ID S38A2_PANPA Reviewed; 506 AA. AC A1YG32; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 1. DT 27-MAR-2024, entry version 67. DE RecName: Full=Sodium-coupled neutral amino acid symporter 2 {ECO:0000250|UniProtKB:Q96QD8}; DE AltName: Full=Amino acid transporter A2; 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 Pan paniscus (Pygmy chimpanzee) (Bonobo). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pan. OX NCBI_TaxID=9597; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Nickel G.C., Tefft D.L., Trevarthen K., Funt J., Adams M.D.; RT "Positive selection in transcription factor genes on the human lineage."; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Symporter that cotransports neutral amino acids and sodium CC ions from the extraccellular to the intracellular side of the cell CC membrane. The trasnport 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ977211; ABM54257.1; -; Genomic_DNA. DR RefSeq; XP_003825811.1; XM_003825763.2. DR AlphaFoldDB; A1YG32; -. DR SMR; A1YG32; -. DR STRING; 9597.ENSPPAP00000015317; -. DR GlyCosmos; A1YG32; 2 sites, No reported glycans. DR Ensembl; ENSPPAT00000038007.1; ENSPPAP00000015317.1; ENSPPAG00000030800.1. DR GeneID; 100975486; -. DR KEGG; pps:100975486; -. DR CTD; 54407; -. DR eggNOG; KOG1305; Eukaryota. DR GeneTree; ENSGT00940000155486; -. DR OMA; SHYADMD; -. DR OrthoDB; 935269at2759; -. DR Proteomes; UP000240080; Chromosome 12. DR Bgee; ENSPPAG00000030800; Expressed in liver and 6 other cell types or tissues. 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: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: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: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 TRANSPORTER 2; 1. DR Pfam; PF01490; Aa_trans; 1. PE 3: Inferred from homology; 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_0000311371" 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:0000250|UniProtKB:Q9JHE5, 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" SQ SEQUENCE 506 AA; 56053 MW; 743D09A3C5DAF4A3 CRC64; MKKAEMGRFN ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN FLLESNLGKK KYETEFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH LLLKTANEGG SLLYEQLGYK AFGLVGKLAA SGSITMQNIG AMSSYLFIVK YELPLVIQAL TNIEDKTGLW YLNGNYLVLL VSLVVILPLS LFRNLGYLGY TSGLSLLCMV FFLIVVICKK FQVPCPVEAA LIINETINTT LTQPTALVPA LSHNVTENDS CRPHYFIFNS QTVYAVPILI FSFVCHPAVL PIYEELKDRS RRRMMNVSKI SFFAMFLMYL LAALFGYLTF YEHVESELLH TYSSILGTDI LLLIVRLAVL MAVTLTVPVV IFPIRSSVTH LLCASKDFSW WRHSLITVSI LAFTNLLVIF VPTIRDIFGF IGASAASMLI FILPSAFYIK LVKKEPMKSV QKIGALFFLL SGVLVMTGSM ALIVLDWVHN APGGGH //