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Synaptic vesicular amine transporter (Monoamine transporter) (Solute carrier family 18 member 2) (Vesicular amine transporter 2) (VAT2)

 VMAT2_HUMAN             Reviewed;         514 AA.
Q05940; B2RC96; D3DRC4; Q15876; Q4G147; Q5VW49; Q9H3P6;
01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 2.
10-OCT-2018, entry version 170.
RecName: Full=Synaptic vesicular amine transporter;
AltName: Full=Monoamine transporter;
AltName: Full=Solute carrier family 18 member 2;
AltName: Full=Vesicular amine transporter 2;
Short=VAT2;
Name=SLC18A2; Synonyms=SVMT, VMAT2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=8095030; DOI=10.1016/0014-5793(93)80539-7;
Surratt C.K., Persico A.M., Yang X.D., Edgar S.R., Bird G.S.,
Hawkins A.L., Griffin C.A., Li X., Jabs E.W., Uhl G.R.;
"A human synaptic vesicle monoamine transporter cDNA predicts
posttranslational modifications, reveals chromosome 10 gene
localization and identifies TaqI RFLPs.";
FEBS Lett. 318:325-330(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=8245983; DOI=10.1111/j.1471-4159.1993.tb07476.x;
Erickson J.D., Eiden L.E.;
"Functional identification and molecular cloning of a human brain
vesicle monoamine transporter.";
J. Neurochem. 61:2314-2317(1993).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Substantia nigra;
PubMed=7905859; DOI=10.1016/S0888-7543(05)80383-0;
Peter D., Finn J.P., Klisak I., Liu Y., Kojis T., Heinzmann C.,
Roghani A., Sparkes R.S., Edwards R.H.;
"Chromosomal localization of the human vesicular amine transporter
genes.";
Genomics 18:720-723(1993).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Brain;
PubMed=8373557; DOI=10.1007/BF01244941;
Lesch K.P., Gross J., Wolozin B.L., Murphy D.L., Riederer P.;
"Extensive sequence divergence between the human and rat brain
vesicular monoamine transporter: possible molecular basis for species
differences in the susceptibility to MPP+.";
J. Neural Transm. 93:75-82(1993).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=11443533; DOI=10.1038/sj.mp.4000895;
Kunugi H., Ishida S., Akahane A., Nanko S.;
"Exon/intron boundaries, novel polymorphisms, and association analysis
with schizophrenia of the human synaptic vesicle monoamine transporter
(SVMT) gene.";
Mol. Psychiatry 6:456-460(2001).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Uterus;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164054; DOI=10.1038/nature02462;
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[10]
DISULFIDE BOND.
PubMed=12009896; DOI=10.1021/bi015779j;
Thiriot D.S., Sievert M.K., Ruoho A.E.;
"Identification of human vesicle monoamine transporter (VMAT2) lumenal
cysteines that form an intramolecular disulfide bond.";
Biochemistry 41:6346-6353(2002).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Platelet;
PubMed=18088087; DOI=10.1021/pr0704130;
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
-!- FUNCTION: Involved in the ATP-dependent vesicular transport of
biogenic amine neurotransmitters. Pumps cytosolic monoamines
including dopamine, norepinephrine, serotonin, and histamine into
synaptic vesicles. Requisite for vesicular amine storage prior to
secretion via exocytosis.
-!- SUBUNIT: Interacts with SLC6A3. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Multi-pass
membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q05940-1; Sequence=Displayed;
Name=2;
IsoId=Q05940-2; Sequence=VSP_057151, VSP_057152;
Note=No experimental confirmation available.;
-!- SIMILARITY: Belongs to the major facilitator superfamily.
Vesicular transporter family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BAB19009.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=Wikipedia; Note=Vesicular monoamine transporter
entry;
URL="https://en.wikipedia.org/wiki/Vesicular_monoamine_transporter";
-----------------------------------------------------------------------
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EMBL; L09118; AAA59877.1; -; mRNA.
EMBL; L23205; AAA61290.1; -; mRNA.
EMBL; L14269; AAA91853.1; -; mRNA.
EMBL; X71354; CAA50489.1; -; mRNA.
EMBL; AB044401; BAB19009.1; ALT_SEQ; Genomic_DNA.
EMBL; AK314997; BAG37493.1; -; mRNA.
EMBL; AL391988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL731557; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471066; EAW49428.1; -; Genomic_DNA.
EMBL; CH471066; EAW49429.1; -; Genomic_DNA.
EMBL; BC030593; AAH30593.1; -; mRNA.
EMBL; BC108927; AAI08928.1; -; mRNA.
EMBL; BC108928; AAI08929.1; -; mRNA.
CCDS; CCDS7599.1; -. [Q05940-1]
PIR; A49368; A49368.
PIR; S29810; S29810.
RefSeq; NP_003045.2; NM_003054.4. [Q05940-1]
UniGene; Hs.596992; -.
ProteinModelPortal; Q05940; -.
BioGrid; 112459; 1.
IntAct; Q05940; 9.
STRING; 9606.ENSP00000298472; -.
BindingDB; Q05940; -.
ChEMBL; CHEMBL1893; -.
DrugBank; DB01472; 4-Methoxyamphetamine.
DrugBank; DB00386; Alseroxylon.
DrugBank; DB00182; Amphetamine.
DrugBank; DB00865; Benzphetamine.
DrugBank; DB01089; Deserpidine.
DrugBank; DB01576; Dextroamphetamine.
DrugBank; DB01363; Ephedra.
DrugBank; DB01364; Ephedrine.
DrugBank; DB06706; Isometheptene.
DrugBank; DB01577; Methamphetamine.
DrugBank; DB01442; MMDA.
DrugBank; DB00368; Norepinephrine.
DrugBank; DB06714; Propylhexedrine.
DrugBank; DB00206; Reserpine.
DrugBank; DB04844; Tetrabenazine.
GuidetoPHARMACOLOGY; 1012; -.
TCDB; 2.A.1.2.29; the major facilitator superfamily (mfs).
iPTMnet; Q05940; -.
PhosphoSitePlus; Q05940; -.
BioMuta; SLC18A2; -.
DMDM; 1722742; -.
EPD; Q05940; -.
PaxDb; Q05940; -.
PeptideAtlas; Q05940; -.
PRIDE; Q05940; -.
ProteomicsDB; 58362; -.
Ensembl; ENST00000298472; ENSP00000298472; ENSG00000165646. [Q05940-1]
Ensembl; ENST00000644641; ENSP00000496339; ENSG00000165646. [Q05940-1]
GeneID; 6571; -.
KEGG; hsa:6571; -.
UCSC; uc001ldd.3; human. [Q05940-1]
CTD; 6571; -.
DisGeNET; 6571; -.
EuPathDB; HostDB:ENSG00000165646.11; -.
GeneCards; SLC18A2; -.
H-InvDB; HIX0035636; -.
HGNC; HGNC:10935; SLC18A2.
HPA; HPA073224; -.
MalaCards; SLC18A2; -.
MIM; 193001; gene.
neXtProt; NX_Q05940; -.
OpenTargets; ENSG00000165646; -.
Orphanet; 352649; Brain dopamine-serotonin vesicular transport disease.
PharmGKB; PA325; -.
eggNOG; KOG3764; Eukaryota.
eggNOG; ENOG410XW69; LUCA.
GeneTree; ENSGT00390000003851; -.
HOGENOM; HOG000018545; -.
HOVERGEN; HBG055082; -.
InParanoid; Q05940; -.
KO; K08155; -.
OMA; RIGYQIP; -.
OrthoDB; EOG091G0534; -.
PhylomeDB; Q05940; -.
TreeFam; TF313494; -.
Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle.
Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle.
Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
SIGNOR; Q05940; -.
GeneWiki; Vesicular_monoamine_transporter_2; -.
GenomeRNAi; 6571; -.
PRO; PR:Q05940; -.
Proteomes; UP000005640; Chromosome 10.
Bgee; ENSG00000165646; Expressed in 143 organ(s), highest expression level in substantia nigra.
CleanEx; HS_SLC18A2; -.
Genevisible; Q05940; HS.
GO; GO:0070083; C:clathrin-sculpted monoamine transport vesicle membrane; TAS:Reactome.
GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0016020; C:membrane; TAS:ProtInc.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0008021; C:synaptic vesicle; TAS:ParkinsonsUK-UCL.
GO; GO:0008504; F:monoamine transmembrane transporter activity; TAS:Reactome.
GO; GO:0015842; P:aminergic neurotransmitter loading into synaptic vesicle; IBA:GO_Central.
GO; GO:0007268; P:chemical synaptic transmission; TAS:ParkinsonsUK-UCL.
GO; GO:0015872; P:dopamine transport; TAS:ParkinsonsUK-UCL.
GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
GO; GO:0015844; P:monoamine transport; TAS:ProtInc.
GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; NAS:ParkinsonsUK-UCL.
GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; TAS:ParkinsonsUK-UCL.
