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Protein

Sodium- and chloride-dependent glycine transporter 2

Gene

SLC6A5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi206Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi208Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi209Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi213Sodium 2By similarity1
Metal bindingi477Sodium 2By similarity1
Metal bindingi509Sodium 2By similarity1
Metal bindingi574Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi577Sodium 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • chemical synaptic transmission Source: ProtInc
  • glycine import Source: FlyBase
  • synaptic transmission, glycinergic Source: FlyBase
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Keywords - Ligandi

Metal-binding, Sodium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165970-MONOMER.
ReactomeiR-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.

Protein family/group databases

TCDBi2.A.22.2.10. the neurotransmitter:sodium symporter (nss) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium- and chloride-dependent glycine transporter 2
Short name:
GlyT-2
Short name:
GlyT2
Alternative name(s):
Solute carrier family 6 member 5
Gene namesi
Name:SLC6A5
Synonyms:GLYT2, NET1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:11051. SLC6A5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 199CytoplasmicSequence analysisAdd BLAST199
Transmembranei200 – 220Helical; Name=1Sequence analysisAdd BLAST21
Transmembranei228 – 247Helical; Name=2Sequence analysisAdd BLAST20
Transmembranei271 – 291Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini292 – 393ExtracellularSequence analysisAdd BLAST102
Transmembranei394 – 412Helical; Name=4Sequence analysisAdd BLAST19
Transmembranei421 – 438Helical; Name=5Sequence analysisAdd BLAST18
Transmembranei474 – 491Helical; Name=6Sequence analysisAdd BLAST18
Transmembranei503 – 524Helical; Name=7Sequence analysisAdd BLAST22
Transmembranei557 – 576Helical; Name=8Sequence analysisAdd BLAST20
Transmembranei604 – 622Helical; Name=9Sequence analysisAdd BLAST19
Transmembranei638 – 658Helical; Name=10Sequence analysisAdd BLAST21
Transmembranei679 – 698Helical; Name=11Sequence analysisAdd BLAST20
Transmembranei717 – 735Helical; Name=12Sequence analysisAdd BLAST19
Topological domaini736 – 797CytoplasmicSequence analysisAdd BLAST62

GO - Cellular componenti

  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hyperekplexia 3 (HKPX3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurologic disorder characterized by neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life.
See also OMIM:614618
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_044168306L → V in HKPX3; compound heterozygote with S-509; impairment of glycine transport when coexpressed with S-509 in vitro. 1 PublicationCorresponds to variant rs121908496dbSNPEnsembl.1
Natural variantiVAR_044169425T → M in HKPX3; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908498dbSNPEnsembl.1
Natural variantiVAR_044171482W → C in HKPX3; no effect on subcellular location; impairs glycine transport. 1 Publication1
Natural variantiVAR_044172491Y → C in HKPX3; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908494dbSNPEnsembl.1
Natural variantiVAR_044174509N → S in HKPX3; compound heterozygote with V-306; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908497dbSNPEnsembl.1
Natural variantiVAR_044175510S → R in HKPX3; results in the formation of large aggregates in the cytoplasm; impairs glycine transport. 1 PublicationCorresponds to variant rs281864926dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi9152.
MalaCardsiSLC6A5.
MIMi614618. phenotype.
OpenTargetsiENSG00000165970.
Orphaneti3197. Hereditary hyperekplexia.
PharmGKBiPA35911.

Chemistry databases

ChEMBLiCHEMBL3060.
DrugBankiDB00145. Glycine.
GuidetoPHARMACOLOGYi936.

Polymorphism and mutation databases

BioMutaiSLC6A5.
DMDMi296452967.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002147621 – 797Sodium- and chloride-dependent glycine transporter 2Add BLAST797

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei56PhosphoserineBy similarity1
Modified residuei57PhosphothreonineBy similarity1
Modified residuei84PhosphoserineBy similarity1
Disulfide bondi311 ↔ 320By similarity
Glycosylationi343N-linked (GlcNAc...)Sequence analysis1
Glycosylationi353N-linked (GlcNAc...)Sequence analysis1
Glycosylationi358N-linked (GlcNAc...)Sequence analysis1
Glycosylationi364N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9Y345.
PeptideAtlasiQ9Y345.
PRIDEiQ9Y345.

PTM databases

iPTMnetiQ9Y345.
PhosphoSitePlusiQ9Y345.

Expressioni

Tissue specificityi

Expressed in medulla, and to a lesser extent in spinal cord and cerebellum.

