Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Y345 (SC6A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC6A5
Synonyms:GLYT2, NET1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length797 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

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

Involvement in disease

Hyperekplexia 3 (HKPX3) [MIM:614618]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A5 subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 797797Sodium- and chloride-dependent glycine transporter 2
PRO_0000214762

Regions

Topological domain1 – 199199Cytoplasmic Potential
Transmembrane200 – 22021Helical; Name=1; Potential
Transmembrane228 – 24720Helical; Name=2; Potential
Transmembrane271 – 29121Helical; Name=3; Potential
Topological domain292 – 393102Extracellular Potential
Transmembrane394 – 41219Helical; Name=4; Potential
Transmembrane421 – 43818Helical; Name=5; Potential
Transmembrane474 – 49118Helical; Name=6; Potential
Transmembrane503 – 52422Helical; Name=7; Potential
Transmembrane557 – 57620Helical; Name=8; Potential
Transmembrane604 – 62219Helical; Name=9; Potential
Transmembrane638 – 65821Helical; Name=10; Potential
Transmembrane679 – 69820Helical; Name=11; Potential
Transmembrane717 – 73519Helical; Name=12; Potential
Topological domain736 – 79762Cytoplasmic Potential

Amino acid modifications

Glycosylation3431N-linked (GlcNAc...) Potential
Glycosylation3531N-linked (GlcNAc...) Potential
Glycosylation3581N-linked (GlcNAc...) Potential
Glycosylation3641N-linked (GlcNAc...) Potential

Natural variations

Natural variant891A → E No effect on subcellular location; no effect on glycine transport. Ref.7
Corresponds to variant rs61736602 [ dbSNP | Ensembl ].
VAR_044163
Natural variant1021G → S. Ref.2
Corresponds to variant rs1443547 [ dbSNP | Ensembl ].
VAR_044164
Natural variant1241F → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs1443548 [ dbSNP | Ensembl ].
VAR_044165
Natural variant1321A → G.
Corresponds to variant rs34243519 [ dbSNP | Ensembl ].
VAR_044166
Natural variant1621A → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs1443549 [ dbSNP | Ensembl ].
VAR_044167
Natural variant1841Q → R. Ref.3
VAR_011591
Natural variant3061L → V in HKPX3; compound heterozygote with S-509; impairment of glycine transport when coexpressed with S-509 in vitro. Ref.7
VAR_044168
Natural variant4251T → M in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7
VAR_044169
Natural variant4571K → N.
Corresponds to variant rs3740870 [ dbSNP | Ensembl ].
VAR_044170
Natural variant4631D → N. Ref.3
Corresponds to variant rs1805091 [ dbSNP | Ensembl ].
VAR_011592
Natural variant4821W → C in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7
VAR_044171
Natural variant4911Y → C in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7
VAR_044172
Natural variant4991Y → F.
Corresponds to variant rs7944684 [ dbSNP | Ensembl ].
VAR_044173
Natural variant5091N → S in HKPX3; compound heterozygote with V-306; no effect on subcellular location; impairs glycine transport. Ref.7
VAR_044174
Natural variant5101S → R in HKPX3; results in the formation of large aggregates in the cytoplasm; impairs glycine transport. Ref.7
VAR_044175
Natural variant6321V → E in a breast cancer sample; somatic mutation. Ref.8
VAR_036160
Natural variant7511V → A. Ref.3
VAR_011593
Natural variant7671G → R.
Corresponds to variant rs16906628 [ dbSNP | Ensembl ].
VAR_044176

Experimental info

Sequence conflict241G → S in AAD27892. Ref.2
Sequence conflict1551S → G in AAD27892. Ref.2
Sequence conflict1881N → D in AAD27892. Ref.2
Sequence conflict3621Q → L in AAD27892. Ref.2
Sequence conflict5821T → S in AAD27892. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y345 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 47D8A9B179896CE0

FASTA79787,434
        10         20         30         40         50         60 
MDCSAPKEMN KLPANSPEAA AAQGHPDGPC APRTSPEQEL PAAAAPPPPR VPRSASTGAQ 

        70         80         90        100        110        120 
TFQSADARAC EAERPGVGSC KLSSPRAQAA SAALRDLREA QGAQASPPPG SSGPGNALHC 

       130        140        150        160        170        180 
KIPFLRGPEG DANVSVGKGT LERNNTPVVG WVNMSQSTVV LATDGITSVL PGSVATVATQ 

       190        200        210        220        230        240 
EDEQGDENKA RGNWSSKLDF ILSMVGYAVG LGNVWRFPYL AFQNGGGAFL IPYLMMLALA 

       250        260        270        280        290        300 
GLPIFFLEVS LGQFASQGPV SVWKAIPALQ GCGIAMLIIS VLIAIYYNVI ICYTLFYLFA 

       310        320        330        340        350        360 
SFVSVLPWGS CNNPWNTPEC KDKTKLLLDS CVISDHPKIQ IKNSTFCMTA YPNVTMVNFT 

       370        380        390        400        410        420 
SQANKTFVSG SEEYFKYFVL KISAGIEYPG EIRWPLALCL FLAWVIVYAS LAKGIKTSGK 