GO; GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
GO; GO:0042137; P:sequestering of neurotransmitter; NAS:ParkinsonsUK-UCL.
CDD; cd06174; MFS; 1.
InterPro; IPR011701; MFS.
InterPro; IPR020846; MFS_dom.
InterPro; IPR036259; MFS_trans_sf.
Pfam; PF07690; MFS_1; 1.
SUPFAM; SSF103473; SSF103473; 2.
PROSITE; PS50850; MFS; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Cytoplasmic vesicle;
Disulfide bond; Glycoprotein; Membrane; Neurotransmitter transport;
Phosphoprotein; Reference proteome; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 514 Synaptic vesicular amine transporter.
/FTId=PRO_0000127514.
TOPO_DOM 1 20 Cytoplasmic. {ECO:0000255}.
TRANSMEM 21 41 Helical. {ECO:0000255}.
TOPO_DOM 42 129 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 130 150 Helical. {ECO:0000255}.
TOPO_DOM 151 159 Cytoplasmic. {ECO:0000255}.
TRANSMEM 160 180 Helical. {ECO:0000255}.
TOPO_DOM 181 189 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 190 210 Helical. {ECO:0000255}.
TOPO_DOM 211 219 Cytoplasmic. {ECO:0000255}.
TRANSMEM 220 242 Helical. {ECO:0000255}.
TOPO_DOM 243 248 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 249 271 Helical. {ECO:0000255}.
TOPO_DOM 272 291 Cytoplasmic. {ECO:0000255}.
TRANSMEM 292 311 Helical. {ECO:0000255}.
TOPO_DOM 312 328 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 329 352 Helical. {ECO:0000255}.
TOPO_DOM 353 357 Cytoplasmic. {ECO:0000255}.
TRANSMEM 358 378 Helical. {ECO:0000255}.
TOPO_DOM 379 389 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 390 410 Helical. {ECO:0000255}.
TOPO_DOM 411 414 Cytoplasmic. {ECO:0000255}.
TRANSMEM 415 435 Helical. {ECO:0000255}.
TOPO_DOM 436 440 Lumenal, vesicle. {ECO:0000255}.
TRANSMEM 441 462 Helical. {ECO:0000255}.
TOPO_DOM 463 514 Cytoplasmic. {ECO:0000255}.
MOD_RES 511 511 Phosphoserine.
{ECO:0000250|UniProtKB:Q01827}.
MOD_RES 513 513 Phosphoserine.
{ECO:0000250|UniProtKB:Q01827}.
CARBOHYD 84 84 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 91 91 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 117 324 {ECO:0000269|PubMed:12009896}.
VAR_SEQ 204 209 MGMLAS -> RCGMPE (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_057151.
VAR_SEQ 210 514 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_057152.
CONFLICT 17 17 R -> H (in Ref. 4; CAA50489).
{ECO:0000305}.
CONFLICT 302 302 C -> S (in Ref. 1; AAA59877).
{ECO:0000305}.
CONFLICT 354 354 K -> T (in Ref. 1; AAA59877).
{ECO:0000305}.
CONFLICT 378 378 A -> P (in Ref. 1; AAA59877).
{ECO:0000305}.
CONFLICT 395 395 I -> N (in Ref. 1; AAA59877).
{ECO:0000305}.
SEQUENCE 514 AA; 55713 MW; 42EA91A225485DB2 CRC64;
MALSELALVR WLQESRRSRK LILFIVFLAL LLDNMLLTVV VPIIPSYLYS IKHEKNATEI
QTARPVHTAS ISDSFQSIFS YYDNSTMVTG NATRDLTLHQ TATQHMVTNA SAVPSDCPSE
DKDLLNENVQ VGLLFASKAT VQLITNPFIG LLTNRIGYPI PIFAGFCIMF VSTIMFAFSS
SYAFLLIARS LQGIGSSCSS VAGMGMLASV YTDDEERGNV MGIALGGLAM GVLVGPPFGS
VLYEFVGKTA PFLVLAALVL LDGAIQLFVL QPSRVQPESQ KGTPLTTLLK DPYILIAAGS
ICFANMGIAM LEPALPIWMM ETMCSRKWQL GVAFLPASIS YLIGTNIFGI LAHKMGRWLC
ALLGMIIVGV SILCIPFAKN IYGLIAPNFG VGFAIGMVDS SMMPIMGYLV DLRHVSVYGS
VYAIADVAFC MGYAIGPSAG GAIAKAIGFP WLMTIIGIID ILFAPLCFFL RSPPAKEEKM
AILMDHNCPI KTKMYTQNNI QSYPIGEDEE SESD


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