S38A6_HUMAN
ID S38A6_HUMAN Reviewed; 456 AA.
AC Q8IZM9; C9JWA6; Q86SY5;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Probable sodium-coupled neutral amino acid transporter 6;
DE AltName: Full=N-system amino acid transporter 1;
DE Short=NAT-1;
DE AltName: Full=Na(+)-coupled neutral amino acid transporter 6;
DE AltName: Full=Solute carrier family 38 member 6;
GN Name=SLC38A6; Synonyms=NAT1, SNAT6;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-70.
RC TISSUE=Brain;
RA Guo J.H., Yu L.;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-70.
RC TISSUE=Duodenum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-456 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP REVIEW, AND 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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-4 AND SER-7, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP VARIANT THR-419.
RX PubMed=28973684; DOI=10.1093/hmg/ddx356;
RA Biswas P., Duncan J.L., Ali M., Matsui H., Naeem M.A., Raghavendra P.B.,
RA Frazer K.A., Arts H.H., Riazuddin S., Akram J., Hejtmancik J.F.,
RA Riazuddin S.A., Ayyagari R.;
RT "A mutation in IFT43 causes non-syndromic recessive retinal degeneration.";
RL Hum. Mol. Genet. 26:4741-4751(2017).
CC -!- FUNCTION: Probable sodium-dependent amino acid/proton antiporter, could
CC be a neuronal transporter for glutamate.
CC {ECO:0000250|UniProtKB:G3UVW3}.
CC -!- INTERACTION:
CC Q8IZM9; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-13377494, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:G3UVW3};
CC Multi-pass membrane protein {ECO:0000255}. Note=Colocalizes with
CC synaptotagmins and SNAP25. {ECO:0000250|UniProtKB:G3UVW3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IZM9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZM9-2; Sequence=VSP_029563;
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AF543422; AAN47144.1; -; mRNA.
DR EMBL; AL160236; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160234; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110378; AAI10379.1; -; mRNA.
DR EMBL; BX248072; CAD62361.1; -; mRNA.
DR CCDS; CCDS53900.1; -. [Q8IZM9-2]
DR CCDS; CCDS9751.1; -. [Q8IZM9-1]
DR RefSeq; NP_001166173.1; NM_001172702.1. [Q8IZM9-2]
DR RefSeq; NP_722518.2; NM_153811.2. [Q8IZM9-1]
DR AlphaFoldDB; Q8IZM9; -.
DR SMR; Q8IZM9; -.
DR BioGRID; 126909; 23.
DR IntAct; Q8IZM9; 2.
DR STRING; 9606.ENSP00000346959; -.
DR TCDB; 2.A.18.6.11; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q8IZM9; 2 sites.
DR iPTMnet; Q8IZM9; -.
DR PhosphoSitePlus; Q8IZM9; -.
DR BioMuta; SLC38A6; -.
DR DMDM; 296452887; -.
DR jPOST; Q8IZM9; -.
DR MassIVE; Q8IZM9; -.
DR PaxDb; Q8IZM9; -.
DR PeptideAtlas; Q8IZM9; -.
DR PRIDE; Q8IZM9; -.
DR Antibodypedia; 11535; 39 antibodies from 11 providers.
DR DNASU; 145389; -.
DR Ensembl; ENST00000267488.9; ENSP00000267488.4; ENSG00000139974.16. [Q8IZM9-1]
DR Ensembl; ENST00000354886.6; ENSP00000346959.2; ENSG00000139974.16. [Q8IZM9-2]
DR GeneID; 145389; -.
DR KEGG; hsa:145389; -.
DR MANE-Select; ENST00000267488.9; ENSP00000267488.4; NM_153811.3; NP_722518.2.
DR UCSC; uc001xfg.3; human. [Q8IZM9-1]
DR CTD; 145389; -.
DR DisGeNET; 145389; -.
DR GeneCards; SLC38A6; -.
DR HGNC; HGNC:19863; SLC38A6.
DR HPA; ENSG00000139974; Low tissue specificity.
DR MIM; 616518; gene.
DR neXtProt; NX_Q8IZM9; -.
DR OpenTargets; ENSG00000139974; -.
DR PharmGKB; PA134932150; -.
DR VEuPathDB; HostDB:ENSG00000139974; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000156982; -.
DR HOGENOM; CLU_009020_0_0_1; -.
DR InParanoid; Q8IZM9; -.
DR OMA; KARMQNV; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; Q8IZM9; -.
DR TreeFam; TF328787; -.
DR PathwayCommons; Q8IZM9; -.
DR SignaLink; Q8IZM9; -.
DR BioGRID-ORCS; 145389; 11 hits in 1065 CRISPR screens.
DR ChiTaRS; SLC38A6; human.
DR GenomeRNAi; 145389; -.
DR Pharos; Q8IZM9; Tdark.
DR PRO; PR:Q8IZM9; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8IZM9; protein.
DR Bgee; ENSG00000139974; Expressed in calcaneal tendon and 159 other tissues.
DR ExpressionAtlas; Q8IZM9; baseline and differential.
DR Genevisible; Q8IZM9; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015186; F:L-glutamine transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0006868; P:glutamine transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Amino-acid transport; Cell membrane;
KW Disulfide bond; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..456
FT /note="Probable sodium-coupled neutral amino acid
FT transporter 6"
FT /id="PRO_0000311421"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..347
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 218..238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 431..456
FT /note="AFVLLIFGILVGNFSLALIIFDWINK -> GLILSHRLACSGVISAHCNLCL
FT PDSSNPPTSASRVAETTGRDTMEMCTQRKGHARTQQEGNCLQAKGRGLRRTKRVHTLIL
FT HFPTSRTVSK (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_029563"
FT VARIANT 70
FT /note="L -> M (in dbSNP:rs976272)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1"
FT /id="VAR_037247"
FT VARIANT 419
FT /note="S -> T (in dbSNP:rs762713377)"
FT /evidence="ECO:0000269|PubMed:28973684"
FT /id="VAR_080631"
SQ SEQUENCE 456 AA; 50929 MW; 007D1339B4FBC618 CRC64;
MEASWGSFNA ERGWYVSVQQ PEEAEAEELS PLLSNELHRQ RSPGVSFGLS VFNLMNAIMG
SGILGLAYVL ANTGVFGFSF LLLTVALLAS YSVHLLLSMC IQTAVTSYED LGLFAFGLPG
KLVVAGTIII QNIGAMSSYL LIIKTELPAA IAEFLTGDYS RYWYLDGQTL LIIICVGIVF
PLALLPKIGF LGYTSSLSFF FMMFFALVVI IKKWSIPCPL TLNYVEKGFQ ISNVTDDCKP
KLFHFSKESA YALPTMAFSF LCHTSILPIY CELQSPSKKR MQNVTNTAIA LSFLIYFISA
LFGYLTFYDK VESELLKGYS KYLSHDVVVM TVKLCILFAV LLTVPLIHFP ARKAVTMMFF
SNFPFSWIRH FLITLALNII IVLLAIYVPD IRNVFGVVGA STSTCLIFIF PGLFYLKLSR
EDFLSWKKLG AFVLLIFGIL VGNFSLALII FDWINK
