Q9Y345 (SC6A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SLC6A5
Synonyms:	GLYT2, NET1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	797 AA.
Sequence status	Complete.
Protein existence	Evidence 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]

Ontologies

Keywords
Biological process	Neurotransmitter transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to membrane Traceable author statement Ref.1. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	glycine:sodium symporter activity Traceable author statement Ref.1. Source: ProtInc neurotransmitter:sodium symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 797	797	Sodium- and chloride-dependent glycine transporter 2		PRO_0000214762
Regions
	Topological domain	1 – 199	199	Cytoplasmic Potential
	Transmembrane	200 – 220	21	Helical; Name=1; Potential
	Transmembrane	228 – 247	20	Helical; Name=2; Potential
	Transmembrane	271 – 291	21	Helical; Name=3; Potential
	Topological domain	292 – 393	102	Extracellular Potential
	Transmembrane	394 – 412	19	Helical; Name=4; Potential
	Transmembrane	421 – 438	18	Helical; Name=5; Potential
	Transmembrane	474 – 491	18	Helical; Name=6; Potential
	Transmembrane	503 – 524	22	Helical; Name=7; Potential
	Transmembrane	557 – 576	20	Helical; Name=8; Potential
	Transmembrane	604 – 622	19	Helical; Name=9; Potential
	Transmembrane	638 – 658	21	Helical; Name=10; Potential
	Transmembrane	679 – 698	20	Helical; Name=11; Potential
	Transmembrane	717 – 735	19	Helical; Name=12; Potential
	Topological domain	736 – 797	62	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Glycosylation	353	1	N-linked (GlcNAc...) Potential
	Glycosylation	358	1	N-linked (GlcNAc...) Potential
	Glycosylation	364	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	89	1	A → E No effect on subcellular location; no effect on glycine transport. Ref.7		VAR_044163
	Natural variant	102	1	G → S. Ref.2 Corresponds to variant rs1443547 [ dbSNP | Ensembl ].		VAR_044164
	Natural variant	124	1	F → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs1443548 [ dbSNP | Ensembl ].		VAR_044165
	Natural variant	132	1	A → G. Corresponds to variant rs34243519 [ dbSNP | Ensembl ].		VAR_044166
	Natural variant	162	1	A → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs1443549 [ dbSNP | Ensembl ].		VAR_044167
	Natural variant	184	1	Q → R. Ref.3		VAR_011591
	Natural variant	306	1	L → V in HKPX3; compound heterozygote with S-509; impairment of glycine transport when coexpressed with S-509 in vitro. Ref.7		VAR_044168
	Natural variant	425	1	T → M in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7		VAR_044169
	Natural variant	457	1	K → N. Corresponds to variant rs3740870 [ dbSNP | Ensembl ].		VAR_044170
	Natural variant	463	1	D → N. Ref.3 Corresponds to variant rs1805091 [ dbSNP | Ensembl ].		VAR_011592
	Natural variant	482	1	W → C in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7		VAR_044171
	Natural variant	491	1	Y → C in HKPX3; no effect on subcellular location; impairs glycine transport. Ref.7		VAR_044172
	Natural variant	499	1	Y → F. Corresponds to variant rs7944684 [ dbSNP | Ensembl ].		VAR_044173
	Natural variant	509	1	N → S in HKPX3; compound heterozygote with V-306; no effect on subcellular location; impairs glycine transport. Ref.7		VAR_044174
	Natural variant	510	1	S → R in HKPX3; results in the formation of large aggregates in the cytoplasm; impairs glycine transport. Ref.7		VAR_044175
	Natural variant	632	1	V → E in a breast cancer sample; somatic mutation. Ref.8		VAR_036160
	Natural variant	751	1	V → A. Ref.3		VAR_011593
	Natural variant	767	1	G → R. Corresponds to variant rs16906628 [ dbSNP | Ensembl ].		VAR_044176
Experimental info
	Sequence conflict	24	1	G → S in AAD27892. Ref.2
	Sequence conflict	155	1	S → G in AAD27892. Ref.2
	Sequence conflict	188	1	N → D in AAD27892. Ref.2
	Sequence conflict	362	1	Q → L in AAD27892. Ref.2
	Sequence conflict	582	1	T → S in AAD27892. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y345 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 47D8A9B179896CE0	FASTA	797	87,434
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00003484.
RefSeq	NP_004202.2. NM_004211.3.
UniGene	Hs.136557.
3D structure databases
ProteinModelPortal	Q9Y345.
SMR	Q9Y345. Positions 191-713.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000298923.
PTM databases
PhosphoSite	Q9Y345.
Polymorphism databases
DMDM	296452967.
Proteomic databases
PaxDb	Q9Y345.
PRIDE	Q9Y345.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000525748; ENSP00000434364; ENSG00000165970.
GeneID	9152.
KEGG	hsa:9152.
UCSC	uc001mqd.3. human.
Organism-specific databases
CTD	9152.
GeneCards	GC11P020620.
H-InvDB	HIX0035860.
HGNC	HGNC:11051. SLC6A5.
HPA	HPA039476.
MIM	604159. gene. 614618. phenotype.
neXtProt	NX_Q9Y345.
Orphanet	3197. Hereditary hyperekplexia.
PharmGKB	PA35911.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0733.
HOGENOM	HOG000116406.
HOVERGEN	HBG071421.
InParanoid	Q9Y345.
KO	K05038.
OMA	GNALHCK.
OrthoDB	EOG4HDST0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_20679. Amine compound SLC transporters.
Gene expression databases
Bgee	Q9Y345.
CleanEx	HS_NET1. HS_SLC6A5.
Genevestigator	Q9Y345.
GermOnline	ENSG00000165970. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. [Graphical view]
PANTHER	PTHR11616. PTHR11616. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR00176. NANEUSMPORT.
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y345.
ChEMBL	CHEMBL3060.
DrugBank	DB00145. Glycine.
GenomeRNAi	9152.
NextBio	34335.
SOURCE	Search...

Entry information

Entry name

SC6A5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.