Q7RTT9 · S29A4_HUMAN

  • Protein
    Equilibrative nucleoside transporter 4
  • Gene
    SLC29A4
  • 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 endogenous bioactive amines, cationic xenobiotics and drugs (PubMed:15448143, PubMed:16099839, PubMed:16873718, PubMed:17018840, PubMed:17121826, PubMed:20592246, PubMed:20858707, PubMed:22396231, PubMed:31537831).
Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations (PubMed:15448143, PubMed:20592246, PubMed:22396231).
Functions as a Na+- and Cl--independent bidirectional transporter (PubMed:15448143, PubMed:16099839, PubMed:22396231, PubMed:31537831).
Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure (PubMed:16873718, PubMed:17018840, PubMed:20592246, PubMed:22396231, PubMed:31537831).
Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system (PubMed:15448143, PubMed:16099839, PubMed:17018840, PubMed:17121826, PubMed:20858707, PubMed:22396231).
Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain (By similarity).
Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia (PubMed:16873718, PubMed:20592246, PubMed:31537831).
May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney (PubMed:17018840).
Also transports guanidine (PubMed:16099839).

Miscellaneous

Does not interact with nucleosides, nucleobases or nucleotides, other than a moderate activity for adenosine (PubMed:15448143, PubMed:17393420, PubMed:20592246).
Mediates the uptake of neurotoxin 1-methyl-4-phenylpyridinium (MPP+) (PubMed:15448143, PubMed:16099839, PubMed:17018840, PubMed:17121826, PubMed:20592246, PubMed:20858707, PubMed:23255610).

Caution

Unlike mouse protein, not able to transport adenine nucleotide in acidic condition.

Catalytic activity

  • serotonin(out) = serotonin(in)
  • dopamine(out) = dopamine(in)
  • (R)-noradrenaline(out) = (R)-noradrenaline(in)
  • (R)-adrenaline(out) = (R)-adrenaline(in)
  • histamine(out) = histamine(in)
  • tyramine(in) = tyramine(out)
  • guanidine(out) = guanidine(in)
  • adenosine(in) = adenosine(out)
    This reaction proceeds in the forward
    and the backward
    directions.

Activity regulation

Activated at acidic pH.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
114 μMserotonin7.4
283 μMserotonin7.4
1900 μMserotonin5.5
283 μMtyramine7.4
329 μMdopamine7.4
406 μMdopamine7.4
15323 μMadrenaline7.4
951 μMadrenaline7.4
1078 μMnoradrenaline7.4
2606 μMnoradrenaline7.4
10471 μMhistamine7.4
4379 μMhistamine7.4
15323 μMhistamine7.4
413 μMadenosine7.4
780 μMadenosine5.5
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
2.01 nmol/min/mg7.4for adenosine uptake
14.19 nmol/min/mg7.4for serotonin uptake
6.5 nmol/min/mg7.4for serotonin uptake
5.05 nmol/min/mg7.4for tyramine uptake
22.4 nmol/min/mg7.4for dopamine uptake
18.2 nmol/min/mg7.4for dopamine uptake
38.4 nmol/min/mg7.4for adrenaline uptake
7.25 nmol/min/mg7.4for adrenaline uptake
20.6 nmol/min/mg7.4for noradrenaline uptake
8.82 nmol/min/mg7.4for noradrenaline uptake
99.61 nmol/min/mg7.4for histamine uptake
42.37 nmol/min/mg7.4for histamine uptake

pH Dependence

Optimum pH is 6.0 for histamine uptake (PubMed:22396231).
Optimum pH is 6.6 for adenosine, serotonin and inosine uptake (PubMed:20592246).
Optimum pH is 6.0 for adenosine uptake (PubMed:16873718, PubMed:31537831).
Does not transport adenosine at pH 7.4 (PubMed:16873718).

Features

Showing features for site.

