S38A4_MOUSE
ID S38A4_MOUSE Reviewed; 547 AA.
AC Q8R1S9; Q3TEZ9; Q3TJ89; Q3TPL5; Q8VIE7;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Sodium-coupled neutral amino acid transporter 4;
DE AltName: Full=Amino acid transporter A3;
DE AltName: Full=Na(+)-coupled neutral amino acid transporter 4;
DE AltName: Full=Solute carrier family 38 member 4;
DE AltName: Full=System A amino acid transporter 3;
GN Name=Slc38a4; Synonyms=Ata3, Nat3, Snat4;
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], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=12537539; DOI=10.1042/bj20030049;
RA Gu S., Langlais P., Liu F., Jiang J.X.;
RT "Mouse system-N amino acid transporter, mNAT3, expressed in hepatocytes and
RT regulated by insulin-activated and phosphoinositide 3-kinase-dependent
RT signalling.";
RL Biochem. J. 371:721-731(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Matsuo H., Kanai Y., Kim D.K., Cha S.H., Chairoungdua A., Fukuda J.,
RA Endou H.;
RT "Molecular cloning and characterization of a novel system A amino acid
RT transporter from human liver.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [5]
RP IMPRINTING, AND MISCELLANEOUS.
RX PubMed=18024232; DOI=10.1016/j.modgep.2007.09.005;
RA Kuzmin A., Han Z., Golding M.C., Mann M.R., Latham K.E., Varmuza S.;
RT "The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues.";
RL Gene Expr. Patterns 8:107-116(2008).
RN [6]
RP DISULFIDE BOND, AND MUTAGENESIS OF CYS-18; CYS-232; CYS-249; CYS-321 AND
RP CYS-345.
RX PubMed=23451088; DOI=10.1371/journal.pone.0056792;
RA Padmanabhan Iyer R., Gu S., Nicholson B.J., Jiang J.X.;
RT "Identification of a disulfide bridge important for transport function of
RT SNAT4 neutral amino acid transporter.";
RL PLoS ONE 8:E56792-E56792(2013).
CC -!- FUNCTION: Sodium-dependent amino acid transporter. Mediates
CC electrogenic symport of neutral amino acids and sodium ions. Has a
CC broad specificity, with a preference for Ala, followed by Ser, His,
CC Gly, Cys, Asn, Thr, Pro, Gln and Met. May mediate sodium-independent
CC transport of cationic amino acids, such as Arg and Lys. Amino acid
CC uptake is pH-dependent, with lower transport activities at pH 6.5,
CC intermediate at pH 7.0 and highest between pH 7.5 and 8.5.
CC {ECO:0000269|PubMed:12537539}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.5. {ECO:0000269|PubMed:12537539};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12537539};
CC Multi-pass membrane protein {ECO:0000269|PubMed:12537539}.
CC -!- TISSUE SPECIFICITY: Detected in liver, in hepatocytes surrounding the
CC central vein. Not detected in heart, kidney, brain, lung, small
CC intestine, spleen and thymus. {ECO:0000269|PubMed:12537539}.
CC -!- PTM: The disulfide bond plays an important role in substrate transport,
CC but has no effect on trafficking to the cell surface.
CC -!- MISCELLANEOUS: Imprinted gene expressed from the paternal allele in
CC blastocysts.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE37721.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY027919; AAK21967.1; -; mRNA.
DR EMBL; AB055004; BAB84091.1; -; mRNA.
DR EMBL; AK051023; BAC34500.1; -; mRNA.
DR EMBL; AK164292; BAE37721.1; ALT_INIT; mRNA.
DR EMBL; AK167539; BAE39606.1; -; mRNA.
DR EMBL; AK169349; BAE41099.1; -; mRNA.
DR EMBL; BC024072; AAH24072.1; -; mRNA.
DR EMBL; BC024123; AAH24123.1; -; mRNA.
DR EMBL; BC031717; AAH31717.1; -; mRNA.
DR CCDS; CCDS27779.1; -.
DR RefSeq; NP_081328.2; NM_027052.3.
DR RefSeq; XP_006521409.1; XM_006521346.3.
DR RefSeq; XP_006521411.1; XM_006521348.3.
DR RefSeq; XP_006521412.1; XM_006521349.3.
DR RefSeq; XP_006521413.1; XM_006521350.3.
DR RefSeq; XP_006521414.1; XM_006521351.2.
DR AlphaFoldDB; Q8R1S9; -.
DR SMR; Q8R1S9; -.
DR STRING; 10090.ENSMUSP00000023101; -.
DR GlyGen; Q8R1S9; 3 sites.
DR iPTMnet; Q8R1S9; -.
