ID   SC6A5_HUMAN             Reviewed;         797 AA.
AC   Q9Y345; O95288; Q4VAM7; Q9BX77;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   24-JAN-2024, entry version 191.
DE   RecName: Full=Sodium- and chloride-dependent glycine transporter 2;
DE            Short=GlyT-2;
DE            Short=GlyT2;
DE   AltName: Full=Solute carrier family 6 member 5;
GN   Name=SLC6A5; Synonyms=GLYT2, NET1;
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], FUNCTION, TRANSPORTER ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND VARIANTS SER-124 AND
RP   GLY-162.
RX   PubMed=9845349; DOI=10.1016/s0014-5793(98)01390-8;
RA   Morrow J.A., Collie I.T., Dunbar D.R., Walker G.B., Shahid M., Hill D.R.;
RT   "Molecular cloning and functional expression of the human glycine
RT   transporter GlyT2 and chromosomal localisation of the gene in the human
RT   genome.";
RL   FEBS Lett. 439:334-340(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING (ISOFORMS 2 AND 3),
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANTS
RP   SER-102; SER-124 AND GLY-162.
RC   TISSUE=Spinal cord;
RX   PubMed=10381548; DOI=10.1016/s0169-328x(99)00135-7;
RA   Gallagher M.J., Burgess L.H., Brunden K.R.;
RT   "Characterization of multiple forms of the human glycine transporter type-
RT   2.";
RL   Brain Res. Mol. Brain Res. 70:101-115(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS SER-124; GLY-162; ARG-184; ASN-463
RP   AND ALA-751, AND CHARACTERIZATION OF VARIANTS ARG-184; ASN-463 AND ALA-751.
RC   TISSUE=Spinal cord;
RX   PubMed=10606742; DOI=10.1016/s0014-5793(99)01636-1;
RA   Evans J., Herdon H., Cairns W., O'Brien E., Chapman C., Terrett J.,
RA   Gloger I.;
RT   "Cloning, functional characterisation and population analysis of a variant
RT   form of the human glycine type 2 transporter.";
RL   FEBS Lett. 463:301-306(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-124 AND GLY-162.
RA   Luyten W.;
RT   "Cloning and expression of a human glycine transporter type II.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-124 AND GLY-162.
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   [7]
RP   VARIANTS HKPX3 VAL-306; MET-425; CYS-482; CYS-491; SER-509 AND ARG-510,
RP   VARIANT GLU-89, CHARACTERIZATION OF VARIANTS HKPX3 VAL-306; MET-425;
RP   CYS-482; CYS-491; SER-509 AND ARG-510, CHARACTERIZATION OF VARIANT GLU-89,
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=16751771; DOI=10.1038/ng1814;
RA   Rees M.I., Harvey K., Pearce B.R., Chung S.K., Duguid I.C., Thomas P.,
RA   Beatty S., Graham G.E., Armstrong L., Shiang R., Abbott K.J., Zuberi S.M.,
RA   Stephenson J.B., Owen M.J., Tijssen M.A., van den Maagdenberg A.M.,
RA   Smart T.G., Supplisson S., Harvey R.J.;
RT   "Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic
RT   component of human startle disease.";
RL   Nat. Genet. 38:801-806(2006).
RN   [8]
RP   VARIANT [LARGE SCALE ANALYSIS] GLU-632.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [9]
RP   VARIANT CYS-705, CHARACTERIZATION OF VARIANT CYS-705, AND MUTAGENESIS OF
RP   TYR-705.
RX   PubMed=22753417; DOI=10.1074/jbc.m111.319244;
RA   Gimenez C., Perez-Siles G., Martinez-Villarreal J., Arribas-Gonzalez E.,
RA   Jimenez E., Nunez E., de Juan-Sanz J., Fernandez-Sanchez E.,
RA   Garcia-Tardon N., Ibanez I., Romanelli V., Nevado J., James V.M., Topf M.,
RA   Chung S.K., Thomas R.H., Desviat L.R., Aragon C., Zafra F., Rees M.I.,
RA   Lapunzina P., Harvey R.J., Lopez-Corcuera B.;
RT   "A novel dominant hyperekplexia mutation Y705C alters trafficking and
RT   biochemical properties of the presynaptic glycine transporter GlyT2.";
RL   J. Biol. Chem. 287:28986-29002(2012).
RN   [10]
RP   VARIANT HKPX3 LEU-429, CHARACTERIZATION OF VARIANT HKPX3 LEU-429, FUNCTION,
RP   SUBCELLULAR LOCATION, GLYCOSYLATION, TRANSPORTER ACTIVITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=31370103; DOI=10.1111/ejn.14533;
RA   Kitzenmaier A., Schaefer N., Kasaragod V.B., Polster T., Hantschmann R.,
RA   Schindelin H., Villmann C.;
RT   "The P429L loss of function mutation of the human glycine transporter 2
RT   associated with hyperekplexia.";
RL   Eur. J. Neurosci. 50:3906-3920(2019).
CC   -!- FUNCTION: Sodium- and chloride-dependent glycine transporter
CC       (PubMed:9845349, PubMed:10381548, PubMed:10606742, PubMed:31370103,
CC       PubMed:16751771). Terminates the action of glycine by its high affinity
CC       sodium-dependent reuptake into presynaptic terminals (PubMed:9845349).
CC       May be responsible for the termination of neurotransmission at
CC       strychnine-sensitive glycinergic synapses (PubMed:9845349).
CC       {ECO:0000269|PubMed:10381548, ECO:0000269|PubMed:10606742,
CC       ECO:0000269|PubMed:16751771, ECO:0000269|PubMed:31370103,
CC       ECO:0000269|PubMed:9845349}.
CC   -!- FUNCTION: [Isoform 2]: Lacks sodium- and chloride-dependent glycine
CC       transporter activity. {ECO:0000269|PubMed:10381548}.
CC   -!- FUNCTION: [Isoform 3]: Lacks sodium- and chloride-dependent glycine
CC       transporter activity. {ECO:0000269|PubMed:10381548}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + glycine(out) + 3 Na(+)(out) = chloride(in) +
CC         glycine(in) + 3 Na(+)(in); Xref=Rhea:RHEA:70695, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC         Evidence={ECO:0000269|PubMed:10381548, ECO:0000269|PubMed:10606742,
CC         ECO:0000269|PubMed:16751771, ECO:0000269|PubMed:31370103,
CC         ECO:0000269|PubMed:9845349};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=108 uM for glycine {ECO:0000269|PubMed:9845349};
CC         KM=10.4 uM for glycine {ECO:0000269|PubMed:10381548};
CC         KM=160 uM for glycine {ECO:0000269|PubMed:10606742};
CC         KM=66 uM for glycine {ECO:0000269|PubMed:16751771};
CC         KM=239 uM for glycine {ECO:0000269|PubMed:31370103};
CC         Vmax=190 pmol/min/mg enzyme for glycine
CC         {ECO:0000269|PubMed:10381548};
CC         Vmax=3734 pmol/min/mg enzyme for glycine
CC         {ECO:0000269|PubMed:10606742};
CC         Vmax=1.64 nmol/min/mg enzyme for glycine
CC         {ECO:0000269|PubMed:16751771};
CC         Vmax=8.8 nmol/min/mg enzyme for glycine
CC         {ECO:0000269|PubMed:31370103};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16751771,
CC       ECO:0000269|PubMed:31370103}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9Y345-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y345-2; Sequence=VSP_061562;
CC       Name=3;
CC         IsoId=Q9Y345-3; Sequence=VSP_061563;
CC   -!- TISSUE SPECIFICITY: Expressed in medulla, and to a lesser extent in
CC       spinal cord and cerebellum. {ECO:0000269|PubMed:9845349}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:31370103}.
CC   -!- DISEASE: Hyperekplexia 3 (HKPX3) [MIM:614618]: A neurologic disorder
CC       characterized by neonatal hypertonia, an exaggerated startle response
CC       to tactile or acoustic stimuli, and life-threatening neonatal apnea
CC       episodes. Notably, in some cases, symptoms resolved in the first year
CC       of life. {ECO:0000269|PubMed:16751771, ECO:0000269|PubMed:31370103}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. SLC6A5 subfamily. {ECO:0000305}.
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DR   EMBL; AF085412; AAC95145.1; -; mRNA.
DR   EMBL; AF142501; AAD27892.1; -; mRNA.
DR   EMBL; AF352733; AAK29670.1; -; mRNA.
DR   EMBL; AF117999; AAK12641.1; -; mRNA.
DR   EMBL; AC090707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC096319; AAH96319.1; -; mRNA.
DR   CCDS; CCDS7854.1; -. [Q9Y345-1]
DR   RefSeq; NP_001305298.1; NM_001318369.1. [Q9Y345-2]
DR   RefSeq; NP_004202.3; NM_004211.4. [Q9Y345-1]
DR   AlphaFoldDB; Q9Y345; -.
DR   SMR; Q9Y345; -.
DR   BioGRID; 114599; 40.
DR   IntAct; Q9Y345; 10.
DR   STRING; 9606.ENSP00000434364; -.
DR   BindingDB; Q9Y345; -.
DR   ChEMBL; CHEMBL3060; -.
DR   DrugBank; DB00145; Glycine.
DR   DrugCentral; Q9Y345; -.
DR   GuidetoPHARMACOLOGY; 936; -.
DR   TCDB; 2.A.22.2.10; the neurotransmitter:sodium symporter (nss) family.
DR   GlyCosmos; Q9Y345; 4 sites, No reported glycans.
DR   GlyGen; Q9Y345; 4 sites.
DR   iPTMnet; Q9Y345; -.
DR   PhosphoSitePlus; Q9Y345; -.
DR   BioMuta; SLC6A5; -.
DR   DMDM; 296452967; -.
DR   MassIVE; Q9Y345; -.
DR   PaxDb; 9606-ENSP00000434364; -.
DR   PeptideAtlas; Q9Y345; -.
DR   ProteomicsDB; 85975; -.
DR   Antibodypedia; 25288; 89 antibodies from 22 providers.
DR   DNASU; 9152; -.
DR   Ensembl; ENST00000525748.6; ENSP00000434364.2; ENSG00000165970.12. [Q9Y345-1]
DR   GeneID; 9152; -.
DR   KEGG; hsa:9152; -.
DR   MANE-Select; ENST00000525748.6; ENSP00000434364.2; NM_004211.5; NP_004202.4.
DR   UCSC; uc001mqd.4; human. [Q9Y345-1]
DR   AGR; HGNC:11051; -.
DR   CTD; 9152; -.
DR   DisGeNET; 9152; -.
DR   GeneCards; SLC6A5; -.
DR   GeneReviews; SLC6A5; -.
DR   HGNC; HGNC:11051; SLC6A5.
DR   HPA; ENSG00000165970; Not detected.
DR   MalaCards; SLC6A5; -.
DR   MIM; 604159; gene.
DR   MIM; 614618; phenotype.
DR   neXtProt; NX_Q9Y345; -.
DR   OpenTargets; ENSG00000165970; -.
DR   Orphanet; 3197; Hereditary hyperekplexia.
DR   PharmGKB; PA35911; -.
DR   VEuPathDB; HostDB:ENSG00000165970; -.
DR   eggNOG; KOG3660; Eukaryota.
DR   GeneTree; ENSGT00940000154963; -.
DR   HOGENOM; CLU_006855_4_0_1; -.
DR   InParanoid; Q9Y345; -.
DR   OMA; GAPKEMN; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; Q9Y345; -.
DR   TreeFam; TF343812; -.
DR   PathwayCommons; Q9Y345; -.
DR   Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR   Reactome; R-HSA-5619089; Defective SLC6A5 causes hyperekplexia 3 (HKPX3).
DR   SignaLink; Q9Y345; -.
DR   BioGRID-ORCS; 9152; 12 hits in 1149 CRISPR screens.
DR   ChiTaRS; SLC6A5; human.
DR   GeneWiki; Glycine_transporter_2; -.
DR   GenomeRNAi; 9152; -.
DR   Pharos; Q9Y345; Tchem.
DR   PRO; PR:Q9Y345; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9Y345; Protein.
DR   Bgee; ENSG00000165970; Expressed in secondary oocyte and 28 other cell types or tissues.
DR   ExpressionAtlas; Q9Y345; baseline and differential.
DR   GO; GO:0031045; C:dense core granule; ISS:ARUK-UCL.
DR   GO; GO:0005768; C:endosome; ISS:ARUK-UCL.
DR   GO; GO:0098690; C:glycinergic synapse; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl.
DR   GO; GO:0015375; F:glycine:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR   GO; GO:1903804; P:glycine import across plasma membrane; IDA:FlyBase.
