P23975 · SC6A2_HUMAN

  • Protein
    Sodium-dependent noradrenaline transporter
  • Gene
    SLC6A2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Catalytic activity

Activity regulation

Inhibited by mazindol, desipramine, nomifensine and nortriptyline.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
457 nMnoradrenaline
0.58 μMnoradrenaline
0.24 μMdopamine
100 mMNa+ in dopamine transport
27 mMCl- in dopamine transport
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
17 pmol/min/mgfor noradrenaline
32 pmol/min/mgfor dopamine

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site71Na+ 1 (UniProtKB | ChEBI)
Binding site73Na+ 2 (UniProtKB | ChEBI)
Binding site74Na+ 1 (UniProtKB | ChEBI)
Binding site78Na+ 2 (UniProtKB | ChEBI)
Binding site318Na+ 2 (UniProtKB | ChEBI)
Binding site350Na+ 2 (UniProtKB | ChEBI)
Binding site415Na+ 1 (UniProtKB | ChEBI)
Binding site418Na+ 1 (UniProtKB | ChEBI)
Binding site419Na+ 1 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcell surface
Cellular Componentmembrane
Cellular Componentneuronal cell body membrane
Cellular Componentplasma membrane
Cellular Componentpresynaptic membrane
Molecular Functionactin binding
Molecular Functionalpha-tubulin binding
Molecular Functionbeta-tubulin binding
Molecular Functiondopamine:sodium symporter activity
Molecular Functionmetal ion binding
Molecular Functionmonoamine transmembrane transporter activity
Molecular Functionneurotransmitter transmembrane transporter activity
Molecular Functionneurotransmitter:sodium symporter activity
Molecular Functionnorepinephrine:sodium symporter activity
Biological Processamino acid transport
Biological Processchemical synaptic transmission
Biological Processdopamine uptake involved in synaptic transmission
Biological Processmonoamine transport
Biological Processneuron cellular homeostasis
Biological Processneurotransmitter transport
Biological Processnorepinephrine transport
Biological Processnorepinephrine uptake
Biological Processresponse to pain
Biological Processresponse to xenobiotic stimulus
Biological Processsodium ion transmembrane transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Sodium-dependent noradrenaline transporter
  • Alternative names
    • Norepinephrine transporter (NET)
    • Solute carrier family 6 member 2

Gene names

    • Name
      SLC6A2
    • Synonyms
      NAT1, NET1, SLC6A5

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P23975
  • Secondary accessions
    • B2R707
    • B4DX48
    • Q96KH8

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-62Cytoplasmic
Transmembrane63-88Helical; Name=1
Topological domain89-92Extracellular
Transmembrane93-116Helical; Name=2
Topological domain117-135Cytoplasmic
Transmembrane136-166Helical; Name=3
Topological domain167-233Extracellular
Transmembrane234-254Helical; Name=4
Topological domain255-257Cytoplasmic
Transmembrane258-282Helical; Name=5
Topological domain283-306Extracellular
Transmembrane307-332Helical; Name=6
Topological domain333-338Cytoplasmic
Transmembrane339-362Helical; Name=7
Topological domain363-402Extracellular
Transmembrane403-428Helical; Name=8
Topological domain429-443Cytoplasmic
Transmembrane444-464Helical; Name=9
Topological domain465Extracellular
Transmembrane466-492Helical; Name=10
Topological domain493-522Cytoplasmic
Transmembrane523-545Helical; Name=11
Topological domain546-548Extracellular
Transmembrane549-569Helical; Name=12
Topological domain570-617Cytoplasmic

Keywords

Disease & Variants

Involvement in disease

Orthostatic intolerance (OI)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An 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 also
    MIM:604715
Natural variants in OI
Variant IDPosition(s)ChangeDescription
VAR_010022457A>Pin OI; loss of function; dbSNP:rs121918126

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_0291577in dbSNP:rs11568323
Natural variantVAR_01175669in dbSNP:rs1805064
Natural variantVAR_01175799in dbSNP:rs1805065
Natural variantVAR_011758245in dbSNP:rs1805066
Natural variantVAR_020048283in dbSNP:rs45564432
Natural variantVAR_011759292in dbSNP:rs5563
Natural variantVAR_011760356in dbSNP:rs5565
Natural variantVAR_011761369in dbSNP:rs5566
Natural variantVAR_011762375in dbSNP:rs5567
Natural variantVAR_014800449in dbSNP:rs2234910
Natural variantVAR_010022457in OI; loss of function; dbSNP:rs121918126
Natural variantVAR_011763463in dbSNP:rs5570
Natural variantVAR_011764478in dbSNP:rs1805067
Natural variantVAR_011765528in dbSNP:rs5558
Natural variantVAR_011766548in dbSNP:rs5559
Natural variantVAR_021861549in dbSNP:rs3743788

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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002147481-617Sodium-dependent noradrenaline transporter
Disulfide bond176↔185
Glycosylation184N-linked (GlcNAc...) asparagine
Glycosylation192N-linked (GlcNAc...) asparagine
Glycosylation198N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with PRKCABP.

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-23Disordered

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

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.

  • Length
    617
  • Mass (Da)
    69,332
  • Last updated
    1992-03-01 v1
  • Checksum
    BDC6DF31316907BB
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI

P23975-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 611-617: LQHWLAI → MKTRQGRRRATNSCQISC

P23975-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-135: MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFK → MGVQWWSHTQGEVAVGLGLGDSYLTPCPCP

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
H3BRS0H3BRS0_HUMANSLC6A2295
H3BRE9H3BRE9_HUMANSLC6A2572
H3BML6H3BML6_HUMANSLC6A2604
H3BM11H3BM11_HUMANSLC6A2561
A0A804HLI4A0A804HLI4_HUMANSLC6A2350

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_0541191-135in isoform 3
Alternative sequenceVSP_044479611-617in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

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