ID   S38A2_BOVIN             Reviewed;         506 AA.
AC   A2VE31; Q95M41;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-MAR-2007, sequence version 1.
DT   02-SEP-2026, entry version 99.
DE   RecName: Full=Sodium-coupled neutral amino acid symporter 2 {ECO:0000250|UniProtKB:Q96QD8};
DE   AltName: Full=Amino acid transporter A2;
DE   AltName: Full=Protein 40-9-1;
DE   AltName: Full=Solute carrier family 38 member 2;
DE   AltName: Full=System A amino acid transporter 2;
DE   AltName: Full=System A transporter 1;
DE   AltName: Full=System N amino acid transporter 2;
GN   Name=SLC38A2 {ECO:0000250|UniProtKB:Q96QD8}; Synonyms=SNAT2;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal skin;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 223-506.
RA   Schmidt T.;
RL   Thesis (2001), University of Goettingen, Germany.
CC   -!- FUNCTION: Symporter that cotransports neutral amino acids and sodium
CC       ions from the extracellular to the intracellular side of the cell
CC       membrane. The transport is pH-sensitive, Li(+)-intolerant,
CC       electrogenic, driven by the Na(+) electrochemical gradient and
CC       cotransports of neutral amino acids and sodium ions with a
CC       stoichiometry of 1:1. May function in the transport of amino acids at
CC       the blood-brain barrier (By similarity). May function in the transport
CC       of amino acids in the supply of maternal nutrients to the fetus through
CC       the placenta (By similarity). Maintains a key metabolic
CC       glutamine/glutamate balance underpinning retrograde signaling by
CC       dendritic release of the neurotransmitter glutamate (By similarity).
CC       Transports L-proline in differentiating osteoblasts for the efficient
CC       synthesis of proline-enriched proteins and provides proline essential
CC       for osteoblast differentiation and bone formation during bone
CC       development (By similarity). {ECO:0000250|UniProtKB:Q8CFE6,
CC       ECO:0000250|UniProtKB:Q9JHE5}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29285;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:68228, ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68230;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:29575, ChEBI:CHEBI:29101, ChEBI:CHEBI:33384;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29577;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:28967, ChEBI:CHEBI:29101, ChEBI:CHEBI:60039;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28969;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-methionine(in) + Na(+)(in) = L-methionine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:68240, ChEBI:CHEBI:29101, ChEBI:CHEBI:57844;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68242;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-histidine(in) + Na(+)(in) = L-histidine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:71583, ChEBI:CHEBI:29101, ChEBI:CHEBI:57595;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71585;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-asparagine(in) + Na(+)(in) = L-asparagine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:71383, ChEBI:CHEBI:29101, ChEBI:CHEBI:58048;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71385;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:68236, ChEBI:CHEBI:29101, ChEBI:CHEBI:58359;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68238;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-threonine(in) + Na(+)(in) = L-threonine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:69999, ChEBI:CHEBI:29101, ChEBI:CHEBI:57926;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70001;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:29263, ChEBI:CHEBI:29101, ChEBI:CHEBI:57427;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29265;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-phenylalanine(in) + Na(+)(in) = L-phenylalanine(out) +
CC         Na(+)(out); Xref=Rhea:RHEA:68244, ChEBI:CHEBI:29101,
CC         ChEBI:CHEBI:58095; Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68246;
CC         Evidence={ECO:0000250|UniProtKB:Q9JHE5};
CC   -!- ACTIVITY REGULATION: Inhibited by N-methyl-D-glucamine. Inhibited by
CC       choline. Allosteric regulation of sodium ions binding by pH.
CC       {ECO:0000250|UniProtKB:Q9JHE5}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9JHE5};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9JHE5}.
CC       Note=Insulin promotes recruitment to the plasma membrane from a pool
CC       localized in the trans-Golgi network or endosomes. Enriched in the
CC       somatodendritic compartment of neurons, it is also detected at the
CC       axonal shaft but excluded from the nerve terminal.
CC       {ECO:0000250|UniProtKB:Q9JHE5}.
CC   -!- DOMAIN: The extracellular C-terminal domain controls the voltage
CC       dependence for amino acid transports activity.
CC       {ECO:0000250|UniProtKB:Q9JHE5}.
CC   -!- PTM: Polyubiquitination by NEDD4L regulates the degradation and the
CC       activity of SLC38A2. {ECO:0000250|UniProtKB:Q8CFE6}.
CC   -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC       {ECO:0000305}.
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DR   EMBL; BC133547; AAI33548.1; -; mRNA.
DR   EMBL; AJ344100; CAC51429.1; -; mRNA.
DR   RefSeq; NP_001075893.1; NM_001082424.1.
DR   AlphaFoldDB; A2VE31; -.
DR   SMR; A2VE31; -.
DR   FunCoup; A2VE31; 965.
DR   STRING; 9913.ENSBTAP00000014749; -.
DR   GlyCosmos; A2VE31; 2 sites, No reported glycans.
DR   GlyGen; A2VE31; 2 sites.
DR   PaxDb; 9913-ENSBTAP00000014749; -.
DR   Ensembl; ENSBTAT00000014749.7; ENSBTAP00000014749.5; ENSBTAG00000011105.8.
DR   Ensembl; ENSBTAT00085075250; ENSBTAP00085047551; ENSBTAG00085021515.
DR   Ensembl; ENSBTAT00090015406; ENSBTAP00090007456; ENSBTAG00090008194.
DR   GeneID; 338044; -.
DR   KEGG; bta:338044; -.
DR   CTD; 54407; -.
DR   VEuPathDB; HostDB:ENSBTAG00000011105; -.
DR   VGNC; VGNC:34849; SLC38A2.
DR   eggNOG; KOG1305; Eukaryota.
DR   GeneTree; ENSGT00940000155486; -.
DR   HOGENOM; CLU_009020_0_1_1; -.
DR   InParanoid; A2VE31; -.
DR   OMA; DSIHHQR; -.
DR   OrthoDB; 655540at2759; -.
DR   Reactome; R-BTA-210500; Glutamate Neurotransmitter Release Cycle.
DR   Reactome; R-BTA-352230; Amino acid transport across the plasma membrane.
DR   PRO; PR:A2VE31; -.
DR   Proteomes; UP000009136; Chromosome 5.
DR   Bgee; ENSBTAG00000011105; Expressed in spermatocyte and 106 other cell types or tissues.
DR   ExpressionAtlas; A2VE31; baseline.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0015172; F:acidic amino acid transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015655; F:alanine:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0015171; F:amino acid transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0005283; F:amino acid:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0015375; F:glycine:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0140901; F:L-asparagine:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0015186; F:L-glutamine transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0005295; F:neutral L-amino acid:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0005298; F:proline:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0032328; P:alanine transport; ISS:UniProtKB.
DR   GO; GO:0043090; P:amino acid import; ISS:UniProtKB.
DR   GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006865; P:amino acid transport; ISS:UniProtKB.
DR   GO; GO:1903841; P:cellular response to arsenite(3-); IEA:Ensembl.
DR   GO; GO:1903803; P:L-glutamine import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:0006868; P:L-glutamine transport; IBA:GO_Central.
DR   GO; GO:1904271; P:L-proline import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:1903812; P:L-serine import across plasma membrane; ISS:UniProtKB.
DR   GO; GO:0015804; P:neutral amino acid transport; ISS:UniProtKB.
DR   GO; GO:0033120; P:positive regulation of RNA splicing; IEA:Ensembl.
DR   GO; GO:0015824; P:proline transport; ISS:UniProtKB.
DR   GO; GO:0080135; P:regulation of cellular response to stress; IEA:Ensembl.
DR   GO; GO:1903294; P:regulation of glutamate secretion, neurotransmission; ISS:UniProtKB.
DR   InterPro; IPR013057; AA_transpt_TM.
DR   PANTHER; PTHR22950; AMINO ACID TRANSPORTER; 1.
DR   PANTHER; PTHR22950:SF207; SODIUM-COUPLED NEUTRAL AMINO ACID SYMPORTER 2; 1.
DR   Pfam; PF01490; Aa_trans; 1.
PE   2: Evidence at transcript level;
KW   Amino-acid transport; Cell membrane; Disulfide bond; Glycoprotein;
KW   Ion transport; Membrane; Phosphoprotein; Reference proteome; Sodium;
KW   Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation.
FT   CHAIN           1..506
FT                   /note="Sodium-coupled neutral amino acid symporter 2"
FT                   /id="PRO_0000311368"
FT   TOPO_DOM        1..76
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        77..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..102
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        103..123
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        124..158
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        159..177
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        178..188
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        189..209
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        210..217
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        218..238
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        239..292
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        293..313
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        314..329
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        330..350
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        351..371
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        372..392
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        393..413
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        414..434
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        435..436
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TRANSMEM        437..457
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        458..472
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        473..495
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   TOPO_DOM        496..506
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5, ECO:0000255"
FT   REGION          1..96
FT                   /note="Regulates protein turnover upon amino acid
FT                   deprivation"
FT                   /evidence="ECO:0000250"
FT   REGION          1..23
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         82
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5"
FT   BINDING         386
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JHE5"
FT   MOD_RES         12
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96QD8"
FT   MOD_RES         21
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CFE6"
FT   MOD_RES         22
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96QD8"
FT   MOD_RES         55
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96QD8"
FT   CARBOHYD        258
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        245..281
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   CONFLICT        409
FT                   /note="S -> N (in Ref. 2; CAC51429)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   506 AA;  56214 MW;  952C9D7F55E1659F CRC64;
     MKKAEMGRFN ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN FLLESNLGKK
     KYETDFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH
     LLLKTANEGG SLLYEQLGHK AFGMVGKLTA SGSITMQNIG AMSSYLFIVK YELPLVIQAL
     MNIEDTNGLW YLNGDYLVLL VSLVLILPLS LLRNLGYLGY TSGLSLLCMM FFLIVVIFKK
     FQISCPAEIA FLVNETVNSS LTQPATFLPD MGFNRTESDS CQPRYFIFNS QTVYAVPILT
     FSFVCHPAIL PIYEELKGRS RRRMMNVSKI SFFAMFLMYL LAALFGYLTF YGHVESELLH
     TYSSVMETDI LLLIVRLAVL VAVTLTVPVV IFPIRSSITH LLCASKEFSW WRHSVITVSI
     LVFTNLLVIF VPNIRDIFGF IGASAAAMLI FILPSAFYIK LVKKEPMKSV QKIGAMFFLL
     SGIVVMTGSM ALIVLDWVHN APGGGH
//