Q99624 · S38A3_HUMAN
- ProteinSodium-coupled neutral amino acid transporter 3
- GeneSLC38A3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids504 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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)CHEBI:15378
+ L-glutamine (out)CHEBI:58359+ Na+ (out)CHEBI:29101= H+ (out)CHEBI:15378+ L-glutamine (in)CHEBI:58359+ Na+ (in)CHEBI:29101 - 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 77 | Modulates L-glutamine-induced conductances and Na+ binding | ||||
Sequence: N |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSodium-coupled neutral amino acid transporter 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ99624
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
Restricted to the basolateral membranes of S3 segment cells of the proximal tubules (By similarity).
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 83-103 | Helical | ||||
Sequence: GILGLAYAMANTGIILFLFLL | ||||||
Transmembrane | 106-126 | Helical | ||||
Sequence: VALLSSYSIHLLLKSSGVVGI | ||||||
Transmembrane | 144-164 | Helical | ||||
Sequence: AAALAITLQNIGAMSSYLYII | ||||||
Transmembrane | 187-207 | Helical | ||||
Sequence: MNGNYLVILVSVTIILPLALM | ||||||
Transmembrane | 213-233 | Helical | ||||
Sequence: LGYSSGFSLSCMVFFLIAVIY | ||||||
Transmembrane | 324-344 | Helical | ||||
Sequence: LSIAVMYIMYFLAALFGYLTF | ||||||
Transmembrane | 366-386 | Helical | ||||
Sequence: ILCVRVAVLTAVTLTVPIVLF | ||||||
Transmembrane | 408-428 | Helical | ||||
Sequence: VLIAVGLLTCINLLVIFAPNI | ||||||
Transmembrane | 431-451 | Helical | ||||
Sequence: IFGVIGATSAPFLIFIFPAIF | ||||||
Transmembrane | 471-491 | Helical | ||||
Sequence: ALCFAMLGFLLMTMSLSFIII |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Developmental and epileptic encephalopathy 102 (DEE102)
- Note
- DescriptionA 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 alsoMIM:619881
Natural variants in DEE102
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087292 | 208 | R>G | in DEE102; uncertain significance | |
VAR_087293 | 296 | A>T | in DEE102; uncertain significance; dbSNP:rs772451600 | |
VAR_087294 | 350-504 | missing | in DEE102 | |
VAR_087295 | 375 | T>P | in DEE102; dbSNP:rs2109158872 | |
VAR_087296 | 387 | P>Q | in DEE102; uncertain significance; dbSNP:rs1559756568 | |
VAR_087297 | 404-504 | missing | in DEE102 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087292 | 208 | in DEE102; uncertain significance | |||
Sequence: R → G | ||||||
Natural variant | VAR_087293 | 296 | in DEE102; uncertain significance; dbSNP:rs772451600 | |||
Sequence: A → T | ||||||
Natural variant | VAR_087294 | 350-504 | in DEE102 | |||
Sequence: Missing | ||||||
Natural variant | VAR_087295 | 375 | in DEE102; dbSNP:rs2109158872 | |||
Sequence: T → P | ||||||
Natural variant | VAR_087296 | 387 | in DEE102; uncertain significance; dbSNP:rs1559756568 | |||
Sequence: P → Q | ||||||
Natural variant | VAR_087297 | 404-504 | in DEE102 | |||
Sequence: Missing |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), glycosylation, disulfide bond.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000093828 | 1-504 | UniProt | Sodium-coupled neutral amino acid transporter 3 | |||
Sequence: MEAPLQTEMVELVPNGKHSEGLLPVITPMAGNQRVEDPARSCMEGKSFLQKSPSKEPHFTDFEGKTSFGMSVFNLSNAIMGSGILGLAYAMANTGIILFLFLLTAVALLSSYSIHLLLKSSGVVGIRAYEQLGYRAFGTPGKLAAALAITLQNIGAMSSYLYIIKSELPLVIQTFLNLEEKTSDWYMNGNYLVILVSVTIILPLALMRQLGYLGYSSGFSLSCMVFFLIAVIYKKFHVPCPLPPNFNNTTGNFSHVEIVKEKVQLQVEPEASAFCTPSYFTLNSQTAYTIPIMAFAFVCHPEVLPIYTELKDPSKKKMQHISNLSIAVMYIMYFLAALFGYLTFYNGVESELLHTYSKVDPFDVLILCVRVAVLTAVTLTVPIVLFPVRRAIQQMLFPNQEFSWLRHVLIAVGLLTCINLLVIFAPNILGIFGVIGATSAPFLIFIFPAIFYFRIMPTEKEPARSTPKILALCFAMLGFLLMTMSLSFIIIDWASGTSRHGGNH | |||||||
Modified residue (large scale data) | 52 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 54 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Glycosylation | 74 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 240↔275 | UniProt | |||||
Sequence: CPLPPNFNNTTGNFSHVEIVKEKVQLQVEPEASAFC | |||||||
Glycosylation | 247 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 248 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 252 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 323 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Sequence
- Sequence statusComplete
- Length504
- Mass (Da)55,773
- Last updated1997-05-01 v1
- Checksum86E7D205C6001C60
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087X175 | A0A087X175_HUMAN | SLC38A3 | 104 | ||
A0A087X1Q4 | A0A087X1Q4_HUMAN | SLC38A3 | 99 | ||
A0A087WVW8 | A0A087WVW8_HUMAN | SLC38A3 | 96 | ||
A0A087WWS5 | A0A087WWS5_HUMAN | SLC38A3 | 216 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 12 | in Ref. 3; CAG33251 | ||||
Sequence: L → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |