VACHT_HUMAN
ID VACHT_HUMAN Reviewed; 532 AA.
AC Q16572; B2R7S1;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Vesicular acetylcholine transporter;
DE Short=VAChT;
DE AltName: Full=Solute carrier family 18 member 3;
GN Name=SLC18A3; Synonyms=VACHT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY, AND
RP VARIANT GLU-520.
RC TISSUE=Brain;
RX PubMed=8071310; DOI=10.1016/s0021-9258(17)31734-9;
RA Erickson J.D., Varoqui H., Schafer M.K.-H., Modi W., Diebler M.-F.,
RA Weihe E., Rand J.B., Eiden L.E., Bonner T.I., Usdin T.B.;
RT "Functional identification of a vesicular acetylcholine transporter and its
RT expression from a 'cholinergic' gene locus.";
RL J. Biol. Chem. 269:21929-21932(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-520.
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-520.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-520.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH SEC14L1.
RX PubMed=17092608; DOI=10.1016/j.neuint.2006.09.010;
RA Ribeiro F.M., Ferreira L.T., Marion S., Fontes S., Gomez M., Ferguson S.S.,
RA Prado M.A., Prado V.F.;
RT "SEC14-like protein 1 interacts with cholinergic transporters.";
RL Neurochem. Int. 50:356-364(2007).
RN [7]
RP VARIANTS CMS21 ALA-186 AND HIS-398, AND INVOLVEMENT IN CMS21.
RX PubMed=27590285; DOI=10.1212/wnl.0000000000003179;
RA O'Grady G.L., Verschuuren C., Yuen M., Webster R., Menezes M., Fock J.M.,
RA Pride N., Best H.A., Benavides Damm T., Turner C., Lek M., Engel A.G.,
RA North K.N., Clarke N.F., MacArthur D.G., Kamsteeg E.J., Cooper S.T.;
RT "Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital
RT myasthenic syndrome.";
RL Neurology 87:1442-1448(2016).
CC -!- FUNCTION: Involved in acetylcholine transport into synaptic vesicles.
CC {ECO:0000269|PubMed:8071310}.
CC -!- SUBUNIT: Interacts with SEC14L1. {ECO:0000269|PubMed:17092608}.
CC -!- INTERACTION:
CC Q16572; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-17598000, EBI-9083477;
CC Q16572; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-17598000, EBI-11956541;
CC Q16572; I3L0A0: PEDS1-UBE2V1; NbExp=3; IntAct=EBI-17598000, EBI-12213001;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Peripheral and central cholinergic nervous systems.
CC {ECO:0000269|PubMed:8071310}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 21, presynaptic (CMS21)
CC [MIM:617239]: A form of congenital myasthenic syndrome, a group of
CC disorders characterized by failure of neuromuscular transmission,
CC including pre-synaptic, synaptic, and post-synaptic disorders that are
CC not of autoimmune origin. Clinical features are easy fatigability and
CC muscle weakness. CMS21 is an autosomal recessive, pre-synaptic form
CC characterized by ptosis, ophthalmoplegia, fatigable weakness, apneic
CC crises, and deterioration of symptoms in cold water. Learning
CC difficulties and left ventricular dysfunction may be present in some
CC patients. {ECO:0000269|PubMed:27590285}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Vesicular
CC transporter family. {ECO:0000305}.
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DR EMBL; U10554; AAB92675.1; -; Genomic_DNA.
DR EMBL; U09210; AAA20497.1; -; mRNA.
DR EMBL; AK313094; BAG35918.1; -; mRNA.
DR EMBL; AC073366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471187; EAW93093.1; -; Genomic_DNA.
DR EMBL; BC007765; AAH07765.1; -; mRNA.
DR CCDS; CCDS7231.1; -.
DR PIR; I38658; I38658.
DR RefSeq; NP_003046.2; NM_003055.2.
DR AlphaFoldDB; Q16572; -.
DR SMR; Q16572; -.
DR BioGRID; 112460; 5.
DR IntAct; Q16572; 4.
DR STRING; 9606.ENSP00000363229; -.
DR BindingDB; Q16572; -.
DR ChEMBL; CHEMBL4767; -.
DR GuidetoPHARMACOLOGY; 1013; -.
DR TCDB; 2.A.1.2.28; the major facilitator superfamily (mfs).
DR GlyGen; Q16572; 2 sites.
DR iPTMnet; Q16572; -.
DR PhosphoSitePlus; Q16572; -.
DR BioMuta; SLC18A3; -.
DR DMDM; 313104043; -.
DR jPOST; Q16572; -.
DR MassIVE; Q16572; -.
DR PaxDb; Q16572; -.
DR PeptideAtlas; Q16572; -.
DR PRIDE; Q16572; -.
DR ProteomicsDB; 60925; -.
DR ABCD; Q16572; 1 sequenced antibody.
DR Antibodypedia; 27651; 271 antibodies from 22 providers.
DR DNASU; 6572; -.
