A0A0G2KTI4 · S12A2_DANRE

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).

Catalytic activity

Activity regulation

Activated following phosphorylation by OXSR1/OSR1 and STK39/SPAK (By similarity).
Inhibited by bumetanide (PubMed:31367042).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site219Na+ (UniProtKB | ChEBI)
Binding site220K+ (UniProtKB | ChEBI)
Binding site221K+ (UniProtKB | ChEBI)
Binding site222Na+ (UniProtKB | ChEBI)
Binding site223chloride 1 (UniProtKB | ChEBI)
Binding site224chloride 1 (UniProtKB | ChEBI)
Binding site225chloride 1 (UniProtKB | ChEBI)
Binding site294chloride 2 (UniProtKB | ChEBI)
Binding site305K+ (UniProtKB | ChEBI)
Binding site417chloride 1 (UniProtKB | ChEBI)
Binding site417K+ (UniProtKB | ChEBI)
Binding site418chloride 1 (UniProtKB | ChEBI)
Binding site418K+ (UniProtKB | ChEBI)
Binding site420K+ (UniProtKB | ChEBI)
Binding site421chloride 1 (UniProtKB | ChEBI)
Binding site422chloride 1 (UniProtKB | ChEBI)
Binding site535Na+ (UniProtKB | ChEBI)
Binding site538Na+ (UniProtKB | ChEBI)
Binding site539Na+ (UniProtKB | ChEBI)
Binding site607chloride 2 (UniProtKB | ChEBI)
Binding site611chloride 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Molecular Functionammonium channel activity
Molecular Functionchloride:monoatomic cation symporter activity
Molecular Functionidentical protein binding
Molecular Functionsodium:potassium:chloride symporter activity
Biological Processammonium transmembrane transport
Biological Processcell volume homeostasis
Biological Processchloride ion homeostasis
Biological Processchloride transmembrane transport
Biological Processear development
Biological Processinner ear morphogenesis
Biological Processpotassium ion homeostasis
Biological Processpotassium ion import across plasma membrane
Biological Processsodium ion homeostasis
Biological Processsodium ion transmembrane transport
Biological Processswim bladder inflation

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Solute carrier family 12 member 2
  • Alternative names
    • Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2 (BSC2)
    • Na-K-Cl cotransporter 1
      (NKCC1
      )

Gene names

    • Name
      slc12a2
    • Synonyms
      nkcc1

Organism names

  • Taxonomic identifier
  • Strain
    • Tuebingen
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio

Accessions

  • Primary accession
    A0A0G2KTI4
  • Secondary accessions
    • A0A0G2KGS0
    • C7EA90
    • Q6IQW8

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-208Cytoplasmic
Transmembrane209-234Discontinuously helical; Name=1
Topological domain235-238Extracellular
Transmembrane239-261Helical; Name=2
Topological domain262-285Cytoplasmic
Transmembrane286-314Helical; Name=3
Topological domain315-327Extracellular
Transmembrane328-351Helical; Name=4
Transmembrane352-376Helical; Name=5
Topological domain377-407Extracellular
Transmembrane408-427Discontinuously helical; Name=6
Topological domain428-438Cytoplasmic
Transmembrane439-462Helical; Name=7
Topological domain463-523Extracellular
Transmembrane524-551Helical; Name=8
Topological domain552-576Cytoplasmic
Transmembrane577-595Helical; Name=9
Transmembrane596-619Helical; Name=10
Topological domain620-636Cytoplasmic
Transmembrane637-656Helical; Name=11
Transmembrane657-672Helical; Name=12
Topological domain673-1136Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis220Moderately impairs transporter activity.
Mutagenesis305Severely impairs transporter activity.
Mutagenesis454Severely impairs transporter activity.
Mutagenesis538Severely impairs transporter activity.
Mutagenesis539Severely impairs transporter activity.
Mutagenesis611Severely impairs transporter activity.
Mutagenesis630Severely impairs transporter activity.
Mutagenesis682Severely impairs transporter activity.
Mutagenesis686Severely impairs transporter activity.
Mutagenesis972-1136In 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.

