Protein detail
S12A2
Solute carrier family 12 member 2 (Basolateral Na-K-Cl symporter) (Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2) (BSC2) (Na-K-2Cl cotransporter 1) (hNKCC1)
Entry name S12A2 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 12 | Protein classification Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted membrane proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Solute carrier family 12 member 2 (Basolateral Na-K-Cl symporter) (Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2) (BSC2) (Na-K-2Cl cotransporter 1) (hNKCC1)
Protein Class
Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted membrane proteinsTransporters
Protein Function
- Transporters:Electrochemical Potential-driven transporters
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- Human disease related genes:Nervous system diseases:Ear disease
Transmembrane
287..316; Discontinuously helical; Name=1; 317..336; Helical; Name=2; 368..395; Helical; Name=3; 406..429; Helical; Name=4; 433..454; Helical; Name=5; 487..504; Discontinuously helical; Name=6; 520..541; Helical; Name=7; 599..623; Helical; Name=8; 652..672; Helical; Name=9; 673..691; Helical; Name=10; 715..732; Helical; Name=11; 733..745; Helical; Name=12
Transmembrane Count
12
Ensembl
Entrez Gene Symbol
Gene Synonym
BSC-2BSC2CCC1NKCC1PPP1R141
Gene Description
Solute carrier family 12 member 2
Chromosome
5
Position
128083766-128189677
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Cell SpecificAstrocytesBlood Cell Specificplasmacytoid DCSecretome LocationIntracellular and membraneSecretome FunctionEnzyme
Function & Pathway
Protein Function
- Transporters:Electrochemical Potential-driven transporters
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- Human disease related genes:Nervous system diseases:Ear disease
Cellular Component
- GO:0005886 plasma membrane
- GO:0009925 basal plasma membrane
- GO:0016020 membrane
- GO:0016323 basolateral plasma membrane
- GO:0016324 apical plasma membrane
- GO:0016328 lateral plasma membrane
- GO:0030659 cytoplasmic vesicle membrane
- GO:0031253 cell projection membrane
- GO:0042995 cell projection
- GO:0043005 neuron projection
- GO:0043025 neuronal cell body
- GO:0044297 cell body
- GO:0044298 cell body membrane
- GO:0070062 extracellular exosome
- GO:0071944 cell periphery
- GO:1903561 extracellular vesicle
Molecular Function
- GO:0005515 protein binding
- GO:0008511 sodium:potassium:chloride symporter activity
- GO:0008519 ammonium channel activity
- GO:0015079 potassium ion transmembrane transporter activity
- GO:0015377 chloride:monoatomic cation symporter activity
- GO:0019901 protein kinase binding
- GO:0046873 metal ion transmembrane transporter activity
- GO:0051087 protein-folding chaperone binding
- GO:0051879 Hsp90 protein binding
Biological Process
KEGG
Reactome
Canonical Pathways
- M251 Pid syndecan 3 pathway
- M266 Pid ncadherin pathway
- M156 Pid ecadherin nascent aj pathway
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
11 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| SLC12A2 | OXSR1 | O95747 | T | 203 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:12145304SIGNOR:16669787KEA:16669787ProtMapper:12145304ProtMapper:16669787 |
| SLC12A2 | OXSR1 | O95747 | T | 212 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:12145304SIGNOR:16669787KEA:16669787ProtMapper:12145304ProtMapper:16669787 |
| SLC12A2 | OXSR1 | O95747 | T | 207 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | KEA:16669787ProtMapper:16669787SIGNOR:16669787 |
| SLC12A2 | OXSR1 | O95747 | T | 230 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A2 | OXSR1 | O95747 | T | 217 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A2 | PRKAA1 | Q13131 | S | 77 | phosphorylation | PhosphoSite | |
| SLC12A2 | PRKAA1 | Q13131 | S | 242 | phosphorylation | PhosphoSite | |
| SLC12A2 | STK39 | Q9UEW8 | T | 207 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A2 | STK39 | Q9UEW8 | T | 203 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:27782176 |
| SLC12A2 | STK39 | Q9UEW8 | T | 212 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPProtMapperRLIMS-P_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:16669787 |
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Ligand-Receptor Signaling
31 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| transmembrane | transmembrane_predicted | Phobius | No | No | No | No | No |
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Regulatory Interaction Network
6 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| OXSR1 | O95747 | S12A2 | P55011 | Yes | Yes | Yes | WangPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefPhosphoPointSIGNORProtMapperiPTMnetHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapperSPIKE_LC | PhosphoSite:16077079PhosphoSite:12145305SIGNOR:12145304SIGNOR:16669787PhosphoSite:21423148PhosphoSite:24702155SPIKE_LC:17721439KEA:16669787PhosphoSite:12145304HPRD:16669787PhosphoSite:16669787ProtMapper:12145304ProtMapper:16669787 |
| STK39 | Q9UEW8 | S12A2 | P55011 | Yes | Yes | No | PhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefPhosphoPointSIGNORProtMapperiPTMnetHPRDRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSite_ProtMapper | SIGNOR:16990453HPRD:14563843ProtMapper:27782176ProtMapper:16669787 |
| WNK3 | Q9BYP7 | S12A2 | P55011 | Yes | Yes | No | iPTMnetSIGNOR | SIGNOR:21613606 |
| COMPLEX:O43741_P54619_P54646_Q13131_Q9UGI9_Q9UGJ0_Q9Y478 | S12A2 | P55011 | Yes | No | Yes | SIGNOR | SIGNOR:24702155 | |
| WNK1 | Q9H4A3 | S12A2 | P55011 | Yes | Yes | No | SIGNOR | SIGNOR:36318922 |
| AAPK1 | Q13131 | S12A2 | P55011 | Yes | No | No | iPTMnetPhosphoSitePhosphoSite_ProtMapperProtMapper | PhosphoSite:20442269 |
Protein Complex Composition
2 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| SEC13SEC23ASEC31ASLC12A2SP100 | O94979P23497P55011P55735Q15436 | 0:0:0:0:0 | Havugimana2012 | Havugimana2012:C_456 | ||
| SLC12A2 | P55011 | 2 | PDB | PDB:7s1yPDB:7n3nPDB:7s1xPDB:7sflPDB:6pztPDB:8stePDB:7s1zPDB:7mxoPDB:9c0hPDB:7d10PDB:9c0gPDB:9c0ePDB:7zgoPDB:7smp |
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 30550287 |
Sequence, Structure & Domains
Sequences
Length
1,212
Mass
131,447