DR   GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0060012; P:synaptic transmission, glycinergic; IMP:FlyBase.
DR   CDD; cd11499; SLC6sbd_GlyT2; 1.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR037272; SNS_sf.
DR   PANTHER; PTHR11616:SF315; SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 2; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR00176; NANEUSMPORT.
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; Q9Y345; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW   Glycoprotein; Membrane; Metal-binding; Neurotransmitter transport;
KW   Phosphoprotein; Reference proteome; Sodium; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..797
FT                   /note="Sodium- and chloride-dependent glycine transporter
FT                   2"
FT                   /id="PRO_0000214762"
FT   TOPO_DOM        1..199
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        200..220
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        228..247
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        271..291
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        292..393
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        394..412
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        421..438
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        474..491
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        503..524
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        557..576
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        604..622
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        638..658
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        679..698
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        717..735
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        736..797
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..118
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         206
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         208
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         209
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         213
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         477
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         509
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         574
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         577
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   MOD_RES         56
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P58295"
FT   MOD_RES         57
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q761V0"
FT   MOD_RES         84
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q761V0"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        364
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        311..320
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   VAR_SEQ         1..234
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10381548"
FT                   /id="VSP_061562"
FT   VAR_SEQ         496..511
FT                   /note="NNCYRDTLIVTCTNSA -> VP (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10381548"
FT                   /id="VSP_061563"
FT   VARIANT         89
FT                   /note="A -> E (no effect on subcellular location; no effect
FT                   on glycine transport; dbSNP:rs61736602)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044163"
FT   VARIANT         102
FT                   /note="G -> S (in dbSNP:rs1443547)"
FT                   /evidence="ECO:0000269|PubMed:10381548"
FT                   /id="VAR_044164"
FT   VARIANT         124
FT                   /note="F -> S (in dbSNP:rs1443548)"
FT                   /evidence="ECO:0000269|PubMed:10381548,
FT                   ECO:0000269|PubMed:10606742, ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:9845349, ECO:0000269|Ref.4"
FT                   /id="VAR_044165"
FT   VARIANT         132
FT                   /note="A -> G (in dbSNP:rs34243519)"
FT                   /id="VAR_044166"
FT   VARIANT         162
FT                   /note="A -> G (in dbSNP:rs1443549)"
FT                   /evidence="ECO:0000269|PubMed:10381548,
FT                   ECO:0000269|PubMed:10606742, ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:9845349, ECO:0000269|Ref.4"
FT                   /id="VAR_044167"
FT   VARIANT         184
FT                   /note="Q -> R (no effect on glycine transport)"
FT                   /evidence="ECO:0000269|PubMed:10606742"
FT                   /id="VAR_011591"
FT   VARIANT         306
FT                   /note="L -> V (in HKPX3; compound heterozygote with S-509;
FT                   impairment of glycine transport when coexpressed with S-509
FT                   in vitro; dbSNP:rs121908496)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044168"
FT   VARIANT         425
FT                   /note="T -> M (in HKPX3; no effect on subcellular location;
