Reactome | UniProt:P23975 SLC6A2

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UniProt:P23975 SLC6A2 Show undefined attributes

chain	chain:1-617
checksum	BDC6DF31316907BB
comment	FUNCTION Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818).CATALYTIC ACTIVITY (R)-noradrenaline(out) + chloride(out) + Na(+)(out) = (R)-noradrenaline(in) + chloride(in) + Na(+)(in)CATALYTIC ACTIVITY dopamine(out) + chloride(out) + Na(+)(out) = dopamine(in) + chloride(in) + Na(+)(in)CATALYTIC ACTIVITY dopamine(out) + chloride(out) + 2 Na(+)(out) = dopamine(in) + chloride(in) + 2 Na(+)(in)ACTIVITY REGULATION Inhibited by mazindol, desipramine, nomifensine and nortriptyline.BIOPHYSICOCHEMICAL PROPERTIES Monomer (PubMed:39048818). Can form homodimers in the cell membrane; homodimerization is mostly mediated by cholesterol and lipids, and regulates neurotransmitter transport activity (PubMed:38750358). Interacts with PRKCABP.INTERACTION Palmitoylated; palmitoylation regulates protein levels and neurotransmitter transport (PubMed:39395208).DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS This protein is the target of psychomotor stimulants such as amphetamines or cocaine.SIMILARITY Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A2 subfamily.
crossReference	[DatabaseIdentifier:12212744] PDB:8Y92 [DatabaseIdentifier:12818846] ZINC - World Drugs:SC6A2_HUMAN [DatabaseIdentifier:12817606] ZINC target:P23975 [DatabaseIdentifier:12814163] ZINC - Substances:SC6A2_HUMAN [DatabaseIdentifier:12810861] ZINC - Predictions - Purchasable:SC6A2_HUMAN [DatabaseIdentifier:12807980] ZINC - Metabolites:SC6A2_HUMAN [DatabaseIdentifier:12807250] ZINC - Investigational:SC6A2_HUMAN [DatabaseIdentifier:12806159] ZINC - FDA approved:SC6A2_HUMAN [DatabaseIdentifier:12805112] ZINC - Biogenic:SC6A2_HUMAN [DatabaseIdentifier:12383908] RefSeq:NP_001165972.1 [DatabaseIdentifier:12383913] RefSeq:XP_054169723.1 [DatabaseIdentifier:12383909] RefSeq:NP_001034.1 [DatabaseIdentifier:12383915] RefSeq:XP_006721326.1 [DatabaseIdentifier:12383911] RefSeq:XP_011521597.1 [DatabaseIdentifier:12383912] RefSeq:NP_001165975.1 [DatabaseIdentifier:12383910] RefSeq:NP_001165973.1 [DatabaseIdentifier:12383914] RefSeq:XP_054169722.1 [DatabaseIdentifier:12290152] Pharos - Targets:P23975 [DatabaseIdentifier:12272591] PRO:P23975 [DatabaseIdentifier:12212731] PDB:8XB2 [DatabaseIdentifier:12212754] PDB:8WTY [DatabaseIdentifier:12212729] PDB:8HFF [DatabaseIdentifier:12212748] PDB:8Y94 [DatabaseIdentifier:12212730] PDB:8WGX [DatabaseIdentifier:12212746] PDB:8Y90 [DatabaseIdentifier:12212728] PDB:8HFI [DatabaseIdentifier:12212753] PDB:8WTV [DatabaseIdentifier:12212742] PDB:8YR2 [DatabaseIdentifier:12212736] PDB:8ZPB [DatabaseIdentifier:12212747] PDB:8Y91 [DatabaseIdentifier:12212751] PDB:8WTX [DatabaseIdentifier:12212735] PDB:8I3V [DatabaseIdentifier:12212727] PDB:8XB4 [DatabaseIdentifier:11479591] ENSEMBL:ENSG00000103546 [DatabaseIdentifier:11579880] ENSEMBL:ENSP00000369237 [DatabaseIdentifier:11579881] ENSEMBL:ENSP00000219833 [DatabaseIdentifier:11579878] ENSEMBL:ENSP00000457375 [DatabaseIdentifier:11579879] ENSEMBL:ENSP00000457473 [DatabaseIdentifier:11702578] ENSEMBL:ENST00000568943 [DatabaseIdentifier:11702577] ENSEMBL:ENST00000379906 [DatabaseIdentifier:11702580] ENSEMBL:ENST00000219833 [DatabaseIdentifier:11702579] ENSEMBL:ENST00000567238 [DatabaseIdentifier:11781300] Guide to Pharmacology - Targets:926 [DatabaseIdentifier:11792307] GeneCards:SLC6A2 [DatabaseIdentifier:11808320] GlyGen:P23975 [DatabaseIdentifier:11834434] HMDB Protein:HMDBP02154 [DatabaseIdentifier:11845302] HPA:ENSG00000103546-SLC6A2 [DatabaseIdentifier:12129941] OpenTargets:ENSG00000103546 [DatabaseIdentifier:12138110] Orphanet:SLC6A2 [DatabaseIdentifier:12212741] PDB:8ZP1 [DatabaseIdentifier:12212738] PDB:8HFE [DatabaseIdentifier:12212732] PDB:8HFG [DatabaseIdentifier:12212740] PDB:8Y8Z [DatabaseIdentifier:12212752] PDB:8WTU [DatabaseIdentifier:12212743] PDB:8ZP2 [DatabaseIdentifier:12212750] PDB:8WTW [DatabaseIdentifier:12212745] PDB:8Y93 [DatabaseIdentifier:12212749] PDB:8Y95 [DatabaseIdentifier:12212737] PDB:8WGR [DatabaseIdentifier:12212726] PDB:8Z1L [DatabaseIdentifier:12212739] PDB:8ZOY [DatabaseIdentifier:12212733] PDB:8XB3 [DatabaseIdentifier:12212734] PDB:8HFL
