S38A3_HUMAN
ID S38A3_HUMAN Reviewed; 504 AA.
AC Q99624; B2R8Q0; Q6IB34;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Sodium-coupled neutral amino acid transporter 3;
DE AltName: Full=N-system amino acid transporter 1;
DE AltName: Full=Na(+)-coupled neutral amino acid transporter 3;
DE AltName: Full=Solute carrier family 38 member 3;
DE AltName: Full=System N amino acid transporter 1;
GN Name=SLC38A3 {ECO:0000312|EMBL:AAH42875.1}; Synonyms=G17, NAT1, SN1, SNAT3;
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] {ECO:0000305, ECO:0000312|EMBL:AAG15313.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Liver {ECO:0000312|EMBL:AAG15313.1};
RX PubMed=10823827; DOI=10.1074/jbc.m002282200;
RA Fei Y.-J., Sugawara M., Nakanishi T., Huang W., Wang H., Prasad P.D.,
RA Leibach F.H., Ganapathy V.;
RT "Primary structure, genomic organization, and functional and electrogenic
RT characteristics of human system N 1, a Na+- and H+-coupled glutamine
RT transporter.";
RL J. Biol. Chem. 275:23707-23717(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAB47236.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Latif F., Lerman M., Minna J., Duh F.-M., Koonin E., Bader S.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAB47236.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Corpus callosum;
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 MRNA].
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7] {ECO:0000305, ECO:0000312|EMBL:AAB47236.1}
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 [8] {ECO:0000312|EMBL:AAH42875.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAH42875.1};
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 [9]
RP DISCUSSION OF SEQUENCE.
RX PubMed=11085536;
RG The international lung cancer chromosome 3p21.3 tumor suppressor gene consortium;
RA Lerman M.I., Minna J.D.;
RT "The 630-kb lung cancer homozygous deletion region on human chromosome
RT 3p21.3: identification and evaluation of the resident candidate tumor
RT suppressor genes.";
RL Cancer Res. 60:6116-6133(2000).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Sodium-dependent amino acid/proton antiporter. Mediates
CC electrogenic cotransport of glutamine and sodium ions in exchange for
CC protons. Also recognizes histidine, asparagine and alanine. May mediate
CC amino acid transport in either direction under physiological
CC conditions. May play a role in nitrogen metabolism and synaptic
CC transmission. {ECO:0000250|UniProtKB:Q9JHZ9,
CC ECO:0000269|PubMed:10823827}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AF244548; AAG15313.1; -; mRNA.
DR EMBL; U49082; AAB47236.1; -; mRNA.
DR EMBL; CR456970; CAG33251.1; -; mRNA.
DR EMBL; AK313461; BAG36247.1; -; mRNA.
DR EMBL; BX537382; CAD97624.1; -; mRNA.
DR EMBL; AC002077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65050.1; -; Genomic_DNA.
DR EMBL; BC042875; AAH42875.1; -; mRNA.
DR CCDS; CCDS74940.1; -.
DR RefSeq; NP_006832.1; NM_006841.5.
DR RefSeq; XP_006713017.1; XM_006712954.2.
DR AlphaFoldDB; Q99624; -.
DR SMR; Q99624; -.
DR BioGRID; 116187; 7.
DR IntAct; Q99624; 5.
DR STRING; 9606.ENSP00000481301; -.
DR DrugBank; DB00174; Asparagine.
DR DrugBank; DB00117; Histidine.
DR DrugBank; DB00130; L-Glutamine.
DR TCDB; 2.A.18.6.3; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q99624; 5 sites.
DR iPTMnet; Q99624; -.
DR PhosphoSitePlus; Q99624; -.
DR BioMuta; SLC38A3; -.
DR DMDM; 52783419; -.
DR jPOST; Q99624; -.
DR MassIVE; Q99624; -.
DR MaxQB; Q99624; -.
DR PeptideAtlas; Q99624; -.
DR PRIDE; Q99624; -.
DR ProteomicsDB; 78365; -.
DR Antibodypedia; 73268; 94 antibodies from 24 providers.
