ID   S6A17_RAT               Reviewed;         727 AA.
AC   P31662;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   24-JAN-2024, entry version 138.
DE   RecName: Full=Sodium-dependent neutral amino acid transporter SLC6A17;
DE   AltName: Full=Sodium-dependent neurotransmitter transporter NTT4;
DE   AltName: Full=Solute carrier family 6 member 17;
GN   Name=Slc6a17 {ECO:0000303|PubMed:18768736};
GN   Synonyms=Ntt4 {ECO:0000303|PubMed:18768736}, Rxt1
GN   {ECO:0000303|PubMed:18768736};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8093354; DOI=10.1016/0014-5793(93)81145-p;
RA   Liu Q.-R., Mandiyan S., Lopez-Corcuera B., Nelson H., Nelson N.;
RT   "A rat brain cDNA encoding the neurotransmitter transporter with an unusual
RT   structure.";
RL   FEBS Lett. 315:114-118(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8294906; DOI=10.1046/j.1471-4159.1994.62020445.x;
RA   el Mestikawy S., Giros B., Pohl M., Hamon M., Kingsmore S.F., Seldin M.F.,
RA   Caron M.G.;
RT   "Characterization of an atypical member of the Na+/Cl(-)-dependent
RT   transporter family: chromosomal localization and distribution in GABAergic
RT   and glutamatergic neurons in the rat brain.";
RL   J. Neurochem. 62:445-455(1994).
RN   [3]
RP   IDENTIFICATION, AND TISSUE SPECIFICITY.
RX   PubMed=16125675; DOI=10.1016/j.bbrc.2005.08.048;
RA   Hoglund P.J., Adzic D., Scicluna S.J., Lindblom J., Fredriksson R.;
RT   "The repertoire of solute carriers of family 6: identification of new human
RT   and rodent genes.";
RL   Biochem. Biophys. Res. Commun. 336:175-189(2005).
RN   [4]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP   SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=18768736; DOI=10.1124/mol.108.050005;
RA   Parra L.A., Baust T., El Mestikawy S., Quiroz M., Hoffman B., Haflett J.M.,
RA   Yao J.K., Torres G.E.;
RT   "The orphan transporter Rxt1/NTT4 (SLC6A17) functions as a synaptic vesicle
RT   amino acid transporter selective for proline, glycine, leucine, and
RT   alanine.";
RL   Mol. Pharmacol. 74:1521-1532(2008).
RN   [5]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=19147495; DOI=10.1074/jbc.m806407200;
RA   Zaia K.A., Reimer R.J.;
RT   "Synaptic vesicle protein NTT4/XT1 (SLC6A17) catalyzes Na+-coupled neutral
RT   amino acid transport.";
RL   J. Biol. Chem. 284:8439-8448(2009).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-665 AND SER-701, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Synaptic vesicle transporter with apparent selectivity for
CC       neutral amino acids. The transport is sodium-coupled but chloride-
CC       independent, likely driven by the proton electrochemical gradient
CC       generated by vacuolar H(+)-ATPase in an overall electrogenic mechanism.
CC       May contribute to the synaptic uptake of neurotransmitter precursors in
CC       a process coupled in part to vesicle exocytosis.
