A0A0G2KTI4 · S12A2_DANRE
- ProteinSolute carrier family 12 member 2
- Geneslc12a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1136 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:31367042).
Plays a vital role in the regulation of ionic balance and cell volume (PubMed:31367042).
Important for maintenance of endolymph volume in the otic vesicle, probably by regulating ion homeostasis (PubMed:19633174).
Also plays a role in normal development of the swim bladder (PubMed:19633174).
Plays a vital role in the regulation of ionic balance and cell volume (PubMed:31367042).
Important for maintenance of endolymph volume in the otic vesicle, probably by regulating ion homeostasis (PubMed:19633174).
Also plays a role in normal development of the swim bladder (PubMed:19633174).
Catalytic activity
- 2 chloride(out) + K+(out) + Na+(out) = 2 chloride(in) + K+(in) + Na+(in)This reaction proceeds in the forward direction.
2 chloride (out)CHEBI:17996+ K+ (out)CHEBI:29103+ Na+ (out)CHEBI:29101= 2 chloride (in)CHEBI:17996+ K+ (in)CHEBI:29103+ Na+ (in)CHEBI:29101
Activity regulation
Activated following phosphorylation by OXSR1/OSR1 and STK39/SPAK (By similarity).
Inhibited by bumetanide (PubMed:31367042).
Inhibited by bumetanide (PubMed:31367042).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 219 | Na+ (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 220 | K+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 221 | K+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 222 | Na+ (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 223 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 224 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 225 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 294 | chloride 2 (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 305 | K+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 417 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: P | ||||||
Binding site | 417 | K+ (UniProtKB | ChEBI) | ||||
Sequence: P | ||||||
Binding site | 418 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 418 | K+ (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 420 | K+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 421 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 422 | chloride 1 (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 535 | Na+ (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 538 | Na+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 539 | Na+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 607 | chloride 2 (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 611 | chloride 2 (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Molecular Function | ammonium channel activity | |
Molecular Function | chloride:monoatomic cation symporter activity | |
Molecular Function | identical protein binding | |
Molecular Function | sodium:potassium:chloride symporter activity | |
Biological Process | ammonium transmembrane transport | |
Biological Process | cell volume homeostasis | |
Biological Process | chloride ion homeostasis | |
Biological Process | chloride transmembrane transport | |
Biological Process | ear development | |
Biological Process | inner ear morphogenesis | |
Biological Process | potassium ion homeostasis | |
Biological Process | potassium ion import across plasma membrane | |
Biological Process | sodium ion homeostasis | |
Biological Process | sodium ion transmembrane transport | |
Biological Process | swim bladder inflation |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSolute carrier family 12 member 2
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio
Accessions
- Primary accessionA0A0G2KTI4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Basolateral cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-208 | Cytoplasmic | ||||
Sequence: MSASPPISAGDYLSAPEPDALKPAGPTPSQSRFQVDLVTESAGDGETTVGFDSSPPEYVAEPPPDGLRDSVSGGEEAKGRFRVVNFAASSPDAAPAETAQNGDTVMSEGSLHSSTGGQQHHHYDTHTNTYYLRTFGHNTIDAVPKIDFYRQTAAPLGEKLIRPTLSELHDELDKEPFEDGFANGEELTPAEESAAKDVSESKGVVKFG | ||||||
Transmembrane | 209-234 | Discontinuously helical; Name=1 | ||||
Sequence: WIKGVLVRCMLNIWGVMLFIRMTWIV | ||||||
Topological domain | 235-238 | Extracellular | ||||
