S38A2_RAT
ID S38A2_RAT Reviewed; 504 AA.
AC Q9JHE5; Q9JI88;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Sodium-coupled neutral amino acid transporter 2;
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; Synonyms=Ata2, Sa1, Sat2, Snat2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Skeletal muscle;
RX PubMed=10747860; DOI=10.1074/jbc.c000205200;
RA Sugawara M., Nakanishi T., Fei Y.-J., Huang W., Ganapathy M.E.,
RA Leibach F.H., Ganapathy V.;
RT "Cloning of an amino acid transporter with functional characteristics and
RT tissue expression pattern identical to that of system A.";
RL J. Biol. Chem. 275:16473-16477(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Cerebellum;
RX PubMed=10811809; DOI=10.1074/jbc.m002965200;
RA Yao D., Mackenzie B., Ming H., Varoqui H., Zhu H., Hediger M.A.,
RA Erickson J.D.;
RT "A novel system A isoform mediating Na+/neutral amino acid cotransport.";
RL J. Biol. Chem. 275:22790-22797(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10859363; DOI=10.1073/pnas.140152797;
RA Reimer R.J., Chaudhry F.A., Gray A.T., Edwards R.H.;
RT "Amino acid transport system A resembles system N in sequence but differs
RT in mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7715-7720(2000).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11311116; DOI=10.1042/bj3550563;
RA Hyde R., Christie G.R., Litherland G.J., Hajduch E., Taylor P.M.,
RA Hundal H.S.;
RT "Subcellular localization and adaptive up-regulation of the system A (SAT2)
RT amino acid transporter in skeletal-muscle cells and adipocytes.";
RL Biochem. J. 355:563-568(2001).
RN [5]
RP INDUCTION BY TGFB1.
RX PubMed=11716780; DOI=10.1042/0264-6021:3600507;
RA Ensenat D., Hassan S., Reyna S.V., Schafer A.I., Durante W.;
RT "Transforming growth factor-beta 1 stimulates vascular smooth muscle cell
RT L-proline transport by inducing system A amino acid transporter 2 (SAT2)
RT gene expression.";
RL Biochem. J. 360:507-512(2001).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=12054432; DOI=10.1016/s0003-9861(02)00006-1;
RA Freeman T.L., Thiele G.M., Tuma D.J., Machu T.K., Mailliard M.E.;
RT "ATA2-mediated amino acid uptake following partial hepatectomy is regulated
RT by redistribution to the plasma membrane.";
RL Arch. Biochem. Biophys. 400:215-222(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11834730; DOI=10.1074/jbc.m108609200;
RA Hyde R., Peyrollier K., Hundal H.S.;
RT "Insulin promotes the cell surface recruitment of the SAT2/ATA2 system A
RT amino acid transporter from an endosomal compartment in skeletal muscle
RT cells.";
RL J. Biol. Chem. 277:13628-13634(2002).
RN [8]
RP FUNCTION.
RX PubMed=11756489; DOI=10.1523/jneurosci.22-01-00062.2002;
RA Chaudhry F.A., Schmitz D., Reimer R.J., Larsson P., Gray A.T., Nicoll R.,
RA Kavanaugh M., Edwards R.H.;
RT "Glutamine uptake by neurons: interaction of protons with system a
RT transporters.";
RL J. Neurosci. 22:62-72(2002).
RN [9]
RP FUNCTION.
RX PubMed=12021389; DOI=10.1124/mol.61.6.1289;
RA Takanaga H., Tokuda N., Ohtsuki S., Hosoya K., Terasaki T.;
RT "ATA2 is predominantly expressed as system A at the blood-brain barrier and
RT acts as brain-to-blood efflux transport for L-proline.";
RL Mol. Pharmacol. 61:1289-1296(2002).
RN [10]
RP FUNCTION, MUTAGENESIS OF HIS-504, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16629640; DOI=10.1042/bj20060026;
RA Baird F.E., Pinilla-Tenas J.J., Ogilvie W.L.J., Ganapathy V., Hundal H.S.,
RA Taylor P.M.;
RT "Evidence for allosteric regulation of pH-sensitive System A (SNAT2) and
RT System N (SNAT5) amino acid transporter activity involving a conserved
RT histidine residue.";
RL Biochem. J. 397:369-375(2006).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16616430; DOI=10.1016/j.neuroscience.2006.02.042;
RA Melone M., Varoqui H., Erickson J.D., Conti F.;
RT "Localization of the Na(+)-coupled neutral amino acid transporter 2 in the
RT cerebral cortex.";
RL Neuroscience 140:281-292(2006).
RN [12]
RP TOPOLOGY, AND INDUCTION.
RX PubMed=17488712; DOI=10.1074/jbc.m611520200;
RA Hyde R., Cwiklinski E.L., MacAulay K., Taylor P.M., Hundal H.S.;
RT "Distinct sensor pathways in the hierarchical control of SNAT2, a putative
RT amino acid transceptor, by amino acid availability.";
RL J. Biol. Chem. 282:19788-19798(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [14]
RP DISULFIDE BOND.
RX PubMed=27355203; DOI=10.1371/journal.pone.0158319;
RA Chen C., Wang J., Cai R., Yuan Y., Guo Z., Grewer C., Zhang Z.;
RT "Identification of a disulfide bridge in sodium-coupled neutral amino acid
RT transporter 2(SNAT2) by chemical modification.";
RL PLoS ONE 11:E0158319-E0158319(2016).
CC -!- FUNCTION: Functions as a sodium-dependent amino acid transporter.
CC Mediates the saturable, pH-sensitive and electrogenic cotransport of
CC neutral amino acids and sodium ions with a stoichiometry of 1:1. May
CC function in the transport of amino acids at the blood-brain barrier and
CC in the supply of maternal nutrients to the fetus through the placenta.
CC {ECO:0000269|PubMed:10747860, ECO:0000269|PubMed:10811809,
CC ECO:0000269|PubMed:10859363, ECO:0000269|PubMed:11756489,
CC ECO:0000269|PubMed:12021389, ECO:0000269|PubMed:16629640}.
CC -!- ACTIVITY REGULATION: Inhibited by N-methyl-D-glucamine and choline.
CC {ECO:0000269|PubMed:10747860, ECO:0000269|PubMed:10811809,
CC ECO:0000269|PubMed:10859363}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.53 mM for alanine (at pH 7.4) {ECO:0000269|PubMed:10747860,
CC ECO:0000269|PubMed:10811809, ECO:0000269|PubMed:10859363,
CC ECO:0000269|PubMed:16629640};
CC KM=1.65 mM for glutamine (at pH 7.4) {ECO:0000269|PubMed:10747860,
CC ECO:0000269|PubMed:10811809, ECO:0000269|PubMed:10859363,
CC ECO:0000269|PubMed:16629640};
CC KM=0.94 mM for serine (at pH 8.0) {ECO:0000269|PubMed:10747860,
CC ECO:0000269|PubMed:10811809, ECO:0000269|PubMed:10859363,
CC ECO:0000269|PubMed:16629640};
CC KM=0.23 mM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.0)
CC {ECO:0000269|PubMed:10747860};
CC KM=0.14 mM for 2-methylamino-isobutyric acid (MeAIB) (at pH 8.0)
CC {ECO:0000269|PubMed:10859363};
CC KM=0.53 mM for 2-methylamino-isobutyric acid (MeAIB) (at pH 7.4)
CC {ECO:0000269|PubMed:10747860, ECO:0000269|PubMed:10811809,
CC ECO:0000269|PubMed:10859363, ECO:0000269|PubMed:16629640};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10859363,
CC ECO:0000269|PubMed:11311116, ECO:0000269|PubMed:11834730,
CC ECO:0000269|PubMed:12054432, ECO:0000269|PubMed:16616430}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10859363,
CC ECO:0000269|PubMed:11311116, ECO:0000269|PubMed:11834730,
CC ECO:0000269|PubMed:12054432, ECO:0000269|PubMed:16616430}. Note=Insulin
CC promotes recruitment to the plasma membrane from a pool localized in
CC the trans-Golgi network or endosomes (By similarity). Enriched in the
CC somatodendritic compartment of neurons, it is also detected at the
CC axonal shaft but excluded from the nerve terminal. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in skeletal muscle and
CC adipose tissue (at protein level). Expressed by glutamatergic and
CC GABAergic neurons together with astrocytes and other non-neuronal cells
CC in the cerebral cortex (at protein level).
CC {ECO:0000269|PubMed:10747860, ECO:0000269|PubMed:10811809,
CC ECO:0000269|PubMed:10859363, ECO:0000269|PubMed:11311116,
CC ECO:0000269|PubMed:16616430}.
CC -!- INDUCTION: Up-regulation upon amino acid deprivation results from both
CC increased transcription and protein stabilization. Up-regulated by
CC TGFB1. {ECO:0000269|PubMed:11311116, ECO:0000269|PubMed:11716780,
CC ECO:0000269|PubMed:17488712}.
CC -!- PTM: Polyubiquitination by NEDD4L regulates the degradation and the
CC activity of SLC38A2. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AF249673; AAF74195.1; -; mRNA.
DR EMBL; AF173682; AAF75589.2; -; mRNA.
DR EMBL; AF273024; AAF81796.1; -; mRNA.
DR RefSeq; NP_851604.1; NM_181090.2.
DR AlphaFoldDB; Q9JHE5; -.
DR SMR; Q9JHE5; -.
DR STRING; 10116.ENSRNOP00000031532; -.
DR TCDB; 2.A.18.6.4; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q9JHE5; 2 sites.
DR iPTMnet; Q9JHE5; -.
DR PhosphoSitePlus; Q9JHE5; -.
DR PaxDb; Q9JHE5; -.
DR PRIDE; Q9JHE5; -.
DR Ensembl; ENSRNOT00000039002; ENSRNOP00000031532; ENSRNOG00000006305.
DR GeneID; 29642; -.
DR KEGG; rno:29642; -.
DR CTD; 54407; -.
DR RGD; 69420; Slc38a2.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000155486; -.
DR HOGENOM; CLU_009020_0_1_1; -.
DR InParanoid; Q9JHE5; -.
DR OMA; QFWITAF; -.
DR OrthoDB; 1109791at2759; -.
DR PhylomeDB; Q9JHE5; -.
DR TreeFam; TF328787; -.
DR Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-RNO-352230; Amino acid transport across the plasma membrane.
DR SABIO-RK; Q9JHE5; -.
DR PRO; PR:Q9JHE5; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000006305; Expressed in esophagus and 19 other tissues.
DR Genevisible; Q9JHE5; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005903; C:brush border; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015194; F:L-serine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005295; F:neutral amino acid:sodium symporter activity; ISO:RGD.
DR GO; GO:0032328; P:alanine transport; IDA:RGD.
DR GO; GO:0003333; P:amino acid transmembrane transport; ISO:RGD.
DR GO; GO:0006865; P:amino acid transport; ISO:RGD.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IEP:RGD.
DR GO; GO:1903841; P:cellular response to arsenite(3-); ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0006868; P:glutamine transport; IDA:ARUK-UCL.
DR GO; GO:0031460; P:glycine betaine transport; IDA:RGD.
DR GO; GO:0015825; P:L-serine transport; IDA:ARUK-UCL.
DR GO; GO:0015804; P:neutral amino acid transport; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISO:RGD.
DR GO; GO:0080135; P:regulation of cellular response to stress; ISO:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein 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..504
FT /note="Sodium-coupled neutral amino acid transporter 2"
FT /id="PRO_0000311372"
FT TOPO_DOM 1..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..102
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..158
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..290
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..311
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 312..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..369
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 391..411
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 433..434
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 494..504
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..96
FT /note="Regulates protein turnover upon amino acid
FT deprivation"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 245..279
FT /evidence="ECO:0000269|PubMed:27355203"
FT MUTAGEN 504
FT /note="H->A: Modifies the transporter pH-sensitivity."
FT /evidence="ECO:0000269|PubMed:16629640"
FT CONFLICT 69
FT /note="G -> S (in Ref. 1; AAF74195)"
FT /evidence="ECO:0000305"
FT CONFLICT 81
FT /note="S -> T (in Ref. 1; AAF74195)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="S -> N (in Ref. 1; AAF74195)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 55554 MW; F53022C07152648C CRC64;
MKKTEMGRFN ISPDEDSSSY SSNGDFNYSY PTKQAALKSH YVDVDPENQN FLLESNLGKK
KYETDFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH
LLLKTANEGG SLLYEQLGHK AYGLAGKLAA SGSITMQNIG AMSSYLFIVK YELPLVIKAL
MNIEDTNGLW YLNGDYLVLL VSFVLILPLS LLRNLGYLGY TSGLSLLCMI FFLIVVICKK
FQIPCPVEVA LMANETVNGT FTQVALAALA SNSTAADTCR PRYFIFNSQT VYAVPILTFS
FVCHPAVLPI YEELKSRSRR RMMNVSKISF FAMFLMYLLA ALFGYLTFYE HVESELLHTY
SAIVGTDILL LVVRLAVLVA VTLTVPVVIF PIRSSVTHLL CPTKEFSWFR HSVITVTILA
FTNLLVIFVP TIRDIFGFIG ASAAAMLIFI LPSAFYIKLV KKEPMRSVQK IGALCFLLSG
VVVMIGSMGL IVLDWVHDAS AGGH
