O75751 · S22A3_HUMAN

  • Protein
    Solute carrier family 22 member 3
  • Gene
    SLC22A3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707).
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924).
Functions as a Na+- and Cl--independent, bidirectional uniporter (PubMed:12538837).
Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707).
Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754).
May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924).
May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity).
Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837).
Also transports guanidine (PubMed:10966924).
May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).

Miscellaneous

Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and platinum-based drug oxaliplatin (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:15817714, PubMed:16263091, PubMed:16581093, PubMed:16914559, PubMed:20858707).
Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity (PubMed:16914559).

Catalytic activity

  • (R)-noradrenaline(out) = (R)-noradrenaline(in)
  • (R)-adrenaline(out) = (R)-adrenaline(in)
  • serotonin(out) = serotonin(in)
  • dopamine(out) = dopamine(in)
  • histamine(out) = histamine(in)
  • tyramine(in) = tyramine(out)
  • guanidine(out) = guanidine(in)
  • agmatine(out) = agmatine(in)
  • spermidine(in) = spermidine(out)
  • L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L-proline diketopiperazine(out)
  • (R)-salsolinol(in) = (R)-salsolinol(out)

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
126 μMcyclo(his-pro)
139 μMsalsolinol
220 μMhistamine
641 μMhistamine
240 μMadrenaline
458 μMadrenaline
923 μMnoradrenaline
2630 μMnoradrenaline
988 μMserotonin
1033 μMdopamine
2500 μMagmatine
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
0.4 nmol/min/mgfor cyclo(his-pro) uptake
0.5 nmol/min/mgfor salsolinol uptake
34.6 nmol/min/mgfor histamine uptake
12.76 nmol/min/mgfor adrenaline uptake
30.13 nmol/min/mgfor noradrenaline uptake
11.56 nmol/min/mgfor serotonin uptake
22.68 nmol/min/mgfor dopamine uptake
15.9 nmol/min/mgfor agmatine uptake

pH Dependence

Optimum pH is 8.5 for agmatine and MPP+ transport.

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentendomembrane system
Cellular Componentmembrane
Cellular Componentmitochondrial membrane
Cellular Componentneuronal cell body
Cellular Componentnuclear outer membrane
Cellular Componentplasma membrane
Cellular Componentpresynapse
Molecular Functionmonoamine transmembrane transporter activity
Molecular Functionneurotransmitter transmembrane transporter activity
Molecular Functionorganic anion transmembrane transporter activity
Molecular Functionorganic cation transmembrane transporter activity
Molecular Functionquaternary ammonium group transmembrane transporter activity
Molecular Functionspermidine transmembrane transporter activity
Molecular Functiontoxin transmembrane transporter activity
Biological Processcellular detoxification
Biological Processdopamine transport
Biological Processdopamine uptake
Biological Processepinephrine transport
Biological Processepinephrine uptake
Biological Processhistamine metabolic process
Biological Processhistamine transport
Biological Processhistamine uptake
Biological Processmonoamine transport
Biological Processmonoatomic ion transport
Biological Processmonocarboxylic acid transport
Biological Processneurotransmitter transport
Biological Processnorepinephrine transport
Biological Processnorepinephrine uptake
Biological Processorganic anion transport
Biological Processorganic cation transport
Biological Processpurine-containing compound transmembrane transport
Biological Processquaternary ammonium group transport
Biological Processregulation of appetite
Biological Processserotonin transport
Biological Processserotonin uptake
Biological Processspermidine transport
Biological Processtransport across blood-brain barrier
Biological Processxenobiotic transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Solute carrier family 22 member 3
  • Alternative names
    • Extraneuronal monoamine transporter
      (EMT
      )
    • Organic cation transporter 3
      (OCT3
      )

Gene names

    • Name
      SLC22A3
    • Synonyms
      EMTH, OCT3

Organism names

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

Accessions

  • Primary accession
    O75751
  • Secondary accessions
    • Q5SYN6
    • Q9UP02

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Basolateral cell membrane
; Multi-pass membrane protein
Endomembrane system
Nucleus membrane
Note: Localized to the apical/brush border membrane of enterocytes (PubMed:16263091).
Localized to the luminal/apical membrane of ciliated epithelial cells in bronchi (PubMed:15817714).
Localized to the basolateral membrane of intermediate cells in bronchi (PubMed:15817714).
Localized to the entire plasma membrane of basal cells in bronchi (PubMed:15817714).