FT                   impairs glycine transport; dbSNP:rs121908498)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044169"
FT   VARIANT         429
FT                   /note="P -> L (in HKPX3; impairs glycine transport; no
FT                   effect on subcellular location; dbSNP:rs745539706)"
FT                   /evidence="ECO:0000269|PubMed:31370103"
FT                   /id="VAR_082588"
FT   VARIANT         457
FT                   /note="K -> N (in dbSNP:rs3740870)"
FT                   /id="VAR_044170"
FT   VARIANT         463
FT                   /note="D -> N (no effect on glycine transport;
FT                   dbSNP:rs1805091)"
FT                   /evidence="ECO:0000269|PubMed:10606742"
FT                   /id="VAR_011592"
FT   VARIANT         482
FT                   /note="W -> C (in HKPX3; no effect on subcellular location;
FT                   impairs glycine transport)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044171"
FT   VARIANT         491
FT                   /note="Y -> C (in HKPX3; no effect on subcellular location;
FT                   impairs glycine transport; dbSNP:rs121908494)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044172"
FT   VARIANT         499
FT                   /note="Y -> F (in dbSNP:rs7944684)"
FT                   /id="VAR_044173"
FT   VARIANT         509
FT                   /note="N -> S (in HKPX3; compound heterozygote with V-306;
FT                   no effect on subcellular location; impairs glycine
FT                   transport; dbSNP:rs121908497)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044174"
FT   VARIANT         510
FT                   /note="S -> R (in HKPX3; results in the formation of large
FT                   aggregates in the cytoplasm; loss of glycine transport;
FT                   dbSNP:rs281864926)"
FT                   /evidence="ECO:0000269|PubMed:16751771"
FT                   /id="VAR_044175"
FT   VARIANT         632
FT                   /note="V -> E (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036160"
FT   VARIANT         705
FT                   /note="Y -> C (mild decrease of glycine transport; Vmax of
FT                   the mutant is reduced to 60% compared to wild-type;
FT                   decreased expression at the cell surface;
FT                   dbSNP:rs143918578)"
FT                   /evidence="ECO:0000269|PubMed:22753417"
FT                   /id="VAR_087307"
FT   VARIANT         751
FT                   /note="V -> A (no effect on glycine transport)"
FT                   /evidence="ECO:0000269|PubMed:10606742"
FT                   /id="VAR_011593"
FT   VARIANT         767
FT                   /note="G -> R (in dbSNP:rs16906628)"
FT                   /id="VAR_044176"
FT   MUTAGEN         705
FT                   /note="Y->A: Decreased surface expression. Decreased
FT                   glycine transport."
FT                   /evidence="ECO:0000269|PubMed:22753417"
FT   MUTAGEN         705
FT                   /note="Y->E: Decreased glycine transport."
FT                   /evidence="ECO:0000269|PubMed:22753417"
FT   MUTAGEN         705
FT                   /note="Y->F: No effect on glycine transport."
FT                   /evidence="ECO:0000269|PubMed:22753417"
FT   MUTAGEN         705
FT                   /note="Y->K: No effect on glycine transport."
FT                   /evidence="ECO:0000269|PubMed:22753417"
FT   CONFLICT        24
FT                   /note="G -> S (in Ref. 2; AAD27892)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        155
FT                   /note="S -> G (in Ref. 2; AAD27892)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        188
FT                   /note="N -> D (in Ref. 2; AAD27892)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        362
FT                   /note="Q -> L (in Ref. 2; AAD27892)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        582
FT                   /note="T -> S (in Ref. 2; AAD27892)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   797 AA;  87434 MW;  47D8A9B179896CE0 CRC64;
     MDCSAPKEMN KLPANSPEAA AAQGHPDGPC APRTSPEQEL PAAAAPPPPR VPRSASTGAQ
     TFQSADARAC EAERPGVGSC KLSSPRAQAA SAALRDLREA QGAQASPPPG SSGPGNALHC
     KIPFLRGPEG DANVSVGKGT LERNNTPVVG WVNMSQSTVV LATDGITSVL PGSVATVATQ
     EDEQGDENKA RGNWSSKLDF ILSMVGYAVG LGNVWRFPYL AFQNGGGAFL IPYLMMLALA
     GLPIFFLEVS LGQFASQGPV SVWKAIPALQ GCGIAMLIIS VLIAIYYNVI ICYTLFYLFA
     SFVSVLPWGS CNNPWNTPEC KDKTKLLLDS CVISDHPKIQ IKNSTFCMTA YPNVTMVNFT
     SQANKTFVSG SEEYFKYFVL KISAGIEYPG EIRWPLALCL FLAWVIVYAS LAKGIKTSGK
     VVYFTATFPY VVLVILLIRG VTLPGAGAGI WYFITPKWEK LTDATVWKDA ATQIFFSLSA
     AWGGLITLSS YNKFHNNCYR DTLIVTCTNS ATSIFAGFVI FSVIGFMANE RKVNIENVAD
     QGPGIAFVVY PEALTRLPLS PFWAIIFFLM LLTLGLDTMF ATIETIVTSI SDEFPKYLRT
     HKPVFTLGCC ICFFIMGFPM ITQGGIYMFQ LVDTYAASYA LVIIAIFELV GISYVYGLQR
     FCEDIEMMIG FQPNIFWKVC WAFVTPTILT FILCFSFYQW EPMTYGSYRY PNWSMVLGWL
     MLACSVIWIP IMFVIKMHLA PGRFIERLKL VCSPQPDWGP FLAQHRGERY KNMIDPLGTS
     SLGLKLPVKD LELGTQC
//