Reviewed, UniProtKB/Swiss-Prot P07140 (ACES_DROME)

Names and origin

Protein names

Recommended name:
    Acetylcholinesterase
      Short name=AChE
    EC=3.1.1.7
Cleaved into the following 2 chains:
    1- Recommended name:
            Acetylcholinesterase 16 kDa subunit
    2- Recommended name:
            Acetylcholinesterase 55 kDa subunit

Gene names

Name:	Ace
ORF Names:	CG17907

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	649 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Rapidly hydrolyzes choline released into the synapse. It can hydrolyze butyrylthiocholine.
Catalytic activity	Acetylcholine + H2O = choline + acetate.
Subunit structure	Homodimer; disulfide-linked. The active unit is formed by non-covalent association of the 55 kDa and 16 kDa subunits. Ref.5
Subcellular location	Cell junction › synapse. Cell membrane; Lipid-anchor › GPI-anchor. Note: Attached to the membrane of the neuronal cholinergic synapses by a GPI-anchor. Ref.6 Ref.7
Post-translational modification	Proteolytic cleavage into the 16 kDa subunit and the 55 kDa subunits originates from the hydrophilic peptide, aa 148-180, and is associated with excretion out of the cell. Neither N-glycosylation nor dimerization is required for enzyme activity or substrate specificity, but protects the protein against proteolytic digestion.
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.

Ontologies

Keywords
Biological process	Neurotransmitter degradation
Cellular component	Cell junction Cell membrane Membrane Synapse
Domain	Signal
Molecular function	Hydrolase Serine esterase
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	acetylcholine catabolic process in synaptic cleft Inferred from electronic annotation. Source: InterPro choline catabolic process Inferred from direct assay. Source: FlyBase phototaxis Inferred from mutant phenotype. Source: FlyBase
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: FlyBase synapse Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	acetylcholinesterase activity Inferred from direct assay. Source: FlyBase cholinesterase activity Inferred from direct assay. Source: FlyBase protein homodimerization activity Inferred from mutant phenotype. Source: FlyBase
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 38

38

Chain

39 – 619

581

Acetylcholinesterase

PRO_0000008603

Chain

39 – ?

Acetylcholinesterase 16 kDa subunit

PRO_0000008604

Chain

? – 619

Acetylcholinesterase 55 kDa subunit

PRO_0000008605

Propeptide

620 – 649

30

Removed in mature form Potential

PRO_0000008606

Sites

Active site

276

1

Acyl-ester intermediate

Active site

405

1

Charge relay system

Active site

518

1

Charge relay system

Amino acid modifications

Lipidation

619

1

GPI-anchor amidated serine Potential

Glycosylation

126

1

N-linked (GlcNAc...) Ref.8

Glycosylation

174

1

N-linked (GlcNAc...) Ref.8

Glycosylation

331

1

N-linked (GlcNAc...) Ref.8

Glycosylation

531

1

N-linked (GlcNAc...) Ref.8

Disulfide bond

104 ↔ 131

Disulfide bond

330 ↔ 345

Disulfide bond

480 ↔ 598

Disulfide bond

615

Interchain

Experimental info

Mutagenesis

126

1

N → D: Decrease in apparent molecular weight of 16 kDa subunit. Ref.8

Mutagenesis

174

1

N → S: Decrease in apparent molecular weight of 55 kDa subunit. Decrease in apparent molecular weight of 55 kDa subunit equivalent to the sum of decreases observed with S-174; D-133 and D-331; when associated with D-331 and D-531. Ref.8

Mutagenesis

328

1

C → V: No effect on apparent molecular weight. Ref.8

Mutagenesis

331

1

N → D: Decrease in apparent molecular weight of the 55 kDa subunit. Decrease in apparent molecular weight of 55 kDa subunit equivalent to the sum of individual decreases observed with S-174; D-331 and D-531; when associated with S-174 and D-531. Ref.8

Mutagenesis

531

1

N → D: Decrease in apparent molecular weight of the 55 kDa subunit. Decrease in apparent molecular weight of 55 kDa subunit equivalent to the sum of individual decreases observed with S-174; D-331 and D-531; when associated with S-174 and D-331. Ref.8

Mutagenesis

569

1

N → D: No change in apparent molecular weight of the 55 kDa subunit. Ref.8

Mutagenesis

615

1

C → R: Formation of 75 kDa monomer. Ref.8

Sequence conflict

99

1

G → R in AAF54915. Ref.3

Secondary structure

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649

Helix Strand Turn

Details...