CC       {ECO:0000269|PubMed:18768736, ECO:0000269|PubMed:19147495}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:28967, ChEBI:CHEBI:29101, ChEBI:CHEBI:60039;
CC         Evidence={ECO:0000305|PubMed:18768736, ECO:0000305|PubMed:19147495};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:29263, ChEBI:CHEBI:29101, ChEBI:CHEBI:57427;
CC         Evidence={ECO:0000305|PubMed:18768736, ECO:0000305|PubMed:19147495};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:68228, ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC         Evidence={ECO:0000305|PubMed:18768736, ECO:0000305|PubMed:19147495};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972;
CC         Evidence={ECO:0000305|PubMed:18768736, ECO:0000305|PubMed:19147495};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out);
CC         Xref=Rhea:RHEA:68236, ChEBI:CHEBI:29101, ChEBI:CHEBI:58359;
CC         Evidence={ECO:0000305|PubMed:18768736, ECO:0000305|PubMed:19147495};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.86 mM for L-proline {ECO:0000269|PubMed:18768736};
CC         KM=0.36 mM for L-proline {ECO:0000269|PubMed:19147495};
CC         KM=1.72 mM for glycine {ECO:0000269|PubMed:18768736};
CC         KM=5.2 mM for L-glutamine {ECO:0000269|PubMed:19147495};
CC         Vmax=172 pmol/min/mg enzyme for L-proline
CC         {ECO:0000269|PubMed:18768736};
CC         Vmax=199 pmol/min/mg enzyme for glycine
CC         {ECO:0000269|PubMed:18768736};
CC       pH dependence:
CC         Optimum pH is 8.5. {ECO:0000269|PubMed:18768736,
CC         ECO:0000269|PubMed:19147495};
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC       vesicle membrane {ECO:0000269|PubMed:18768736,
CC       ECO:0000269|PubMed:19147495}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:18768736, ECO:0000269|PubMed:19147495}. Postsynapse
CC       {ECO:0000250|UniProtKB:Q8BJI1}. Presynapse
CC       {ECO:0000250|UniProtKB:Q8BJI1}. Note=Localizes at synaptic junctions
CC       - at both pre- and post-synaptic sites - particularly in excitatory
CC       glutamatergic terminals. {ECO:0000250|UniProtKB:Q8BJI1}.
CC   -!- TISSUE SPECIFICITY: Found exclusively in the central nervous system and
CC       is more abundant in the cerebellum and the cerebral cortex. Expressed
CC       in PC-12 cell line. {ECO:0000269|PubMed:16125675,
CC       ECO:0000269|PubMed:18768736}.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. {ECO:0000305}.
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DR   EMBL; L06434; AAB24776.1; -; mRNA.
DR   EMBL; S68944; AAC60673.1; -; mRNA.
DR   PIR; I56506; I56506.
DR   PIR; S27043; S27043.
DR   RefSeq; NP_001028251.1; NM_001033079.1.
DR   AlphaFoldDB; P31662; -.
DR   SMR; P31662; -.
DR   BioGRID; 565981; 1.
DR   STRING; 10116.ENSRNOP00000065179; -.
DR   TCDB; 2.A.22.6.2; the neurotransmitter:sodium symporter (nss) family.
DR   GlyCosmos; P31662; 2 sites, No reported glycans.
DR   GlyGen; P31662; 2 sites.
DR   iPTMnet; P31662; -.
DR   PhosphoSitePlus; P31662; -.
DR   SwissPalm; P31662; -.
DR   PaxDb; 10116-ENSRNOP00000065179; -.
DR   Ensembl; ENSRNOT00000075653.3; ENSRNOP00000065179.1; ENSRNOG00000050090.3.
DR   Ensembl; ENSRNOT00055034824; ENSRNOP00055028241; ENSRNOG00055020383.
DR   Ensembl; ENSRNOT00060042446; ENSRNOP00060035162; ENSRNOG00060024513.
DR   Ensembl; ENSRNOT00065039458; ENSRNOP00065032084; ENSRNOG00065023082.
DR   GeneID; 613226; -.
DR   KEGG; rno:613226; -.
DR   AGR; RGD:1587185; -.
DR   CTD; 388662; -.
DR   RGD; 1587185; Slc6a17.
DR   eggNOG; KOG3659; Eukaryota.
DR   GeneTree; ENSGT00940000156542; -.
DR   HOGENOM; CLU_006855_7_1_1; -.
DR   InParanoid; P31662; -.
DR   OMA; DYTEMYK; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; P31662; -.
DR   PRO; PR:P31662; -.
DR   Proteomes; UP000002494; Chromosome 2.
DR   Bgee; ENSRNOG00000050090; Expressed in frontal cortex and 15 other cell types or tissues.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; IEA:InterPro.
DR   GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IDA:SynGO.
DR   GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR   GO; GO:0032328; P:alanine transport; IDA:UniProtKB.
