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Protein

Sodium-coupled neutral amino acid transporter 4

Gene

Slc38a4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sodium-dependent amino acid transporter. Mediates electrogenic symport of neutral amino acids and sodium ions. Has a broad specificity, with a preference for Ala, followed by Ser, His, Gly, Cys, Asn, Thr, Pro, Gln and Met. May mediate sodium-independent transport of cationic amino acids, such as Arg and Lys. Amino acid uptake is pH-dependent, with lower transport activities at pH 6.5, intermediate at pH 7.0 and highest between pH 7.5 and 8.5.1 Publication

pH dependencei

Optimum pH is 7.5-8.5.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Amino-acid transport, Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-MMU-352230. Amino acid transport across the plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-coupled neutral amino acid transporter 4
Alternative name(s):
Amino acid transporter A3
Na(+)-coupled neutral amino acid transporter 4
Solute carrier family 38 member 4
System A amino acid transporter 3
Gene namesi
Name:Slc38a4
Synonyms:Ata3, Nat3, Snat4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1916604. Slc38a4.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 104104ExtracellularSequence analysisAdd
BLAST
Transmembranei105 – 12521HelicalSequence analysisAdd
BLAST
Topological domaini126 – 15126CytoplasmicSequence analysisAdd
BLAST
Transmembranei152 – 17221HelicalSequence analysisAdd
BLAST
Topological domaini173 – 19523ExtracellularSequence analysisAdd
BLAST
Transmembranei196 – 21621HelicalSequence analysisAdd
BLAST
Topological domaini217 – 2204CytoplasmicSequence analysis
Transmembranei221 – 24121HelicalSequence analysisAdd
BLAST
Topological domaini242 – 33291ExtracellularSequence analysisAdd
BLAST
Transmembranei333 – 35321HelicalSequence analysisAdd
BLAST
Topological domaini354 – 36916CytoplasmicSequence analysisAdd
BLAST
Transmembranei370 – 39021HelicalSequence analysisAdd
BLAST
Topological domaini391 – 41121ExtracellularSequence analysisAdd
BLAST
Transmembranei412 – 43221HelicalSequence analysisAdd
BLAST
Topological domaini433 – 45321CytoplasmicSequence analysisAdd
BLAST
Transmembranei454 – 47421HelicalSequence analysisAdd
BLAST
Topological domaini475 – 4762ExtracellularSequence analysis
Transmembranei477 – 49721HelicalSequence analysisAdd
BLAST
Topological domaini498 – 51417CytoplasmicSequence analysisAdd
BLAST
Transmembranei515 – 53521HelicalSequence analysisAdd
BLAST
Topological domaini536 – 54712ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi18 – 181C → A: No significant effect on alanine uptake. 1 Publication
Mutagenesisi232 – 2321C → A: 40% decrease in alanine uptake. 1 Publication
Mutagenesisi249 – 2491C → A: Abolishes transport activity. 1 Publication
Mutagenesisi321 – 3211C → A: Abolishes transport activity. 1 Publication
Mutagenesisi345 – 3451C → A: No significant effect on alanine uptake. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 547547Sodium-coupled neutral amino acid transporter 4PRO_0000247861Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei49 – 491PhosphoserineBy similarity
Disulfide bondi249 ↔ 3211 Publication
Glycosylationi260 – 2601N-linked (GlcNAc...)Sequence analysis
Glycosylationi264 – 2641N-linked (GlcNAc...)Sequence analysis
Glycosylationi276 – 2761N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

The disulfide bond plays an important role in substrate transport, but has no effect on trafficking to the cell surface.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8R1S9.
MaxQBiQ8R1S9.
PaxDbiQ8R1S9.
PRIDEiQ8R1S9.

PTM databases

iPTMnetiQ8R1S9.
PhosphoSiteiQ8R1S9.

Expressioni

Tissue specificityi

Detected in liver, in hepatocytes surrounding the central vein. Not detected in heart, kidney, brain, lung, small intestine, spleen and thymus.1 Publication

Gene expression databases

BgeeiQ8R1S9.
CleanExiMM_NAT3.
MM_SLC38A4.
GenevisibleiQ8R1S9. MM.

Interactioni

Protein-protein interaction databases

IntActiQ8R1S9. 1 interaction.
MINTiMINT-4118642.
STRINGi10090.ENSMUSP00000023101.

Structurei

3D structure databases

ProteinModelPortaliQ8R1S9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1305. Eukaryota.
COG0814. LUCA.
GeneTreeiENSGT00760000119147.
HOGENOMiHOG000013088.
HOVERGENiHBG059571.
InParanoidiQ8R1S9.
KOiK14991.
OMAiNTLPMHV.
OrthoDBiEOG7WHH9J.
PhylomeDBiQ8R1S9.
TreeFamiTF328787.

Family and domain databases

InterProiIPR013057. AA_transpt_TM.
[Graphical view]
PfamiPF01490. Aa_trans. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8R1S9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPMELNNVS IEPDGDSCSG DSIQDSYTGM ENSDKDAMNS QFANEDAESQ
60 70 80 90 100
KFLTNGFLGK KKLADYADEH HPGMTSFGMS SFNLSNAIMG SGILGLSYAM
110 120 130 140 150
ANTGIILFII MLLTVAILSL YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG
160 170 180 190 200
KIGAFISITM QNIGAMSSYL FIIKYELPEV IRAFMGLEEN TGEWYLNGNY
210 220 230 240 250
LVLFVSVGII LPLSLLKNLG YLGYTSGFSL SCMVFFVSVV IYKKFQIPCP
260 270 280 290 300
LPALDHNNGN LTFNNTLPIH MISLPNDSES SGVNFMMDYA HHNPAGLDEK
310 320 330 340 350
QVAGPLHSNG VEYEAQGAEK CQPKYFVFNS RTAYAIPILA FAFVCHPEVL
360 370 380 390 400
PIYSELKDRS RRKMQTVSNI SISGMLVMYL LAALFGYLSF YGDVEDELLH
410 420 430 440 450
AYSKVYTFDT ALLMVRLAVL VAVTLTVPIV LFPIRTSVIT LLFPRKPFSW
460 470 480 490 500
LKHFGIAAII IALNNILVIL VPTIKYIFGF IGASSATMLI FILPAAFYLK
510 520 530 540
LVKKEPLRSP QKIGALVFLV TGIIFMMGSM ALIILDWIYN PPNPNHH
Length:547
Mass (Da):60,464
Last modified:June 1, 2002 - v1
Checksum:i7A3B615B6CA09D08
GO

Sequence cautioni

The sequence BAE37721.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti90 – 901G → S in BAE41099 (PubMed:16141072).Curated
Sequence conflicti143 – 1431E → G in BAE37721 (PubMed:16141072).Curated
Sequence conflicti316 – 3161Q → K in BAE37721 (PubMed:16141072).Curated
Sequence conflicti345 – 3451C → R in BAB84091 (Ref. 2) Curated
Sequence conflicti546 – 5472HH → PP in BAE39606 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027919 mRNA. Translation: AAK21967.1.
AB055004 mRNA. Translation: BAB84091.1.
AK051023 mRNA. Translation: BAC34500.1.
AK164292 mRNA. Translation: BAE37721.1. Different initiation.
AK167539 mRNA. Translation: BAE39606.1.
AK169349 mRNA. Translation: BAE41099.1.
BC024072 mRNA. Translation: AAH24072.1.
BC024123 mRNA. Translation: AAH24123.1.
BC031717 mRNA. Translation: AAH31717.1.
CCDSiCCDS27779.1.
RefSeqiNP_081328.2. NM_027052.3.
XP_006521409.1. XM_006521346.2.
XP_006521411.1. XM_006521348.2.
XP_006521412.1. XM_006521349.2.
XP_006521413.1. XM_006521350.2.
XP_006521414.1. XM_006521351.1.
UniGeneiMm.250980.

