S38A4_HUMAN
ID S38A4_HUMAN Reviewed; 547 AA.
AC Q969I6; A8K553;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
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;
DE AltName: Full=System N amino acid transporter 3;
GN Name=SLC38A4; Synonyms=ATA3, NAT3, SNAT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Hepatoma;
RX PubMed=11342143; DOI=10.1016/s0005-2736(00)00390-4;
RA Hatanaka T., Huang W., Ling R., Prasad P.D., Sugawara M., Leibach F.H.,
RA Ganapathy V.;
RT "Evidence for the transport of neutral as well as cationic amino acids by
RT ATA3, a novel and liver-specific subtype of amino acid transport system
RT A.";
RL Biochim. Biophys. Acta 1510:10-17(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11414754; DOI=10.1006/geno.2001.6567;
RA Gu S., Adan-Rice D., Leach R.J., Jiang J.X.;
RT "A novel human amino acid transporter, hNAT3: cDNA cloning, chromosomal
RT mapping, genomic structure, expression, and functional characterization.";
RL Genomics 74:262-272(2001).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [7]
RP REVIEW, AND GENE NOMENCLATURE.
RX PubMed=12845534; DOI=10.1007/s00424-003-1117-9;
RA Mackenzie B., Erickson J.D.;
RT "Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38
RT gene family.";
RL Pflugers Arch. 447:784-795(2004).
RN [8]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16148032; DOI=10.1152/ajpcell.00258.2005;
RA Desforges M., Lacey H.A., Glazier J.D., Greenwood S.L., Mynett K.J.,
RA Speake P.F., Sibley C.P.;
RT "SNAT4 isoform of system A amino acid transporter is expressed in human
RT placenta.";
RL Am. J. Physiol. 290:C305-C312(2006).
RN [9]
RP TOPOLOGY, AND GLYCOSYLATION AT ASN-260 AND ASN-264.
RX PubMed=21917917; DOI=10.1074/jbc.m111.220277;
RA Shi Q., Padmanabhan R., Villegas C.J., Gu S., Jiang J.X.;
RT "Membrane topological structure of neutral system N/A amino acid
RT transporter 4 (SNAT4) protein.";
RL J. Biol. Chem. 286:38086-38094(2011).
RN [10]
RP VARIANT 446-ARG--HIS-547 DEL.
RX PubMed=29961568; DOI=10.1016/j.ajhg.2018.06.001;
RG NIHR BioResource;
RG Care4Rare Canada Consortium;
RA Ito Y., Carss K.J., Duarte S.T., Hartley T., Keren B., Kurian M.A.,
RA Marey I., Charles P., Mendonca C., Nava C., Pfundt R., Sanchis-Juan A.,
RA van Bokhoven H., van Essen A., van Ravenswaaij-Arts C., Boycott K.M.,
RA Kernohan K.D., Dyack S., Raymond F.L.;
RT "De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with
RT Seizures.";
RL Am. J. Hum. Genet. 103:144-153(2018).
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 His, Cys,
CC Asn, Ser, Gly, Val, Thr, 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 low 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:11342143, ECO:0000269|PubMed:11414754}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.5. {ECO:0000269|PubMed:11342143};
CC -!- INTERACTION:
CC Q969I6; P48165: GJA8; NbExp=3; IntAct=EBI-17459810, EBI-17458373;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11414754,
CC ECO:0000269|PubMed:16148032}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11414754, ECO:0000269|PubMed:16148032}.
CC -!- TISSUE SPECIFICITY: Detected in embryonic and adult liver, and at lower
CC levels in adult muscle, kidney and pancreas. Detected in placenta
CC syncytiotrophoblasts throughout gestation. Detected in fetal blood
CC vessels. {ECO:0000269|PubMed:11342143, ECO:0000269|PubMed:11414754,
CC ECO:0000269|PubMed:16148032}.
CC -!- PTM: The disulfide bond plays an important role in substrate transport,
CC but has no effect on trafficking to the cell surface. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AF305814; AAK43528.1; -; mRNA.
DR EMBL; AF193836; AAK71508.1; -; mRNA.
DR EMBL; AB055003; BAB84090.1; -; mRNA.
DR EMBL; AK291168; BAF83857.1; -; mRNA.
DR EMBL; CH471111; EAW57919.1; -; Genomic_DNA.
DR EMBL; BC069819; AAH69819.1; -; mRNA.
DR EMBL; BC101827; AAI01828.1; -; mRNA.
DR EMBL; BC104913; AAI04914.1; -; mRNA.
DR CCDS; CCDS8750.1; -.
DR RefSeq; NP_001137296.1; NM_001143824.1.
DR RefSeq; NP_060488.2; NM_018018.4.
DR RefSeq; XP_005269054.1; XM_005268997.2.
DR AlphaFoldDB; Q969I6; -.
DR SMR; Q969I6; -.
DR BioGRID; 120402; 2.
DR IntAct; Q969I6; 1.
DR STRING; 9606.ENSP00000389843; -.
DR DrugBank; DB00174; Asparagine.
DR TCDB; 2.A.18.6.17; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q969I6; 3 sites.
DR iPTMnet; Q969I6; -.
DR PhosphoSitePlus; Q969I6; -.
DR BioMuta; SLC38A4; -.
DR DMDM; 74731046; -.
DR MassIVE; Q969I6; -.
DR PaxDb; Q969I6; -.
DR PeptideAtlas; Q969I6; -.
DR PRIDE; Q969I6; -.
DR ProteomicsDB; 75771; -.
DR Antibodypedia; 13384; 52 antibodies from 22 providers.
DR DNASU; 55089; -.
DR Ensembl; ENST00000266579.9; ENSP00000266579.4; ENSG00000139209.16.
DR Ensembl; ENST00000447411.5; ENSP00000389843.1; ENSG00000139209.16.
DR GeneID; 55089; -.
DR KEGG; hsa:55089; -.
DR MANE-Select; ENST00000266579.9; ENSP00000266579.4; NM_018018.5; NP_060488.2.
DR UCSC; uc001rpi.3; human.
DR CTD; 55089; -.
DR DisGeNET; 55089; -.
DR GeneCards; SLC38A4; -.
DR HGNC; HGNC:14679; SLC38A4.
DR HPA; ENSG00000139209; Tissue enriched (liver).
DR MIM; 608065; gene.
DR neXtProt; NX_Q969I6; -.
DR OpenTargets; ENSG00000139209; -.
DR PharmGKB; PA37908; -.
DR VEuPathDB; HostDB:ENSG00000139209; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000158917; -.
DR HOGENOM; CLU_009020_0_1_1; -.
DR InParanoid; Q969I6; -.
DR OMA; IRTFMGL; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q969I6; -.
DR TreeFam; TF328787; -.
DR PathwayCommons; Q969I6; -.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
DR SignaLink; Q969I6; -.
DR BioGRID-ORCS; 55089; 15 hits in 1069 CRISPR screens.
DR ChiTaRS; SLC38A4; human.
DR GenomeRNAi; 55089; -.
DR Pharos; Q969I6; Tbio.
DR PRO; PR:Q969I6; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q969I6; protein.
DR Bgee; ENSG00000139209; Expressed in right lobe of liver and 106 other tissues.
DR ExpressionAtlas; Q969I6; baseline and differential.
DR Genevisible; Q969I6; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
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:0006865; P:amino acid transport; TAS:Reactome.
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_0000247860"
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..30
FT /note="Disordered"
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:0000269|PubMed:21917917"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21917917"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 249..321
FT /evidence="ECO:0000250"
FT VARIANT 29
FT /note="G -> R (in dbSNP:rs2429467)"
FT /id="VAR_048123"
FT VARIANT 366
FT /note="T -> M (in dbSNP:rs11183610)"
FT /id="VAR_048124"
FT VARIANT 446..547
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:29961568"
FT /id="VAR_083479"
SQ SEQUENCE 547 AA; 60764 MW; D47289AA386F3373 CRC64;
MDPMELRNVN IEPDDESSSG ESAPDSYIGI GNSEKAAMSS QFANEDTESQ KFLTNGFLGK
KKLADYADEH HPGTTSFGMS SFNLSNAIMG SGILGLSYAM ANTGIILFII MLLAVAILSL
YSVHLLLKTA KEGGSLIYEK LGEKAFGWPG KIGAFVSITM QNIGAMSSYL FIIKYELPEV
IRAFMGLEEN TGEWYLNGNY LIIFVSVGII LPLSLLKNLG YLGYTSGFSL TCMVFFVSVV
IYKKFQIPCP LPVLDHSVGN LSFNNTLPMH VVMLPNNSES SDVNFMMDYT HRNPAGLDEN
QAKGSLHDSG VEYEAHSDDK CEPKYFVFNS RTAYAIPILV FAFVCHPEVL PIYSELKDRS
RRKMQTVSNI SITGMLVMYL LAALFGYLTF YGEVEDELLH AYSKVYTLDI PLLMVRLAVL
VAVTLTVPIV LFPIRTSVIT LLFPKRPFSW IRHFLIAAVL IALNNVLVIL VPTIKYIFGF
IGASSATMLI FILPAVFYLK LVKKETFRSP QKVGALIFLV VGIFFMIGSM ALIIIDWIYD
PPNSKHH
