Protein detail

S12A5

Solute carrier family 12 member 5 (Electroneutral potassium-chloride cotransporter 2) (K-Cl cotransporter 2) (hKCC2) (Neuronal K-Cl cotransporter)

Entry name S12A5	UniProt ID Q9H2X9	EVMP confidence score 0.25
Supporting publications (n) 1	Transmembrane count 12	Protein classification Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

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

Basic Information13

Protein Names

Solute carrier family 12 member 5 (Electroneutral potassium-chloride cotransporter 2) (K-Cl cotransporter 2) (hKCC2) (Neuronal K-Cl cotransporter)

Protein Class (7)

Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters

Protein Function (5)

Predicted intracellular proteins
Human disease related genes:Nervous system diseases:Epilepsy
Transporters:Electrochemical Potential-driven transporters
Disease related genes
FDA approved drug targets:Small molecule drugs

Transmembrane

99..120; Discontinuously helical; Name=1; 130..151; Helical; Name=2; 175..203; Helical; Name=3; 230..250; Helical; Name=4; 251..276; Helical; Name=5; 403..420; Helical; Name=6; 430..453; Helical; Name=7; 486..513; Helical; Name=8; 535..555; Helical; Name=9; 556..578; Helical; Name=10; 593..615; Helical; Name=11; 616..632; Helical; Name=12

Transmembrane Count

Ensembl

ENSG00000124140

Entrez Gene Symbol

SLC12A5

Gene Synonym (2)

KCC2KIAA1176

Gene Description

Solute carrier family 12 member 5

Chromosome

Position

46021690-46060150

Supporting publications (n)

EVMP confidence score

0.25

Fluorescence & Localization3

Cell SpecificAstrocytesSingle-Nuclei Brain Specificendothelial cellBlood Cell Specificneutrophil

Function & Pathway7

Protein Function (5)

Predicted intracellular proteins
Human disease related genes:Nervous system diseases:Epilepsy
Transporters:Electrochemical Potential-driven transporters
Disease related genes
FDA approved drug targets:Small molecule drugs

Cellular Component (9)

Molecular Function (5)

Biological Process (3)

KEGG

hsa04727 GABAergic synapse

Reactome (4)

Mediation Categories (2)

Clinical-translation mediationFusion and delivery mediation

Relations & Evidence40

Enzyme-Mediated Modification (13)

13 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
SLC12A5	LEP	P41159	T	1,030	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:30106375
SLC12A5	LEP	P41159	T	929	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:30106375
SLC12A5	OXT	P01178	S	963	phosphorylation	REACH_ProtMapperSparser_ProtMapperProtMapper	ProtMapper:27052180

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Ligand-Receptor Signaling (23)

23 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
transmembrane	transmembrane	UniProt_location	No	No	No	No	No
transmembrane	transmembrane	UniProt_topology	No	No	No	No	No
transmembrane	transmembrane	UniProt_keyword	No	No	No	No	No
transmembrane	transmembrane	TopDB	No	No	No	No	No
transmembrane	transmembrane	LOCATE	No	No	No	No	No
transmembrane	transmembrane	Ramilowski_location	No	No	No	No	No
transmembrane	transmembrane	OmniPath	No	No	No	No	No
plasma_membrane	plasma_membrane	UniProt_location	No	No	No	No	No
plasma_membrane	plasma_membrane	OmniPath	No	No	No	No	No
cell_surface	cell_surface	Surfaceome	No	No	No	No	No

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Regulatory Interaction Network (1)

1 record.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
WNK3	Q9BYP7	S12A5	Q9H2X9	Yes	No	Yes	REACH_ProtMapperSIGNORProtMapper	ProtMapper:24139641 SIGNOR:21613606

Protein Complex Composition (2)

2 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	DCK DGUOK ERC2 SLC12A5	O15083 P27707 Q16854 Q9H2X9	0:0:0:0	hu.MAP
	SLC12A5	Q9H2X9	2	PDB	PDB:7d8zPDB:6m23

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion Chromatography	Mass spectrometry	2	27487081 35763629