TypeIDPosition(s)Description
Site206Essential for cation selectivity

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentplasma membrane
Cellular Componentpresynapse
Molecular Functionefflux transmembrane transporter activity
Molecular Functionmonoamine transmembrane transporter activity
Molecular Functionmonoatomic cation transmembrane transporter activity
Molecular Functionneurotransmitter transmembrane transporter activity
Molecular Functionnucleoside transmembrane transporter activity
Molecular Functionorganic acid transmembrane transporter activity
Molecular Functionorganic cation transmembrane transporter activity
Molecular Functiontoxin transmembrane transporter activity
Molecular Functionxenobiotic transmembrane transporter activity
Biological Processadenosine transport
Biological Processcellular detoxification
Biological Processdopamine transport
Biological Processdopamine uptake
Biological Processepinephrine transport
Biological Processepinephrine uptake
Biological Processexport across plasma membrane
Biological Processhistamine metabolic process
Biological Processhistamine transport
Biological Processhistamine uptake
Biological Processmonoamine transport
Biological Processmonoatomic cation transmembrane transport
Biological Processneurotransmitter transport
Biological Processnorepinephrine transport
Biological Processnorepinephrine uptake
Biological Processorganic acid transmembrane transport
Biological Processorganic cation transport
Biological Processserotonin transport
Biological Processserotonin uptake
Biological Processtransport across blood-brain barrier
Biological Processxenobiotic transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Equilibrative nucleoside transporter 4
  • Short names
    hENT4
  • Alternative names
    • Plasma membrane monoamine transporter
      (PMAT
      )
    • Solute carrier family 29 member 4

Gene names

    • Name
      SLC29A4
    • Synonyms
      ENT4, PMAT
    • ORF names
      PSEC0113

Organism names

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

Accessions

  • Primary accession
    Q7RTT9
  • Secondary accessions
    • Q6PJ08
    • Q86WY8
    • Q8NAR3
    • Q8NBM2

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Note: Located to the plasma membranes of ventricular myocytes and vascular endothelial cells (PubMed:16873718).
Targeted to the apical membranes of differentiated kidney epithelial cells (PubMed:17018840).
Localized to the apical blood-cerebrospinal fluid (CSF)-facing membrane of the choroid plexus epithelium (PubMed:23255610).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-68Extracellular
Transmembrane69-89Helical
Topological domain90-101Cytoplasmic
Transmembrane102-122Helical
Topological domain123-139Extracellular
Transmembrane140-160Helical
Topological domain161-166Cytoplasmic
Transmembrane167-187Helical
Topological domain188-231Extracellular
Transmembrane232-252Helical
Topological domain253-351Cytoplasmic
Transmembrane352-372Helical
Topological domain373-381Extracellular
Transmembrane382-402Helical
Topological domain403-416Cytoplasmic
Transmembrane417-437Helical
Topological domain438-450Extracellular
Transmembrane451-471Helical
Topological domain472-486Cytoplasmic
Transmembrane487-509Helical
Topological domain510-530Extracellular

Keywords

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_04004479in dbSNP:rs17854505
Mutagenesis91No significant change in dopamine, serotonin and MPP+ uptake.
Mutagenesis107Loss of dopamine, serotonin and MPP+ uptake.
Natural variantVAR_040045124in dbSNP:rs17855675
Mutagenesis128No significant change in dopamine, serotonin and MPP+ uptake.
Mutagenesis154Loss of dopamine, serotonin and MPP+ uptake; increased uridine uptake.
Mutagenesis163Loss of dopamine, serotonin and MPP+ uptake.
Mutagenesis206Loss of dopamine, serotonin and MPP+ uptake; gain of uridine transport activity.
Mutagenesis206No change in dopamine, serotonin and MPP+ uptake; no uridine uptake activity.
Mutagenesis206Loss of dopamine, serotonin, adenosine and MPP+ uptake; gain of uridine transport activity.
Mutagenesis206Loss of dopamine, serotonin and MPP+ uptake; no uridine uptake activity.
Mutagenesis220Reduced dopamine, serotonin and MPP+ uptake.
Mutagenesis220Loss of dopamine, serotonin and MPP+ uptake.
Mutagenesis220Reduced dopamine, serotonin and MPP+ uptake.
Mutagenesis227Functional with slight increased dopamine, serotonin and MPP+ uptake.
Mutagenesis242Reduced dopamine, serotonin and MPP+ uptake.
Mutagenesis336Loss of dopamine, serotonin and MPP+ uptake.
Mutagenesis375Functional with increased dopamine, serotonin and MPP+ uptake.
Mutagenesis375No change in adenosine uptake.
Natural variantVAR_040046429in dbSNP:rs17857336

Variants

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

The viewer provides 868 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, modified residue (large scale data), glycosylation.

