SC6A7_RAT
ID SC6A7_RAT Reviewed; 637 AA.
AC P28573;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Sodium-dependent proline transporter;
DE AltName: Full=Solute carrier family 6 member 7;
GN Name=Slc6a7; Synonyms=Prot {ECO:0000303|PubMed:10414958};
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 STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1350201; DOI=10.1016/0896-6273(92)90206-s;
RA Fremeau R.T. Jr., Caron M.G., Blakely R.D.;
RT "Molecular cloning and expression of a high affinity L-proline transporter
RT expressed in putative glutamatergic pathways of rat brain.";
RL Neuron 8:915-926(1992).
RN [2]
RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10414958; DOI=10.1523/jneurosci.19-15-06290.1999;
RA Galli A., Jayanthi L.D., Ramsey I.S., Miller J.W., Fremeau R.T. Jr.,
RA DeFelice L.J.;
RT "L-proline and L-pipecolate induce enkephalin-sensitive currents in human
RT embryonic kidney 293 cells transfected with the high-affinity mammalian
RT brain L-proline transporter.";
RL J. Neurosci. 19:6290-6297(1999).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-573; SER-582; THR-588 AND
RP TYR-591, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-20 AND SER-22, 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: Brain specific sodium (and chloride)-dependent proline
CC transporter (PubMed:10414958). Terminates the action of proline by its
CC high affinity sodium-dependent reuptake into presynaptic terminals
CC (Probable). {ECO:0000269|PubMed:10414958, ECO:0000305|PubMed:10414958}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + L-proline(out) + 2 Na(+)(out) = chloride(in) +
CC L-proline(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71263, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29101, ChEBI:CHEBI:60039;
CC Evidence={ECO:0000269|PubMed:10414958};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + L-pipecolate(out) + 2 Na(+)(out) =
CC chloride(in) + L-pipecolate(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71267,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:61185;
CC Evidence={ECO:0000269|PubMed:10414958};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20.12 uM for L-proline {ECO:0000269|PubMed:10414958};
CC -!- SUBCELLULAR LOCATION: Synaptic cell membrane
CC {ECO:0000250|UniProtKB:Q99884}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in subpopulations of putative
CC glutamatergic pathways of rat brain.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A7 subfamily. {ECO:0000305}.
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DR EMBL; M88111; AAA41541.1; ALT_TERM; mRNA.
DR PIR; JH0674; JH0674.
DR RefSeq; NP_446448.2; NM_053996.2.
DR AlphaFoldDB; P28573; -.
DR SMR; P28573; -.
DR STRING; 10116.ENSRNOP00000025209; -.
DR TCDB; 2.A.22.2.1; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P28573; 1 site.
DR iPTMnet; P28573; -.
DR PhosphoSitePlus; P28573; -.
DR PaxDb; P28573; -.
DR PRIDE; P28573; -.
DR GeneID; 117100; -.
DR KEGG; rno:117100; -.
DR UCSC; RGD:620928; rat.
DR CTD; 6534; -.
DR RGD; 620928; Slc6a7.
DR eggNOG; KOG3660; Eukaryota.
DR InParanoid; P28573; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P28573; -.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-RNO-71288; Creatine metabolism.
DR PRO; PR:P28573; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0015193; F:L-proline transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005298; F:proline:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0035524; P:proline transmembrane transport; ISO:RGD.
DR GO; GO:0015824; P:proline transport; IDA:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 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.
PE 1: Evidence at protein level;
KW Amino-acid transport; Cell membrane; Glycoprotein; Membrane;
KW Neurotransmitter transport; Phosphoprotein; Reference proteome; Symport;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..637
FT /note="Sodium-dependent proline transporter"
FT /id="PRO_0000214772"
FT TOPO_DOM 1..45
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..93
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..233
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..259
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..312
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..345
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..397
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..443
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 500..519
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..556
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 588
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 591
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGE7"
FT MOD_RES 600
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGE7"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 637 AA; 71091 MW; 9627E6DD5BBC9408 CRC64;
MKKLQEAHLR KPVTPDLLMT PSDQGDVDLD VDFAADRGNW TGKLDFLLSC IGYCVGLGNV
WRFPYRAYTN GGGAFLVPYF LMLAICGIPL FFLELSLGQF SSLGPLAVWK ISPLFKGAGA
AMLLIVGLVA IYYNMIIAYV LFYLFASLTS NLPWEHCGNW WNTERCLEHR GPKDGNGALP
LNLSSTVSPS EEYWSRYVLH IQGSQGIGRP GEIRWNLCLC LLLAWVIVFL CILKGVKSSG
KVVYFTATFP YLILLMLLVR GVTLPGAWKG IQFYLTPQFH HLLSSKVWIE AALQIFYSLG
VGFGGLLTFA SYNTFHQNIY RDTFIVTLGN AITSILAGFA IFSVLGYMSQ ELGVPVDQVA
KAGPGLAFVI YPQAMTMLPL SPFWSFLFFF MLLTLGLDSQ FAFLETIVTA VTDEFPYYLR
PKKAVFSGLI CVAMYLMGLI LTTDGGMYWL VLLDDYSASF GLMVVVITTC LAVTRVYGIQ
RFCRDIHMML GFKPGLYFRA CWLFLSPATL LALLVYSIVK YQPSEYGSYR FPAWAELLGI
LMGLLSCLMI PAGMLVAVLR EEGSLWERLQ QASRPAIDWG PSLEENRTGM YVATLAGSQS
PKPLMVHMRK YGGITSFENT AIEVDREIAE EEEESMM
