P23975 · SC6A2_HUMAN
- ProteinSodium-dependent noradrenaline transporter
- GeneSLC6A2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids617 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921).
Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921).
Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921).
Miscellaneous
This protein is the target of psychomotor stimulants such as amphetamines or cocaine.
Catalytic activity
- (R)-noradrenaline(out) + chloride(out) + Na+(out) = (R)-noradrenaline(in) + chloride(in) + Na+(in)(R)-noradrenaline (out)CHEBI:72587
+ chloride (out)CHEBI:17996+ Na+ (out)CHEBI:29101= (R)-noradrenaline (in)CHEBI:72587+ chloride (in)CHEBI:17996+ Na+ (in)CHEBI:29101 - chloride(out) + dopamine(out) + Na+(out) = chloride(in) + dopamine(in) + Na+(in)
- chloride(out) + dopamine(out) + 2 Na+(out) = chloride(in) + dopamine(in) + 2 Na+(in)
Activity regulation
Inhibited by mazindol, desipramine, nomifensine and nortriptyline.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
457 nM | noradrenaline | |||||
0.58 μM | noradrenaline | |||||
0.24 μM | dopamine | |||||
100 mM | Na+ in dopamine transport | |||||
27 mM | Cl- in dopamine transport |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
17 pmol/min/mg | for noradrenaline | ||||
32 pmol/min/mg | for dopamine |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 71 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 73 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 74 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 78 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 318 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 350 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 415 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 418 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 419 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: S |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSodium-dependent noradrenaline transporter
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP23975
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-62 | Cytoplasmic | ||||
Sequence: MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKK | ||||||
Transmembrane | 63-88 | Helical; Name=1 | ||||
Sequence: IDFLLSVVGFAVDLANVWRFPYLCYK | ||||||
Topological domain | 89-92 | Extracellular | ||||
Sequence: NGGG | ||||||
Transmembrane | 93-116 | Helical; Name=2 | ||||
Sequence: AFLIPYTLFLIIAGMPLFYMELAL | ||||||
Topological domain | 117-135 | Cytoplasmic | ||||
Sequence: GQYNREGAATVWKICPFFK | ||||||
Transmembrane | 136-166 | Helical; Name=3 | ||||
Sequence: GVGYAVILIALYVGFYYNVIIAWSLYYLFSS | ||||||
Topological domain | 167-233 | Extracellular | ||||
Sequence: FTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLP | ||||||
Transmembrane | 234-254 | Helical; Name=4 | ||||
Sequence: QWQLLLCLMVVVIVLYFSLWK | ||||||
Topological domain | 255-257 | Cytoplasmic | ||||
Sequence: GVK | ||||||
Transmembrane | 258-282 | Helical; Name=5 | ||||
Sequence: TSGKVVWITATLPYFVLFVLLVHGV | ||||||
Topological domain | 283-306 | Extracellular | ||||
Sequence: TLPGASNGINAYLHIDFYRLKEAT | ||||||
Transmembrane | 307-332 | Helical; Name=6 | ||||
Sequence: VWIDAATQIFFSLGAGFGVLIAFASY | ||||||
Topological domain | 333-338 | Cytoplasmic | ||||
Sequence: NKFDNN | ||||||
Transmembrane | 339-362 | Helical; Name=7 | ||||
Sequence: CYRDALLTSSINCITSFVSGFAIF | ||||||
Topological domain | 363-402 | Extracellular | ||||
Sequence: SILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGST | ||||||
Transmembrane | 403-428 | Helical; Name=8 | ||||
Sequence: FWAVVFFVMLLALGLDSSMGGMEAVI | ||||||
Topological domain | 429-443 | Cytoplasmic | ||||
Sequence: TGLADDFQVLKRHRK | ||||||
Transmembrane | 444-464 | Helical; Name=9 | ||||
Sequence: LFTFGVTFSTFLLALFCITKG | ||||||
Topological domain | 465 | Extracellular | ||||
Sequence: G | ||||||
Transmembrane | 466-492 | Helical; Name=10 | ||||
Sequence: IYVLTLLDTFAAGTSILFAVLMEAIGV | ||||||
Topological domain | 493-522 | Cytoplasmic | ||||
Sequence: SWFYGVDRFSNDIQQMMGFRPGLYWRLCWK | ||||||
Transmembrane | 523-545 | Helical; Name=11 | ||||
Sequence: FVSPAFLLFVVVVSIINFKPLTY | ||||||
Topological domain | 546-548 | Extracellular | ||||
Sequence: DDY | ||||||
Transmembrane | 549-569 | Helical; Name=12 | ||||
Sequence: IFPPWANWVGWGIALSSMVLV | ||||||
Topological domain | 570-617 | Cytoplasmic | ||||
Sequence: PIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Orthostatic intolerance (OI)
- Note
- DescriptionAn autosomal dominant disorder characterized by lightheadedness, palpitations, fatigue, blurred vision and tachycardia following postural change from a supine to an upright position, in the absence of hypotension. A syncope with transient cognitive impairment and dyspnea may also occur. Plasma norepinephrine concentration is abnormally high.