TypeIDPosition(s)SourceDescription
ChainPRO_00003262511-530UniProtEquilibrative nucleoside transporter 4
Modified residue (large scale data)306PRIDEPhosphoserine
Modified residue (large scale data)310PRIDEPhosphoserine
Glycosylation523UniProtN-linked (GlcNAc...) asparagine

Post-translational modification

N-glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Mainly expressed in brain and skeletal muscle (PubMed:15448143, PubMed:16873718, PubMed:20592246, PubMed:20858707).
In brain, expressed in cerebellum, cerebral cortex, medulla oblongata, occipital pole, frontal and temporal lobes putamen, spinal cord, substancia nigra, hippocampus, caudate nucleus, nucleus accumbens, pons and choroid plexus (PubMed:15448143, PubMed:16873718, PubMed:20858707, PubMed:23255610).
Expressed in heart, in both cardiomyocytes and vascular endothelial cells (PubMed:15448143, PubMed:16873718, PubMed:20858707).
Also expressed in adrenal gland, small intestine, pancreas, kidney, liver, bone marrow, lymph node (PubMed:15448143, PubMed:16873718, PubMed:17018840, PubMed:20858707).
Located in endometrial stroma, where the expression is high in the proliferative phase, decreases during the secretory phase, and is no longer detectable in the menstrual phase (PubMed:17393420).

Gene expression databases

Organism-specific databases

Interaction

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-21Disordered

Domain

Glu-206 is essential for cation selectivity and may function as the charge sensor for cationic substrates.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q7RTT9-1

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
    530
  • Mass (Da)
    58,059
  • Last updated
    2003-12-15 v1
  • Checksum
    3FE5D5ED1D248A13
MGSVGSQRLEEPSVAGTPDPGVVMSFTFDSHQLEEAAEAAQGQGLRARGVPAFTDTTLDEPVPDDRYHAIYFAMLLAGVGFLLPYNSFITDVDYLHHKYPGTSIVFDMSLTYILVALAAVLLNNVLVERLTLHTRITAGYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGCTVQQSSFYGYTGMLPKRYTQGVMTGESTAGVMISLSRILTKLLLPDERASTLIFFLVSVALELLCFLLHLLVRRSRFVLFYTTRPRDSHRGRPGLGRGYGYRVHHDVVAGDVHFEHPAPALAPNESPKDSPAHEVTGSGGAYMRFDVPRPRVQRSWPTFRALLLHRYVVARVIWADMLSIAVTYFITLCLFPGLESEIRHCILGEWLPILIMAVFNLSDFVGKILAALPVDWRGTHLLACSCLRVVFIPLFILCVYPSGMPALRHPAWPCIFSLLMGISNGYFGSVPMILAAGKVSPKQRELAGNTMTVSYMSGLTLGSAVAYCTYSLTRDAHGSCLHASTANGSILAGL

Q7RTT9-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 139-182: GYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGCTV → ASATCGCSSSLGTRPTPSTWPLWAPWPSAA

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
C9IYM7C9IYM7_HUMANSLC29A4163
C9JZA2C9JZA2_HUMANSLC29A4151

Sequence caution

The sequence BAC11612.1 differs from that shown. Reason: Erroneous initiation

Features

Showing features for sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict25in Ref. 2; BAC03836
Sequence conflict41in Ref. 2; BAC03836
Alternative sequenceVSP_032647139-182in isoform 2
Sequence conflict196in Ref. 2; BAC03836
Sequence conflict261in Ref. 2; BAC11612
Sequence conflict301in Ref. 2; BAC03836

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY485959
EMBL· GenBank· DDBJ
AAS65965.1
EMBL· GenBank· DDBJ
mRNA
AK075422
EMBL· GenBank· DDBJ
BAC11612.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK092242
EMBL· GenBank· DDBJ
BAC03836.1
EMBL· GenBank· DDBJ
mRNA
CH471144
EMBL· GenBank· DDBJ
EAW87329.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471144
EMBL· GenBank· DDBJ
EAW87330.1
EMBL· GenBank· DDBJ
Genomic DNA
BC025325
EMBL· GenBank· DDBJ
AAH25325.1
EMBL· GenBank· DDBJ
mRNA
BC047592
EMBL· GenBank· DDBJ
AAH47592.1
EMBL· GenBank· DDBJ
mRNA
BK000627
EMBL· GenBank· DDBJ
DAA00308.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp