ID   CLAT_DROME              Reviewed;         721 AA.
AC   P07668; Q8MQR2; Q9TXC6; Q9VE41;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 3.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Choline O-acetyltransferase {ECO:0000303|PubMed:3086876};
DE            Short=CHOACTase {ECO:0000305};
DE            Short=Choline acetylase {ECO:0000303|PubMed:3086876};
DE            EC=2.3.1.6 {ECO:0000269|PubMed:1851526};
DE   Contains:
DE     RecName: Full=Choline O-acetyltransferase 67 kDa chain {ECO:0000303|PubMed:2723644};
DE   Contains:
DE     RecName: Full=Choline O-acetyltransferase 54 kDa chain {ECO:0000303|PubMed:2723644};
DE   Contains:
DE     RecName: Full=Choline O-acetyltransferase 13 kDa chain {ECO:0000303|PubMed:2723644};
GN   Name=ChAT {ECO:0000303|PubMed:1717651,
GN   ECO:0000312|FlyBase:FBgn0000303};
GN   Synonyms=Cha {ECO:0000303|PubMed:3086876};
GN   ORFNames=CG12345 {ECO:0000312|FlyBase:FBgn0000303};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC   TISSUE=Head;
RX   PubMed=3086876; DOI=10.1073/pnas.83.11.4081;
RA   Itoh N., Slemmon J.R., Hawke D.H., Williamson R., Morita E., Itakura K.,
RA   Roberts E., Shively J.E., Crawford G.D., Salvaterra P.M.;
RT   "Cloning of Drosophila choline acetyltransferase cDNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:4081-4085(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), SEQUENCE REVISION, AND INITIATION
RP   CODON GTG.
RX   PubMed=2123874; DOI=10.1016/s0021-9258(18)45799-7;
RA   Sugihara H., Andrisani V., Salvaterra P.M.;
RT   "Drosophila choline acetyltransferase uses a non-AUG initiation codon and
RT   full length RNA is inefficiently translated.";
RL   J. Biol. Chem. 265:21714-21719(1990).
RN   [3]
RP   SEQUENCE REVISION.
RA   Salvaterra P.M.;
RL   Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM C).
RX   PubMed=1717651; DOI=10.1111/j.1471-4159.1991.tb06362.x;
RA   Sugihara H., Andrisani V., Salvaterra P.M.;
RT   "Genomic organization of Drosophila choline acetyltransferase.";
RL   J. Neurochem. 57:1636-1642(1991).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [6]
RP   GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [8]
RP   PROTEIN SEQUENCE OF 585-594, AND CLEAVAGE.
RX   PubMed=2723644; DOI=10.1111/j.1471-4159.1989.tb07274.x;
RA   Slemmon J.R.;
RT   "Sequence analysis of a proteolyzed site in Drosophila choline
RT   acetyltransferase.";
RL   J. Neurochem. 52:1898-1904(1989).
RN   [9]
RP   FUNCTION, CLEAVAGE, AND CATALYTIC ACTIVITY.
RX   PubMed=1851526; DOI=10.1016/0169-328x(91)90008-l;
RA   Slemmon J.R., Campbell G.A., Selski D.J., Bramson H.N.;
RT   "The amino terminus of the putative Drosophila choline acetyltransferase
RT   precursor is cleaved to yield the 67 kDa enzyme.";
RL   Brain Res. Mol. Brain Res. 9:245-252(1991).
RN   [10]
RP   INTERACTION BETWEEN 54 KDA AND 13 KDA CHAINS.
RA   Slemmon J.R., Salvaterra P.M., Roberts E.;
RT   "Molecular characterization of choline acetyltransferase from Drosophila
RT   melanogaster.";
RL   Neurochem. Int. 6:519-525(1984).
RN   [11]
RP   MUTAGENESIS OF HIS-261; HIS-386 AND HIS-419, AND ACTIVE SITE.
RX   PubMed=8515270; DOI=10.1111/j.1471-4159.1993.tb03561.x;
RA   Carbini L.A., Hersh L.B.;
RT   "Functional analysis of conserved histidines in choline acetyltransferase
RT   by site-directed mutagenesis.";
RL   J. Neurochem. 61:247-253(1993).
