S38A1_MOUSE
ID S38A1_MOUSE Reviewed; 485 AA.
AC Q8K2P7; Q3TNM1; Q3TQ53; Q6NXZ2; Q8BHI3; Q8BXE2; Q99PR1;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Sodium-coupled neutral amino acid transporter 1;
DE AltName: Full=Amino acid transporter A1;
DE AltName: Full=MNat2;
DE AltName: Full=N-system amino acid transporter 2;
DE AltName: Full=Solute carrier family 38 member 1;
DE AltName: Full=System A amino acid transporter 1;
DE AltName: Full=System N amino acid transporter 1;
GN Name=Slc38a1; Synonyms=Nat2, Snat1;
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 [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11325958; DOI=10.1074/jbc.m009003200;
RA Gu S., Roderick H.L., Camacho P., Jiang J.X.;
RT "Characterization of an N-system amino acid transporter expressed in retina
RT and its involvement in glutamine transport.";
RL J. Biol. Chem. 276:24137-24144(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Cerebellum, Diencephalon, Embryo, Embryonic head,
RC Embryonic stem cell, and Head;
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] (ISOFORMS 1 AND 3).
RC STRAIN=CD-1, and FVB/N-3; TISSUE=Mammary tumor, and Neural stem cell;
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 BY BDNF.
RX PubMed=17179157; DOI=10.1074/jbc.m608548200;
RA Burkhalter J., Fiumelli H., Erickson J.D., Martin J.-L.;
RT "A critical role for system A amino acid transport in the regulation of
RT dendritic development by brain-derived neurotrophic factor (BDNF).";
RL J. Biol. Chem. 282:5152-5159(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND THR-11, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 glutamine and sodium ions with a stoichiometry of 1:1. May also
CC transport small zwitterionic and aliphatic amino acids with a lower
CC affinity. May supply glutamatergic and GABAergic neurons with glutamine
CC which is required for the synthesis of the neurotransmitters glutamate
CC and GABA. {ECO:0000269|PubMed:11325958}.
CC -!- ACTIVITY REGULATION: Inhibited by lithium, potassium, choline ions, N-
CC methyl-D-glucamine and 2-methylamino-isobutyric acid (MeAIB).
CC {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2400 uM for L-glutamine (at pH 7.0) {ECO:0000269|PubMed:11325958};
CC KM=890 uM for L-glutamine (at pH 7.5) {ECO:0000269|PubMed:11325958};
CC KM=540 uM for L-glutamine (at pH 8.0) {ECO:0000269|PubMed:11325958};
CC Note=Decrease in pH from 8.0 to 7.0 results in decreased affinity for
CC L-glutamine.;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Note=Restricted to the somatodendritic
CC compartment of neurons. Found in the cellular processes of neurons in
CC the developing brain. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8K2P7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K2P7-2; Sequence=VSP_029307, VSP_029308;
CC Name=3;
CC IsoId=Q8K2P7-3; Sequence=VSP_029305, VSP_029306;
CC -!- TISSUE SPECIFICITY: Specifically expressed in brain and retina (at
CC protein level). Also detected in spleen, small intestine and lung.
CC {ECO:0000269|PubMed:11325958}.
CC -!- INDUCTION: Up-regulated by BDNF. {ECO:0000269|PubMed:17179157}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AF184240; AAG43433.2; -; mRNA.
DR EMBL; AK029189; BAC26341.1; -; mRNA.
DR EMBL; AK034130; BAC28597.1; -; mRNA.
DR EMBL; AK035098; BAC28944.1; -; mRNA.
DR EMBL; AK047459; BAC33064.1; -; mRNA.
DR EMBL; AK049294; BAC33663.1; -; mRNA.
DR EMBL; AK050914; BAC34457.1; -; mRNA.
DR EMBL; AK081724; BAC38310.1; -; mRNA.
DR EMBL; AK162612; BAE36989.1; -; mRNA.
DR EMBL; AK163914; BAE37532.1; -; mRNA.
DR EMBL; AK165188; BAE38067.1; -; mRNA.
DR EMBL; BC030378; AAH30378.1; -; mRNA.
DR EMBL; BC066815; AAH66815.1; -; mRNA.
DR CCDS; CCDS27777.1; -. [Q8K2P7-1]
DR RefSeq; NP_001159928.1; NM_001166456.1. [Q8K2P7-1]
DR RefSeq; NP_001159930.1; NM_001166458.1. [Q8K2P7-1]
DR RefSeq; NP_598847.2; NM_134086.4. [Q8K2P7-1]
DR RefSeq; XP_006520298.1; XM_006520235.3. [Q8K2P7-1]
DR AlphaFoldDB; Q8K2P7; -.
DR SMR; Q8K2P7; -.
DR BioGRID; 222905; 1.
DR STRING; 10090.ENSMUSP00000097833; -.
DR GlyGen; Q8K2P7; 2 sites.
DR iPTMnet; Q8K2P7; -.
DR PhosphoSitePlus; Q8K2P7; -.
DR SwissPalm; Q8K2P7; -.
DR EPD; Q8K2P7; -.
DR MaxQB; Q8K2P7; -.
DR PaxDb; Q8K2P7; -.
DR PeptideAtlas; Q8K2P7; -.
DR PRIDE; Q8K2P7; -.
DR ProteomicsDB; 256568; -. [Q8K2P7-1]
DR ProteomicsDB; 256569; -. [Q8K2P7-2]
DR ProteomicsDB; 256570; -. [Q8K2P7-3]
DR ABCD; Q8K2P7; 2 sequenced antibodies.
DR Antibodypedia; 7400; 199 antibodies from 29 providers.
DR DNASU; 105727; -.
DR Ensembl; ENSMUST00000088452; ENSMUSP00000085799; ENSMUSG00000023169. [Q8K2P7-1]
DR Ensembl; ENSMUST00000088454; ENSMUSP00000085801; ENSMUSG00000023169. [Q8K2P7-1]
DR Ensembl; ENSMUST00000100262; ENSMUSP00000097833; ENSMUSG00000023169. [Q8K2P7-1]
DR Ensembl; ENSMUST00000230767; ENSMUSP00000155160; ENSMUSG00000023169. [Q8K2P7-3]
DR GeneID; 105727; -.
DR KEGG; mmu:105727; -.
DR UCSC; uc007xkh.2; mouse. [Q8K2P7-1]
DR UCSC; uc007xkk.2; mouse. [Q8K2P7-2]
DR UCSC; uc007xkl.2; mouse. [Q8K2P7-3]
DR CTD; 81539; -.
DR MGI; MGI:2145895; Slc38a1.
DR VEuPathDB; HostDB:ENSMUSG00000023169; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000160716; -.
DR HOGENOM; CLU_009020_0_2_1; -.
DR InParanoid; Q8K2P7; -.
DR OMA; LTQRIWA; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q8K2P7; -.
DR TreeFam; TF328787; -.
DR Reactome; R-MMU-210455; Astrocytic Glutamate-Glutamine Uptake And Metabolism.
DR Reactome; R-MMU-352230; Amino acid transport across the plasma membrane.
DR BioGRID-ORCS; 105727; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Slc38a1; mouse.
DR PRO; PR:Q8K2P7; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K2P7; protein.
DR Bgee; ENSMUSG00000023169; Expressed in placenta labyrinth and 252 other tissues.
DR Genevisible; Q8K2P7; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098591; C:external side of apical plasma membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; IDA:MGI.
DR GO; GO:0005295; F:neutral amino acid:sodium symporter activity; ISO:MGI.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0006868; P:glutamine transport; IDA:MGI.
DR GO; GO:1902475; P:L-alpha-amino acid transmembrane transport; ISO:MGI.
DR GO; GO:0015804; P:neutral amino acid transport; ISO:MGI.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amino-acid transport; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..485
FT /note="Sodium-coupled neutral amino acid transporter 1"
FT /id="PRO_0000310476"
FT TOPO_DOM 1..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..112
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..348
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 413..414
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..485
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 11
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT MOD_RES 54
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2H9"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 245..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 67..72
FT /note="IPGTTS -> VSIICM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029305"
FT VAR_SEQ 73..485
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029306"
FT VAR_SEQ 333..344
FT /note="EKVQSDLLHKYQ -> GKLLPLAMPICT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029307"
FT VAR_SEQ 345..485
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029308"
FT CONFLICT 48
FT /note="E -> G (in Ref. 2; BAE38067)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="P -> H (in Ref. 2; BAC33064)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="V -> A (in Ref. 1; AAG43433)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="V -> A (in Ref. 1; AAG43433)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 485 AA; 53795 MW; 1171E1458818977C CRC64;
MMHFKSGLEL TELQNMTVPE DDNVSNDSND FTEVENGQIN SKFISDRESR RSLTNSHLEK
RKCDEYIPGT TSLGMSVFNL SNAIMGSGIL GLAFALANTG ILLFLILLTS VTLLSIYSIN
LLLICSKETG CMVYEKLGEQ VFGTTGKLVI FGATSLQNTG AMLSYLFIVK NELPSAIKSL
MGEEDAFSAW YVDGRVLVVM VTFGIILPLC LLKNLGYLGY TSGFSLSCMM FFLIVVIYKK
FQTPCMSVEQ NSTVSANVTD ACTPKYVTFN SKTVYALPTI AFAFVCHPSV LPIYSELKDR
SQKKMQMVSN ISFFAMFVMY FLTAIFGYLT FYEKVQSDLL HKYQSTGDIL ILTVRLAVIV
AVILTVPVLF FTVRSSLFEL AKKTKFHLCR HVLVTIILLI IINLLVIFIP SMKDIFGVVG
VTSANMLIFI LPSSLYLKIT NQDGDKGTQR IWAALFLGLG VLFSLISIPL VIYDWACSSG
TDEGH