Gene expression databases

BgeeiENSG00000165970.
CleanExiHS_NET1.
HS_SLC6A5.
ExpressionAtlasiQ9Y345. baseline and differential.
GenevisibleiQ9Y345. HS.

Interactioni

Protein-protein interaction databases

BioGridi114599. 12 interactors.
STRINGi9606.ENSP00000434364.

Chemistry databases

BindingDBiQ9Y345.

Structurei

3D structure databases

ProteinModelPortaliQ9Y345.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiQ9Y345.
KOiK05038.
OMAiGNALHCK.
OrthoDBiEOG091G08PX.
PhylomeDBiQ9Y345.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 2 hits.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y345-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDCSAPKEMN KLPANSPEAA AAQGHPDGPC APRTSPEQEL PAAAAPPPPR
60 70 80 90 100
VPRSASTGAQ TFQSADARAC EAERPGVGSC KLSSPRAQAA SAALRDLREA
110 120 130 140 150
QGAQASPPPG SSGPGNALHC KIPFLRGPEG DANVSVGKGT LERNNTPVVG
160 170 180 190 200
WVNMSQSTVV LATDGITSVL PGSVATVATQ EDEQGDENKA RGNWSSKLDF
210 220 230 240 250
ILSMVGYAVG LGNVWRFPYL AFQNGGGAFL IPYLMMLALA GLPIFFLEVS
260 270 280 290 300
LGQFASQGPV SVWKAIPALQ GCGIAMLIIS VLIAIYYNVI ICYTLFYLFA
310 320 330 340 350
SFVSVLPWGS CNNPWNTPEC KDKTKLLLDS CVISDHPKIQ IKNSTFCMTA
360 370 380 390 400
YPNVTMVNFT SQANKTFVSG SEEYFKYFVL KISAGIEYPG EIRWPLALCL
410 420 430 440 450
FLAWVIVYAS LAKGIKTSGK VVYFTATFPY VVLVILLIRG VTLPGAGAGI
460 470 480 490 500
WYFITPKWEK LTDATVWKDA ATQIFFSLSA AWGGLITLSS YNKFHNNCYR
510 520 530 540 550
DTLIVTCTNS ATSIFAGFVI FSVIGFMANE RKVNIENVAD QGPGIAFVVY
560 570 580 590 600
PEALTRLPLS PFWAIIFFLM LLTLGLDTMF ATIETIVTSI SDEFPKYLRT
610 620 630 640 650
HKPVFTLGCC ICFFIMGFPM ITQGGIYMFQ LVDTYAASYA LVIIAIFELV
660 670 680 690 700
GISYVYGLQR FCEDIEMMIG FQPNIFWKVC WAFVTPTILT FILCFSFYQW
710 720 730 740 750
EPMTYGSYRY PNWSMVLGWL MLACSVIWIP IMFVIKMHLA PGRFIERLKL
760 770 780 790
VCSPQPDWGP FLAQHRGERY KNMIDPLGTS SLGLKLPVKD LELGTQC
Length:797
Mass (Da):87,434
Last modified:May 18, 2010 - v3
Checksum:i47D8A9B179896CE0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24G → S in AAD27892 (PubMed:10381548).Curated1
Sequence conflicti155S → G in AAD27892 (PubMed:10381548).Curated1
Sequence conflicti188N → D in AAD27892 (PubMed:10381548).Curated1
Sequence conflicti362Q → L in AAD27892 (PubMed:10381548).Curated1
Sequence conflicti582T → S in AAD27892 (PubMed:10381548).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04416389A → E No effect on subcellular location; no effect on glycine transport. 1 PublicationCorresponds to variant rs61736602dbSNPEnsembl.1
Natural variantiVAR_044164102G → S.1 PublicationCorresponds to variant rs1443547dbSNPEnsembl.1
Natural variantiVAR_044165124F → S.5 PublicationsCorresponds to variant rs1443548dbSNPEnsembl.1
Natural variantiVAR_044166132A → G.Corresponds to variant rs34243519dbSNPEnsembl.1
Natural variantiVAR_044167162A → G.5 PublicationsCorresponds to variant rs1443549dbSNPEnsembl.1
Natural variantiVAR_011591184Q → R.1 Publication1
Natural variantiVAR_044168306L → V in HKPX3; compound heterozygote with S-509; impairment of glycine transport when coexpressed with S-509 in vitro. 1 PublicationCorresponds to variant rs121908496dbSNPEnsembl.1
Natural variantiVAR_044169425T → M in HKPX3; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908498dbSNPEnsembl.1
Natural variantiVAR_044170457K → N.Corresponds to variant rs3740870dbSNPEnsembl.1
Natural variantiVAR_011592463D → N.1 PublicationCorresponds to variant rs1805091dbSNPEnsembl.1
Natural variantiVAR_044171482W → C in HKPX3; no effect on subcellular location; impairs glycine transport. 1 Publication1
Natural variantiVAR_044172491Y → C in HKPX3; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908494dbSNPEnsembl.1
Natural variantiVAR_044173499Y → F.Corresponds to variant rs7944684dbSNPEnsembl.1
Natural variantiVAR_044174509N → S in HKPX3; compound heterozygote with V-306; no effect on subcellular location; impairs glycine transport. 1 PublicationCorresponds to variant rs121908497dbSNPEnsembl.1
Natural variantiVAR_044175510S → R in HKPX3; results in the formation of large aggregates in the cytoplasm; impairs glycine transport. 1 PublicationCorresponds to variant rs281864926dbSNPEnsembl.1
Natural variantiVAR_036160632V → E in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_011593751V → A.1 Publication1
Natural variantiVAR_044176767G → R.Corresponds to variant rs16906628dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF085412 mRNA. Translation: AAC95145.1.
AF142501 mRNA. Translation: AAD27892.1.
AF352733 mRNA. Translation: AAK29670.1.
AF117999 mRNA. Translation: AAK12641.1.
AC090707 Genomic DNA. No translation available.
BC096319 mRNA. Translation: AAH96319.1.
CCDSiCCDS7854.1.
RefSeqiNP_001305298.1. NM_001318369.1.
NP_004202.3. NM_004211.4.
UniGeneiHs.136557.