Beta strand

43 – 47

5

Beta strand

50 – 53

4

Beta strand

55 – 59

5

Beta strand

62 – 71

10

Helix

78 – 80

3

Helix

116 – 119

4

Beta strand

133 – 139

7

Beta strand

177 – 185

9

Turn

189 – 191

3

Helix

198 – 200

3

Helix

203 – 209

7

Beta strand

212 – 216

5

Helix

222 – 225

4

Helix

229 – 231

3

Helix

234 – 236

3

Helix

244 – 258

15

Helix

261 – 263

3

Beta strand

265 – 275

11

Helix

277 – 287

11

Turn

289 – 293

5

Beta strand

297 – 302

6

Helix

308 – 310

3

Helix

314 – 327

14

Helix

332 – 335

4

Helix

339 – 346

8

Helix

351 – 357

7

Helix

358 – 361

4

Beta strand

376 – 379

4

Turn

383 – 386

4

Helix

387 – 389

3

Helix

392 – 394

3

Beta strand

396 – 402

7

Beta strand

404 – 406

3

Helix

407 – 413

7

Turn

414 – 417

4

Beta strand

420 – 422

3

Helix

428 – 438

11

Turn

439 – 441

3

Helix

444 – 453

10

Helix

464 – 477

14

Helix

479 – 491

13

Beta strand

495 – 501

7

Helix

512 – 514

3

Helix

520 – 525

6

Helix

528 – 530

3

Helix

538 – 557

20

Beta strand

572 – 575

4

Beta strand

578 – 580

3

Beta strand

584 – 586

3

Helix

592 – 602

11

Helix

605 – 609

5

Sequences

	Sequence		Length	Mass (Da)
	P07140-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 5863C73FF99028C0	FASTA	649	71,785
	10 20 30 40 50 60 MAISCRQSRV LPMSLPLPLT IPLPLVLVLS LHLSGVCGVI DRLVVQTSSG PVRGRSVTVQ 70 80 90 100 110 120 GREVHVYTGI PYAKPPVEDL RFRKPVPAEP WHGVLDATGL SATCVQERYE YFPGFSGEEI 130 140 150 160 170 180 WNPNTNVSED CLYINVWAPA KARLRHGRGA NGGEHPNGKQ ADTDHLIHNG NPQNTTNGLP 190 200 210 220 230 240 ILIWIYGGGF MTGSATLDIY NADIMAAVGN VIVASFQYRV GAFGFLHLAP EMPSEFAEEA 250 260 270 280 290 300 PGNVGLWDQA LAIRWLKDNA HAFGGNPEWM TLFGESAGSS SVNAQLMSPV TRGLVKRGMM 310 320 330 340 350 360 QSGTMNAPWS HMTSEKAVEI GKALINDCNC NASMLKTNPA HVMSCMRSVD AKTISVQQWN 370 380 390 400 410 420 SYSGILSFPS APTIDGAFLP ADPMTLMKTA DLKDYDILMG NVRDEGTYFL LYDFIDYFDK 430 440 450 460 470 480 DDATALPRDK YLEIMNNIFG KATQAEREAI IFQYTSWEGN PGYQNQQQIG RAVGDHFFTC 490 500 510 520 530 540 PTNEYAQALA ERGASVHYYY FTHRTSTSLW GEWMGVLHGD EIEYFFGQPL NNSLQYRPVE 550 560 570 580 590 600 RELGKRMLSA VIEFAKTGNP AQDGEEWPNF SKEDPVYYIF STDDKIEKLA RGPLAARCSF 610 620 630 640 WNDYLPKVRS WAGTCDGDSG SASISPRLQL LGIAALIYIC AALRTKRVF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Ace locus of Drosophila melanogaster: structural gene for acetylcholinesterase with an unusual 5' leader." Hall L.M.C., Spierer P. EMBO J. 5:2949-2954(1986) [PubMed: 3024971] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Drosophila melanogaster acetylcholinesterase gene. Structure, evolution and mutations." Fournier D., Karch F., Bride J.-M., Hall L.M.C., Berge J.-B., Spierer P. J. Mol. Biol. 210:15-22(1989) [PubMed: 2511327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Canton-S, MH19 and Oregon-R. Tissue: Embryo and Pupae.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[5]	"Acetylcholinesterase from Drosophila melanogaster. Identification of two subunits encoded by the same gene." Fournier D., Bride J.-M., Karsch F., Berge J.-B. FEBS Lett. 238:333-337(1988) [PubMed: 3139459] [Abstract] Cited for: SUBUNIT.