DR DNASU; 10991; -.
DR Ensembl; ENST00000614032.5; ENSP00000481301.1; ENSG00000188338.15.
DR GeneID; 10991; -.
DR KEGG; hsa:10991; -.
DR MANE-Select; ENST00000614032.5; ENSP00000481301.1; NM_006841.6; NP_006832.1.
DR UCSC; uc032rmu.2; human.
DR CTD; 10991; -.
DR DisGeNET; 10991; -.
DR GeneCards; SLC38A3; -.
DR HGNC; HGNC:18044; SLC38A3.
DR HPA; ENSG00000188338; Group enriched (liver, retina).
DR MIM; 604437; gene.
DR neXtProt; NX_Q99624; -.
DR OpenTargets; ENSG00000188338; -.
DR PharmGKB; PA38281; -.
DR VEuPathDB; HostDB:ENSG00000188338; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000157127; -.
DR HOGENOM; CLU_009020_0_2_1; -.
DR InParanoid; Q99624; -.
DR OMA; CWGVAVM; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q99624; -.
DR PathwayCommons; Q99624; -.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
DR SignaLink; Q99624; -.
DR BioGRID-ORCS; 10991; 7 hits in 211 CRISPR screens.
DR ChiTaRS; SLC38A3; human.
DR GeneWiki; SLC38A3; -.
DR GenomeRNAi; 10991; -.
DR Pharos; Q99624; Tbio.
DR PRO; PR:Q99624; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q99624; protein.
DR Bgee; ENSG00000188338; Expressed in right lobe of liver and 103 other tissues.
DR ExpressionAtlas; Q99624; baseline and differential.
DR Genevisible; Q99624; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015180; F:L-alanine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015182; F:L-asparagine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005290; F:L-histidine transmembrane transporter activity; IDA:UniProtKB.
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:0006867; P:asparagine transport; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0051365; P:cellular response to potassium ion starvation; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0006868; P:glutamine transport; IDA:UniProtKB.
DR GO; GO:0015817; P:histidine transport; IDA:UniProtKB.
DR GO; GO:0015808; P:L-alanine transport; IDA:UniProtKB.
DR GO; GO:2000487; P:positive regulation of glutamine transport; IEA:Ensembl.
DR GO; GO:0061402; P:positive regulation of transcription from RNA polymerase II promoter in response to acidic pH; IEA:Ensembl.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Antiport; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion transport; Membrane; Reference proteome; Sodium;
KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..504
FT /note="Sodium-coupled neutral amino acid transporter 3"
FT /id="PRO_0000093828"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..344
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 366..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 471..491
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 240..275
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 12
FT /note="L -> P (in Ref. 3; CAG33251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 55773 MW; 86E7D205C6001C60 CRC64;
MEAPLQTEMV ELVPNGKHSE GLLPVITPMA GNQRVEDPAR SCMEGKSFLQ KSPSKEPHFT
DFEGKTSFGM SVFNLSNAIM GSGILGLAYA MANTGIILFL FLLTAVALLS SYSIHLLLKS
SGVVGIRAYE QLGYRAFGTP GKLAAALAIT LQNIGAMSSY LYIIKSELPL VIQTFLNLEE
KTSDWYMNGN YLVILVSVTI ILPLALMRQL GYLGYSSGFS LSCMVFFLIA VIYKKFHVPC
PLPPNFNNTT GNFSHVEIVK EKVQLQVEPE ASAFCTPSYF TLNSQTAYTI PIMAFAFVCH
PEVLPIYTEL KDPSKKKMQH ISNLSIAVMY IMYFLAALFG YLTFYNGVES ELLHTYSKVD
PFDVLILCVR VAVLTAVTLT VPIVLFPVRR AIQQMLFPNQ EFSWLRHVLI AVGLLTCINL
LVIFAPNILG IFGVIGATSA PFLIFIFPAI FYFRIMPTEK EPARSTPKIL ALCFAMLGFL
LMTMSLSFII IDWASGTSRH GGNH