Genome annotation databases

EnsembliENST00000525748; ENSP00000434364; ENSG00000165970.
GeneIDi9152.
KEGGihsa:9152.
UCSCiuc001mqd.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF085412 mRNA. Translation: AAC95145.1.
AF142501 mRNA. Translation: AAD27892.1.
AF352733 mRNA. Translation: AAK29670.1.
AF117999 mRNA. Translation: AAK12641.1.
AC090707 Genomic DNA. No translation available.
BC096319 mRNA. Translation: AAH96319.1.
CCDSiCCDS7854.1.
RefSeqiNP_001305298.1. NM_001318369.1.
NP_004202.3. NM_004211.4.
UniGeneiHs.136557.

3D structure databases

ProteinModelPortaliQ9Y345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114599. 12 interactors.
STRINGi9606.ENSP00000434364.

Chemistry databases

BindingDBiQ9Y345.
ChEMBLiCHEMBL3060.
DrugBankiDB00145. Glycine.
GuidetoPHARMACOLOGYi936.

Protein family/group databases

TCDBi2.A.22.2.10. the neurotransmitter:sodium symporter (nss) family.

PTM databases

iPTMnetiQ9Y345.
PhosphoSitePlusiQ9Y345.

Polymorphism and mutation databases

BioMutaiSLC6A5.
DMDMi296452967.

Proteomic databases

PaxDbiQ9Y345.
PeptideAtlasiQ9Y345.
PRIDEiQ9Y345.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000525748; ENSP00000434364; ENSG00000165970.
GeneIDi9152.
KEGGihsa:9152.
UCSCiuc001mqd.4. human.

Organism-specific databases

CTDi9152.
DisGeNETi9152.
GeneCardsiSLC6A5.
GeneReviewsiSLC6A5.
H-InvDBHIX0035860.
HGNCiHGNC:11051. SLC6A5.
MalaCardsiSLC6A5.
MIMi604159. gene.
614618. phenotype.
neXtProtiNX_Q9Y345.
OpenTargetsiENSG00000165970.
Orphaneti3197. Hereditary hyperekplexia.
PharmGKBiPA35911.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiQ9Y345.
KOiK05038.
OMAiGNALHCK.
OrthoDBiEOG091G08PX.
PhylomeDBiQ9Y345.
TreeFamiTF343812.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165970-MONOMER.
ReactomeiR-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.

Miscellaneous databases

GeneWikiiGlycine_transporter_2.
GenomeRNAii9152.
PROiQ9Y345.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165970.
CleanExiHS_NET1.
HS_SLC6A5.
ExpressionAtlasiQ9Y345. baseline and differential.
GenevisibleiQ9Y345. HS.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 2 hits.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSC6A5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y345
Secondary accession number(s): O95288, Q4VAM7, Q9BX77
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.