SLC12A5
entrez
57468
canonical
uniprot
Q9H2X9
canonical
ensembl
ENSG00000124140
resolver
ensp
ENSP00000243964
resolver
ensp
ENSP00000387694
resolver
genesymbol
SLC12A5
resolver
genesymbol_syn
KCC2
resolver
genesymbol_syn
KIAA1176
resolver
hgnc
HGNC:13818
resolver
uniprot
A2RTX2
resolver
uniprot
Q5VZ41
resolver
uniprot
Q9H4Z0
resolver
uniprot
Q9ULP4
resolver
uniprot_entry
S12A5_HUMAN
resolver
uniprot_sec
A2RTX2
resolver
uniprot_sec
Q5VZ41
resolver
uniprot_sec
Q9H4Z0
resolver
uniprot_sec
Q9ULP4
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited following phosphorylation by OXSR1/OSR1 and STK39/SPAK: phosphorylation takes place downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and subsequent cell shrinkage. {ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21613606}.
uniprot
proteins
amino_acid_sequence
MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVKGDGNPKESSPFINSTDTEKGKEYDGKNMALFEEEMDTSPMVSSLLSGLANYTNLPQGSREHEEAENNEGGKKKPVQAPRMGTFMGVYLPCLQNIFGVILFLRLTWVVGIAGIMESFCMVFICCSCTMLTAISMSAIATNGVVPAGGSYYMISRSLGPEFGGAVGLCFYLGTTFAGAMYILGTIEILLAYLFPAMAIFKAEDASGEAAAMLNNMRVYGTCVLTCMATVVFVGVKYVNKFALVFLGCVILSILAIYAGVIKSAFDPPNFPICLLGNRTLSRHGFDVCAKLAWEGNETVTTRLWGLFCSSRFLNATCDEYFTRNNVTEIQGIPGAASGLIKENLWSSYLTKGVIVERSGMTSVGLADGTPIDMDHPYVFSDMTSYFTLLVGIYFPSVTGIMAGSNRSGDLRDAQKSIPTGTILAIATTSAVYISSVVLFGACIEGVVLRDKFGEAVNGNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAISRDGIVPFLQVFGHGKANGEPTWALLLTACICEIGILIASLDEVAPILSMFFLMCYMFVNLACAVQTLLRTPNWRPRFRYYHWTLSFLGMSLCLALMFICSWYYALVAMLIAGLIYKYIEYRGAEKEWGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLVRVDQDQNVVHPQLLSLTSQLKAGKGLTIVGSVLEGTFLENHPQAQRAEESIRRLMEAEKVKGFCQVVISSNLRDGVSHLIQSGGLGGLQHNTVLVGWPRNWRQKEDHQTWRNFIELVRETTAGHLALLVTKNVSMFPGNPERFSEGSIDVWWIVHDGGMLMLLPFLLRHHKVWRKCKMRIFTVAQMDDNSIQMKKDLTTFLYHLRITAEVEVVEMHESDISAYTYEKTLVMEQRSQILKQMHLTKNEREREIQSITDESRGSIRRKNPANTRLRLNVPEETAGDSEEKPEEEVQLIHDQSAPSCPSSSPSPGEEPEGEGETDPEKVHLTWTKDKSVAEKNKGPSPVSSEGIKDFFSMKPEWENLNQSNVRRMHTAVRLNEVIVKKSRDAKLVLLNMPGPPRNRNGDENYMEFLEVLTEHLDRVMLVRGGGREVITIYS
uniprot
proteins
disease_involvement
DISEASE: Developmental and epileptic encephalopathy 34 (DEE34) [MIM:616645]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE34 is characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally. {ECO:0000269|PubMed:26333769}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685]: An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. {ECO:0000269|PubMed:24668262, ECO:0000269|PubMed:24928908, ECO:0000269|PubMed:26528127}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (PubMed:12106695). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262). {ECO:0000250|UniProtKB:Q63633, ECO:0000269|PubMed:12106695, ECO:0000269|PubMed:24668262}.
uniprot
proteins
mass_dalton
126184
uniprot
proteins
mutagenesis
MUTAGEN 91; /note="Y->A: 2-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 92; /note="T->E: 2-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 93; /note="N->A: 2-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 94; /note="L->A: 3-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 96; /note="Q->A: 3-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 101; /note="H->A: 2-fold increase in K(+) influx."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 102; /note="E->A: 3-fold increase in K(+) influx; when associated with A-105."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 105; /note="E->A: 3-fold increase in K(+) influx; when associated with A-102."; /evidence="ECO:0000269|PubMed:33310850"; MUTAGEN 929; /note="T->A: Decreased phosphorylation by WNK kinases, leading to increased potassium-chloride cotransport activity; when associated with A-1030."; /evidence="ECO:0000269|PubMed:19665974"; MUTAGEN 1030; /note="T->A: Decreased phosphorylation by WNK kinases, leading to increased potassium-chloride cotransport activity; when associated with A-929."; /evidence="ECO:0000269|PubMed:19665974
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-929 and Thr-1030 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity. {ECO:0000269|PubMed:19665974}.
uniprot
proteins
protein_family
K/Cl co-transporter subfamily
uniprot
proteins
protein_family
SLC12A transporter family
uniprot
proteins
pubmed
10574461
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12106695
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16344560
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
19665974
uniprot
proteins
pubmed
21613606
uniprot
proteins
pubmed
24668262
uniprot
proteins
pubmed
24928908
uniprot
proteins
pubmed
26333769
uniprot
proteins
pubmed
26528127
uniprot
proteins
pubmed
33199848
uniprot
proteins
pubmed
33310850
uniprot
proteins
pubmed
34267353
uniprot
proteins
sequence_length
1139
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q91V14}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q91V14}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q91V14}. Note=Detected on dendrites, but not on axons of spinal cord neurons and at GPHN-positive inhibitory synapses. {ECO:0000250|UniProtKB:Q91V14}.
uniprot
proteins
transmembrane_region
TRANSMEM 99..120; /note="Discontinuously helical; Name=1"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 130..151; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 175..203; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 230..250; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 251..276; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 403..420; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 430..453; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 486..513; /note="Helical; Name=8"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 535..555; /note="Helical; Name=9"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 556..578; /note="Helical; Name=10"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 593..615; /note="Helical; Name=11"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23"; TRANSMEM 616..632; /note="Helical; Name=12"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M23
uniprot
proteins