CLAT_DROME
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 03-AUG-2022, entry version 178.
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, 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; P07668; -.
DR PRIDE; P07668; -.
DR EnsemblMetazoa; FBtr0089367; FBpp0088397; FBgn0000303. [P07668-1]
DR EnsemblMetazoa; FBtr0089368; FBpp0088977; FBgn0000303. [P07668-2]
DR GeneID; 42249; -.
DR KEGG; dme:Dmel_CG12345; -.
DR CTD; 1103; -.
DR FlyBase; FBgn0000303; ChAT.
DR VEuPathDB; VectorBase:FBgn0000303; -.
DR eggNOG; KOG3717; Eukaryota.
DR GeneTree; ENSGT01050000244830; -.
DR InParanoid; P07668; -.
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 tissues.
DR Genevisible; P07668; DM.
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; -; 1.
DR Gene3D; 3.30.559.70; -; 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; PTHR22589; 1.
DR Pfam; PF00755; Carn_acyltransf; 1.
DR PROSITE; PS00439; ACYLTRANSF_C_1; 1.
DR PROSITE; PS00440; ACYLTRANSF_C_2; 1.
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