[6]	"Drosophila acetylcholinesterase: demonstration of a glycoinositol phospholipid anchor and an endogenous proteolytic cleavage." Haas R., Marshall T.L., Rosenberry T.L. Biochemistry 27:6453-6457(1988) [PubMed: 2975507] [Abstract] Cited for: PROTEOLYTIC PROCESSING, GPI-ANCHOR, PROTEIN SEQUENCE OF 40-43.
[7]	"Acetylcholinesterases from Musca domestica and Drosophila melanogaster brain are linked to membranes by a glycophospholipid anchor sensitive to an endogenous phospholipase." Fournier D., Berge J.-B., Cardoso de Almeida M.L., Bordier C. J. Neurochem. 50:1158-1163(1988) [PubMed: 2831298] [Abstract] Cited for: GPI-ANCHOR.
[8]	"Post-translational modifications of Drosophila acetylcholinesterase. In vitro mutagenesis and expression in Xenopus oocytes." Mutero A., Fournier D. J. Biol. Chem. 267:1695-1700(1992) [PubMed: 1730712] [Abstract] Cited for: GLYCOSYLATION AT ASN-126; ASN-174; ASN-331 AND ASN-531, ABSENCE OF GYCOSYLATION AT ASN-569, INTERCHAIN AT CYS-615, MUTAGENESIS OF ASN-126; ASN-174; CYS-328; ASN-331; ASN-531; ASN-569 AND CYS-615.
[9]	"Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors." Harel M., Kryger G., Rosenberry T.L., Mallender W.D., Lewis T., Fletcher R.J., Guss J.M., Silman I., Sussman J.L. Protein Sci. 9:1063-1072(2000) [PubMed: 10892800] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 41-623 IN COMPLEX WITH INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X05893 mRNA. Translation: CAA29326.1.
AE014297 Genomic DNA. Translation: AAF54915.1.

PIR

A25363.

RefSeq

NP_476953.1.

UniGene

Dm.1179

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DX4	X-ray	2.70	A	39-623	[»]
1QO9	X-ray	2.70	A	39-623	[»]
1QON	X-ray	2.72	A	39-623	[»]

DisProt

DP00346.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07140. 1 interaction.

Protein family/group databases

MEROPS

S09.979.

Proteomic databases

PRIDE

P07140.

Genome annotation databases

Ensembl

FBgn0000024. Drosophila melanogaster. [Contig view]

GeneID

41625.

KEGG

dme:Dmel_CG17907.

Organism-specific databases

FlyBase

FBgn0000024. Ace.

Phylogenomic databases

HOGENOM

P07140.

Enzyme and pathway databases

BRENDA

3.1.1.7. 48.

Gene expression databases

ArrayExpress

P07140.

GermOnline

CG17907. Drosophila melanogaster.

Family and domain databases

InterPro

IPR001445. Acylcholinesterase_insect.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
IPR000997. Cholinesterase.
[Graphical view]

PANTHER

PTHR11559. CarbesteraseB. 1 hit.

Pfam

PF00135. COesterase. 1 hit.
[Graphical view]

PRINTS

PR00880. ACHEINSECT.
PR00878. CHOLNESTRASE.

PROSITE

PS00122. CARBOXYLESTERASE_B_1. 1 hit.
PS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00772. Malathion.

NextBio

824699.

Entry information

Entry name

ACES_DROME

Accession

Primary (citable) accession number: P07140
Secondary accession number(s): Q9VFY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	June 16, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project