PTM/Processing

Features

Showing features for chain, modified residue, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00004517171-1136Solute carrier family 12 member 2
Modified residue125Phosphothreonine
Modified residue129Phosphothreonine
Modified residue134Phosphothreonine
Modified residue139Phosphothreonine
Modified residue152Phosphothreonine
Glycosylation475N-linked (GlcNAc...) asparagine
Glycosylation481N-linked (GlcNAc...) asparagine
Disulfide bond496↔507
Modified residue1059Phosphothreonine

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

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

TypeEntry 1Entry 2Number of experimentsIntact
BINARY A0A0G2KTI4slc12a2 A0A0G2KTI42EBI-25645251, EBI-25645251

Protein-protein interaction databases

Family & Domains

Features

Showing features for region, compositional bias.

TypeIDPosition(s)Description
Region1-73Disordered
Region91-121Disordered
Compositional bias94-121Polar residues
Region689-702Scissor helix
Region875-921Disordered
Compositional bias898-916Basic and acidic residues

Sequence similarities

Belongs to the SLC12A transporter family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    1,136
  • Mass (Da)
    124,112
  • Last updated
    2018-06-20 v3
  • Checksum
    B58CE5774EF4411D
MSASPPISAGDYLSAPEPDALKPAGPTPSQSRFQVDLVTESAGDGETTVGFDSSPPEYVAEPPPDGLRDSVSGGEEAKGRFRVVNFAASSPDAAPAETAQNGDTVMSEGSLHSSTGGQQHHHYDTHTNTYYLRTFGHNTIDAVPKIDFYRQTAAPLGEKLIRPTLSELHDELDKEPFEDGFANGEELTPAEESAAKDVSESKGVVKFGWIKGVLVRCMLNIWGVMLFIRMTWIVGQAGIAYSCIIVIMATVVTTITGCSTSAIATNGFVRGGGAYYLISRSLGPEFGGSIGLIFAFANAVAVAMYVVGFAETVVELLMDSGLLMIDQTNDIRVIGTITVILLLGISVAGMEWEAKAQIFLLVILITAIFNYFIGSFIAVDSKKKFGFFSYDAGILAENFGPDFRGQTFFSVFSIFFPAATGILAGANISGDLADPQMAIPKGTLLAILITGLVYVGVAISAGACIVRDATGIESNFTLISNCTDAACKYGYDFSSCRPTVEGEVSSCKFGLHNDFQVMSVVSGFSPLISAGIFSATLSSALASLVSAPKVFQALCKDNIYPGIAIFGKGYGKNNEPLRGYFLTFGIALAFILIAELNVIAPIISNFFLASYALINFSVFHASLANSPGWRPSFKYYNMWASLAGAILCCVVMFIINWWAALLTNVIVLSLYIYVSYKKPDVNWGSSTQALTYHQALTHSLQLCGVADHIKTFRPQCLVMTGAPNSRPAILHLVHAFTKNVGLMLCGHVRISSRRPNFKELNSDMLRYQRWLLNNNSKAFYTCVVAEDLRQGTQYMLQAAGLGRLRPNTLVIGFKNDWRTGDIKEVETYINLIHDAFDFQYGVVILRLREGLDISHIQGQDDSSGMKDVVVSVDISKDSDGDSSKPSSKATSVQNSPAVQKDEDDDGKAHTQPLLKKDKKSPTVPLNVADQRLLDASQQFQQKQGKGTVDVWWLFDDGGLTLLIPYLIANKKKWKDCKIRVFIGGKINRIDHDRRAMATLLSKFRIDFSDITVLGDINTKPKSEGLTEFAEMIEPYKLREDDMEQEAAEKLKSEEPWRITDNELELYKAKGNRQIRLNELLKEHSSTANLIVMSMPLARKGAVSSALYMAWLDTLSKDLPPILLVRGNHQSVLTFYS

A0A0G2KTI4-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8M9PTH8A0A8M9PTH8_DANREslc12a21134

Features

Showing features for sequence conflict, compositional bias, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict76in Ref. 3; AAH71283
Compositional bias94-121Polar residues
Sequence conflict321in Ref. 1; ACT52814
Sequence conflict819in Ref. 3; AAH71283 and 1; ACT52814
Compositional bias898-916Basic and acidic residues
Alternative sequenceVSP_060837900-915in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp