S38A2_MOUSE
ID S38A2_MOUSE Reviewed; 504 AA.
AC Q8CFE6; Q3TEX3; Q6PFR1; Q6ZPS7; Q810U9; Q8CC66; Q8CD21;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 126.
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, Kiaa1382, Sat2, Snat2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Epididymis, Kidney, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INDUCTION.
RX PubMed=14623874; DOI=10.1074/jbc.m310483200;
RA Palii S.S., Chen H., Kilberg M.S.;
RT "Transcriptional control of the human sodium-coupled neutral amino acid
RT transporter system A gene by amino acid availability is mediated by an
RT intronic element.";
RL J. Biol. Chem. 279:3463-3471(2004).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12971909; DOI=10.1016/s0197-0186(03)00123-2;
RA Dolinska M., Zablocka B., Sonnewald U., Albrecht J.;
RT "Glutamine uptake and expression of mRNA's of glutamine transporting
RT proteins in mouse cerebellar and cerebral cortical astrocytes and
RT neurons.";
RL Neurochem. Int. 44:75-81(2004).
RN [6]
RP FUNCTION.
RX PubMed=16365304; DOI=10.1073/pnas.0504468103;
RA Constancia M., Angiolini E., Sandovici I., Smith P., Smith R., Kelsey G.,
RA Dean W., Ferguson-Smith A., Sibley C.P., Reik W., Fowden A.;
RT "Adaptation of nutrient supply to fetal demand in the mouse involves
RT interaction between the Igf2 gene and placental transporter systems.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:19219-19224(2005).
RN [7]
RP SUBCELLULAR LOCATION, AND UBIQUITINATION BY NEDD4L.
RX PubMed=17003038; DOI=10.1074/jbc.m606577200;
RA Hatanaka T., Hatanaka Y., Setou M.;
RT "Regulation of amino acid transporter ATA2 by ubiquitin ligase Nedd4-2.";
RL J. Biol. Chem. 281:35922-35930(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=17050538; DOI=10.1074/jbc.m604534200;
RA Hatanaka T., Hatanaka Y., Tsuchida J., Ganapathy V., Setou M.;
RT "Amino acid transporter ATA2 is stored at the trans-Golgi network and
RT released by insulin stimulus in adipocytes.";
RL J. Biol. Chem. 281:39273-39284(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:16365304}.
CC -!- ACTIVITY REGULATION: Inhibited by N-methyl-D-glucamine and choline.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17003038,
CC ECO:0000269|PubMed:17050538}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17003038, ECO:0000269|PubMed:17050538}.
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. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in cerebral and cerebellar astrocytes and
CC neurons. {ECO:0000269|PubMed:12971909}.
CC -!- INDUCTION: Up-regulated upon amino acid deprivation.
CC {ECO:0000269|PubMed:14623874}.
CC -!- PTM: Polyubiquitination by NEDD4L regulates the degradation and the
CC activity of SLC38A2. {ECO:0000269|PubMed:17003038}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98152.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK129342; BAC98152.1; ALT_INIT; mRNA.
DR EMBL; AK031615; BAC27479.1; -; mRNA.
DR EMBL; AK033812; BAC28483.1; -; mRNA.
DR EMBL; AK169378; BAE41125.1; -; mRNA.
DR EMBL; BC041108; AAH41108.1; -; mRNA.
DR EMBL; BC048178; AAH48178.1; -; mRNA.
DR EMBL; BC049271; AAH49271.1; -; mRNA.
DR EMBL; BC057454; AAH57454.1; -; mRNA.
DR CCDS; CCDS27778.1; -.
DR RefSeq; NP_780330.2; NM_175121.3.
DR AlphaFoldDB; Q8CFE6; -.
DR SMR; Q8CFE6; -.
DR BioGRID; 212424; 1.
DR IntAct; Q8CFE6; 1.
DR MINT; Q8CFE6; -.
DR STRING; 10090.ENSMUSP00000023099; -.
DR GlyGen; Q8CFE6; 2 sites.
DR iPTMnet; Q8CFE6; -.
DR PhosphoSitePlus; Q8CFE6; -.
DR SwissPalm; Q8CFE6; -.
DR EPD; Q8CFE6; -.
DR MaxQB; Q8CFE6; -.
DR PaxDb; Q8CFE6; -.
DR PeptideAtlas; Q8CFE6; -.
DR PRIDE; Q8CFE6; -.
DR ProteomicsDB; 256571; -.
DR Antibodypedia; 13370; 139 antibodies from 23 providers.
DR DNASU; 67760; -.
DR Ensembl; ENSMUST00000023099; ENSMUSP00000023099; ENSMUSG00000022462.
DR GeneID; 67760; -.
DR KEGG; mmu:67760; -.
DR UCSC; uc007xkm.1; mouse.
DR CTD; 54407; -.
DR MGI; MGI:1915010; Slc38a2.
DR VEuPathDB; HostDB:ENSMUSG00000022462; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000155486; -.
DR HOGENOM; CLU_009020_0_1_1; -.
DR InParanoid; Q8CFE6; -.
DR OMA; QFWITAF; -.
DR OrthoDB; 1109791at2759; -.
DR PhylomeDB; Q8CFE6; -.
DR TreeFam; TF328787; -.
DR Reactome; R-MMU-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-MMU-352230; Amino acid transport across the plasma membrane.
DR BioGRID-ORCS; 67760; 23 hits in 76 CRISPR screens.
DR ChiTaRS; Slc38a2; mouse.
DR PRO; PR:Q8CFE6; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8CFE6; protein.
DR Bgee; ENSMUSG00000022462; Expressed in ureteric bud tip and 273 other tissues.
DR Genevisible; Q8CFE6; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005903; C:brush border; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:MGI.
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:UniProtKB.
DR GO; GO:0015194; F:L-serine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005295; F:neutral amino acid:sodium symporter activity; ISO:MGI.
DR GO; GO:0032328; P:alanine transport; ISO:MGI.
DR GO; GO:0003333; P:amino acid transmembrane transport; ISO:MGI.
DR GO; GO:0006865; P:amino acid transport; IDA:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:1903841; P:cellular response to arsenite(3-); ISO:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0006868; P:glutamine transport; IDA:UniProtKB.
DR GO; GO:0031460; P:glycine betaine transport; ISO:MGI.
DR GO; GO:0015825; P:L-serine transport; ISO:MGI.
DR GO; GO:0015804; P:neutral amino acid transport; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISO:MGI.
DR GO; GO:0080135; P:regulation of cellular response to stress; ISO:MGI.
DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
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_0000311370"
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..289
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 311..326
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..347
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 348..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..433
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..471
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 472..492
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..504
FT /note="Extracellular"
FT /evidence="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 MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QD8"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QD8"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
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..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 245
FT /note="C -> R (in Ref. 2; BAC27479)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 55503 MW; E69A497E350B5AEF CRC64;
MKKTEMGRFN ISPDEDSSSY SSNSDFNYSY PTKQAALKSH YADVDPENQN FLLESNLGKK
KYETDFHPGT TSFGMSVFNL SNAIVGSGIL GLSYAMANTG IALFIILLTF VSIFSLYSVH
LLLKTANEGG SLLYEQLGHK AYGLAGKLAA SGSITMQNIG AMSSYLFIVK YELPLVIKAL
MNIEDTNGLW YLNGDYLVLL VSLVLILPLS LLRNLGYLGY TSGLSLLCMI FFLIVVICKK
FQIPCPVEAA LVANETVNGT FTQAALALAF NSTADDACRP RYFIFNSQTV YAVPILTFSF
VCHPAVLPIY EELKSRSRRR MMNVSKISFF AMFLMYLLAA LFGYLTFYGH VESELLHTYS
EIVGTDILLL VVRLAVLVAV TLTVPVVIFP IRSSVTHLLC PTKEFSWLRH SIITVTILSF
TNLLVIFVPT IRDIFGFIGA SAAAMLIFIL PSAFYIKLVK KEPMRSVQKI GALCFLLSGI
VVMIGSMGLI VLDWVHDASA AGGH
