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Protein

Sodium-coupled neutral amino acid transporter 4

Gene

SLC38A4

Organism
Homo sapiens (Human)
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 His, Cys, Asn, Ser, Gly, Val, Thr, Gln and Met. May mediate sodium-independent transport of cationic amino acids, such as Arg and Lys. Amino acid uptake is pH-dependent, with low transport activities at pH 6.5, intermediate at pH 7.0 and highest between pH 7.5 and 8.5.2 Publications

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

ReactomeiREACT_13796. Amino acid transport across the plasma membrane.

Protein family/group databases

TCDBi2.A.18.6.17. the amino acid/auxin permease (aaap) family.

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
System N amino acid transporter 3
Gene namesi
Name:SLC38A4
Synonyms:ATA3, NAT3, SNAT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:14679. SLC38A4.

Subcellular locationi

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

Organism-specific databases

PharmGKBiPA37908.

Polymorphism and mutation databases

BioMutaiSLC38A4.
DMDMi74731046.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 547547Sodium-coupled neutral amino acid transporter 4PRO_0000247860Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi249 ↔ 321By similarity
Glycosylationi260 – 2601N-linked (GlcNAc...)1 Publication
Glycosylationi264 – 2641N-linked (GlcNAc...)1 Publication
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.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ969I6.
PRIDEiQ969I6.

PTM databases

PhosphoSiteiQ969I6.

Expressioni

Tissue specificityi

Detected in embryonic and adult liver, and at lower levels in adult muscle, kidney and pancreas. Detected in placenta syncytiotrophoblasts throughout gestation. Detected in fetal blood vessels.3 Publications

Gene expression databases

BgeeiQ969I6.
CleanExiHS_SLC38A4.
ExpressionAtlasiQ969I6. baseline and differential.
GenevisibleiQ969I6. HS.

Organism-specific databases

HPAiHPA038910.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000266579.

Structurei

3D structure databases

ProteinModelPortaliQ969I6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0814.
GeneTreeiENSGT00760000119147.
HOGENOMiHOG000013088.
HOVERGENiHBG059571.
InParanoidiQ969I6.
KOiK14991.
OMAiDDKCQPK.
OrthoDBiEOG7WHH9J.
PhylomeDBiQ969I6.
TreeFamiTF328787.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q969I6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPMELRNVN IEPDDESSSG ESAPDSYIGI GNSEKAAMSS QFANEDTESQ
60 70 80 90 100
KFLTNGFLGK KKLADYADEH HPGTTSFGMS SFNLSNAIMG SGILGLSYAM
110 120 130 140 150
ANTGIILFII MLLAVAILSL YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG
160 170 180 190 200
KIGAFVSITM QNIGAMSSYL FIIKYELPEV IRAFMGLEEN TGEWYLNGNY
210 220 230 240 250
LIIFVSVGII LPLSLLKNLG YLGYTSGFSL TCMVFFVSVV IYKKFQIPCP
260 270 280 290 300
LPVLDHSVGN LSFNNTLPMH VVMLPNNSES SDVNFMMDYT HRNPAGLDEN
310 320 330 340 350
QAKGSLHDSG VEYEAHSDDK CEPKYFVFNS RTAYAIPILV FAFVCHPEVL
360 370 380 390 400
PIYSELKDRS RRKMQTVSNI SITGMLVMYL LAALFGYLTF YGEVEDELLH
410 420 430 440 450
AYSKVYTLDI PLLMVRLAVL VAVTLTVPIV LFPIRTSVIT LLFPKRPFSW
460 470 480 490 500
IRHFLIAAVL IALNNVLVIL VPTIKYIFGF IGASSATMLI FILPAVFYLK
510 520 530 540
LVKKETFRSP QKVGALIFLV VGIFFMIGSM ALIIIDWIYD PPNSKHH
Length:547
Mass (Da):60,764
Last modified:December 1, 2001 - v1
Checksum:iD47289AA386F3373
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti29 – 291G → R.
Corresponds to variant rs2429467 [ dbSNP | Ensembl ].
VAR_048123
Natural varianti366 – 3661T → M.
Corresponds to variant rs11183610 [ dbSNP | Ensembl ].
VAR_048124

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305814 mRNA. Translation: AAK43528.1.
AF193836 mRNA. Translation: AAK71508.1.
AB055003 mRNA. Translation: BAB84090.1.
AK291168 mRNA. Translation: BAF83857.1.
CH471111 Genomic DNA. Translation: EAW57919.1.
BC069819 mRNA. Translation: AAH69819.1.
BC101827 mRNA. Translation: AAI01828.1.
BC104913 mRNA. Translation: AAI04914.1.
CCDSiCCDS8750.1.
RefSeqiNP_001137296.1. NM_001143824.1.
NP_060488.2. NM_018018.4.
XP_005269054.1. XM_005268997.2.
UniGeneiHs.446077.