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane21-41Helical
Transmembrane182-202Helical
Transmembrane241-261Helical
Transmembrane269-289Helical
Transmembrane381-401Helical
Transmembrane468-488Helical
Transmembrane498-518Helical

Keywords

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_02035144in dbSNP:rs8187715
Natural variantVAR_020352116in dbSNP:rs8187717
Mutagenesis289Decreased TEA uptake.
Mutagenesis363Decreased TEA uptake.
Mutagenesis380Decreased TEA uptake.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 700 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002205031-556Solute carrier family 22 member 3
Glycosylation72N-linked (GlcNAc...) asparagine
Glycosylation99N-linked (GlcNAc...) asparagine
Glycosylation119N-linked (GlcNAc...) asparagine
Glycosylation322N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in liver (PubMed:10196521, PubMed:9933568).
Expressed in intestine (PubMed:16263091, PubMed:20858707).
Expressed in kidney in proximal tubular cells (PubMed:10966924).
Expressed in placenta (PubMed:10966924, PubMed:9933568).
Expressed throughout the brain, including cerebral cortex, cerebrellum, substancia nigra, medulla oblongata, hippocampus, caudate nucleus, nucleus accumbens and pons with low levels of expression detected in nearly all brain regions (PubMed:10196521, PubMed:20858707).
In testis, mostly localized to peritubular myoid cells and Leydig cells, and weakly expressed in developing germ cells (PubMed:35307651).
Expressed in tracheal and bronchial epithelium of the respiratory tract, where it localizes to the apical membrane of ciliated cells, the entire membrane of basal cells and the basolateral membrane of intermediate cells (PubMed:15817714).
Expressed in skeletal muscle, adrenal gland, heart, prostate, aorta, salivary gland, adrenal gland, uterus, lymph node, lung, trachea and spinal cord (PubMed:10196521, PubMed:20858707, PubMed:9933568).
Expressed in fetal lung and liver (PubMed:9933568).

Gene expression databases

Organism-specific databases

Interaction

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY O75751ABL1 P005192EBI-1752674, EBI-375543

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif289-293Proline-rich sequence

Domain

Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    556
  • Mass (Da)
    61,280
  • Last updated
    1998-11-01 v1
  • Checksum
    C3CA2D77DD21C658
MPSFDEALQRVGEFGRFQRRVFLLLCLTGVTFAFLFVGVVFLGTQPDHYWCRGPSAAALAERCGWSPEEEWNRTAPASRGPEPPERRGRCQRYLLEAANDSASATSALSCADPLAAFPNRSAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDKALQILRRIAKCNGKYLSSNYSEITVTDEEVSNPSFLDLVRTPQMRKCTLILMFAWFTSAVVYQGLVMRLGIIGGNLYIDFFISGVVELPGALLILLTIERLGRRLPFAASNIVAGVACLVTAFLPEGIAWLRTTVATLGRLGITMAFEIVYLVNSELYPTTLRNFGVSLCSGLCDFGGIIAPFLLFRLAAVWLELPLIIFGILASICGGLVMLLPETKGIALPETVDDVEKLGSPHSCKCGRNKKTPVSRSHL

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ001417
EMBL· GenBank· DDBJ
CAA04751.1
EMBL· GenBank· DDBJ
mRNA
AK314590
EMBL· GenBank· DDBJ
BAG37164.1
EMBL· GenBank· DDBJ
mRNA
AL591069
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL355506
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471051
EMBL· GenBank· DDBJ
EAW47599.1
EMBL· GenBank· DDBJ
Genomic DNA
AF078749
EMBL· GenBank· DDBJ
AAD20977.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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