       430        440        450        460        470        480 
VVYFTATFPY VVLVILLIRG VTLPGAGAGI WYFITPKWEK LTDATVWKDA ATQIFFSLSA 

       490        500        510        520        530        540 
AWGGLITLSS YNKFHNNCYR DTLIVTCTNS ATSIFAGFVI FSVIGFMANE RKVNIENVAD 

       550        560        570        580        590        600 
QGPGIAFVVY PEALTRLPLS PFWAIIFFLM LLTLGLDTMF ATIETIVTSI SDEFPKYLRT 

       610        620        630        640        650        660 
HKPVFTLGCC ICFFIMGFPM ITQGGIYMFQ LVDTYAASYA LVIIAIFELV GISYVYGLQR 

       670        680        690        700        710        720 
FCEDIEMMIG FQPNIFWKVC WAFVTPTILT FILCFSFYQW EPMTYGSYRY PNWSMVLGWL 

       730        740        750        760        770        780 
MLACSVIWIP IMFVIKMHLA PGRFIERLKL VCSPQPDWGP FLAQHRGERY KNMIDPLGTS 

       790 
SLGLKLPVKD LELGTQC 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome."
Morrow J.A., Collie I.T., Dunbar D.R., Walker G.B., Shahid M., Hill D.R.
FEBS Lett. 439:334-340(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-124 AND GLY-162.
[2]"Characterization of multiple forms of the human glycine transporter type-2."
Gallagher M.J., Burgess L.H., Brunden K.R.
Brain Res. Mol. Brain Res. 70:101-115(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-102; SER-124 AND GLY-162.
Tissue: Spinal cord.
[3]"Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter."
Evans J., Herdon H., Cairns W., O'Brien E., Chapman C., Terrett J., Gloger I.
FEBS Lett. 463:301-306(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-124; GLY-162; ARG-184; ASN-463 AND ALA-751.
Tissue: Spinal cord.
[4]"Cloning and expression of a human glycine transporter type II."
Luyten W.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-124 AND GLY-162.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-124 AND GLY-162.
[7]"Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease."
Rees M.I., Harvey K., Pearce B.R., Chung S.K., Duguid I.C., Thomas P., Beatty S., Graham G.E., Armstrong L., Shiang R., Abbott K.J., Zuberi S.M., Stephenson J.B., Owen M.J., Tijssen M.A., van den Maagdenberg A.M., Smart T.G., Supplisson S., Harvey R.J.
Nat. Genet. 38:801-806(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HKPX3 VAL-306; MET-425; CYS-482; CYS-491; SER-509 AND ARG-510, VARIANT GLU-89, CHARACTERIZATION OF VARIANTS HKPX3 VAL-306; MET-425; CYS-482; CYS-491; SER-509 AND ARG-510, CHARACTERIZATION OF VARIANT GLU-89.
[8]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-632.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS7854.1.
RefSeqNP_004202.2. NM_004211.3.
UniGeneHs.136557.

3D structure databases

ProteinModelPortalQ9Y345.
SMRQ9Y345. Positions 191-757.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114599. 3 interactions.
STRING9606.ENSP00000298923.

Chemistry

BindingDBQ9Y345.
ChEMBLCHEMBL3060.
DrugBankDB00145. Glycine.
GuidetoPHARMACOLOGY936.

Protein family/group databases

TCDB2.A.22.2.10. the neurotransmitter:sodium symporter (nss) family.

PTM databases

PhosphoSiteQ9Y345.

Polymorphism databases

DMDM296452967.

Proteomic databases

PaxDbQ9Y345.
PRIDEQ9Y345.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000525748; ENSP00000434364; ENSG00000165970.
GeneID9152.
KEGGhsa:9152.
UCSCuc001mqd.3. human.

Organism-specific databases

CTD9152.
GeneCardsGC11P020620.
GeneReviewsSLC6A5.
H-InvDBHIX0035860.
HGNCHGNC:11051. SLC6A5.
HPAHPA039476.
MIM604159. gene.
614618. phenotype.
neXtProtNX_Q9Y345.
Orphanet3197. Hereditary hyperekplexia.
PharmGKBPA35911.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0733.
HOGENOMHOG000116406.
HOVERGENHBG071421.
InParanoidQ9Y345.
KOK05038.
OMAGNALHCK.
OrthoDBEOG793B71.
PhylomeDBQ9Y345.
TreeFamTF343812.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_20679. Amine compound SLC transporters.

Gene expression databases

ArrayExpressQ9Y345.
BgeeQ9Y345.
CleanExHS_NET1.
HS_SLC6A5.
GenevestigatorQ9Y345.

Family and domain databases

InterProIPR000175. Na/ntran_symport.
[Graphical view]
PANTHERPTHR11616. PTHR11616. 1 hit.
PfamPF00209. SNF. 1 hit.
[Graphical view]
PRINTSPR00176. NANEUSMPORT.
PROSITEPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGlycine_transporter_2.
GenomeRNAi9152.
NextBio34335.
PROQ9Y345.
SOURCESearch...

Entry information

Entry nameSC6A5_HUMAN
AccessionPrimary (citable) accession number: Q9Y345
Secondary accession number(s): O95288, Q4VAM7, Q9BX77
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM