ACES_BUNFA
ID ACES_BUNFA Reviewed; 606 AA.
AC Q92035; O73748; Q10720;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Acetylcholinesterase;
DE Short=BfAChE {ECO:0000303|PubMed:25411244};
DE EC=3.1.1.7 {ECO:0000269|PubMed:8674549, ECO:0000269|PubMed:9545320};
DE Flags: Precursor;
GN Name=ACHE;
OS Bungarus fasciatus (Banded krait) (Pseudoboa fasciata).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Bungarinae; Bungarus.
OX NCBI_TaxID=8613;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM S), CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF MET-101 AND
RP LYS-316.
RC TISSUE=Venom gland;
RX PubMed=8662867; DOI=10.1074/jbc.271.25.15099;
RA Cousin X., Bon S., Duval N., Massoulie J., Bon C.;
RT "Cloning and expression of acetylcholinesterase from Bungarus fasciatus
RT venom. A new type of COOH-terminal domain; involvement of a positively
RT charged residue in the peripheral site.";
RL J. Biol. Chem. 271:15099-15108(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 512-606 (ISOFORMS S AND T), FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Liver, and Muscle;
RX PubMed=9545320; DOI=10.1074/jbc.273.16.9812;
RA Cousin X., Bon S., Massoulie J., Bon C.;
RT "Identification of a novel type of alternatively spliced exon from the
RT acetylcholinesterase gene of Bungarus fasciatus. Molecular forms of
RT acetylcholinesterase in the snake liver and muscle.";
RL J. Biol. Chem. 273:9812-9820(1998).
RN [3]
RP PROTEIN SEQUENCE OF 206-220; 253-272; 321-340; 347-372 AND 503-511,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=8674549; DOI=10.1016/0014-5793(96)00447-4;
RA Cousin X., Creminon C., Grassi J., Meflah K., Cornu G., Saliou B., Bon S.,
RA Massoulie J., Bon C.;
RT "Acetylcholinesterase from Bungarus venom: a monomeric species.";
RL FEBS Lett. 387:196-200(1996).
RN [4]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=4197660; DOI=10.1111/j.1432-1033.1973.tb02799.x;
RA Kumar V., Elliott W.B.;
RT "The acetylcholinesterase of Bungarus fasciatus venom.";
RL Eur. J. Biochem. 34:586-592(1973).
RN [5]
RP ACTIVITY REGULATION.
RX PubMed=9187246; DOI=10.1016/s0167-4838(97)00009-5;
RA Frobert Y., Creminon C., Cousin X., Remy M.H., Chatel J.M., Bon S., Bon C.,
RA Grassi J.;
RT "Acetylcholinesterases from Elapidae snake venoms: biochemical,
RT immunological and enzymatic characterization.";
RL Biochim. Biophys. Acta 1339:253-267(1997).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 32-566 IN COMPLEX WITH ANTIBODY,
RP FUNCTION, CATALYTIC ACTIVITY, DISULFIDE BOND, GLYCOSYLATION AT ASN-289;
RP ASN-374 AND ASN-484, ACTIVITY REGULATION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=25411244; DOI=10.1074/jbc.m114.603902;
RA Bourne Y., Renault L., Marchot P.;
RT "Crystal structure of snake venom acetylcholinesterase in complex with
RT inhibitory antibody fragment Fab410 bound at the peripheral site: evidence
RT for open and closed states of a back door channel.";
RL J. Biol. Chem. 290:1522-1535(2015).