- See alsoMIM:604715
Natural variants in OI
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_010022 | 457 | A>P | in OI; loss of function; dbSNP:rs121918126 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_029157 | 7 | in dbSNP:rs11568323 | |||
Sequence: N → K | ||||||
Natural variant | VAR_011756 | 69 | in dbSNP:rs1805064 | |||
Sequence: V → I | ||||||
Natural variant | VAR_011757 | 99 | in dbSNP:rs1805065 | |||
Sequence: T → I | ||||||
Natural variant | VAR_011758 | 245 | in dbSNP:rs1805066 | |||
Sequence: V → I | ||||||
Natural variant | VAR_020048 | 283 | in dbSNP:rs45564432 | |||
Sequence: T → R | ||||||
Natural variant | VAR_011759 | 292 | in dbSNP:rs5563 | |||
Sequence: N → T | ||||||
Natural variant | VAR_011760 | 356 | in dbSNP:rs5565 | |||
Sequence: V → L | ||||||
Natural variant | VAR_011761 | 369 | in dbSNP:rs5566 | |||
Sequence: A → P | ||||||
Natural variant | VAR_011762 | 375 | in dbSNP:rs5567 | |||
Sequence: N → S | ||||||
Natural variant | VAR_014800 | 449 | in dbSNP:rs2234910 | |||
Sequence: V → I | ||||||
Natural variant | VAR_010022 | 457 | in OI; loss of function; dbSNP:rs121918126 | |||
Sequence: A → P | ||||||
Natural variant | VAR_011763 | 463 | in dbSNP:rs5570 | |||
Sequence: K → R | ||||||
Natural variant | VAR_011764 | 478 | in dbSNP:rs1805067 | |||
Sequence: G → S | ||||||
Natural variant | VAR_011765 | 528 | in dbSNP:rs5558 | |||
Sequence: F → C | ||||||
Natural variant | VAR_011766 | 548 | in dbSNP:rs5559 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_021861 | 549 | in dbSNP:rs3743788 | |||
Sequence: I → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 715 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000214748 | 1-617 | Sodium-dependent noradrenaline transporter | |||
Sequence: MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI | ||||||
Disulfide bond | 176↔185 | |||||
Sequence: CGHTWNSPNC | ||||||
Glycosylation | 184 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 192 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 198 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-23 | Disordered | ||||
Sequence: MLLARMNPQVQPENNGADTGPEQ |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
P23975-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length617
- Mass (Da)69,332
- Last updated1992-03-01 v1
- ChecksumBDC6DF31316907BB
P23975-2
- Name2
- Differences from canonical
- 611-617: LQHWLAI → MKTRQGRRRATNSCQISC
P23975-3
- Name3
- Differences from canonical
- 1-135: MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFK → MGVQWWSHTQGEVAVGLGLGDSYLTPCPCP
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H3BRS0 | H3BRS0_HUMAN | SLC6A2 | 295 | ||
H3BRE9 | H3BRE9_HUMAN | SLC6A2 | 572 | ||
H3BML6 | H3BML6_HUMAN | SLC6A2 | 604 | ||
H3BM11 | H3BM11_HUMAN | SLC6A2 | 561 | ||
A0A804HLI4 | A0A804HLI4_HUMAN | SLC6A2 | 350 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054119 | 1-135 | in isoform 3 | |||
Sequence: MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFK → MGVQWWSHTQGEVAVGLGLGDSYLTPCPCP | ||||||
Alternative sequence | VSP_044479 | 611-617 | in isoform 2 | |||
Sequence: LQHWLAI → MKTRQGRRRATNSCQISC |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M65105 EMBL· GenBank· DDBJ | AAA59943.1 EMBL· GenBank· DDBJ | mRNA | ||
X91117 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91120 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91121 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91122 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91123 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91124 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91125 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91126 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91127 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91118 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91119 EMBL· GenBank· DDBJ | CAA62566.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91117 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91118 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91119 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91120 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91121 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91122 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91123 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91124 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91125 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91126 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X91127 EMBL· GenBank· DDBJ | CAC39181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK301811 EMBL· GenBank· DDBJ | BAG63260.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312793 EMBL· GenBank· DDBJ | BAG35654.1 EMBL· GenBank· DDBJ | mRNA | ||
AC136621 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471092 EMBL· GenBank· DDBJ | EAW82831.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471092 EMBL· GenBank· DDBJ | EAW82833.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471092 EMBL· GenBank· DDBJ | EAW82835.1 EMBL· GenBank· DDBJ | Genomic DNA |