Slc12a3
entrez
54300
canonical
uniprot
P55018
canonical
ensembl
ENSRNOG00000057072
resolver
ensembl
ENSRNOG00055022313
resolver
ensembl
ENSRNOG00060016359
resolver
ensembl
ENSRNOG00065003778
resolver
ensp
ENSRNOP00000070064
resolver
ensp
ENSRNOP00055031223
resolver
ensp
ENSRNOP00060022562
resolver
ensp
ENSRNOP00065004022
resolver
enst
ENSRNOT00000081246
resolver
enst
ENSRNOT00055038354
resolver
enst
ENSRNOT00060028040
resolver
enst
ENSRNOT00065005526
resolver
genesymbol
Slc12a3
resolver
genesymbol_syn
Tsc
resolver
uniprot
G3V8G0
resolver
uniprot_entry
G3V8G0_RAT
resolver
uniprot_entry
S12A3_RAT
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation by OXSR1/OSR1 and STK39/SPAK in kidney distal convoluted tubules downstream of WNK4 promotes its activity (PubMed:16887815). Also activated by OXSR1/OSR1 and STK39/SPAK downstream of WNK3 (By similarity). Activated by isotonic conditions (PubMed:10894798). Inhibited by thiazide-type diuretics including polythiazide, metolazone, bendroflumethiazide, trichloromethiazide, hydrochlorothiazide and chlorthalidone (PubMed:10894798). Thiazide drugs specifically inhibit SLC12A3/NCC transporter activity by competing with chloride for binding (By similarity). {ECO:0000250|UniProtKB:P55017, ECO:0000269|PubMed:10894798, ECO:0000269|PubMed:16887815}.
uniprot
proteins
amino_acid_sequence
MAELPVTEMPGDALCSGRFTISTLLGGDEPPPAACDNSQPSHLTHGSTLYLRTFGYNTIDVVPAYEHYANSALPGEPRKVRPTLADLHSFLKQEGSHLHALAFDGRPGHELTDGLVEDETGANSEKSPGEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWLIILLSVMVTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQENGTPIVDPINDIRIIGVVTVTVLLAISLAGMEWESKAQVLFFLVIMVSFANYLVGTLIPASKDKASKGFYSYHGDIFVQNLVPDWRGIDGSFFGMFSIFFPSATGILAGANISGDLKDPAVAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGDVNDTITPGPGLCEGLACGYGWNFTECSQQHSCRYGLINYYQTMSMVSAFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRPSFRYYSKWAALFGAVISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVSTFTQNLSLMICGHVLIAPGKQRVPELRLIASGHTKWLNKRKIKAFYSDVIAEDLRSGVQILMQASGLGRMKPNILVVGFKKNWQSAHPATLEDYIGILHDAFDFNYGVCIMRMREGLNVSEALQTHTAPEALVQEEQTSTIFQSEQGKKTIDIYWLFDDGGLTLLIPYLLHRKKRWGKCKIRVFVGGQINRMDEERKAIISLLSKFRLGFHEVHVLPDINQKPQVEHTKRFEDMIAPFRLNDGFKDEATVAEMRRDYPWKISDEEINKNRIKSLRQVRLNEILLDYSRDAALIILTLPIGRKGKCPSSLYMAWLETLSQDLSPPVLLIRGNQENVLTFYCQ
uniprot
proteins
function
FUNCTION: Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:10894798, PubMed:16887815, PubMed:8021284). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:10894798, ECO:0000269|PubMed:16887815, ECO:0000269|PubMed:8021284}.
uniprot
proteins
mass_dalton
110554
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="T->A: Decreased response to intracellular chloride depletion. Abolished response to intracellular chloride depletion; when associated with A-58 and A-71."; /evidence="ECO:0000269|PubMed:16887815"; MUTAGEN 58; /note="T->A: Decreased response to intracellular chloride depletion. Abolished response to intracellular chloride depletion; when associated with A-53 and A-71."; /evidence="ECO:0000269|PubMed:16887815"; MUTAGEN 71; /note="S->A: Decreased response to intracellular chloride depletion. Abolished response to intracellular chloride depletion; when associated with A-53 and A-58."; /evidence="ECO:0000269|PubMed:16887815"; MUTAGEN 404; /note="N->Q: Abolished N-glycosylation, leading to reduced localization to the cell membrane; when associated with Q-424."; /evidence="ECO:0000269|PubMed:16887815"; MUTAGEN 424; /note="N->Q: Abolsihed N-glycosylation, leading to reduced localization to the cell membrane; when associated with Q-404."; /evidence="ECO:0000269|PubMed:16887815
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; ubiquitination is essential for regulation of endocytosis. {ECO:0000250|UniProtKB:P59158}.; PTM: Phosphorylated at Thr-53, Thr-58 and Ser-71 by OXSR1/OSR1 and STK39/SPAK downstream of WNK4, promoting its activity (PubMed:16887815). Phosphorylated in response to IL18 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:16887815}.
uniprot
proteins
protein_family
SLC12A transporter family
uniprot
proteins
pubmed
10894798
uniprot
proteins
pubmed
16887815
uniprot
proteins
pubmed
8021284
uniprot
proteins
sequence_length
1002
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16887815}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:P59158}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 136..165; /note="Discontinuously helical; Name=1"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 166..187; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 219..241; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 254..278; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 279..301; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 337..358; /note="Discontinuously helical; Name=6"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 370..391; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 452..475; /note="Helical; Name=8"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 506..520; /note="Helical; Name=9"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 526..542; /note="Helical; Name=10"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 566..585; /note="Helical; Name=11"; /evidence="ECO:0000250|UniProtKB:P55017"; TRANSMEM 586..597; /note="Helical; Name=12"; /evidence="ECO:0000250|UniProtKB:P55017
uniprot
proteins