Sequence
MEPRPTAPSSGAPGLAGVGETPSAAALAAARVELPGTAVPSVPEDAAPASRDGGGVRDEGPAAAGDGLGRPLGPTPSQSRFQVDLVSENAGRAAAAAAAAAAAAAAAGAGAGAKQTPADGEASGESEPAKGSEEAKGRFRVNFVDPAASSSAEDSLSDAAGVGVDGPNVSFQNGGDTVLSEGSSLHSGGGGGSGHHQHYYYDTHTNTYYLRTFGHNTMDAVPRIDHYRHTAAQLGEKLLRPSLAELHDELEKEPFEDGFANGEESTPTRDAVVTYTAESKGVVKFGWIKGVLVRCMLNIWGVMLFIRLSWIVGQAGIGLSVLVIMMATVVTTITGLSTSAIATNGFVRGGGAYYLISRSLGPEFGGAIGLIFAFANAVAVAMYVVGFAETVVELLKEHSILMIDEINDIRIIGAITVVILLGISVAGMEWEAKAQIVLLVILLLAIGDFVIGTFIPLESKKPKGFFGYKSEIFNENFGPDFREEETFFSVFAIFFPAATGILAGANISGDLADPQSAIPKGTLLAILITTLVYVGIAVSVGSCVVRDATGNVNDTIVTELTNCTSAACKLNFDFSSCESSPCSYGLMNNFQVMSMVSGFTPLISAGIFSATLSSALASLVSAPKIFQALCKDNIYPAFQMFAKGYGKNNEPLRGYILTFLIALGFILIAELNVIAPIISNFFLASYALINFSVFHASLAKSPGWRPAFKYYNMWISLLGAILCCIVMFVINWWAALLTYVIVLGLYIYVTYKKPDVNWGSSTQALTYLNALQHSIRLSGVEDHVKNFRPQCLVMTGAPNSRPALLHLVHDFTKNVGLMICGHVHMGPRRQAMKEMSIDQAKYQRWLIKNKMKAFYAPVHADDLREGAQYLMQAAGLGRMKPNTLVLGFKKDWLQADMRDVDMYINLFHDAFDIQYGVVVIRLKEGLDISHLQGQEELLSSQEKSPGTKDVVVSVEYSKKSDLDTSKPLSEKPITHKVEEEDGKTATQPLLKKESKGPIVPLNVADQKLLEASTQFQKKQGKNTIDVWWLFDDGGLTLLIPYLLTTKKKWKDCKIRVFIGGKINRIDHDRRAMATLLSKFRIDFSDIMVLGDINTKPKKENIIAFEEIIEPYRLHEDDKEQDIADKMKEDEPWRITDNELELYKTKTYRQIRLNELLKEHSSTANIIVMSLPVARKGAVSSALYMAWLEALSKDLPPILLVRGNHQSVLTFYS
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P55011-1; Sequence=Displayed; Name=2; IsoId=P55011-3; Sequence=VSP_006105
Alternative Sequence
976..991; Missing (in isoform 2)
3D Structural Models
Turn
458..464; 501..507; 514..516; 556..558; 566..570; 578..581; 586..588; 646..649; 672..674; 798..800; 811..814; 890..894; 1175..1177
Helix
208..210; 224..227; 243..247; 287..290; 292..299; 303..305; 308..314; 317..342; 352..360; 362..397; 405..426; 428..453; 470..476; 487..494; 495..497; 508..510; 518..541; 552..554; 592..596; 600..631; 636..642; 652..668; 675..698; 713..729; 732..752; 761..777; 784..786; 802..810; 828..848; 863..873; 897..912; 1003..1014; 1035..1045; 1065..1078; 1098..1108; 1109..1111; 1115..1117; 1121..1128; 1136..1141; 1143..1159; 1180..1191
Beta Strand
215..219; 300..302; 344..346; 482..484; 511..513; 546..548; 572..574; 583..585; 597..599; 755..757; 791..793; 818..824; 854..859; 874..876; 883..887; 916..921; 1019..1022; 1023..1027; 1032..1034; 1046..1049; 1053..1059; 1086..1090; 1092..1094; 1131..1134; 1160..1162; 1164..1169; 1195..1201
3D Structure
Electron microscopy (14)
Domain & Motif Annotations
Compositional Bias
127..137; Basic and acidic residues; 150..160; Low complexity; 962..978; Basic and acidic residues
Motif
80..83; RFXV motif 1; 138..141; RFXV motif 2
Domain (CC)
The RFXV motifs mediate binding with OXSR1/OSR1 and STK39/SPAK.
Region
36..81; Disordered; 112..138; Disordered; 150..193; Disordered; 761..778; Scissor helix; 962..989; Disordered
Protein Families
SLC12A transporter family
Sequence Similarities
Belongs to the SLC12A transporter family.
Clinical Relevance
Disease Involvement
DeafnessDisease variantFDA approved drug targetsIntellectual disabilityNon-syndromic deafness
Drug Targets
FDA approved drug targets
Drugs
Interaction Protein
ENSG00000127022
Interaction Count
1
Interaction Dataset
biogrid_opencell