Reactome | UniProt:Q9UHW9 SLC12A6

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UniProt:Q9UHW9 SLC12A6 Show undefined attributes

chain	chain:1-1150
checksum	F8BDD39181294EDD
comment	FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:11551954, PubMed:10600773, PubMed:19665974, PubMed:18566107, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015).FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:34031912, PubMed:33199848). May contribute to cell volume homeostasis in single cells (Probable).FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).FUNCTION Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)CATALYTIC ACTIVITY chloride(in) + K(+)(in) = chloride(out) + K(+)(out)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 (PubMed:19665974, PubMed:21613606). Activated by N-ethylmaleimide (NEM) (PubMed:10600773). Inhibited by DIOA, bumetanide and furosemide (PubMed:10600773).BIOPHYSICOCHEMICAL PROPERTIES Homodimer (PubMed:21628467). Homomultimer and heteromultimer with other K-Cl cotransporters (Probable). Interacts (via C-terminus) with CKB; the interaction may be required for potassium-chloride cotransport activity (PubMed:18566107).SUBCELLULAR LOCATION Expressed in brain (at protein level) (PubMed:21628467). Highly expressed in heart, brain and kidney. Detected at lower levels in skeletal muscle, placenta, lung and pancreas (PubMed:10600773). Detected in umbilical vein endothelial cells (PubMed:16048901).TISSUE SPECIFICITY More abundant in kidney.TISSUE SPECIFICITY Testis specific.INDUCTION Up-regulated by VEGF. Down-regulated by TNF.DOMAIN N-terminal loop binds to the intracellular vestibule of the transporter, arresting the transporter in an inhibited state.PTM Phosphorylated, phosphorylation regulates transporter activity (PubMed:34031912, PubMed:19665974, PubMed:21613606). Phosphorylated at Thr-991 and Thr-1048 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity (PubMed:19665974, PubMed:21613606).PTM N-glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Does not differ in the osmotic set point of swelling activation but, activation is more rapid.MISCELLANEOUS Does not differ in the osmotic set point of swelling activation but, activation is more rapid.SIMILARITY Belongs to the SLC12A transporter family.
crossReference	[DatabaseIdentifier:10976385] Pharos - Targets:Q9UHW9 [DatabaseIdentifier:10982920] Guide to Pharmacology - Targets:973 [DatabaseIdentifier:11076617] OpenTargets:ENSG00000140199 [DatabaseIdentifier:11616893] RefSeq:NP_001035959.1 [DatabaseIdentifier:11616905] RefSeq:NP_001035960.1 [DatabaseIdentifier:11616918] RefSeq:NP_001035961.1 [DatabaseIdentifier:11616932] RefSeq:NP_001035962.1 [DatabaseIdentifier:11616950] RefSeq:NP_005126.1 [DatabaseIdentifier:11616976] RefSeq:NP_598408.1 [DatabaseIdentifier:11764920] PDB:6M1Y [DatabaseIdentifier:11764932] PDB:6M22 [DatabaseIdentifier:11764944] PDB:6Y5R [DatabaseIdentifier:11764956] PDB:6Y5V [DatabaseIdentifier:11764968] PDB:7AIN [DatabaseIdentifier:11764981] PDB:7AIO [DatabaseIdentifier:11764993] PDB:7D90 [DatabaseIdentifier:11765006] PDB:7NGB [DatabaseIdentifier:11832203] PRO:Q9UHW9 [DatabaseIdentifier:11852074] GeneCards:Q9UHW9 [DatabaseIdentifier:11884906] Orphanet:15301 [DatabaseIdentifier:11886714] HMDB Protein:HMDBP03070 [DatabaseIdentifier:11901835] HPA:ENSG00000140199-SLC12A6 [DatabaseIdentifier:12175482] Ensembl:ENST00000397707 [DatabaseIdentifier:12175483] Ensembl:ENSG00000140199 [DatabaseIdentifier:12175484] Ensembl:ENST00000397702 [DatabaseIdentifier:12175485] Ensembl:ENST00000558667 [DatabaseIdentifier:12175486] Ensembl:ENST00000458406 [DatabaseIdentifier:12175487] Ensembl:ENSP00000346112 [DatabaseIdentifier:12175488] Ensembl:ENST00000558589 [DatabaseIdentifier:12175489] Ensembl:ENST00000560611 [DatabaseIdentifier:12175490] Ensembl:ENSP00000380819 [DatabaseIdentifier:12175491] Ensembl:ENSP00000387725 [DatabaseIdentifier:12175492] Ensembl:ENST00000354181 [DatabaseIdentifier:12175493] Ensembl:ENSP00000453473 [DatabaseIdentifier:12175494] Ensembl:ENSP00000452776 [DatabaseIdentifier:12175495] Ensembl:ENSP00000380814 [DatabaseIdentifier:12175496] Ensembl:ENSP00000290209 [DatabaseIdentifier:12175497] Ensembl:ENSP00000454168 [DatabaseIdentifier:12175498] Ensembl:ENST00000290209
databaseName	UniProt
dbId	63956
description	recommendedName: Solute carrier family 12 member 6 alternativeName: Electroneutral potassium-chloride cotransporter 3 alternativeName: K-Cl cotransporter 3
displayName	UniProt:Q9UHW9 SLC12A6
geneName	SLC12A6 KCC3
identifier	Q9UHW9
isSequenceChanged	false
keyword	3D-structure Alternative promoter usage Alternative splicing Cell membrane Charcot-Marie-Tooth disease Chloride Disease variant Disulfide bond Glycoprotein Ion transport Membrane Metal-binding Neurodegeneration Neuropathy Phosphoprotein Potassium Potassium transport Reference proteome Symport Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:12187927] Wright, Adam, 2024-03-12
name	SLC12A6
otherIdentifier	11724323_a_at 11724324_a_at 11737894_a_at 16806870 220740_PM_s_at 220740_s_at 223596_PM_at 223596_at 226741_PM_at 226741_at 3617311 3617313 3617314 3617315 3617316 3617317 3617318 3617322 3617323 3617324 3617327 3617328 3617329 3617331 3617332 3617334 3617335 3617336 3617337 3617338 3617339 3617341 3617342 3617343 3617344 3617345 3617346 3617347 3617348 3617349 3617350 3617357 3617368 3617369 3617375 3617376 3617377 3617378 3617380 3617381 3617382 3617383 3617384 3617402 45662_at 7987192 9990 A_23_P65877 A_33_P3212112 GE56488 GE84975 GE85570 GO:0001525 GO:0005215 GO:0005886 GO:0006811 GO:0006813 GO:0006884 GO:0007268 GO:0008519 GO:0015079 GO:0015293 GO:0015377 GO:0015379 GO:0016020 GO:0016323 GO:0019901 GO:0022857 GO:0023052 GO:0030424 GO:0045202 GO:0046872 GO:0048856 GO:0055064 GO:0055065 GO:0055075 GO:0055085 GO:0071333 GO:0071476 GO:0071477 GO:0071805 GO:0140157 GO:1902476 GO:1990573 HMNXSV003019844 HMNXSV003053992 Hs.250905.2.A1_3p_at ILMN_1682606 ILMN_1767992 ILMN_2266573 PH_hs_0000495 TC15001192.hg g4826779_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5623819] SLC12A6 R675* [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5623790] SLC12A6 F529fs532 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5623779] SLC12A6 T813fs813 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5623808] SLC12A6 R1134* [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5623780] SLC12A6 R1011* [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-426107] SLC12A6 [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8989794] ENSEMBL:ENSG00000140199 SLC12A6 [ReferenceDNASequence:11026136] KEGG Gene (Homo sapiens):9990 SLC12A6 [ReferenceDNASequence:11263454] NCBI Gene:9990 SLC12A6 [ReferenceDNASequence:11263455] BioGPS Gene:9990 SLC12A6 [ReferenceDNASequence:11263456] CTD Gene:9990 SLC12A6 [ReferenceDNASequence:11263457] dbSNP Gene:9990 SLC12A6 [ReferenceDNASequence:11263458] Monarch:9990 SLC12A6 [ReferenceDNASequence:11351347] ENSEMBL_homo_sapiens_GENE:ENSG00000140199.13 SLC12A6 [ReferenceDNASequence:11515616] UCSC:Q9UHW9 SLC12A6 [ReferenceDNASequence:11797069] OMIM:604878 SLC12A6 [ReferenceDNASequence:11879419] HGNC:10914 SLC12A6 [ReferenceDNASequence:12197206] COSMIC (genes):SLC12A6 SLC12A6
referenceTranscript	[ReferenceRNASequence:11459193] RefSeq:NM_001042494.1 SLC12A6 [ReferenceRNASequence:11459198] RefSeq:NM_001042495.1 SLC12A6 [ReferenceRNASequence:11459205] RefSeq:NM_001042496.1 SLC12A6 [ReferenceRNASequence:11459210] RefSeq:NM_001042497.1 SLC12A6 [ReferenceRNASequence:11459216] RefSeq:NM_005135.2 SLC12A6 [ReferenceRNASequence:11459221] RefSeq:NM_133647.1 SLC12A6
schemaClass	ReferenceGeneProduct
secondaryIdentifier	S12A6_HUMAN A0AV76 Q2VI00 Q7Z2E7 Q7Z4G5 Q8TDD4 Q9UFR2 Q9Y642 Q9Y665
sequenceLength	1150
species	[Species:48887] Homo sapiens
url	https://purl.uniprot.org/uniprot/Q9UHW9

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