CC -!- FUNCTION: In muscle, it terminates signal transduction at the
CC neuromuscular junction by rapid hydrolysis of the acetylcholine
CC released into the synaptic cleft. In liver, its function is unclear: it
CC could serve as a safeguard against any diffusion of acetylcholine from
CC synapses into the circulation. In venom, its toxic role is unclear: it
CC could result in less musculatory control by rapidly hydrolyzing
CC acetylcholine, or that it works synergistically with alkaline
CC phosphatase (ALP) in paralyzing prey through hypotension.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetylcholine + H2O = acetate + choline + H(+);
CC Xref=Rhea:RHEA:17561, ChEBI:CHEBI:15354, ChEBI:CHEBI:15355,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089; EC=3.1.1.7;
CC Evidence={ECO:0000269|PubMed:25411244, ECO:0000269|PubMed:4197660,
CC ECO:0000269|PubMed:8674549, ECO:0000269|PubMed:9545320};
CC -!- ACTIVITY REGULATION: Inhibited by active site inhibitors: edrophonium,
CC trimethyl-(m-acetamidopheny1)-ammonium iodide, and trimethyl-(p-
CC acetarnidopheny1)-ammonium iodide (PubMed:4197660, PubMed:9187246).
CC Inhibited by both active and peripheral site inhibitors: decamethonium,
CC and BW284c51 (PubMed:8662867, PubMed:9187246). Inhibited by peripheral
CC site inhibitors: snake acetylcholinesterase fasciculin-2, propidium,
CC gallamine, D-tubocurarine, and tacrine (PubMed:8662867, PubMed:9187246,
CC PubMed:25411244). Also inhibited by antibodies Elec410 and Fab410
CC (PubMed:25411244). {ECO:0000269|PubMed:25411244,
CC ECO:0000269|PubMed:4197660, ECO:0000269|PubMed:8662867,
CC ECO:0000269|PubMed:9187246}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=41.7 uM for acetylcholine (at pH 7.5)
CC {ECO:0000269|PubMed:4197660};
CC KM=78.8 uM for acetylthiocholine (at pH 7.4)
CC {ECO:0000269|PubMed:8662867};
CC Vmax=8.6 mmol/min/mg enzyme {ECO:0000269|PubMed:4197660};
CC -!- SUBUNIT: Isoform S is monomeric (PubMed:9545320, PubMed:8674549,
CC PubMed:9187246). Isoform T can form oligomers, including collagen-
CC tailed forms (PubMed:9545320). {ECO:0000269|PubMed:8674549,
CC ECO:0000269|PubMed:9545320}.
CC -!- SUBCELLULAR LOCATION: Synapse. Secreted. Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=T;
CC IsoId=Q92035-2; Sequence=Displayed;
CC Name=S;
CC IsoId=Q92035-1; Sequence=VSP_008215;
CC -!- TISSUE SPECIFICITY: Liver and muscle contain both isoform T and isoform
CC S. Venom gland predominantly contains isoform S.
CC {ECO:0000269|PubMed:9545320}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:8674549}.
CC -!- MISCELLANEOUS: [Isoform S]: A cleavage of the very basic 8-residue C-
CC terminal fragment occurs upon secretion. {ECO:0000269|PubMed:8662867}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC {ECO:0000305}.
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DR EMBL; U54591; AAC59905.1; -; mRNA.
DR EMBL; AF045238; AAC16420.1; -; Genomic_DNA.
DR EMBL; AF045238; AAC16421.1; -; Genomic_DNA.
DR PDB; 4QWW; X-ray; 2.70 A; A/B=32-566.
DR PDBsum; 4QWW; -.
DR AlphaFoldDB; Q92035; -.
DR SMR; Q92035; -.
DR ESTHER; bunfa-ACHE; AChE.
DR MEROPS; S09.979; -.
DR iPTMnet; Q92035; -.
DR PRIDE; Q92035; -.
DR ABCD; Q92035; 1 sequenced antibody.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0043083; C:synaptic cleft; IEA:GOC.
DR GO; GO:0003990; F:acetylcholinesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0001507; P:acetylcholine catabolic process in synaptic cleft; IEA:InterPro.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR014788; AChE_tetra.
DR InterPro; IPR000908; Acylcholinesterase_fish/snake.
DR InterPro; IPR002018; CarbesteraseB.
DR InterPro; IPR019826; Carboxylesterase_B_AS.
DR InterPro; IPR019819; Carboxylesterase_B_CS.
DR InterPro; IPR000997; Cholinesterase.
DR Pfam; PF08674; AChE_tetra; 1.
DR Pfam; PF00135; COesterase; 1.
DR PRINTS; PR00879; ACHEFISH.
DR PRINTS; PR00878; CHOLNESTRASE.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Neurotransmitter degradation; Secreted; Serine esterase; Signal;
KW Synapse; Toxin.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..606
FT /note="Acetylcholinesterase"
FT /id="PRO_0000008592"
FT ACT_SITE 231
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 358
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 471
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT DISULFID 98..125
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT DISULFID 285..296
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT DISULFID 433..552
FT /evidence="ECO:0000269|PubMed:25411244,
FT ECO:0007744|PDB:4QWW"
FT DISULFID 603
FT /note="Interchain; in isoform T"
FT /evidence="ECO:0000250"
FT VAR_SEQ 567..606
FT /note="DNIEEAERQWKLEFHLWSAYMMHWKSQFDHYNKQDRCSEL -> VDPPRADR
FT RRRSARA (in isoform S)"
FT /evidence="ECO:0000303|PubMed:8662867"
FT /id="VSP_008215"
FT MUTAGEN 101
FT /note="M->Y: Increases peripheral site inhibitor binding."
FT /evidence="ECO:0000269|PubMed:8662867"
FT MUTAGEN 316
FT /note="K->D: Increases peripheral site inhibitor binding."
FT /evidence="ECO:0000269|PubMed:8662867"
FT CONFLICT 268
FT /note="T -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="V -> L (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 56..67
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 127..135
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 138..146
FT /evidence="ECO:0007829|PDB:4QWW"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 164..170
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 199..214
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 220..230
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 232..242
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 251..257
FT /evidence="ECO:0007829|PDB:4QWW"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 269..282
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 291..299
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 302..309
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 336..342
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 350..359
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 360..363
FT /evidence="ECO:0007829|PDB:4QWW"
FT TURN 364..366
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 380..390
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 396..405
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 415..430
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 432..443
FT /evidence="ECO:0007829|PDB:4QWW"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 465..467
FT /evidence="ECO:0007829|PDB:4QWW"
FT TURN 471..474
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 475..478
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 491..509
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 528..530
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:4QWW"
FT STRAND 542..545
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 549..556
FT /evidence="ECO:0007829|PDB:4QWW"
FT HELIX 558..565
FT /evidence="ECO:0007829|PDB:4QWW"
SQ SEQUENCE 606 AA; 68074 MW; B95998AEEA0E5709 CRC64;
MPSCQPGKMP APWPWWLQLL LCIPSCVAVL PGRAGELKVS TQTGSVRGLS LPVLDGHVSA
FLGIPFAEPP LGRMRFLRPE PVKPWQHVLD ATSYKPACYQ MVDTSYPGFQ GTEMWNPNRG
MSEDCLYLNI WVPSPRPKDA PVLVWIYGGG FYSGAASLDV YDGRFLTYTQ NVILVSLSYR
VGAFGFLGLP GSPEAPGNMG LLDQRLALQW IQNNIHPFGG NPRAVTVFGE SAGAASVGMH
LLSTQSRTLF QRAILQSGGP NAPWATVTPA ESRGRAALLG KQLGCHFNND SELVSCLRSK
NPQELIDEEW SVLPYKSIFR FPFVPVIDGD FFPDTPEAML SSGNFKETQV LLGVVKDEGS
YFLIYGLPGF SKDNESLISR ADFLEGVRMS VPHANDIATD AVVLQYTDWQ DQDNREKNRE
ALDDIVGDHN VICPVVQFAN DYAKRNSKVY AYLFDHRASN LLWPPWMGVP HGYEIEFVFG
LPLNDSLNYT PQEKELSRRM MRYWANFART GNPTDPADKS GAWPTYTASQ PQYVQLNTQP
LATQPSLRAQ ICAFWNHFLP KLLNATDNIE EAERQWKLEF HLWSAYMMHW KSQFDHYNKQ
DRCSEL