Genome annotation databases

EnsembliENSMUST00000023101; ENSMUSP00000023101; ENSMUSG00000022464.
ENSMUST00000166223; ENSMUSP00000127676; ENSMUSG00000022464.
GeneIDi69354.
KEGGimmu:69354.
UCSCiuc007xko.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027919 mRNA. Translation: AAK21967.1.
AB055004 mRNA. Translation: BAB84091.1.
AK051023 mRNA. Translation: BAC34500.1.
AK164292 mRNA. Translation: BAE37721.1. Different initiation.
AK167539 mRNA. Translation: BAE39606.1.
AK169349 mRNA. Translation: BAE41099.1.
BC024072 mRNA. Translation: AAH24072.1.
BC024123 mRNA. Translation: AAH24123.1.
BC031717 mRNA. Translation: AAH31717.1.
CCDSiCCDS27779.1.
RefSeqiNP_081328.2. NM_027052.3.
XP_006521409.1. XM_006521346.2.
XP_006521411.1. XM_006521348.2.
XP_006521412.1. XM_006521349.2.
XP_006521413.1. XM_006521350.2.
XP_006521414.1. XM_006521351.1.
UniGeneiMm.250980.

3D structure databases

ProteinModelPortaliQ8R1S9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8R1S9. 1 interaction.
MINTiMINT-4118642.
STRINGi10090.ENSMUSP00000023101.

PTM databases

iPTMnetiQ8R1S9.
PhosphoSiteiQ8R1S9.

Proteomic databases

EPDiQ8R1S9.
MaxQBiQ8R1S9.
PaxDbiQ8R1S9.
PRIDEiQ8R1S9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023101; ENSMUSP00000023101; ENSMUSG00000022464.
ENSMUST00000166223; ENSMUSP00000127676; ENSMUSG00000022464.
GeneIDi69354.
KEGGimmu:69354.
UCSCiuc007xko.1. mouse.

Organism-specific databases

CTDi55089.
MGIiMGI:1916604. Slc38a4.

Phylogenomic databases

eggNOGiKOG1305. Eukaryota.
COG0814. LUCA.
GeneTreeiENSGT00760000119147.
HOGENOMiHOG000013088.
HOVERGENiHBG059571.
InParanoidiQ8R1S9.
KOiK14991.
OMAiNTLPMHV.
OrthoDBiEOG7WHH9J.
PhylomeDBiQ8R1S9.
TreeFamiTF328787.

Enzyme and pathway databases

ReactomeiR-MMU-352230. Amino acid transport across the plasma membrane.

Miscellaneous databases

ChiTaRSiSlc38a4. mouse.
NextBioi329200.
PROiQ8R1S9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R1S9.
CleanExiMM_NAT3.
MM_SLC38A4.
GenevisibleiQ8R1S9. MM.

Family and domain databases

InterProiIPR013057. AA_transpt_TM.
[Graphical view]
PfamiPF01490. Aa_trans. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse system-N amino acid transporter, mNAT3, expressed in hepatocytes and regulated by insulin-activated and phosphoinositide 3-kinase-dependent signalling."
    Gu S., Langlais P., Liu F., Jiang J.X.
    Biochem. J. 371:721-731(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Strain: C57BL/6J.
    Tissue: Liver.
  2. "Molecular cloning and characterization of a novel system A amino acid transporter from human liver."
    Matsuo H., Kanai Y., Kim D.K., Cha S.H., Chairoungdua A., Fukuda J., Endou H.
    Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Embryo and Placenta.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver.
  5. "The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues."
    Kuzmin A., Han Z., Golding M.C., Mann M.R., Latham K.E., Varmuza S.
    Gene Expr. Patterns 8:107-116(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IMPRINTING, MISCELLANEOUS.
  6. "Identification of a disulfide bridge important for transport function of SNAT4 neutral amino acid transporter."
    Padmanabhan Iyer R., Gu S., Nicholson B.J., Jiang J.X.
    PLoS ONE 8:E56792-E56792(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BOND, MUTAGENESIS OF CYS-18; CYS-232; CYS-249; CYS-321 AND CYS-345.

Entry informationi

Entry nameiS38A4_MOUSE
AccessioniPrimary (citable) accession number: Q8R1S9
Secondary accession number(s): Q3TEZ9
, Q3TJ89, Q3TPL5, Q8VIE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: June 1, 2002
Last modified: May 11, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Imprinted gene expressed from the paternal allele in blastocysts.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.