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Q969I6 (S38A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC38A4
Synonyms:ATA3, NAT3, SNAT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length547 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.2 Ref.8.

Tissue specificity

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. Ref.1 Ref.2 Ref.8

Post-translational modification

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

Sequence similarities

Belongs to the amino acid/polyamine transporter 2 family.

Biophysicochemical properties

pH dependence:

Optimum pH is 7.5-8.5. Ref.1

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 547547Sodium-coupled neutral amino acid transporter 4
PRO_0000247860

Regions

Topological domain1 – 104104Extracellular Potential
Transmembrane105 – 12521Helical; Potential
Topological domain126 – 15126Cytoplasmic Potential
Transmembrane152 – 17221Helical; Potential
Topological domain173 – 19523Extracellular Potential
Transmembrane196 – 21621Helical; Potential
Topological domain217 – 2204Cytoplasmic Potential
Transmembrane221 – 24121Helical; Potential
Topological domain242 – 33291Extracellular Potential
Transmembrane333 – 35321Helical; Potential
Topological domain354 – 36916Cytoplasmic Potential
Transmembrane370 – 39021Helical; Potential
Topological domain391 – 41121Extracellular Potential
Transmembrane412 – 43221Helical; Potential
Topological domain433 – 45321Cytoplasmic Potential
Transmembrane454 – 47421Helical; Potential
Topological domain475 – 4762Extracellular Potential
Transmembrane477 – 49721Helical; Potential
Topological domain498 – 51417Cytoplasmic Potential
Transmembrane515 – 53521Helical; Potential
Topological domain536 – 54712Extracellular Potential

Amino acid modifications

Glycosylation2601N-linked (GlcNAc...) Ref.9
Glycosylation2641N-linked (GlcNAc...) Ref.9
Glycosylation2761N-linked (GlcNAc...) Potential
Disulfide bond249 ↔ 321 By similarity

Natural variations

Natural variant291G → R.
Corresponds to variant rs2429467 [ dbSNP | Ensembl ].
VAR_048123
Natural variant3661T → M.
Corresponds to variant rs11183610 [ dbSNP | Ensembl ].
VAR_048124

Sequences

Sequence LengthMass (Da)Tools
Q969I6 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: D47289AA386F3373

FASTA54760,764
        10         20         30         40         50         60 
MDPMELRNVN IEPDDESSSG ESAPDSYIGI GNSEKAAMSS QFANEDTESQ KFLTNGFLGK 

        70         80         90        100        110        120 
KKLADYADEH HPGTTSFGMS SFNLSNAIMG SGILGLSYAM ANTGIILFII MLLAVAILSL 

       130        140        150        160        170        180 
YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG KIGAFVSITM QNIGAMSSYL FIIKYELPEV 

       190        200        210        220        230        240 
IRAFMGLEEN TGEWYLNGNY LIIFVSVGII LPLSLLKNLG YLGYTSGFSL TCMVFFVSVV 

       250        260        270        280        290        300 
IYKKFQIPCP LPVLDHSVGN LSFNNTLPMH VVMLPNNSES SDVNFMMDYT HRNPAGLDEN 

       310        320        330        340        350        360 
QAKGSLHDSG VEYEAHSDDK CEPKYFVFNS RTAYAIPILV FAFVCHPEVL PIYSELKDRS 

       370        380        390        400        410        420 
RRKMQTVSNI SITGMLVMYL LAALFGYLTF YGEVEDELLH AYSKVYTLDI PLLMVRLAVL 

       430        440        450        460        470        480 
VAVTLTVPIV LFPIRTSVIT LLFPKRPFSW IRHFLIAAVL IALNNVLVIL VPTIKYIFGF 

       490        500        510        520        530        540 
IGASSATMLI FILPAVFYLK LVKKETFRSP QKVGALIFLV VGIFFMIGSM ALIIIDWIYD 


PPNSKHH 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS8750.1.
RefSeqNP_001137296.1. NM_001143824.1.
NP_060488.2. NM_018018.4.
XP_005269054.1. XM_005268997.2.
UniGeneHs.446077.

3D structure databases

ProteinModelPortalQ969I6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000266579.

Chemistry

GuidetoPHARMACOLOGY1171.

Protein family/group databases

TCDB2.A.18.6.17. the amino acid/auxin permease (aaap) family.

PTM databases

PhosphoSiteQ969I6.

Polymorphism databases

DMDM74731046.

Proteomic databases

PaxDbQ969I6.
PRIDEQ969I6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266579; ENSP00000266579; ENSG00000139209.
ENST00000447411; ENSP00000389843; ENSG00000139209.
GeneID55089.
KEGGhsa:55089.
UCSCuc001rpi.2. human.

Organism-specific databases

CTD55089.
GeneCardsGC12M047138.
HGNCHGNC:14679. SLC38A4.
HPAHPA038910.
MIM608065. gene.
neXtProtNX_Q969I6.
PharmGKBPA37908.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0814.
HOGENOMHOG000013088.
HOVERGENHBG059571.
InParanoidQ969I6.
KOK14991.
OMADDKCQPK.
OrthoDBEOG7WHH9J.
PhylomeDBQ969I6.
TreeFamTF328787.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

ArrayExpressQ969I6.
BgeeQ969I6.
CleanExHS_SLC38A4.
GenevestigatorQ969I6.

Family and domain databases

InterProIPR013057. AA_transpt_TM.
[Graphical view]
PfamPF01490. Aa_trans. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi55089.
NextBio58661.
PROQ969I6.
SOURCESearch...

Entry information

Entry nameS38A4_HUMAN
AccessionPrimary (citable) accession number: Q969I6
Secondary accession number(s): A8K553
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM