S38A9_DANRE
ID S38A9_DANRE Reviewed; 549 AA.
AC Q08BA4;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Sodium-coupled neutral amino acid transporter 9 {ECO:0000305};
DE AltName: Full=Solute carrier family 38 member 9;
GN Name=slc38a9; ORFNames=zgc:154088;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:6C08}
RP X-RAY CRYSTALLOGRAPHY (3.17 ANGSTROMS) OF 71-549 IN COMPLEX WITH ARGININE,
RP ACTIVITY REGULATION, TOPOLOGY, MUTAGENESIS OF MET-118 AND MET-119, AND
RP DISULFIDE BONDS.
RX PubMed=29872228; DOI=10.1038/s41594-018-0072-2;
RA Lei H.T., Ma J., Sanchez Martinez S., Gonen T.;
RT "Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the
RT cytosol-open state.";
RL Nat. Struct. Mol. Biol. 25:522-527(2018).
CC -!- FUNCTION: Lysosomal amino acid transporter involved in the activation
CC of mTORC1 in response to amino acid levels. Probably acts as an amino
CC acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes
CC involved in amino acid sensing and activation of mTORC1, a signaling
CC complex promoting cell growth in response to growth factors, energy
CC levels, and amino acids. Following activation by amino acids, the
CC Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to
CC lysosomes where it is in turn activated. SLC38A9 mediates transport of
CC amino acids with low capacity and specificity with a slight preference
CC for polar amino acids. Acts as an arginine sensor. Following activation
CC by arginine binding, mediates transport of leucine, tyrosine and
CC phenylalanine with high efficiency, and is required for the efficient
CC utilization of these amino acids after lysosomal protein degradation.
CC {ECO:0000250|UniProtKB:Q8NBW4}.
CC -!- ACTIVITY REGULATION: Amino acid transport is sodium-dependent
CC (PubMed:29872228). Transport of leucine, tyrosine and phenylalanine is
CC increased by arginine binding (By similarity).
CC {ECO:0000250|UniProtKB:Q8NBW4, ECO:0000269|PubMed:29872228}.
CC -!- SUBUNIT: Associated component of the Ragulator complex. Associated
CC component of the Rag GTPases heterodimers.
CC {ECO:0000250|UniProtKB:Q8NBW4}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8NBW4};
CC Multi-pass membrane protein {ECO:0000269|PubMed:29872228}. Late
CC endosome membrane {ECO:0000250|UniProtKB:Q8NBW4}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:29872228}.
CC -!- DOMAIN: The cytosolic N-terminus part of the protein mediates
CC interaction with the Ragulator complex and the Rag GTPases
CC heterodimers. {ECO:0000250|UniProtKB:Q8NBW4}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC SLC38A9 subfamily. {ECO:0000305}.
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DR EMBL; BC124808; AAI24809.1; -; mRNA.
DR RefSeq; NP_001073468.1; NM_001079999.1.
DR PDB; 6C08; X-ray; 3.17 A; C/F=71-549.
DR PDB; 7KGV; X-ray; 3.40 A; A/B=1-549.
DR PDBsum; 6C08; -.
DR PDBsum; 7KGV; -.
DR AlphaFoldDB; Q08BA4; -.
DR SMR; Q08BA4; -.
DR STRING; 7955.ENSDARP00000041067; -.
DR TCDB; 2.A.18.9.2; the amino acid/auxin permease (aaap) family.
DR PaxDb; Q08BA4; -.
DR ABCD; Q08BA4; 1 sequenced antibody.
DR Ensembl; ENSDART00000041068; ENSDARP00000041067; ENSDARG00000032769.
DR GeneID; 562137; -.
DR KEGG; dre:562137; -.
DR CTD; 153129; -.
DR ZFIN; ZDB-GENE-061013-597; slc38a9.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00390000005646; -.
DR HOGENOM; CLU_037564_0_0_1; -.
DR InParanoid; Q08BA4; -.
DR OMA; HWFTPTE; -.
DR OrthoDB; 941044at2759; -.
DR PhylomeDB; Q08BA4; -.
DR TreeFam; TF312989; -.