Sequence: GQAG | ||||||
Transmembrane | 239-261 | Helical; Name=2 | ||||
Sequence: IAYSCIIVIMATVVTTITGCSTS | ||||||
Topological domain | 262-285 | Cytoplasmic | ||||
Sequence: AIATNGFVRGGGAYYLISRSLGPE | ||||||
Transmembrane | 286-314 | Helical; Name=3 | ||||
Sequence: FGGSIGLIFAFANAVAVAMYVVGFAETVV | ||||||
Topological domain | 315-327 | Extracellular | ||||
Sequence: ELLMDSGLLMIDQ | ||||||
Transmembrane | 328-351 | Helical; Name=4 | ||||
Sequence: TNDIRVIGTITVILLLGISVAGME | ||||||
Transmembrane | 352-376 | Helical; Name=5 | ||||
Sequence: WEAKAQIFLLVILITAIFNYFIGSF | ||||||
Topological domain | 377-407 | Extracellular | ||||
Sequence: IAVDSKKKFGFFSYDAGILAENFGPDFRGQT | ||||||
Transmembrane | 408-427 | Discontinuously helical; Name=6 | ||||
Sequence: FFSVFSIFFPAATGILAGAN | ||||||
Topological domain | 428-438 | Cytoplasmic | ||||
Sequence: ISGDLADPQMA | ||||||
Transmembrane | 439-462 | Helical; Name=7 | ||||
Sequence: IPKGTLLAILITGLVYVGVAISAG | ||||||
Topological domain | 463-523 | Extracellular | ||||
Sequence: ACIVRDATGIESNFTLISNCTDAACKYGYDFSSCRPTVEGEVSSCKFGLHNDFQVMSVVSG | ||||||
Transmembrane | 524-551 | Helical; Name=8 | ||||
Sequence: FSPLISAGIFSATLSSALASLVSAPKVF | ||||||
Topological domain | 552-576 | Cytoplasmic | ||||
Sequence: QALCKDNIYPGIAIFGKGYGKNNEP | ||||||
Transmembrane | 577-595 | Helical; Name=9 | ||||
Sequence: LRGYFLTFGIALAFILIAE | ||||||
Transmembrane | 596-619 | Helical; Name=10 | ||||
Sequence: LNVIAPIISNFFLASYALINFSVF | ||||||
Topological domain | 620-636 | Cytoplasmic | ||||
Sequence: HASLANSPGWRPSFKYY | ||||||
Transmembrane | 637-656 | Helical; Name=11 | ||||
Sequence: NMWASLAGAILCCVVMFIIN | ||||||
Transmembrane | 657-672 | Helical; Name=12 | ||||
Sequence: WWAALLTNVIVLSLYI | ||||||
Topological domain | 673-1136 | Cytoplasmic | ||||
Sequence: YVSYKKPDVNWGSSTQALTYHQALTHSLQLCGVADHIKTFRPQCLVMTGAPNSRPAILHLVHAFTKNVGLMLCGHVRISSRRPNFKELNSDMLRYQRWLLNNNSKAFYTCVVAEDLRQGTQYMLQAAGLGRLRPNTLVIGFKNDWRTGDIKEVETYINLIHDAFDFQYGVVILRLREGLDISHIQGQDDSSGMKDVVVSVDISKDSDGDSSKPSSKATSVQNSPAVQKDEDDDGKAHTQPLLKKDKKSPTVPLNVADQRLLDASQQFQQKQGKGTVDVWWLFDDGGLTLLIPYLIANKKKWKDCKIRVFIGGKINRIDHDRRAMATLLSKFRIDFSDITVLGDINTKPKSEGLTEFAEMIEPYKLREDDMEQEAAEKLKSEEPWRITDNELELYKAKGNRQIRLNELLKEHSSTANLIVMSMPLARKGAVSSALYMAWLDTLSKDLPPILLVRGNHQSVLTFYS |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 220 | Moderately impairs transporter activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 305 | Severely impairs transporter activity. | ||||
Sequence: Y → F, H, or W | ||||||
Mutagenesis | 454 | Severely impairs transporter activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 538 | Severely impairs transporter activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 539 | Severely impairs transporter activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 611 | Severely impairs transporter activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 630 | Severely impairs transporter activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 682 | Severely impairs transporter activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 686 | Severely impairs transporter activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 972-1136 | In tg414b; Lethality between 6 and 14 days post-fertilization. Early ear development appears normal. The developing otic vesicle begins to collapse at 72 hours post-fertilization, probably due loss of endolymphatic fluid, and is significantly reduced in size by 5 days post-fertilization. Hair cells appear normal and there is no evidence of reduced cell numbers or apoptosis. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000451717 | 1-1136 | Solute carrier family 12 member 2 | |||
Sequence: MSASPPISAGDYLSAPEPDALKPAGPTPSQSRFQVDLVTESAGDGETTVGFDSSPPEYVAEPPPDGLRDSVSGGEEAKGRFRVVNFAASSPDAAPAETAQNGDTVMSEGSLHSSTGGQQHHHYDTHTNTYYLRTFGHNTIDAVPKIDFYRQTAAPLGEKLIRPTLSELHDELDKEPFEDGFANGEELTPAEESAAKDVSESKGVVKFGWIKGVLVRCMLNIWGVMLFIRMTWIVGQAGIAYSCIIVIMATVVTTITGCSTSAIATNGFVRGGGAYYLISRSLGPEFGGSIGLIFAFANAVAVAMYVVGFAETVVELLMDSGLLMIDQTNDIRVIGTITVILLLGISVAGMEWEAKAQIFLLVILITAIFNYFIGSFIAVDSKKKFGFFSYDAGILAENFGPDFRGQTFFSVFSIFFPAATGILAGANISGDLADPQMAIPKGTLLAILITGLVYVGVAISAGACIVRDATGIESNFTLISNCTDAACKYGYDFSSCRPTVEGEVSSCKFGLHNDFQVMSVVSGFSPLISAGIFSATLSSALASLVSAPKVFQALCKDNIYPGIAIFGKGYGKNNEPLRGYFLTFGIALAFILIAELNVIAPIISNFFLASYALINFSVFHASLANSPGWRPSFKYYNMWASLAGAILCCVVMFIINWWAALLTNVIVLSLYIYVSYKKPDVNWGSSTQALTYHQALTHSLQLCGVADHIKTFRPQCLVMTGAPNSRPAILHLVHAFTKNVGLMLCGHVRISSRRPNFKELNSDMLRYQRWLLNNNSKAFYTCVVAEDLRQGTQYMLQAAGLGRLRPNTLVIGFKNDWRTGDIKEVETYINLIHDAFDFQYGVVILRLREGLDISHIQGQDDSSGMKDVVVSVDISKDSDGDSSKPSSKATSVQNSPAVQKDEDDDGKAHTQPLLKKDKKSPTVPLNVADQRLLDASQQFQQKQGKGTVDVWWLFDDGGLTLLIPYLIANKKKWKDCKIRVFIGGKINRIDHDRRAMATLLSKFRIDFSDITVLGDINTKPKSEGLTEFAEMIEPYKLREDDMEQEAAEKLKSEEPWRITDNELELYKAKGNRQIRLNELLKEHSSTANLIVMSMPLARKGAVSSALYMAWLDTLSKDLPPILLVRGNHQSVLTFYS | ||||||
Modified residue | 125 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 129 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 134 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 139 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 152 | Phosphothreonine | ||||
Sequence: T | ||||||
Glycosylation | 475 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 481 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 496↔507 | |||||
Sequence: CRPTVEGEVSSC | ||||||
Modified residue | 1059 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylated at Thr-125, Thr-129 and Thr-134 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Developmental stage
Expressed in the otic vesicle at 6 days post-fertilization, with highest expression in the developing semicircular canals (at protein level). Detected in the notochord at the tailbud stage. Expressed in somites, notochord and intermediate mesoderm during early somitogenesis. Expressed in the otic vesicle from 24 hours post-fertilization onwards.
Gene expression databases
Interaction
Subunit
Homodimer; adopts a domain-swap conformation at the scissor helices connecting the transmembrane domain and C-terminal domain.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | A0A0G2KTI4 | slc12a2 A0A0G2KTI4 | 2 | EBI-25645251, EBI-25645251 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-73 | Disordered | ||||
Sequence: MSASPPISAGDYLSAPEPDALKPAGPTPSQSRFQVDLVTESAGDGETTVGFDSSPPEYVAEPPPDGLRDSVSG | ||||||
Region | 91-121 | Disordered | ||||
Sequence: PDAAPAETAQNGDTVMSEGSLHSSTGGQQHH | ||||||
Compositional bias | 94-121 | Polar residues | ||||
Sequence: APAETAQNGDTVMSEGSLHSSTGGQQHH | ||||||
Region | 689-702 | Scissor helix | ||||
Sequence: ALTYHQALTHSLQL | ||||||
Region | 875-921 | Disordered | ||||
Sequence: SKDSDGDSSKPSSKATSVQNSPAVQKDEDDDGKAHTQPLLKKDKKSP | ||||||
Compositional bias | 898-916 | Basic and acidic residues | ||||
Sequence: VQKDEDDDGKAHTQPLLKK |
Sequence similarities
Belongs to the SLC12A transporter family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
A0A0G2KTI4-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length1,136
- Mass (Da)124,112
- Last updated2018-06-20 v3
- ChecksumB58CE5774EF4411D
A0A0G2KTI4-2
- Name2
- Differences from canonical
- 900-915: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8M9PTH8 | A0A8M9PTH8_DANRE | slc12a2 | 1134 |
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 76 | in Ref. 3; AAH71283 | ||||
Sequence: E → K | ||||||
Compositional bias | 94-121 | Polar residues | ||||
Sequence: APAETAQNGDTVMSEGSLHSSTGGQQHH | ||||||
Sequence conflict | 321 | in Ref. 1; ACT52814 | ||||
Sequence: G → D | ||||||
Sequence conflict | 819 | in Ref. 3; AAH71283 and 1; ACT52814 | ||||
Sequence: T → I | ||||||
Compositional bias | 898-916 | Basic and acidic residues | ||||
Sequence: VQKDEDDDGKAHTQPLLKK | ||||||
Alternative sequence | VSP_060837 | 900-915 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
GQ259737 EMBL· GenBank· DDBJ | ACT52814.1 EMBL· GenBank· DDBJ | mRNA | ||
CABZ01010036 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CABZ01081744 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CABZ01081745 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CABZ01081746 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CR628409 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CU459120 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CU633864 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC071283 EMBL· GenBank· DDBJ | AAH71283.1 EMBL· GenBank· DDBJ | mRNA |