Q99624 · S38A3_HUMAN

  • Protein
    Sodium-coupled neutral amino acid transporter 3
  • Gene
    SLC38A3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Symporter that cotransports specific neutral amino acids and sodium ions, coupled to an H+ antiporter activity (PubMed:10823827).
Mainly participates in the glutamate-GABA-glutamine cycle in brain where it transports L-glutamine from astrocytes in the intercellular space for the replenishment of both neurotransmitters glutamate and gamma-aminobutyric acid (GABA) in neurons and also functions as the major influx transporter in ganglion cells mediating the uptake of glutamine (By similarity).
The transport activity is specific for L-glutamine, L-histidine and L-asparagine (PubMed:10823827).
The transport is electroneutral coupled to the cotransport of 1 Na+ and the antiport of 1 H+ (By similarity).
The transport is pH dependent, saturable, Li+ tolerant and functions in both direction depending on the concentration gradients of its substrates and cotransported ions (PubMed:10823827).
Also mediates an amino acid-gated H+ conductance that is not stoichiometrically coupled to the amino acid transport but which influences the ionic gradients that drive the amino acid transport (By similarity).
In addition, may play a role in nitrogen metabolism, amino acid homeostasis, glucose metabolism and renal ammoniagenesis (By similarity).

Caution

PMID:10823827 shows that the transport process is electrogenic with a Na+:L-glutamine stoichiometry of 2:1, contrary to the conclusions of Chaudhry et al (PMID:10619430) who finds that the transport is electroneutral with a Na+:L-glutamine stoichiometry of 1:1. Chaudhry et al (PMID:11742981) shows that this electrogenic transport describes by Fei et al (PMID:10823827) would correspond to an amino acid-gated H+ conductance that is not stoichiometrically coupled to the amino acid transport but which influences the ionic gradients that drive the amino acid transport (By similarity).

Catalytic activity

  • H+(in) + L-glutamine(out) + Na+(out) = H+(out) + L-glutamine(in) + Na+(in)
    This reaction proceeds in the forward
    and the backward
    directions.
  • H+(in) + L-asparagine(out) + Na+(out) = H+(out) + L-asparagine(in) + Na+(in)
    This reaction proceeds in the forward
    and the backward
    directions.
  • H+(in) + L-histidine(out) + Na+(out) = H+(out) + L-histidine(in) + Na+(in)
    This reaction proceeds in the forward
    and the backward
    directions.

Features

Showing features for site.

TypeIDPosition(s)Description
Site77Modulates L-glutamine-induced conductances and Na+ binding

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentplasma membrane
Molecular Functionamino acid transmembrane transporter activity
Molecular FunctionL-alanine transmembrane transporter activity
Molecular FunctionL-asparagine transmembrane transporter activity
Molecular FunctionL-asparagine, sodium:proton antiporter activity
Molecular FunctionL-glutamine transmembrane transporter activity
Molecular FunctionL-glutamine, sodium:proton antiporter activity
Molecular FunctionL-histidine transmembrane transporter activity
Molecular FunctionL-histidine, sodium:proton antiporter activity
Molecular Functionneutral L-amino acid:sodium symporter activity
Biological Processamino acid transmembrane transport
Biological Processamino acid transport
Biological Processasparagine transport
Biological Processcellular response to potassium ion starvation
Biological Processfemale pregnancy
Biological Processglutamine secretion
Biological Processglutamine transport
Biological Processhistidine transport
Biological Processintracellular amino acid homeostasis
Biological ProcessL-alanine transport
Biological ProcessL-asparagine import across plasma membrane
Biological ProcessL-glutamine import across plasma membrane
Biological ProcessL-histidine import across plasma membrane
Biological ProcessL-histidine transport
Biological Processpositive regulation of glutamine transport
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processtransport across blood-brain barrier

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Sodium-coupled neutral amino acid transporter 3
  • Alternative names
    • N-system amino acid transporter 1
    • Na(+)-coupled neutral amino acid transporter 3
    • Solute carrier family 38 member 3
    • System N amino acid transporter 1

Gene names

    • Name
      SLC38A3
    • Synonyms
      G17, NAT1, SN1
      , SNAT3

Organism names

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

Accessions

  • Primary accession
    Q99624
  • Secondary accessions
    • B2R8Q0
    • Q6IB34

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Note: The localization appears to be basolateral in the plasma membrane of hepatocytes surrounding the central vein. Localized at the cerebrospinal fluid (CSF)-facing membrane of the choroid plexus epithelial cells. In astrocytes, the localization at cell membrane is decreased by ammonia through the PKC signaling. Expressed in both luminal and abluminal plasma membranes of larger microvessels and blood brain barrier (BBB) capillaries (By similarity).
Restricted to the basolateral membranes of S3 segment cells of the proximal tubules (By similarity).

