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 P55017	EVMP confidence score 0.38
Supporting publications (n)	Transmembrane count 12	Protein classification Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPlasma proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information12

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

Ensembl

ENSG00000070915

Entrez Gene Symbol

SLC12A3

Gene Synonym (2)

NCCNCCT

Gene Description

Solute carrier family 12 member 3

Chromosome

Position

56865207-56915850

EVMP confidence score

0.38

Fluorescence & Localization5

Tissue SpecificretinaCell SpecificAdrenal cortex cellsSingle-Nuclei Brain Specificcommitted oligodendrocyte precursorSecretome LocationIntracellular and membraneSecretome FunctionNo annotated function

Function & Pathway8

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	STK39	Q9UEW8	T	46	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
SLC12A3	STK39	Q9UEW8	S	73	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:26728390

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Ligand-Receptor Signaling (24)

24 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	OmniPath	No	Yes	No	No	No
extracellular	extracellular	OmniPath	No	No	No	No	No
intracellular	intracellular	GO_Intercell	No	No	No	No	No
intracellular	intracellular	OmniPath	No	No	No	No	No
transporter	transporter	Surfaceome	No	Yes	No	No	No
solute_carrier	transporter	Almen2009	No	Yes	No	No	No
apc	transporter	Surfaceome	No	Yes	No	No	No
slc	transporter	Surfaceome	No	Yes	No	No	No
slc12	transporter	Surfaceome	No	Yes	No	No	No
transporter	transporter	OmniPath	No	Yes	No	No	No

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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	No	SIGNOR	SIGNOR:21613606
STK39	Q9UEW8	S12A3	P55017	Yes	Yes	Yes	PhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperELMLMPIDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSite_ProtMapper	ProtMapper:26728390 ProtMapper:25651566 ProtMapper:21907141 SIGNOR:25651566 ProtMapper:30248150 LMPID:18270262 ELM:18270262
WNK4	Q96J92	S12A3	P55017	Yes	Yes	Yes	WangSparser_ProtMapperPhosphoSite_norefPhosphoPointSIGNORProtMapperHPRDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:22342722 ProtMapper:27942049 PhosphoSite:28274929 HPRD:12515852 SIGNOR:22342722
OXSR1	O95747	S12A3	P55017	Yes	Yes	No	PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperELMLMPIDSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:18270262 PhosphoSite:21164023 SIGNOR:18270262 ProtMapper:30248150 LMPID:18270262 ELM:18270262

Protein Complex Composition (2)

2 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	SLC12A3	P55017	2	PDB	PDB:8fhqPDB:8fhpPDB:8fhoPDB:7yg1PDB:7y6iPDB:8fhtPDB:7yg0PDB:8fhrPDB:8fhn
	IL16 SLC12A3	P55017 Q14005	0:0	hu.MAP2

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 & Domains13

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 Relevance6

Disease Involvement (2)

Disease variantFDA approved drug targets

Related Diseases (3)

Essential hypertension Hypertension Oedema

Biomarker

Approved

Drug Targets

FDA approved drug targets

Drugs (19)

CHLOROTHIAZIDE SODIUM CHLORTHALIDONE NULL BUMETANIDE DIAZOXIDE CHLOROTHIAZIDE BENZTHIAZIDE INDAPAMIDE POLYTHIAZIDE HYDROCHLOROTHIAZIDE HYDROFLUMETHIAZIDE METOLAZONE CYCLOTHIAZIDE BENDROFLUMETHIAZIDE QUINETHAZONE FUROSEMIDE TORSEMIDE TRICHLORMETHIAZIDE METHYCLOTHIAZIDE

Antibody

HPA028748