databaseName	UniProt
dbId	64072
description	recommendedName: Sodium-dependent noradrenaline transporter alternativeName: fullName evidence="14 16"Norepinephrine transporter shortName evidence="14 16"NET alternativeName: Solute carrier family 6 member 2
displayName	UniProt:P23975 SLC6A2
geneName	SLC6A2 NAT1 NET1 SLC6A5
identifier	P23975
isSequenceChanged	false
keyword	3D-structure Alternative splicing Cell membrane Cell projection Disease variant Disulfide bond Glycoprotein Lipoprotein Membrane Metal-binding Neurotransmitter transport Palmitate Proteomics identification Reference proteome Sodium Symport Synapse Synaptosome Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	SLC6A2
otherIdentifier	11740324_a_at 11740325_a_at 11753967_a_at 16819109 210353_PM_s_at 210353_s_at 215715_PM_at 215715_at 216611_PM_s_at 216611_s_at 217621_PM_at 217621_at 239394_PM_at 239394_at 3661769 3661770 3661771 3661772 3661775 3661776 3661777 3661778 3661782 3661784 3661785 3661786 3661787 3661788 3661790 3661791 3661792 3661793 3661794 3661795 3661797 40402_at 65249_at 6530 70572_at 7995714 A_14_P106852 A_14_P116863 A_23_P358345 A_24_P910660 A_33_P3259022 A_33_P3394689 GE60137 GE689390 GO:0003779 GO:0005326 GO:0005328 GO:0005330 GO:0005334 GO:0005515 GO:0005886 GO:0006836 GO:0006865 GO:0007268 GO:0008092 GO:0008504 GO:0009410 GO:0009986 GO:0015293 GO:0015378 GO:0015844 GO:0015874 GO:0016020 GO:0030424 GO:0030672 GO:0032809 GO:0035725 GO:0042734 GO:0042995 GO:0043005 GO:0043014 GO:0045202 GO:0046872 GO:0048265 GO:0048487 GO:0051583 GO:0051620 GO:0055085 GO:0070050 GO:0090493 GO:0098810 GO:1902476 HMNXSV003034135 HMNXSV003036203 Hs.14468.0.A1_3p_at Hs.14468.0.A1_3p_x_at Hs.208021.0.A1_3p_at Hs.78036.1.S1_3p_at ILMN_1765607 PH_hs_0004507 TC16000458.hg X91117_rna1_at g189257_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-444009] SLC6A2 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5659768] SLC6A2 A457P [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000103546] ENSEMBL:ENSG00000103546 SLC6A2 [ReferenceDNASequence:12692158] UCSC:P23975 SLC6A2 [ReferenceDNASequence:11345279] BioGPS Gene:6530 SLC6A2 [ReferenceDNASequence:11392959] COSMIC - genes:NET1 SLC6A2 [ReferenceDNASequence:11392958] COSMIC - genes:NAT1 SLC6A2 [ReferenceDNASequence:11392960] COSMIC - genes:SLC6A5 SLC6A2 [ReferenceDNASequence:11392957] COSMIC - genes:SLC6A2 SLC6A2 [ReferenceDNASequence:11420403] CTD Gene:6530 SLC6A2 [ReferenceDNASequence:11428880] dbSNP Gene:6530 SLC6A2 [ReferenceDNASequence:11823987] HGNC:11048 SLC6A2 [ReferenceDNASequence:11885600] KEGG:hsa:6530 SLC6A2 [ReferenceDNASequence:11975068] Monarch:6530 SLC6A2 [ReferenceDNASequence:12059161] NCBI Gene:6530 SLC6A2 [ReferenceDNASequence:12114553] OMIM:163970 SLC6A2
referenceTranscript	[ReferenceRNASequence:12565696] RefSeq:XM_054313748.1 SLC6A2 [ReferenceRNASequence:12565690] RefSeq:XM_006721263.2 SLC6A2 [ReferenceRNASequence:12565691] RefSeq:NM_001172502.1 SLC6A2 [ReferenceRNASequence:12565693] RefSeq:NM_001043.3 SLC6A2 [ReferenceRNASequence:12565692] RefSeq:XM_011523295.3 SLC6A2 [ReferenceRNASequence:12565694] RefSeq:NM_001172501.3 SLC6A2 [ReferenceRNASequence:12565697] RefSeq:XM_054313747.1 SLC6A2 [ReferenceRNASequence:12565695] RefSeq:NM_001172504.1 SLC6A2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	SC6A2_HUMAN B2R707 B4DX48 Q96KH8
sequenceLength	617
species	[Species:48887] Homo sapiens
stId	uniprot:P23975
url	http://purl.uniprot.org/uniprot/P23975

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-444009] SLC6A2 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5659768] SLC6A2 A457P [plasma membrane]
(referenceSequence)	[ReplacedResidue:5659770] L-alanine 457 replaced with L-proline
(interactor)	[UndirectedInteraction:11174679] UniProt:P23975 <-> UniProt:Q9NRD5 (IntAct)

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