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane83-103Helical
Transmembrane106-126Helical
Transmembrane144-164Helical
Transmembrane187-207Helical
Transmembrane213-233Helical
Transmembrane324-344Helical
Transmembrane366-386Helical
Transmembrane408-428Helical
Transmembrane431-451Helical
Transmembrane471-491Helical

Keywords

Disease & Variants

Involvement in disease

Developmental and epileptic encephalopathy 102 (DEE102)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE102 is an autosomal recessive form characterized by onset of variable types of seizures in infancy.
  • See also
    MIM:619881
Natural variants in DEE102
Variant IDPosition(s)ChangeDescription
VAR_087292208R>Gin DEE102; uncertain significance
VAR_087293296A>Tin DEE102; uncertain significance; dbSNP:rs772451600
VAR_087294350-504missingin DEE102
VAR_087295375T>Pin DEE102; dbSNP:rs2109158872
VAR_087296387P>Qin DEE102; uncertain significance; dbSNP:rs1559756568
VAR_087297404-504missingin DEE102

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_087292208in DEE102; uncertain significance
Natural variantVAR_087293296in DEE102; uncertain significance; dbSNP:rs772451600
Natural variantVAR_087294350-504in DEE102
Natural variantVAR_087295375in DEE102; dbSNP:rs2109158872
Natural variantVAR_087296387in DEE102; uncertain significance; dbSNP:rs1559756568
Natural variantVAR_087297404-504in DEE102

Variants

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

The viewer provides 471 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, modified residue (large scale data), glycosylation, disulfide bond.

TypeIDPosition(s)SourceDescription
ChainPRO_00000938281-504UniProtSodium-coupled neutral amino acid transporter 3
Modified residue (large scale data)52PRIDEPhosphoserine
Modified residue (large scale data)54PRIDEPhosphoserine
Glycosylation74UniProtN-linked (GlcNAc...) asparagine
Disulfide bond240↔275UniProt
Glycosylation247UniProtN-linked (GlcNAc...) asparagine
Glycosylation248UniProtN-linked (GlcNAc...) asparagine
Glycosylation252UniProtN-linked (GlcNAc...) asparagine
Glycosylation323UniProtN-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    504
  • Mass (Da)
    55,773
  • Last updated
    1997-05-01 v1
  • Checksum
    86E7D205C6001C60
MEAPLQTEMVELVPNGKHSEGLLPVITPMAGNQRVEDPARSCMEGKSFLQKSPSKEPHFTDFEGKTSFGMSVFNLSNAIMGSGILGLAYAMANTGIILFLFLLTAVALLSSYSIHLLLKSSGVVGIRAYEQLGYRAFGTPGKLAAALAITLQNIGAMSSYLYIIKSELPLVIQTFLNLEEKTSDWYMNGNYLVILVSVTIILPLALMRQLGYLGYSSGFSLSCMVFFLIAVIYKKFHVPCPLPPNFNNTTGNFSHVEIVKEKVQLQVEPEASAFCTPSYFTLNSQTAYTIPIMAFAFVCHPEVLPIYTELKDPSKKKMQHISNLSIAVMYIMYFLAALFGYLTFYNGVESELLHTYSKVDPFDVLILCVRVAVLTAVTLTVPIVLFPVRRAIQQMLFPNQEFSWLRHVLIAVGLLTCINLLVIFAPNILGIFGVIGATSAPFLIFIFPAIFYFRIMPTEKEPARSTPKILALCFAMLGFLLMTMSLSFIIIDWASGTSRHGGNH

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A087X175A0A087X175_HUMANSLC38A3104
A0A087X1Q4A0A087X1Q4_HUMANSLC38A399
A0A087WVW8A0A087WVW8_HUMANSLC38A396
A0A087WWS5A0A087WWS5_HUMANSLC38A3216

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict12in Ref. 3; CAG33251

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF244548
EMBL· GenBank· DDBJ
AAG15313.1
EMBL· GenBank· DDBJ
mRNA
U49082
EMBL· GenBank· DDBJ
AAB47236.1
EMBL· GenBank· DDBJ
mRNA
CR456970
EMBL· GenBank· DDBJ
CAG33251.1
EMBL· GenBank· DDBJ
mRNA
AK313461
EMBL· GenBank· DDBJ
BAG36247.1
EMBL· GenBank· DDBJ
mRNA
BX537382
EMBL· GenBank· DDBJ
CAD97624.1
EMBL· GenBank· DDBJ
mRNA
AC002077
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471055
EMBL· GenBank· DDBJ
EAW65050.1
EMBL· GenBank· DDBJ
Genomic DNA
BC042875
EMBL· GenBank· DDBJ
AAH42875.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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