Protein detail
S12A3
Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter)
Entry name S12A3 | UniProt ID | EVMP confidence score 0.35 |
Supporting publications (n) 0 | Transmembrane count 12 | Protein classification Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPlasma proteinsPredicted membrane proteinsTransporters |
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.70High >= 0.60Medium >= 0.40Low >= 0.30Basic Information
Protein Names
Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter)
Protein Class (7)
Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPlasma proteinsPredicted membrane proteinsTransporters
Protein Function (4)
- Human disease related genes:Endocrine and metabolic diseases:Other endocrine and metabolic diseases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- Transporters:Electrochemical Potential-driven transporters
Transmembrane
138..167; Discontinuously helical; Name=1; 168..189; Helical; Name=2; 221..243; Helical; Name=3; 256..280; Helical; Name=4; 281..303; Helical; Name=5; 339..360; Discontinuously helical; Name=6; 372..393; Helical; Name=7; 454..477; Helical; Name=8; 508..522; Helical; Name=9; 528..544; Helical; Name=10; 568..587; Helical; Name=11; 588..599; Helical; Name=12
Transmembrane Count
12
Ensembl
Entrez Gene Symbol
Gene Synonym (2)
NCCNCCT
Gene Description
Solute carrier family 12 member 3
Chromosome
16
Position
56865207-56915850
Supporting publications (n)
0
EVMP confidence score
0.35
Fluorescence & Localization
Tissue SpecificretinaCell SpecificAdrenal cortex cellsSingle-Nuclei Brain Specificcommitted oligodendrocyte precursorSecretome LocationIntracellular and membraneSecretome FunctionNo annotated function
Function & Pathway
Protein Function (4)
- Human disease related genes:Endocrine and metabolic diseases:Other endocrine and metabolic diseases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
- Transporters:Electrochemical Potential-driven transporters
Cellular Component (5)
Molecular Function (4)
Biological Process (3)
KEGG (2)
- hsa04928 Parathyroid hormone synthesis
- secretion and action
Reactome (6)
Canonical Pathways
M15 Pid lysophospholipid pathway
Mediation Categories (2)
Clinical-translation mediationFusion and delivery mediation
Relations & Evidence43
Enzyme-Mediated Modification (12)
12 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| SLC12A3 | WNK4 | Q96J92 | T | 55 | phosphorylation | REACH_ProtMapperPhosphoSiteProtMapper | ProtMapper:27942049 |
| SLC12A3 | WNK4 | Q96J92 | T | 50 | phosphorylation | Sparser_ProtMapperSIGNORProtMapperREACH_ProtMapperPhosphoSite | SIGNOR:22342722ProtMapper:22342722 |
| SLC12A3 | WNK4 | Q96J92 | T | 46 | phosphorylation | PhosphoSite | |
| SLC12A3 | WNK4 | Q96J92 | S | 73 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:27942049 |
| SLC12A3 | OXSR1 | O95747 | T | 60 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:30248150ProtMapper:18270262SIGNOR:18270262 |
| SLC12A3 | OXSR1 | O95747 | S | 73 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A3 | OXSR1 | O95747 | T | 46 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A3 | OXSR1 | O95747 | T | 55 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper | |
| SLC12A3 | STK39 | Q9UEW8 | T | 55 | phosphorylation | PhosphoSite_MIMPMIMPSIGNORProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:25651566ProtMapper:21907141ProtMapper:26728390 |
| SLC12A3 | STK39 | Q9UEW8 | T | 60 | phosphorylation | PhosphoSite_MIMPMIMPProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:30248150ProtMapper:26728390 |
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Ligand-Receptor Signaling (24)
24 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| cell_surface | cell_surface | Surfaceome | |||||
| cell_surface | cell_surface | OmniPath | |||||
| receptor | receptor | scConnect | Yes | ||||
| transmembrane | transmembrane_predicted | Phobius |
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Regulatory Interaction Network (4)
4 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| WNK3 | Q9BYP7 | S12A3 | P55017 | Yes | Yes | SIGNOR | SIGNOR:21613606 | |
| STK39 | Q9UEW8 | S12A3 | P55017 | Yes | Yes | Yes | PhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperELMLMPIDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSite_ProtMapper | ProtMapper:26728390ProtMapper:25651566ProtMapper:21907141SIGNOR:25651566ProtMapper:30248150LMPID:18270262ELM:18270262 |
| WNK4 | Q96J92 | S12A3 | P55017 | Yes | Yes | Yes | WangSparser_ProtMapperPhosphoSite_norefPhosphoPointSIGNORProtMapperHPRDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:22342722ProtMapper:27942049PhosphoSite:28274929HPRD:12515852SIGNOR:22342722 |
| OXSR1 | O95747 | S12A3 | P55017 | Yes | Yes | PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperELMLMPIDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:18270262PhosphoSite:21164023SIGNOR:18270262ProtMapper:30248150LMPID:18270262ELM:18270262 |
Protein Complex Composition (2)
Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| PRotein Organic Solvent Precipitation；Differential Ultracentrifugation | Mass spectrometry | 1 | 32384937 |
Sequence, Structure & Domains
Sequences
Length
1,021
Mass
113,139
Sequence
MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNTIDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEGEAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVTVTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANYLVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANISGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLACSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRGVQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGLNVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDGGLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDINQNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLNEIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYCQ
Alternative Products
Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P55017-1; Sequence=Displayed; Name=2; IsoId=P55017-2; Sequence=VSP_036318; Name=3; IsoId=P55017-3; Sequence=VSP_040100, VSP_036318
Alternative Sequence
95; Missing (in isoform 3); 807; V -> GARPSVSGAL (in isoform 2 and isoform 3)
3D Structural Models
Turn
68..70; 354..360; 394..396; 440..442; 501..503; 526..528; 666..669; 744..748; 885..887; 967..969; 982..984
Helix
86..90; 138..141; 143..150; 154..157; 159..165; 167..193; 202..204; 205..211; 213..249; 258..263; 265..276; 280..303; 310..314; 322..327; 340..347; 348..350; 361..363; 367..393; 419..423; 428..433; 446..450; 455..483; 493..495; 506..522; 529..552; 567..584; 586..604; 615..630; 631..633; 652..654; 656..665; 688..702; 717..727; 751..766; 821..823; 842..851; 854..856; 869..871; 872..879; 881..884; 905..915; 916..918; 927..934; 943..947; 950..966; 987..996
Beta Strand
253..255; 335..337; 411..413; 451..453; 489..491; 645..648; 672..675; 677..681; 712..716; 737..740; 770..775; 830..835; 860..865; 899..901; 938..940; 971..976; 998..1000; 1005..1009
3D Structure
Electron microscopy (9)
Domain & Motif Annotations
Domain (CC)
Interaction between the cytoplasmic N-terminal and C-terminal domains (NTD and CTD, respectively) is essential for SLC12A3/NCC transporter activity (PubMed:36792826). Phosphorylation by OXSR1/OSR1 and STK39/SPAK may activate SLC12A3/NCC by facilitating this interaction (PubMed:36792826).
Region
615..630; Scissor helix
Protein Families
SLC12A transporter family
Sequence Similarities
Belongs to the SLC12A transporter family.
Clinical Relevance
Disease Involvement (2)
Disease variantFDA approved drug targets
Related Diseases (3)
Biomarker
Approved
Drug Targets
FDA approved drug targets
Drugs (19)
Antibody