DR   GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR   GO; GO:0015816; P:glycine transport; IDA:UniProtKB.
DR   GO; GO:0015820; P:leucine transport; IDA:UniProtKB.
DR   GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR   GO; GO:0015804; P:neutral amino acid transport; IDA:UniProtKB.
DR   GO; GO:0015824; P:proline transport; IDA:UniProtKB.
DR   GO; GO:0030163; P:protein catabolic process; IDA:SynGO.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   CDD; cd11521; SLC6sbd_NTT4; 1.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR002438; Neutral_aa_SLC6.
DR   InterPro; IPR037272; SNS_sf.
DR   NCBIfam; NF037979; Na_transp; 1.
DR   PANTHER; PTHR11616:SF102; SODIUM-DEPENDENT NEUTRAL AMINO ACID TRANSPORTER SLC6A17; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR00176; NANEUSMPORT.
DR   PRINTS; PR01206; ORPHTRNSPORT.
DR   SUPFAM; SSF161070; SNF-like; 1.
DR   PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR   PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR   PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
DR   Genevisible; P31662; RN.
PE   1: Evidence at protein level;
KW   Amino-acid transport; Cell projection; Cytoplasmic vesicle; Glycoprotein;
KW   Ion transport; Membrane; Neurotransmitter transport; Phosphoprotein;
KW   Reference proteome; Sodium; Sodium transport; Symport; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..727
FT                   /note="Sodium-dependent neutral amino acid transporter
FT                   SLC6A17"
FT                   /id="PRO_0000214805"
FT   TOPO_DOM        1..68
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        69..89
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        90..96
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..116
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        117..140
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        141..161
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        162..224
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..243
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        244..251
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        252..269
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        270..304
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        305..322
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        323..333
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        334..355
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        356..451
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        452..471
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        472..494
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        495..513
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        514..528
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        529..549
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        550..569
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        570..591
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        592..618
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        619..641
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        642..727
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          680..727
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        693..712
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT   MOD_RES         20
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT   MOD_RES         377
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT   MOD_RES         665
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         701
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        393
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        261
FT                   /note="Y -> C (in Ref. 2; AAC60673)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        499
FT                   /note="G -> S (in Ref. 2; AAC60673)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   727 AA;  81055 MW;  C676048C0A6BDF7C CRC64;
     MPKNSKVTQR EHSNEHVTES VADLLALEEP VDYKQSVLNV AGETGGKQKV AEEELDAEDR
     PAWNSKLQYI LAQIGFSVGL GNIWRFPYLC QKNGGGAYLV PYLVLLIIIG IPLFFLELAV
     GQRIRRGSIG VWHYVCPRLG GIGFSSCIVC LFVGLYYNVI IGWSVFYFFK SFQYPLPWSE
     CPVIRNGTVA VVEPECEKSS ATTYFWYREA LDISNSISES GGLNWKMTVC LLVAWSIVGM
     AVVKGIQSSG KVMYFSSLFP YVVLACFLVR GLLLRGAVDG ILHMFTPKLD KMLDPQVWRE
     AATQVFFALG LGFGGVIAFS SYNKQDNNCH FDAALVSFIN FFTSVLATLV VFAVLGFKAN
     IMNEKCVVEN AEKILGYLNS NVLSRDLIPP HVNFSHLTTK DYSEMYNVIM TVKEKQFSAL
     GLDPCLLEDE LDKSVQGTGL AFIAFTEAMT HFPASPFWSV MFFLMLINLG LGSMIGTMAG
     ITTPIIDTFK VPKEMFTVGC CVFAFFVGLL FVQRSGNYFV TMFDDYSATL PLTVIVILEN
     IAVAWIYGTK KFMQELTEML GFRPYRFYFY MWKFVSPLCM AVLTTASIIQ LGVSPPGYSA
     WIKEEAAERY LYFPNWAMAL LITLIAVATL PIPVVFILRH FHLLSDGSNT LSVSYKKGRM
     MKDISNLEEN DETRFILSKV PSEAPSPMPT HRSYLGPGST SPLESSSHPN GRYGSGYLLA
     STPESEL
//