Sequence, Structure & Domains13

Sequences

Length

1,139

Mass

126,184

Sequence

MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVKGDGNPKESSPFINSTDTEKGKEYDGKNMALFEEEMDTSPMVSSLLSGLANYTNLPQGSREHEEAENNEGGKKKPVQAPRMGTFMGVYLPCLQNIFGVILFLRLTWVVGIAGIMESFCMVFICCSCTMLTAISMSAIATNGVVPAGGSYYMISRSLGPEFGGAVGLCFYLGTTFAGAMYILGTIEILLAYLFPAMAIFKAEDASGEAAAMLNNMRVYGTCVLTCMATVVFVGVKYVNKFALVFLGCVILSILAIYAGVIKSAFDPPNFPICLLGNRTLSRHGFDVCAKLAWEGNETVTTRLWGLFCSSRFLNATCDEYFTRNNVTEIQGIPGAASGLIKENLWSSYLTKGVIVERSGMTSVGLADGTPIDMDHPYVFSDMTSYFTLLVGIYFPSVTGIMAGSNRSGDLRDAQKSIPTGTILAIATTSAVYISSVVLFGACIEGVVLRDKFGEAVNGNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAISRDGIVPFLQVFGHGKANGEPTWALLLTACICEIGILIASLDEVAPILSMFFLMCYMFVNLACAVQTLLRTPNWRPRFRYYHWTLSFLGMSLCLALMFICSWYYALVAMLIAGLIYKYIEYRGAEKEWGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLVRVDQDQNVVHPQLLSLTSQLKAGKGLTIVGSVLEGTFLENHPQAQRAEESIRRLMEAEKVKGFCQVVISSNLRDGVSHLIQSGGLGGLQHNTVLVGWPRNWRQKEDHQTWRNFIELVRETTAGHLALLVTKNVSMFPGNPERFSEGSIDVWWIVHDGGMLMLLPFLLRHHKVWRKCKMRIFTVAQMDDNSIQMKKDLTTFLYHLRITAEVEVVEMHESDISAYTYEKTLVMEQRSQILKQMHLTKNEREREIQSITDESRGSIRRKNPANTRLRLNVPEETAGDSEEKPEEEVQLIHDQSAPSCPSSSPSPGEEPEGEGETDPEKVHLTWTKDKSVAEKNKGPSPVSSEGIKDFFSMKPEWENLNQSNVRRMHTAVRLNEVIVKKSRDAKLVLLNMPGPPRNRNGDENYMEFLEVLTEHLDRVMLVRGGGREVITIYS

Alternative Products

Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=KCC2a; IsoId=Q9H2X9-1; Sequence=Displayed; Name=2; Synonyms=KCC2b; IsoId=Q9H2X9-2; Sequence=VSP_029909

Alternative Sequence

1..40; MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVK -> MLNNLTDCEDGDGGANP (in isoform 2)

3D Structural Models

Turn

152..154; 156..162; 192..194; 300..302; 371..373; 477..479; 489..495; 521..524; 572..574; 577..579; 618..620; 757..760; 808..810; 904..906; 923..927; 946..948; 953..957; 1107..1110; 1118..1120

Helix

82..88; 99..102; 103..105; 122..125; 127..133; 137..141; 143..149; 163..177; 188..191; 198..201; 203..228; 245..270; 272..277; 279..299; 341..344; 356..359; 378..380; 423..430; 431..433; 437..441; 450..463; 466..476; 482..485; 500..502; 508..520; 525..538; 543..549; 559..567; 569..571; 581..605; 621..634; 638..644; 646..663; 667..681; 713..722; 738..741; 743..756; 773..782; 812..823; 834..836; 859..868; 894..903; 931..940; 1078..1087; 1104..1106; 1111..1117

Beta Strand

241..243; 308..314; 326..328; 332..334; 348..352; 364..369; 395..397; 412..414; 442..446; 503..505; 555..558; 614..616; 664..666; 685..687; 688..691; 698..700; 729..736; 763..772; 793..796; 803..806; 827..832; 850..852; 854..856; 871..876; 880..885; 887..889; 910..915; 949..951; 1088..1091; 1093..1096; 1122..1128

3D Structure

Electron microscopy (2)

Domain & Motif Annotations

Compositional Bias

19..45; Basic and acidic residues; 46..55; Polar residues; 98..111; Basic and acidic residues; 945..962; Basic and acidic residues; 982..994; Acidic residues; 1003..1012; Low complexity; 1023..1042; Basic and acidic residues

Region

1..63; Disordered; 92..116; Disordered; 667..681; Scissor helix; 942..1052; Disordered

Protein Families (2)

SLC12A transporter family
K/Cl co-transporter subfamily

Sequence Similarities

Belongs to the SLC12A transporter family. K/Cl co-transporter subfamily.

Clinical Relevance6

Disease Involvement (3)

Disease variantEpilepsyFDA approved drug targets

Related Diseases

Epilepsy/seizure

Biomarker

Investigative

Drug Targets

FDA approved drug targets

Drugs

BUMETANIDE

Antibody

HPA072058

Supporting Publications1

PMID	Title	Abstract
32795414	Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.	Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.