DR Ensembl; ENST00000374115.5; ENSP00000363229.3; ENSG00000187714.7.
DR GeneID; 6572; -.
DR KEGG; hsa:6572; -.
DR MANE-Select; ENST00000374115.5; ENSP00000363229.3; NM_003055.3; NP_003046.2.
DR UCSC; uc001jhw.3; human.
DR CTD; 6572; -.
DR DisGeNET; 6572; -.
DR GeneCards; SLC18A3; -.
DR HGNC; HGNC:10936; SLC18A3.
DR HPA; ENSG00000187714; Tissue enriched (brain).
DR MalaCards; SLC18A3; -.
DR MIM; 600336; gene.
DR MIM; 617239; phenotype.
DR neXtProt; NX_Q16572; -.
DR OpenTargets; ENSG00000187714; -.
DR Orphanet; 994; Fetal akinesia deformation sequence.
DR Orphanet; 98914; Presynaptic congenital myasthenic syndromes.
DR PharmGKB; PA326; -.
DR VEuPathDB; HostDB:ENSG00000187714; -.
DR eggNOG; KOG3764; Eukaryota.
DR GeneTree; ENSGT00940000159449; -.
DR HOGENOM; CLU_001265_10_9_1; -.
DR InParanoid; Q16572; -.
DR OMA; PDYIAHM; -.
DR PhylomeDB; Q16572; -.
DR TreeFam; TF313494; -.
DR PathwayCommons; Q16572; -.
DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q16572; -.
DR BioGRID-ORCS; 6572; 10 hits in 1058 CRISPR screens.
DR GenomeRNAi; 6572; -.
DR Pharos; Q16572; Tchem.
DR PRO; PR:Q16572; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q16572; protein.
DR Bgee; ENSG00000187714; Expressed in putamen and 39 other tissues.
DR Genevisible; Q16572; HS.
DR GO; GO:0030121; C:AP-1 adaptor complex; IBA:GO_Central.
DR GO; GO:0030122; C:AP-2 adaptor complex; IBA:GO_Central.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0060201; C:clathrin-sculpted acetylcholine transport vesicle membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0006836; P:neurotransmitter transport; TAS:Reactome.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Congenital myasthenic syndrome; Disease variant; Glycoprotein; Membrane;
KW Neurotransmitter transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..532
FT /note="Vesicular acetylcholine transporter"
FT /id="PRO_0000127517"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..125
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..182
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..213
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..242
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..289
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 311..325
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 378..388
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..422
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..447
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 469..532
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 471..532
FT /note="Mediates interaction with SEC14L1"
FT /evidence="ECO:0000250|UniProtKB:O35304"
FT REGION 502..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 11
FT /note="R -> Q (in dbSNP:rs8187732)"
FT /id="VAR_029152"
FT VARIANT 13
FT /note="A -> P (in dbSNP:rs8187733)"
FT /id="VAR_020034"
FT VARIANT 29
FT /note="R -> W (in dbSNP:rs8187734)"
FT /id="VAR_020035"
FT VARIANT 186
FT /note="G -> A (in CMS21; dbSNP:rs1057517665)"
FT /evidence="ECO:0000269|PubMed:27590285"
FT /id="VAR_078030"
FT VARIANT 398
FT /note="D -> H (in CMS21; dbSNP:rs1057517666)"
FT /evidence="ECO:0000269|PubMed:27590285"
FT /id="VAR_078031"
FT VARIANT 520
FT /note="A -> E (in dbSNP:rs8187730)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8071310,
FT ECO:0000269|Ref.4"
FT /id="VAR_024638"
SQ SEQUENCE 532 AA; 56903 MW; 445CDF48F08ED31D CRC64;
MESAEPAGQA RAAATKLSEA VGAALQEPRR QRRLVLVIVC VALLLDNMLY MVIVPIVPDY
IAHMRGGGEG PTRTPEVWEP TLPLPTPANA SAYTANTSAS PTAAWPAGSA LRPRYPTESE
DVKIGVLFAS KAILQLLVNP LSGPFIDRMS YDVPLLIGLG VMFASTVLFA FAEDYATLFA
ARSLQGLGSA FADTSGIAMI ADKYPEEPER SRALGVALAF ISFGSLVAPP FGGILYEFAG
KRVPFLVLAA VSLFDALLLL AVAKPFSAAA RARANLPVGT PIHRLMLDPY IAVVAGALTT
CNIPLAFLEP TIATWMKHTM AASEWEMGMA WLPAFVPHVL GVYLTVRLAA RYPHLQWLYG
ALGLAVIGAS SCIVPACRSF APLVVSLCGL CFGIALVDTA LLPTLAFLVD VRHVSVYGSV
YAIADISYSV AYALGPIVAG HIVHSLGFEQ LSLGMGLANL LYAPVLLLLR NVGLLTRSRS
ERDVLLDEPP QGLYDAVRLR ERPVSGQDGE PRSPPGPFDA CEDDYNYYYT RS