DR PhosphoSitePlus; Q8R1S9; -.
DR jPOST; Q8R1S9; -.
DR MaxQB; Q8R1S9; -.
DR PaxDb; Q8R1S9; -.
DR PeptideAtlas; Q8R1S9; -.
DR PRIDE; Q8R1S9; -.
DR ProteomicsDB; 256891; -.
DR Antibodypedia; 13384; 52 antibodies from 22 providers.
DR DNASU; 69354; -.
DR Ensembl; ENSMUST00000023101; ENSMUSP00000023101; ENSMUSG00000022464.
DR Ensembl; ENSMUST00000166223; ENSMUSP00000127676; ENSMUSG00000022464.
DR Ensembl; ENSMUST00000230086; ENSMUSP00000154818; ENSMUSG00000022464.
DR Ensembl; ENSMUST00000231039; ENSMUSP00000155158; ENSMUSG00000022464.
DR GeneID; 69354; -.
DR KEGG; mmu:69354; -.
DR UCSC; uc007xko.1; mouse.
DR CTD; 55089; -.
DR MGI; MGI:1916604; Slc38a4.
DR VEuPathDB; HostDB:ENSMUSG00000022464; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000158917; -.
DR HOGENOM; CLU_009020_0_1_1; -.
DR InParanoid; Q8R1S9; -.
DR OMA; IRTFMGL; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q8R1S9; -.
DR TreeFam; TF328787; -.
DR Reactome; R-MMU-352230; Amino acid transport across the plasma membrane.
DR BioGRID-ORCS; 69354; 3 hits in 69 CRISPR screens.
DR ChiTaRS; Slc38a4; mouse.
DR PRO; PR:Q8R1S9; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8R1S9; protein.
DR Bgee; ENSMUSG00000022464; Expressed in placenta labyrinth and 165 other tissues.
DR ExpressionAtlas; Q8R1S9; baseline and differential.
DR Genevisible; Q8R1S9; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 2.
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.
FT CHAIN 1..547
FT /note="Sodium-coupled neutral amino acid transporter 4"
FT /id="PRO_0000247861"
FT TOPO_DOM 1..104
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 242..332
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 333..353
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 354..369
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 391..411
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 433..453
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..476
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 477..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..514
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 515..535
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 536..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 12..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQ25"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 249..321
FT /evidence="ECO:0000269|PubMed:23451088"
FT MUTAGEN 18
FT /note="C->A: No significant effect on alanine uptake."
FT /evidence="ECO:0000269|PubMed:23451088"
FT MUTAGEN 232
FT /note="C->A: 40% decrease in alanine uptake."
FT /evidence="ECO:0000269|PubMed:23451088"
FT MUTAGEN 249
FT /note="C->A: Abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:23451088"
FT MUTAGEN 321
FT /note="C->A: Abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:23451088"
FT MUTAGEN 345
FT /note="C->A: No significant effect on alanine uptake."
FT /evidence="ECO:0000269|PubMed:23451088"
FT CONFLICT 90
FT /note="G -> S (in Ref. 3; BAE41099)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="E -> G (in Ref. 3; BAE37721)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="Q -> K (in Ref. 3; BAE37721)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="C -> R (in Ref. 2; BAB84091)"
FT /evidence="ECO:0000305"
FT CONFLICT 546..547
FT /note="HH -> PP (in Ref. 3; BAE39606)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 547 AA; 60464 MW; 7A3B615B6CA09D08 CRC64;
MDPMELNNVS IEPDGDSCSG DSIQDSYTGM ENSDKDAMNS QFANEDAESQ KFLTNGFLGK
KKLADYADEH HPGMTSFGMS SFNLSNAIMG SGILGLSYAM ANTGIILFII MLLTVAILSL
YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG KIGAFISITM QNIGAMSSYL FIIKYELPEV
IRAFMGLEEN TGEWYLNGNY LVLFVSVGII LPLSLLKNLG YLGYTSGFSL SCMVFFVSVV
IYKKFQIPCP LPALDHNNGN LTFNNTLPIH MISLPNDSES SGVNFMMDYA HHNPAGLDEK
QVAGPLHSNG VEYEAQGAEK CQPKYFVFNS RTAYAIPILA FAFVCHPEVL PIYSELKDRS
RRKMQTVSNI SISGMLVMYL LAALFGYLSF YGDVEDELLH AYSKVYTFDT ALLMVRLAVL
VAVTLTVPIV LFPIRTSVIT LLFPRKPFSW LKHFGIAAII IALNNILVIL VPTIKYIFGF
IGASSATMLI FILPAAFYLK LVKKEPLRSP QKIGALVFLV TGIIFMMGSM ALIILDWIYN
PPNPNHH