CC   -!- FUNCTION: Catalyzes the reversible synthesis of acetylcholine (ACh)
CC       from acetyl CoA and choline at cholinergic synapses.
CC       {ECO:0000269|PubMed:1851526}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + choline = acetylcholine + CoA;
CC         Xref=Rhea:RHEA:18821, ChEBI:CHEBI:15354, ChEBI:CHEBI:15355,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.6;
CC         Evidence={ECO:0000269|PubMed:1851526};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18822;
CC         Evidence={ECO:0000305|PubMed:1851526};
CC   -!- SUBUNIT: The 54 kDa and 13 kDa chains exist as a heterodimer.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=A;
CC         IsoId=P07668-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=P07668-2; Sequence=VSP_008316;
CC       Name=C;
CC         IsoId=P07668-3; Sequence=VSP_011397;
CC   -!- PTM: The N-terminus of choline O-acetyltransferase 67 kDa and 54 kDa
CC       chains are blocked.
CC   -!- SIMILARITY: Belongs to the carnitine/choline acetyltransferase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAM75026.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M63724; AAA28406.2; -; mRNA.
DR   EMBL; AE014297; AAF55588.5; -; Genomic_DNA.
DR   EMBL; AE014297; AAS65177.2; -; Genomic_DNA.
DR   EMBL; AY128433; AAM75026.1; ALT_FRAME; mRNA.
DR   PIR; A24889; A24889.
DR   PIR; A36526; A36526.
DR   RefSeq; NP_477004.5; NM_057656.3. [P07668-1]
DR   RefSeq; NP_996239.2; NM_206517.2. [P07668-2]
DR   AlphaFoldDB; P07668; -.
DR   SMR; P07668; -.
DR   BioGRID; 67255; 5.
DR   DIP; DIP-20557N; -.
DR   IntAct; P07668; 3.
DR   STRING; 7227.FBpp0088397; -.
DR   PaxDb; 7227-FBpp0088397; -.
DR   EnsemblMetazoa; FBtr0089367; FBpp0088397; FBgn0000303. [P07668-1]
DR   EnsemblMetazoa; FBtr0089368; FBpp0088977; FBgn0000303. [P07668-2]
DR   GeneID; 42249; -.
DR   KEGG; dme:Dmel_CG12345; -.
DR   AGR; FB:FBgn0000303; -.
DR   CTD; 1103; -.
DR   FlyBase; FBgn0000303; ChAT.
DR   VEuPathDB; VectorBase:FBgn0000303; -.
DR   eggNOG; KOG3717; Eukaryota.
DR   GeneTree; ENSGT01060000248556; -.
DR   InParanoid; P07668; -.
DR   OMA; MAMSSYE; -.
DR   OrthoDB; 1429709at2759; -.
DR   PhylomeDB; P07668; -.
DR   BRENDA; 2.3.1.6; 1994.
DR   Reactome; R-DME-1483191; Synthesis of PC.
DR   Reactome; R-DME-264642; Acetylcholine Neurotransmitter Release Cycle.
DR   BioGRID-ORCS; 42249; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 42249; -.
DR   PRO; PR:P07668; -.
DR   Proteomes; UP000000803; Chromosome 3R.
DR   Bgee; FBgn0000303; Expressed in brain and 9 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR   GO; GO:0043195; C:terminal bouton; IDA:FlyBase.
DR   GO; GO:0004102; F:choline O-acetyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0008292; P:acetylcholine biosynthetic process; IMP:FlyBase.
DR   GO; GO:0007274; P:neuromuscular synaptic transmission; IMP:FlyBase.
DR   Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR   Gene3D; 3.30.559.70; Choline/Carnitine o-acyltransferase, domain 2; 1.
DR   InterPro; IPR000542; Carn_acyl_trans.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR039551; Cho/carn_acyl_trans.
DR   InterPro; IPR042231; Cho/carn_acyl_trans_2.
DR   PANTHER; PTHR22589; CARNITINE O-ACYLTRANSFERASE; 1.
DR   PANTHER; PTHR22589:SF14; CHOLINE O-ACETYLTRANSFERASE; 1.
DR   Pfam; PF00755; Carn_acyltransf; 1.
DR   SUPFAM; SSF52777; CoA-dependent acyltransferases; 2.
DR   PROSITE; PS00439; ACYLTRANSF_C_1; 1.
DR   PROSITE; PS00440; ACYLTRANSF_C_2; 1.
DR   Genevisible; P07668; DM.
PE   1: Evidence at protein level;
KW   Acyltransferase; Alternative splicing; Direct protein sequencing;
KW   Neurotransmitter biosynthesis; Reference proteome; Transferase.
FT   CHAIN           1..721
FT                   /note="Choline O-acetyltransferase"
FT                   /id="PRO_0000004420"
FT   CHAIN           ?..584
FT                   /note="Choline O-acetyltransferase 54 kDa chain"
FT                   /id="PRO_0000004421"
FT   CHAIN           585..721
FT                   /note="Choline O-acetyltransferase 13 kDa chain"
FT                   /id="PRO_0000004422"
FT   CHAIN           ?..721
FT                   /note="Choline O-acetyltransferase 67 kDa chain"
FT                   /id="PRO_0000004423"
FT   ACT_SITE        419
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000269|PubMed:8515270"
FT   BINDING         496..508
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         534
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         656
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   SITE            584..585
FT                   /note="Cleavage"
FT   VAR_SEQ         60..85
FT                   /note="GWKDSILSIPKKWLSTAESVDEFGFP -> MERLDSVDTKEMALNGRVCGRV
FT                   WIP (in isoform C)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_011397"
FT   VAR_SEQ         583..589
FT                   /note="Missing (in isoform B)"
FT                   /evidence="ECO:0000303|PubMed:12537569"
FT                   /id="VSP_008316"
FT   MUTAGEN         261
FT                   /note="H->L,Q: No effect."
FT                   /evidence="ECO:0000269|PubMed:8515270"
FT   MUTAGEN         386
FT                   /note="H->L: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8515270"
FT   MUTAGEN         386
FT                   /note="H->Q: No effect."
FT                   /evidence="ECO:0000269|PubMed:8515270"
FT   MUTAGEN         419
FT                   /note="H->L,Q: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:8515270"
SQ   SEQUENCE   721 AA;  81328 MW;  1867F3B8421F994E CRC64;
     MASNEASTSA AGSGPESAAL FSKLRSFSIG SGPNSPQRVV SNLRGFLTHR LSNITPSDTG
     WKDSILSIPK KWLSTAESVD EFGFPDTLPK VPVPALDETM ADYIRALEPI TTPAQLERTK
     ELIRQFSAPQ GIGARLHQYL LDKREAEDNW AYYYWLNEMY MDIRIPLPIN SNPGMVFPPR
     RFKTVHDVAH FAARLLDGIL SHREMLDSGE LPLERAASRE KNQPLCMAQY YRLLGSCRRP
     GVKQDSQFLP SRERLNDEDR HVVVICRNQM YCVVLQASDR GKLSESEIAS QILYVLSDAP
     CLPAKPVPVG LLTAEPRSTW ARDREMLQED ERNQRNLELI ETAQVVLCLD EPLAGNFNAR
     GFTGATPTVH RAGDRDETNM AHEMIHGGGS EYNSGNRWFD KTMQLIICTD GTWGLCYEHS
     CSEGIAVVQL LEKIYKKIEE HPDEDNGLPQ HHLPPPERLE WHVGPQLQLR FAQASKSVDK
     CIDDLDFYVY RYQSYGKTFI KSCQVSPDVY IQLALQLAHY KLYGRLVATY ESASTRRFLH
     GRVDCIRAAS TEALEWAKAM CQGEGANVPL ESDREDEEES RKVKFSIYSK DHLRELFRCA
     VARQTEVMVK NILGNGIDIP LLGLREASIE VTGEMHELFK DESYIISQCF LLSTSQVACS
     TDSFMGYGPV TPRGYGCSYN PHPEQIVFCV SAFYSCEDTS ASRYAKSLQD SLDIMRDLLQ
     N
//