Reactome | UniProt:Q92581 SLC9A6

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UniProt:Q92581 SLC9A6 Show undefined attributes

chain	chain:1-701
checksum	A2BE0E4EF07A62EC
comment	FUNCTION Endosomal Na(+), K(+)/H(+) antiporter (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A6 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Responsible for alkalizing and maintaining the endosomal pH, and consequently in, e.g., endosome maturation and trafficking of recycling endosomal cargo (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Plays a critical role during neurodevelopment by regulating synaptic development and plasticity (By similarity). Implicated in the maintenance of cell polarity in a manner that is dependent on its ability to modulate intravesicular pH (PubMed:20130086). Regulates intracellular pH in some specialized cells, osteoclasts and stereocilia where this transporter localizes to the plasma membrane (By similarity).CATALYTIC ACTIVITY Na(+)(in) + H(+)(out) = Na(+)(out) + H(+)(in)CATALYTIC ACTIVITY K(+)(in) + H(+)(out) = K(+)(out) + H(+)(in)SUBUNIT Homodimer (PubMed:30296617, PubMed:32277048). Interacts with RACK1; regulates the distribution of SLC9A6 between endosomes and the plasma membrane (PubMed:18057008, PubMed:28635961).INTERACTION Present predominantly in the recycling compartments including early and recycling endosomes, but undergoes plasma membrane localization during vesicular recycling, which is enhanced upon certain stimuli, such as hypoxia (PubMed:11940519, PubMed:28635961, PubMed:30296617). Has a major plasmalemmal distribution in a few specialized cells, such as in vestibular hair bundles and osteoblasts (By similarity).ALTERNATIVE PRODUCTS Ubiquitous. High expression in brain, skeletal muscle, and heart, but is also detected at lower levels in most other tissues.PTM Ubiquitinated (in vitro).PTM Glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease may be caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.CAUTION Was originally (PubMed:9507001) identified as a mitochondrial inner membrane protein, but was later shown to be localized in early and recycling endosomes and not mitochondria (PubMed:11641397, PubMed:11940519).
crossReference	[DatabaseIdentifier:12135163] Orphanet:SLC9A6 [DatabaseIdentifier:12463372] RefSeq:NP_001387839.1 [DatabaseIdentifier:12463377] RefSeq:NP_006350.1 [DatabaseIdentifier:12463375] RefSeq:NP_001387840.1 [DatabaseIdentifier:12463371] RefSeq:NP_001387838.1 [DatabaseIdentifier:12463374] RefSeq:NP_001387841.1 [DatabaseIdentifier:12463376] RefSeq:NP_001036002.1 [DatabaseIdentifier:12463373] RefSeq:NP_001171122.1 [DatabaseIdentifier:12287528] Pharos - Targets:Q92581 [DatabaseIdentifier:12268184] PRO:Q92581 [DatabaseIdentifier:11517441] ENSEMBL:ENSG00000198689 [DatabaseIdentifier:11634944] ENSEMBL:ENSP00000490527 [DatabaseIdentifier:11634941] ENSEMBL:ENSP00000359729 [DatabaseIdentifier:11634942] ENSEMBL:ENSP00000490648 [DatabaseIdentifier:11634946] ENSEMBL:ENSP00000359735 [DatabaseIdentifier:11634945] ENSEMBL:ENSP00000359732 [DatabaseIdentifier:11634943] ENSEMBL:ENSP00000490406 [DatabaseIdentifier:11634947] ENSEMBL:ENSP00000490731 [DatabaseIdentifier:11757640] ENSEMBL:ENST00000370701 [DatabaseIdentifier:11757645] ENSEMBL:ENST00000636092 [DatabaseIdentifier:11757642] ENSEMBL:ENST00000637234 [DatabaseIdentifier:11757644] ENSEMBL:ENST00000370695 [DatabaseIdentifier:11757643] ENSEMBL:ENST00000636347 [DatabaseIdentifier:11757641] ENSEMBL:ENST00000637581 [DatabaseIdentifier:11757646] ENSEMBL:ENST00000370698 [DatabaseIdentifier:11779191] Guide to Pharmacology - Targets:953 [DatabaseIdentifier:11789672] GeneCards:SLC9A6 [DatabaseIdentifier:11805344] GlyGen:Q92581 [DatabaseIdentifier:11829528] HMDB Protein:HMDBP07998 [DatabaseIdentifier:11842699] HPA:ENSG00000198689-SLC9A6 [DatabaseIdentifier:12127292] OpenTargets:ENSG00000198689
databaseName	UniProt
dbId	59899
description	recommendedName: Sodium/hydrogen exchanger 6 alternativeName: Na(+)/H(+) exchanger 6 shortName: NHE-6 alternativeName: Solute carrier family 9 member 6
displayName	UniProt:Q92581 SLC9A6
geneName	SLC9A6 KIAA0267 NHE6
identifier	Q92581
isSequenceChanged	false
keyword	Alternative splicing Antiport Cell membrane Disease variant Endosome Epilepsy Glycoprotein Intellectual disability Ion transport Isopeptide bond Membrane Neurodegeneration Parkinsonism Proteomics identification Reference proteome Sodium Sodium transport Transmembrane Transmembrane helix Transport Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	SLC9A6
otherIdentifier	10479 11719516_a_at 11719517_a_at 17107206 17107211 203909_PM_at 203909_at 36542_at 3992352 3992353 3992355 3992356 3992360 3992361 3992362 3992363 3992364 3992365 3992366 3992367 3992370 3992372 3992373 3992376 3992377 3992378 3992379 3992381 3992382 3992383 3992384 3992385 64264_r_at 8170097 A_14_P135399 A_23_P22625 A_24_P410562 A_33_P3263027 D87743_at GE54235 GO:0005515 GO:0005768 GO:0005769 GO:0005770 GO:0005789 GO:0005886 GO:0006811 GO:0006812 GO:0006814 GO:0006885 GO:0007163 GO:0010008 GO:0015297 GO:0015385 GO:0015386 GO:0016020 GO:0030010 GO:0030425 GO:0031410 GO:0031547 GO:0031901 GO:0031902 GO:0034330 GO:0035725 GO:0042802 GO:0043679 GO:0044308 GO:0045202 GO:0048675 GO:0048812 GO:0048856 GO:0050808 GO:0051386 GO:0051453 GO:0055037 GO:0055038 GO:0055085 GO:0060996 GO:0071805 GO:0097484 GO:0098685 GO:0098719 GO:0098978 GO:0099072 GO:1902600 HMNXSV003003261 HMNXSV003044497 ILMN_1655892 ILMN_1677829 ILMN_2269619 ILMN_2363097 PH_hs_0003938 TC0X000656.hg TC0X000657.hg g5454069_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-425984] SLC9A6 [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5661079] SLC9A6 H171fs60 [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5661042] SLC9A6 338-340del [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5661072] SLC9A6 R468 [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5661037] SLC9A6 E547* [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5661066] SLC9A6 E255_S256del [early endosome membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000198689] ENSEMBL:ENSG00000198689 SLC9A6 [ReferenceDNASequence:12766126] UCSC:Q92581 SLC9A6 [ReferenceDNASequence:11381385] BioGPS Gene:10479 SLC9A6 [ReferenceDNASequence:11403573] COSMIC - genes:SLC9A6 SLC9A6 [ReferenceDNASequence:11416480] CTD Gene:10479 SLC9A6 [ReferenceDNASequence:11441195] dbSNP Gene:10479 SLC9A6 [ReferenceDNASequence:11821329] HGNC:11079 SLC9A6 [ReferenceDNASequence:11918279] KEGG:hsa:10479 SLC9A6 [ReferenceDNASequence:12011174] Monarch:10479 SLC9A6 [ReferenceDNASequence:12095267] NCBI Gene:10479 SLC9A6 [ReferenceDNASequence:12112187] OMIM:300231 SLC9A6
referenceTranscript	[ReferenceRNASequence:12644850] RefSeq:NM_001400910.1 SLC9A6 [ReferenceRNASequence:12644851] RefSeq:NM_006359.3 SLC9A6 [ReferenceRNASequence:12644848] RefSeq:NM_001042537.2 SLC9A6 [ReferenceRNASequence:12644846] RefSeq:NM_001177651.2 SLC9A6 [ReferenceRNASequence:12644845] RefSeq:NM_001400909.1 SLC9A6 [ReferenceRNASequence:12644847] RefSeq:NM_001400912.1 SLC9A6 [ReferenceRNASequence:12644849] RefSeq:NM_001400911.1 SLC9A6
schemaClass	ReferenceGeneProduct
secondaryIdentifier	SL9A6_HUMAN A6NIQ9 A8K160 B4DU30 B7ZAE0 Q3ZCW7 Q5JPP8 Q5JPP9 Q86VS0 Q8WYK8
sequenceLength	701
species	[Species:48887] Homo sapiens
stId	uniprot:Q92581
url	http://purl.uniprot.org/uniprot/Q92581

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-425984] SLC9A6 [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5661079] SLC9A6 H171fs60 [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5661042] SLC9A6 338-340del [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5661072] SLC9A6 R468 [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5661037] SLC9A6 E547* [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5661066] SLC9A6 E255_S256del [early endosome membrane]
(referenceSequence)	[FragmentReplacedModification:5661058] Replacement of residues 171 to 229 [FragmentDeletionModification:5661078] Deletion of residues 338 to 340 [NonsenseMutation:5661077] Nonsense mutation at L-arginine 468 [NonsenseMutation:5661026] Nonsense mutation at L-glutamic acid 547 [FragmentDeletionModification:5661004] Deletion of residues 255 to 256
(interactor)	[UndirectedInteraction:11136801] UniProt:Q8NAT1 <-> UniProt:Q92581 (IntAct) [UndirectedInteraction:11271759] UniProt:P17931 <-> UniProt:Q92581 (IntAct) [UndirectedInteraction:11281677] UniProt:Q9BYC5 <-> UniProt:Q92581 (IntAct) [UndirectedInteraction:11292743] UniProt:P43353 <-> UniProt:Q92581 (IntAct) [UndirectedInteraction:11299415] UniProt:P27824 <-> UniProt:Q92581 (IntAct)