DR Reactome; R-DRE-1632852; Macroautophagy.
DR Reactome; R-DRE-165159; MTOR signalling.
DR Reactome; R-DRE-166208; mTORC1-mediated signalling.
DR Reactome; R-DRE-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-DRE-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DRE-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-DRE-9639288; Amino acids regulate mTORC1.
DR PRO; PR:Q08BA4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 10.
DR Bgee; ENSDARG00000032769; Expressed in mature ovarian follicle and 20 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IDA:ZFIN.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003333; P:amino acid transmembrane transport; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid transport; Disulfide bond; Endosome; Glycoprotein;
KW Lysosome; Membrane; Metal-binding; Reference proteome; Sodium;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..549
FT /note="Sodium-coupled neutral amino acid transporter 9"
FT /id="PRO_0000328843"
FT TOPO_DOM 1..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 108..128
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 129..134
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 135..155
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 156..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 187..213
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 214..271
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 272..288
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 289..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 298..322
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 323..344
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 345..365
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 366..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 383..403
FT /note="Helical; Name=7"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 404..425
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 426..446
FT /note="Helical; Name=8"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 447..467
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 468..488
FT /note="Helical; Name=9"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 489..495
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 496..516
FT /note="Helical; Name=10"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TOPO_DOM 517..528
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29872228"
FT TRANSMEM 529..549
FT /note="Helical; Name=11"
FT /evidence="ECO:0000269|PubMed:29872228"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 117..122
FT /note="Important for arginine binding and amino acid
FT transport"
FT /evidence="ECO:0000269|PubMed:29872228"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 242..412
FT /evidence="ECO:0000269|PubMed:29872228,
FT ECO:0007744|PDB:6C08"
FT MUTAGEN 118
FT /note="M->A: Loss of arginine transport."
FT /evidence="ECO:0000269|PubMed:29872228"
FT MUTAGEN 119
FT /note="M->A: Loss of arginine transport."
FT /evidence="ECO:0000269|PubMed:29872228"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 126..133
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 135..154
FT /evidence="ECO:0007829|PDB:6C08"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 188..217
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 304..324
FT /evidence="ECO:0007829|PDB:6C08"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:7KGV"
FT HELIX 347..355
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:6C08"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 378..402
FT /evidence="ECO:0007829|PDB:6C08"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:7KGV"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 426..447
FT /evidence="ECO:0007829|PDB:6C08"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 451..456
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 472..485
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:6C08"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 496..504
FT /evidence="ECO:0007829|PDB:6C08"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 508..516
FT /evidence="ECO:0007829|PDB:6C08"
FT HELIX 528..547
FT /evidence="ECO:0007829|PDB:6C08"
SQ SEQUENCE 549 AA; 61897 MW; EC5E5534EF888B57 CRC64;
MDEDSKPLLG SVPTGDYYTD SLDPKQRRPF HVEPRNIVGE DVQERVSAEA AVLSSRVHYY
SRLTGSSDRL LAPPDHVIPS HEDIYIYSPL GTAFKVQGGD SPIKNPSIVT IFAIWNTMMG
TSILSIPWGI KQAGFTLGII IIVLMGLLTL YCCYRVLKST KSIPYVDTSD WEFPDVCKYY
FGGFGKWSSL VFSLVSLIGA MVVYWVLMSN FLFNTGKFIF NYVHNVNTSD AFGTNGTERV
ICPYPDVDPH GNSSTSLYSG SDNSTGLEFD HWWSKTNTIP FYLILLLLPL LNFRSASFFA
RFTFLGTISV IYLIFLVTYK AIQLGFHLEF HWFDSSMFFV PEFRTLFPQL SGVLTLAFFI
HNCIITLMKN NKHQENNVRD LSLAYLLVGL TYLYVGVLIF AAFPSPPLSK ECIEPNFLDN
FPSSDILVFV ARTFLLFQMT TVYPLLGYLV RVQLMGQIFG NHYPGFLHVF VLNVFVVGAG
VLMARFYPNI GSIIRYSGAL CGLALVFVLP SLIHMVSLKR RGELRWTSTL FHGFLILLGV
ANLLGQFFM
