Slc12a3
entrez
20497
canonical
uniprot
P59158
canonical
ensembl
ENSMUSG00000031766
resolver
ensp
ENSMUSP00000034218
resolver
enst
ENSMUST00000034218
resolver
genesymbol
Slc12a3
resolver
genesymbol_syn
Ncc
resolver
genesymbol_syn
Tsc
resolver
uniprot
Q543E4
resolver
uniprot_entry
Q543E4_MOUSE
resolver
uniprot_entry
S12A3_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation by OXSR1/OSR1 and STK39/SPAK in kidney distal convoluted tubules promotes its activity (PubMed:16263722, PubMed:17488636, PubMed:19633012). Also activated by OXSR1/OSR1 and STK39/SPAK downstream of WNK3 (By similarity). Inhibited by thiazide-type diuretic metolazone (PubMed:15068971). Thiazide drugs, such as polythiazide, specifically inhibit SLC12A3/NCC transporter activity by competing with chloride for binding (By similarity). {ECO:0000250|UniProtKB:P55017, ECO:0000269|PubMed:15068971, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17488636, ECO:0000269|PubMed:19633012}.
uniprot
proteins
amino_acid_sequence
MAELPVTELPGDALCSGRFTISTLMGGDEPPPAACDSSQPSHLTHGSTLYMRTFGYNTIDVVPAYEHYANSALPGEPRKVRPTLADLHSFLKQEGSHLHALAFDGRQGRELTDGLVEDETGTNSEKSPGEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWLIILLSVMVTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQEYGTPIVDPINDIRIIGVVTVTVLLAISLAGMEWESKAQVLFFLVIMVSFANYLVGTLIPASEDKASKGFYSYHGDIFVQNLVPDWRGIDGSFFGMFSIFFPSATGILAGANISGDLKDPAVAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGDVNDTMTPGPGPCEGLACGYGWNFTECSQQRSCRYGLINYYQTMSMVSAFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYPLIGFFGKGYGKNREPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRPSFRYYSKWAALFGAVISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVSTFTQNLSLMICGHVLIGPGKQRVPELRLIASGHTKWLNKRKIKAFYSDVIAEDLRSGVQILMQASGLGRMKPNILVVGFKRNWQSAHPATVEDYIGVLHDAFDFNYGVCVMRMREGLNVSEALQTHTTPEALIQEEQASTIFQSEQGKKTIDIYWLFDDGGLTLLIPYLLHRKKRWGKCKIRVFVGGQINRMDEERKAIISLLSKFRLGFHEVHVLPDINQKPQAEHTKRFEDMIAPFRLNDGFKDEATVTEMRRDCPWKISDEEINKNRIKSLRQVRLSEILLDYSRDAALIILTLPIGRKGKCPSSLYMAWLETLSQDLRPPVLLIRGNQENVLTFYCQ
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:15068971, PubMed:17488636, PubMed:19633012, PubMed:36370249). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (PubMed:26099046). May act either independently of IL18R1, or in a complex with IL18R1 (PubMed:26099046). {ECO:0000269|PubMed:15068971, ECO:0000269|PubMed:17488636, ECO:0000269|PubMed:19633012, ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:36370249}.
uniprot
proteins
mass_dalton
110694
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="T->A: Reduced phosphorylation by OXSR1/OSR1 and STK39/SPAK; when associated with A-58 and A-71. Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12."; /evidence="ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:26099046"; MUTAGEN 58; /note="T->A: Reduced phosphorylation by OXSR1/OSR1 and STK39/SPAK; when associated with A-53 and A-71. No effect on MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12. Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12; when associated with A-53 and A-71."; /evidence="ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:26099046"; MUTAGEN 71; /note="S->A: Reduced phosphorylation by OXSR1/OSR1 and STK39/SPAK; when associated with A-53 and A-58. No effect on MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12. Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12; when associated with A-53 and A-58."; /evidence="ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:26099046"; MUTAGEN 156; /note="R->Q: Knockin mice display typical Gitelman syndrome features, characterized by hypokalemia, hypomagnesemia and increased fractional excretion of K(+) and Mg(2+) with a normal blood pressure level; when associated with S-210."; /evidence="ECO:0000269|PubMed:36370249"; MUTAGEN 210; /note="G->S: Knockin mice display typical Gitelman syndrome features, characterized by hypokalemia, hypomagnesemia and increased fractional excretion of K(+) and Mg(2+) with a normal blood pressure level; when associated with Q-156."; /evidence="ECO:0000269|PubMed:36370249"; MUTAGEN 224; /note="A->T: Does not affect protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 347; /note="P->L: Impairs protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 586; /note="A->V: Does not affect protein processing and glycosylation. Decreases localization at the plasma membrane."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 611; /note="G->S: Does not affect protein processing and glycosylation. Decreases localization at the plasma membrane and affinity for sodium and chloride ions."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 628; /note="G->V: Does not affect protein processing and glycosylation. Decreases localization at the plasma membrane."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 831; /note="L->P: Impairs protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 833; /note="R->C: Does not affect protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 900; /note="R->C: Does not affect protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 936; /note="R->Q: Does not affect protein processing and glycosylation. Decreases localization at the plasma membrane."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 949..1002; /note="Missing: Impairs protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 990..1002; /note="Missing: Impairs protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 996; /note="V->M: Does not affect protein processing and glycosylation. Decreases localization at the plasma membrane."; /evidence="ECO:0000269|PubMed:15068971"; MUTAGEN 998; /note="T->I: Impairs protein processing and glycosylation."; /evidence="ECO:0000269|PubMed:15068971
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; ubiquitination is essential for regulation of endocytosis. {ECO:0000269|PubMed:20392800}.; PTM: Phosphorylated at Thr-53, Thr-58 and Ser-71 by OXSR1/OSR1 and STK39/SPAK downstream of WNK4, promoting its activity (PubMed:16263722, PubMed:17488636, PubMed:19633012). Phosphorylated in response to IL18 (PubMed:26099046). {ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17488636, ECO:0000269|PubMed:19633012, ECO:0000269|PubMed:26099046}.
uniprot
proteins
protein_family
SLC12A transporter family
uniprot
proteins
pubmed
15068971
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16263722
uniprot
proteins
pubmed
17488636
uniprot
proteins
pubmed
19633012
uniprot
proteins
pubmed
20392800
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
26099046
uniprot
proteins
pubmed
29993276
uniprot
proteins
pubmed
36370249
uniprot
proteins
sequence_length
1002
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:36370249}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:29993276}; 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