833479 | |||
Sequence: G → S | ||||||
Natural variant | VAR_007429 | 124 | in DIAR1; dbSNP:rs121913030 | |||
Sequence: H → L | ||||||
Natural variant | VAR_066062 | 129 | in DIAR1; dbSNP:rs386833480 | |||
Sequence: P → L | ||||||
Natural variant | VAR_066063 | 131 | in DIAR1; dbSNP:rs386833481 | |||
Sequence: P → L | ||||||
Natural variant | VAR_007430 | 131 | in DIAR1; dbSNP:rs386833481 | |||
Sequence: P → R | ||||||
Natural variant | VAR_077354 | 134 | in DIAR1 | |||
Sequence: S → N | ||||||
Natural variant | VAR_066064 | 136 | in DIAR1; dbSNP:rs386833483 | |||
Sequence: M → I | ||||||
Natural variant | VAR_077355 | 175 | in DIAR1; dbSNP:rs386833484 | |||
Sequence: R → S | ||||||
Natural variant | VAR_066065 | 204 | in DIAR1; dbSNP:rs386833487 | |||
Sequence: Y → D | ||||||
Natural variant | VAR_012777 | 206 | in DIAR1; dbSNP:rs386833488 | |||
Sequence: S → P | ||||||
Natural variant | VAR_066066 | 220 | in DIAR1; dbSNP:rs386833489 | |||
Sequence: H → P | ||||||
Natural variant | VAR_007431 | 307 | in dbSNP:rs34407351 | |||
Sequence: C → W | ||||||
Natural variant | VAR_007432 | 318 | in DIAR1; dbSNP:rs386833491 | |||
Sequence: Missing | ||||||
Natural variant | VAR_066067 | 343 | in DIAR1; dbSNP:rs386833444 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_066068 | 344-349 | in DIAR1 | |||
Sequence: FGIAMV → DA | ||||||
Natural variant | VAR_066069 | 379 | in DIAR1; dbSNP:rs386833446 | |||
Sequence: G → A | ||||||
Natural variant | VAR_077356 | 394 | in DIAR1; dbSNP:rs1228273365 | |||
Sequence: S → I | ||||||
Natural variant | VAR_066070 | 398 | in DIAR1; dbSNP:rs143839547 | |||
Sequence: S → F | ||||||
Natural variant | VAR_077357 | 438 | in DIAR1; dbSNP:rs763669046 | |||
Sequence: S → P | ||||||
Natural variant | VAR_012778 | 468 | in DIAR1; dbSNP:rs386833454 | |||
Sequence: D → V | ||||||
Natural variant | VAR_077358 | 495 | in DIAR1 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_066071 | 496 | in DIAR1; dbSNP:rs386833457 | |||
Sequence: L → R | ||||||
Natural variant | VAR_077359 | 508 | in DIAR1 | |||
Sequence: C → R | ||||||
Natural variant | VAR_066072 | 520 | in DIAR1; dbSNP:rs386833462 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_066073 | 521 | in DIAR1; dbSNP:rs386833463 | |||
Sequence: K → N | ||||||
Natural variant | VAR_007433 | 527 | in DIAR1; dbSNP:rs386833464 | |||
Sequence: Missing | ||||||
Natural variant | VAR_066074 | 544 | in DIAR1; dbSNP:rs386833467 | |||
Sequence: I → N | ||||||
Natural variant | VAR_077360 | 547 | in DIAR1 | |||
Sequence: A → E | ||||||
Natural variant | VAR_053661 | 554 | in dbSNP:rs2301635 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_066075 | 652 | in DIAR1; dbSNP:rs140426439 | |||
Sequence: D → N | ||||||
Natural variant | VAR_077361 | 654 | in DIAR1 | |||
Sequence: S → P | ||||||
Natural variant | VAR_077362 | 675 | in DIAR1; dbSNP:rs121913031 | |||
Sequence: I → II | ||||||
Natural variant | VAR_053662 | 753 | in dbSNP:rs35342296 | |||
Sequence: N → S | ||||||
Mutagenesis | 761-764 | Loss of interaction with NHERF4. No effect on localization to cell membrane or its exchanger activity. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 954 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000080161 | 1-764 | Chloride anion exchanger | |||
Sequence: MIEPFGNQYIVARPVYSTNAFEENHKKTGRHHKTFLDHLKVCCSCSPQKAKRIVLSLFPIASWLPAYRLKEWLLSDIVSGISTGIVAVLQGLAFALLVDIPPVYGLYASFFPAIIYLFFGTSRHISVGPFPILSMMVGLAVSGAVSKAVPDRNATTLGLPNNSNNSSLLDDERVRVAAAASVTVLSGIIQLAFGILRIGFVVIYLSESLISGFTTAAAVHVLVSQLKFIFQLTVPSHTDPVSIFKVLYSVFSQIEKTNIADLVTALIVLLVVSIVKEINQRFKDKLPVPIPIEFIMTVIAAGVSYGCDFKNRFKVAVVGDMNPGFQPPITPDVETFQNTVGDCFGIAMVAFAVAFSVASVYSLKYDYPLDGNQELIALGLGNIVCGVFRGFAGSTALSRSAVQESTGGKTQIAGLIGAIIVLIVVLAIGFLLAPLQKSVLAALALGNLKGMLMQFAEIGRLWRKDKYDCLIWIMTFIFTIVLGLGLGLAASVAFQLLTIVFRTQFPKCSTLANIGRTNIYKNKKDYYDMYEPEGVKIFRCPSPIYFANIGFFRRKLIDAVGFSPLRILRKRNKALRKIRKLQKQGLLQVTPKGFICTVDTIKDSDEELDNNQIEVLDQPINTTDLPFHIDWNDDLPLNIEVPKISLHSLILDFSAVSFLDVSSVRGLKSILQEFIRIKVDVYIVGTDDDFIEKLNRYEFFDGEVKSSIFFLTIHDAVLHILMKKDYSTSKFNPSQEKDGKIDFTINTNGGLRNRVYEVPVETKF | ||||||
Glycosylation | 153 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 161 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 165 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylation is required for efficient cell surface expression, and protection from proteolytic degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the colon. Expression is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with CFTR, SLC26A6 and NHERF1 (By similarity).
Interacts with PDZK1 (PubMed:15766278).
Interacts (via PDZ-binding motif) with NHERF4 (via the third PDZ domain); interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity (PubMed:22627094).
Interacts with PDZK1 (PubMed:15766278).
Interacts (via PDZ-binding motif) with NHERF4 (via the third PDZ domain); interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity (PubMed:22627094).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P40879 | NHERF2 Q15599 | 5 | EBI-8542350, EBI-1149760 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 525-720 | STAS | ||||
Sequence: DYYDMYEPEGVKIFRCPSPIYFANIGFFRRKLIDAVGFSPLRILRKRNKALRKIRKLQKQGLLQVTPKGFICTVDTIKDSDEELDNNQIEVLDQPINTTDLPFHIDWNDDLPLNIEVPKISLHSLILDFSAVSFLDVSSVRGLKSILQEFIRIKVDVYIVGTDDDFIEKLNRYEFFDGEVKSSIFFLTIHDAVLHI | ||||||
Motif | 761-764 | PDZ-binding | ||||
Sequence: ETKF |
Sequence similarities
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length764
- Mass (Da)84,505
- Last updated1995-02-01 v1
- Checksum694C5BC2D4121F6D
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L02785 EMBL· GenBank· DDBJ | AAA58443.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025671 EMBL· GenBank· DDBJ | AAH25671.1 EMBL· GenBank· DDBJ | mRNA |