Q8NDX2 (VGLU3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vesicular glutamate transporter 3
Short name=VGluT3

Alternative name(s):
Solute carrier family 17 member 8

Gene names

Name:	SLC17A8
Synonyms:	VGLUT3

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	589 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. May also mediate the transport of inorganic phosphate. Ref.1
Subcellular location	Cytoplasmic vesicle › secretory vesicle › synaptic vesicle membrane By similarity. Membrane; Multi-pass membrane protein Potential. Cell junction › synapse › synaptosome By similarity.
Tissue specificity	Expressed in amygdala, cerebellum, hippocampus, medulla, spinal cord and thalamus. Ref.1
Involvement in disease	Deafness, autosomal dominant, 25 (DFNA25) [MIM:605583]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA25 expression is variable in terms of onset and rate of progression, with an age-dependent penetrance resembling an early-onset presbycusis, or senile deafness, a progressive bilateral loss of hearing that occurs in the aged. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.

Ontologies

Keywords
Biological process	Hearing Ion transport Neurotransmitter transport Sodium transport Symport Transport
Cellular component	Cell junction Cytoplasmic vesicle Membrane Synapse Synaptosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ion transport Traceable author statement. Source: Reactome neurotransmitter transport Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle membrane Traceable author statement. Source: Reactome
Molecular_function	L-glutamate transmembrane transporter activity Inferred from electronic annotation. Source: Compara symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NDX2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NDX2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     302-351: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 589	589	Vesicular glutamate transporter 3		PRO_0000331614
Regions
	Topological domain	1 – 76	76	Cytoplasmic Potential
	Transmembrane	77 – 97	21	Helical; Potential
	Topological domain	98 – 130	33	Vesicular Potential
	Transmembrane	131 – 151	21	Helical; Potential
	Topological domain	152 – 153	2	Cytoplasmic Potential
	Transmembrane	154 – 174	21	Helical; Potential
	Topological domain	175 – 182	8	Vesicular Potential
	Transmembrane	183 – 203	21	Helical; Potential
	Topological domain	204 – 221	18	Cytoplasmic Potential
	Transmembrane	222 – 242	21	Helical; Potential
	Topological domain	243 – 249	7	Vesicular Potential
	Transmembrane	250 – 270	21	Helical; Potential
	Topological domain	271 – 314	44	Cytoplasmic Potential
	Transmembrane	315 – 335	21	Helical; Potential
	Topological domain	336 – 353	18	Vesicular Potential
	Transmembrane	354 – 374	21	Helical; Potential
	Topological domain	375 – 390	16	Cytoplasmic Potential
	Transmembrane	391 – 411	21	Helical; Potential
	Topological domain	412 – 413	2	Vesicular Potential
	Transmembrane	414 – 434	21	Helical; Potential
	Topological domain	435 – 447	13	Cytoplasmic Potential
	Transmembrane	448 – 468	21	Helical; Potential
	Topological domain	469 – 481	13	Vesicular Potential
	Transmembrane	482 – 502	21	Helical; Potential
	Topological domain	503 – 586	84	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	302 – 351	50	Missing in isoform 2.		VSP_033265
	Natural variant	8	1	T → I. Corresponds to variant rs45610843 [ dbSNP | Ensembl ].		VAR_042905
	Natural variant	211	1	A → V in DFNA25. Ref.5		VAR_054130
	Natural variant	220	1	A → T. Corresponds to variant rs11568530 [ dbSNP | Ensembl ].		VAR_054131
	Natural variant	246	1	G → E. Corresponds to variant rs11568543 [ dbSNP | Ensembl ].		VAR_054132

