SC6A7_HUMAN
ID SC6A7_HUMAN Reviewed; 636 AA.
AC Q99884; Q0VG81; Q52LU6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Sodium-dependent proline transporter {ECO:0000305};
DE AltName: Full=Solute carrier family 6 member 7;
GN Name=SLC6A7 {ECO:0000312|HGNC:HGNC:11054};
GN Synonyms=PROT {ECO:0000303|PubMed:7651355};
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 [MRNA], TRANSPORTER ACTIVITY, TISSUE SPECIFICITY,
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RC TISSUE=Hippocampus;
RX PubMed=7651355;
RA Shafqat S., Velaz-Faircloth M., Henzi V.A., Whitney K.D., Yang-Feng T.L.,
RA Seldin M.F., Fremeau R.T. Jr.;
RT "Human brain-specific L-proline transporter: molecular cloning, functional
RT expression, and chromosomal localization of the gene in human and mouse
RT genomes.";
RL Mol. Pharmacol. 48:219-229(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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).
CC -!- FUNCTION: Brain specific sodium (and chloride)-dependent proline
CC transporter (PubMed:7651355). Terminates the action of proline by its
CC high affinity sodium-dependent reuptake into presynaptic terminals
CC (Probable). {ECO:0000269|PubMed:7651355, ECO:0000305|PubMed:7651355}.
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:7651355};
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:0000250|UniProtKB:P28573};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.2 uM for L-proline {ECO:0000269|PubMed:7651355};
CC -!- SUBCELLULAR LOCATION: Synaptic cell membrane
CC {ECO:0000269|PubMed:7651355}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Brain specific (at protein level) (PubMed:7651355).
CC Highly expressed in hippocampus, corpus striatum and temporal cortex.
CC Also expressed in frontal cortex, occipital cortex and, at lower
CC levels, in cerebellum and parietal cortex (at protein level)
CC (PubMed:7651355). {ECO:0000269|PubMed:7651355}.
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; S80071; AAB47007.2; -; mRNA.
DR EMBL; AC005895; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069631; AAH69631.1; -; mRNA.
DR EMBL; BC093785; AAH93785.1; -; mRNA.
DR EMBL; BC113425; AAI13426.1; -; mRNA.
DR CCDS; CCDS4305.1; -.
DR RefSeq; NP_055043.2; NM_014228.4.
DR AlphaFoldDB; Q99884; -.
DR SMR; Q99884; -.
DR STRING; 9606.ENSP00000230671; -.
DR BindingDB; Q99884; -.
DR ChEMBL; CHEMBL3317335; -.
DR DrugBank; DB00172; Proline.
DR GuidetoPHARMACOLOGY; 938; -.
DR TCDB; 2.A.22.2.11; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q99884; 1 site.
DR iPTMnet; Q99884; -.
DR PhosphoSitePlus; Q99884; -.
DR BioMuta; SLC6A7; -.
DR DMDM; 296452899; -.
DR EPD; Q99884; -.
DR MassIVE; Q99884; -.
DR PaxDb; Q99884; -.
DR PeptideAtlas; Q99884; -.
DR PRIDE; Q99884; -.
DR ProteomicsDB; 78518; -.
DR Antibodypedia; 27933; 84 antibodies from 17 providers.
DR DNASU; 6534; -.
DR Ensembl; ENST00000230671.7; ENSP00000230671.2; ENSG00000011083.9.
DR GeneID; 6534; -.
DR KEGG; hsa:6534; -.
DR MANE-Select; ENST00000230671.7; ENSP00000230671.2; NM_014228.5; NP_055043.2.
DR UCSC; uc003lrr.3; human.
DR CTD; 6534; -.
DR DisGeNET; 6534; -.
DR GeneCards; SLC6A7; -.
DR HGNC; HGNC:11054; SLC6A7.
DR HPA; ENSG00000011083; Tissue enriched (brain).
DR MIM; 606205; gene.
DR neXtProt; NX_Q99884; -.
DR OpenTargets; ENSG00000011083; -.
DR PharmGKB; PA35914; -.
DR VEuPathDB; HostDB:ENSG00000011083; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000160823; -.
DR HOGENOM; CLU_006855_9_4_1; -.
DR InParanoid; Q99884; -.
DR OMA; REEGTLW; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; Q99884; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; Q99884; -.
DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-HSA-71288; Creatine metabolism.
DR BioGRID-ORCS; 6534; 10 hits in 1065 CRISPR screens.
DR ChiTaRS; SLC6A7; human.
DR GenomeRNAi; 6534; -.
DR Pharos; Q99884; Tchem.
DR PRO; PR:Q99884; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q99884; protein.
DR Bgee; ENSG00000011083; Expressed in right hemisphere of cerebellum and 70 other tissues.
DR ExpressionAtlas; Q99884; baseline and differential.
DR Genevisible; Q99884; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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: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..636
FT /note="Sodium-dependent proline transporter"
FT /id="PRO_0000214770"
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..636
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGE7"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGE7"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28573"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28573"
FT MOD_RES 588
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P28573"
FT MOD_RES 591
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P28573"
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"
FT VARIANT 345
FT /note="L -> V (in dbSNP:rs1468564)"
FT /id="VAR_011390"
FT CONFLICT 514
FT /note="M -> L (in Ref. 1; AAB47007 and 3; AAH69631/
FT AAH93785/AAI13426)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 636 AA; 70911 MW; 9B9D10C1F49E409B CRC64;
MKKLQGAHLR KPVTPDLLMT PSDQGDVDLD VDFAAHRGNW TGKLDFLLSC IGYCVGLGNV
WRFPYRAYTN GGGAFLVPYF LMLAICGIPL FFLELSLGQF SSLGPLAVWK ISPLFKGAGA
AMLLIVGLVA IYYNMIIAYV LFYLFASLTS DLPWEHCGNW WNTELCLEHR VSKDGNGALP
LNLTCTVSPS EEYWSRYVLH IQGSQGIGSP GEIRWNLCLC LLLAWVIVFL CILKGVKSSG
KVVYFTATFP YLILLMLLVR GVTLPGAWKG IQFYLTPQFH HLLSSKVWIE AALQIFYSLG
VGFGGLLTFA SYNTFHQNIY RDTFIVTLGN AITSILAGFA IFSVLGYMSQ ELGVPVDQVA
KAGPGLAFVV YPQAMTMLPL SPFWSFLFFF MLLTLGLDSQ FAFLETIVTA VTDEFPYYLR
PKKAVFSGLI CVAMYLMGLI LTTDGGMYWL VLLDDYSASF GLMVVVITTC LAVTRVYGIQ
RFCRDIHMML GFKPGLYFRA CWLFLSPATL LALMVYSIVK YQPSEYGSYR FPPWAELLGI
LMGLLSCLMI PAGMLVAVLR EEGSLWERLQ QASRPAMDWG PSLEENRTGM YVATLAGSQS
PKPLMVHMRK YGGITSFENT AIEVDREIAE EEESMM