Genome annotation databases

EnsembliENST00000266579; ENSP00000266579; ENSG00000139209.
ENST00000447411; ENSP00000389843; ENSG00000139209.
GeneIDi55089.
KEGGihsa:55089.
UCSCiuc001rpi.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF305814 mRNA. Translation: AAK43528.1.
AF193836 mRNA. Translation: AAK71508.1.
AB055003 mRNA. Translation: BAB84090.1.
AK291168 mRNA. Translation: BAF83857.1.
CH471111 Genomic DNA. Translation: EAW57919.1.
BC069819 mRNA. Translation: AAH69819.1.
BC101827 mRNA. Translation: AAI01828.1.
BC104913 mRNA. Translation: AAI04914.1.
CCDSiCCDS8750.1.
RefSeqiNP_001137296.1. NM_001143824.1.
NP_060488.2. NM_018018.4.
XP_005269054.1. XM_005268997.2.
UniGeneiHs.446077.

3D structure databases

ProteinModelPortaliQ969I6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000266579.

Chemistry

GuidetoPHARMACOLOGYi1171.

Protein family/group databases

TCDBi2.A.18.6.17. the amino acid/auxin permease (aaap) family.

PTM databases

PhosphoSiteiQ969I6.

Polymorphism and mutation databases

BioMutaiSLC38A4.
DMDMi74731046.

Proteomic databases

PaxDbiQ969I6.
PRIDEiQ969I6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266579; ENSP00000266579; ENSG00000139209.
ENST00000447411; ENSP00000389843; ENSG00000139209.
GeneIDi55089.
KEGGihsa:55089.
UCSCiuc001rpi.2. human.

Organism-specific databases

CTDi55089.
GeneCardsiGC12M047138.
HGNCiHGNC:14679. SLC38A4.
HPAiHPA038910.
MIMi608065. gene.
neXtProtiNX_Q969I6.
PharmGKBiPA37908.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0814.
GeneTreeiENSGT00760000119147.
HOGENOMiHOG000013088.
HOVERGENiHBG059571.
InParanoidiQ969I6.
KOiK14991.
OMAiDDKCQPK.
OrthoDBiEOG7WHH9J.
PhylomeDBiQ969I6.
TreeFamiTF328787.

Enzyme and pathway databases

ReactomeiREACT_13796. Amino acid transport across the plasma membrane.

Miscellaneous databases

GenomeRNAii55089.
NextBioi58661.
PROiQ969I6.
SOURCEiSearch...

Gene expression databases

BgeeiQ969I6.
CleanExiHS_SLC38A4.
ExpressionAtlasiQ969I6. baseline and differential.
GenevisibleiQ969I6. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A."
    Hatanaka T., Huang W., Ling R., Prasad P.D., Sugawara M., Leibach F.H., Ganapathy V.
    Biochim. Biophys. Acta 1510:10-17(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
    Tissue: Hepatoma.
  2. "A novel human amino acid transporter, hNAT3: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization."
    Gu S., Adan-Rice D., Leach R.J., Jiang J.X.
    Genomics 74:262-272(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  3. "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.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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].
    Tissue: Liver.
  7. "Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family."
    Mackenzie B., Erickson J.D.
    Pflugers Arch. 447:784-795(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW, GENE NOMENCLATURE.
  8. "SNAT4 isoform of system A amino acid transporter is expressed in human placenta."
    Desforges M., Lacey H.A., Glazier J.D., Greenwood S.L., Mynett K.J., Speake P.F., Sibley C.P.
    Am. J. Physiol. 290:C305-C312(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  9. "Membrane topological structure of neutral system N/A amino acid transporter 4 (SNAT4) protein."
    Shi Q., Padmanabhan R., Villegas C.J., Gu S., Jiang J.X.
    J. Biol. Chem. 286:38086-38094(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY, GLYCOSYLATION AT ASN-260 AND ASN-264.

Entry informationi

Entry nameiS38A4_HUMAN
AccessioniPrimary (citable) accession number: Q969I6
Secondary accession number(s): A8K553
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: December 1, 2001
Last modified: June 24, 2015
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.