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: E74DDC91495F8775	FASTA	589	64,991
	10 20 30 40 50 60 MPFKAFDTFK EKILKPGKEG VKNAVGDSLG ILQRKIDGTT EEEDNIELNE EGRPVQTSRP 70 80 90 100 110 120 SPPLCDCHCC GLPKRYIIAI MSGLGFCISF GIRCNLGVAI VEMVNNSTVY VDGKPEIQTA 130 140 150 160 170 180 QFNWDPETVG LIHGSFFWGY IMTQIPGGFI SNKFAANRVF GAAIFLTSTL NMFIPSAARV 190 200 210 220 230 240 HYGCVMCVRI LQGLVEGVTY PACHGMWSKW APPLERSRLA TTSFCGSYAG AVVAMPLAGV 250 260 270 280 290 300 LVQYIGWSSV FYIYGMFGII WYMFWLLQAY ECPAAHPTIS NEEKTYIETS IGEGANVVSL 310 320 330 340 350 360 SKFSTPWKRF FTSLPVYAII VANFCRSWTF YLLLISQPAY FEEVFGFAIS KVGLLSAVPH 370 380 390 400 410 420 MVMTIVVPIG GQLADYLRSR QILTTTAVRK IMNCGGFGME ATLLLVVGFS HTKGVAISFL 430 440 450 460 470 480 VLAVGFSGFA ISGFNVNHLD IAPRYASILM GISNGVGTLS GMVCPLIVGA MTRHKTREEW 490 500 510 520 530 540 QNVFLIAALV HYSGVIFYGV FASGEKQEWA DPENLSEEKC GIIDQDELAE EIELNHESFA 550 560 570 580 SPKKKMSYGA TSQNCEVQKK EWKGQRGATL DEEELTSYQN EERNFSTIS
	Isoform 2 [UniParc]. Checksum: 5B73AD50FF5DC6F2	FASTA	539	59,077
	10 20 30 40 50 60 MPFKAFDTFK EKILKPGKEG VKNAVGDSLG ILQRKIDGTT EEEDNIELNE EGRPVQTSRP 70 80 90 100 110 120 SPPLCDCHCC GLPKRYIIAI MSGLGFCISF GIRCNLGVAI VEMVNNSTVY VDGKPEIQTA 130 140 150 160 170 180 QFNWDPETVG LIHGSFFWGY IMTQIPGGFI SNKFAANRVF GAAIFLTSTL NMFIPSAARV 190 200 210 220 230 240 HYGCVMCVRI LQGLVEGVTY PACHGMWSKW APPLERSRLA TTSFCGSYAG AVVAMPLAGV 250 260 270 280 290 300 LVQYIGWSSV FYIYGMFGII WYMFWLLQAY ECPAAHPTIS NEEKTYIETS IGEGANVVSL 310 320 330 340 350 360 SVGLLSAVPH MVMTIVVPIG GQLADYLRSR QILTTTAVRK IMNCGGFGME ATLLLVVGFS 370 380 390 400 410 420 HTKGVAISFL VLAVGFSGFA ISGFNVNHLD IAPRYASILM GISNGVGTLS GMVCPLIVGA 430 440 450 460 470 480 MTRHKTREEW QNVFLIAALV HYSGVIFYGV FASGEKQEWA DPENLSEEKC GIIDQDELAE 490 500 510 520 530 EIELNHESFA SPKKKMSYGA TSQNCEVQKK EWKGQRGATL DEEELTSYQN EERNFSTIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional characterization of human vesicular glutamate transporter 3." Takamori S., Malherbe P., Broger C., Jahn R. EMBO Rep. 3:798-803(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Thymus.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 2). Tissue: Heart and Lung.
[5]	"Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice." Ruel J., Emery S., Nouvian R., Bersot T., Amilhon B., Van Rybroek J.M., Rebillard G., Lenoir M., Eybalin M., Delprat B., Sivakumaran T.A., Giros B., El Mestikawy S., Moser T., Smith R.J.H., Lesperance M.M., Puel J.-L. Am. J. Hum. Genet. 83:278-292(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNA25 VAL-211.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ459241 mRNA. Translation: CAD30553.1. AK128319 mRNA. Translation: BAG54658.1. CH471054 Genomic DNA. Translation: EAW97637.1. BC117229 mRNA. Translation: AAI17230.1. BC143396 mRNA. Translation: AAI43397.1.
IPI	IPI00168611. IPI00783759.
RefSeq	NP_001138760.1. NM_001145288.1. NP_647480.1. NM_139319.2.
UniGene	Hs.116871.
3D structure databases
ProteinModelPortal	Q8NDX2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000316909.
Polymorphism databases
DMDM	74723817.
Proteomic databases
PaxDb	Q8NDX2.
PRIDE	Q8NDX2.
Protocols and materials databases
DNASU	246213.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323346; ENSP00000316909; ENSG00000179520. ENST00000392989; ENSP00000376715; ENSG00000179520.
GeneID	246213.
KEGG	hsa:246213.
UCSC	uc009ztx.3. human. uc010svi.2. human.
Organism-specific databases
CTD	246213.
GeneCards	GC12P100750.
HGNC	HGNC:20151. SLC17A8.
MIM	605583. phenotype. 607557. gene.
neXtProt	NX_Q8NDX2.
Orphanet	90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
PharmGKB	PA223010.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOGENOM	HOG000230812.
HOVERGEN	HBG008834.
InParanoid	Q8NDX2.
KO	K12302.
OMA	INMDQKN.
OrthoDB	EOG4XWFXC.
PhylomeDB	Q8NDX2.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
Bgee	Q8NDX2.
CleanEx	HS_SLC17A8.
Genevestigator	Q8NDX2.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	246213.
NextBio	91891.
SOURCE	Search...

Entry information

Entry name

VGLU3_HUMAN

Accession

Primary (citable) accession number: Q8NDX2
Secondary accession number(s): B3KXZ6, B7ZKV4, Q17RQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 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.