Reviewed, UniProtKB/Swiss-Prot P04058 (ACES_TORCA)

Names and origin

Protein names

Recommended name:
    Acetylcholinesterase
      Short name=AChE
    EC=3.1.1.7

Gene names

Name:

ache

Organism

Torpedo californica (Pacific electric ray)

Taxonomic identifier

7787 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Chondrichthyes › Elasmobranchii › Squalea › Hypnosqualea › Pristiorajea › Batoidea › Torpediniformes › Torpedinoidei › Torpedinidae › Torpedo

Protein attributes

Sequence length	586 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	Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
Catalytic activity	Acetylcholine + H(2)O = choline + acetate.
Enzyme regulation	Inhibited by substrate concentrations above 0.5 mM.
Subunit structure	Isoform H form is an homodimer; the asymmetric form is a disulfide-bonded oligomer composed of a collagenic subunit (Q) and a variable number of T catalytic subunits.
Subcellular location	Isoform H: Cell membrane; Lipid-anchor › GPI-anchor. Cell junction › synapse. Isoform T: Cell membrane; Peripheral membrane protein. Cell junction › synapse. Note= Attached to the membrane through disulfide linkage with the collagenic subunit, itself bound to the membrane.
Tissue specificity	Found in the synapses and to a lower extent in extrajunctional areas of muscle and nerve, and on erythrocyte membranes.
Post-translational modification	An interchain disulfide bond is present in what becomes position 593 of the T isoform.
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.

Ontologies

Keywords
Biological process	Neurotransmitter degradation
Cellular component	Cell junction Cell membrane Membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hydrolase Serine esterase
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	acetylcholine catabolic process in synaptic cleft Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell junction Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	acetylcholinesterase activity Inferred from electronic annotation. Source: InterPro cholinesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.

Isoform H (identifier: P04058-1)

Also known as: Globular;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Notes: GPI-anchored form.

Isoform T (identifier: P04058-2)

The sequence of this isoform differs from the canonical sequence as follows:
     557-586: ACDGELSSSGTSSSKGIIFYVLFSILYLIF → ETIDEAERQWKTEFHRWSSYMMHWKNQFDHYSRHESCAEL

Notes: Attached to the membrane through disulfide linkage with the collagenic subunit, itself bound to the membrane.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 564

543

Acetylcholinesterase

PRO_0000008595

Propeptide

565 – 586

22

Removed in mature form

PRO_0000008596

Sites

Active site

221

1

Acyl-ester intermediate

Active site

348

1

Charge relay system

Active site

461

1

Charge relay system

Amino acid modifications

Lipidation

564

1

GPI-anchor amidated serine

Glycosylation

80

1

N-linked (GlcNAc...)

Glycosylation

437

1

N-linked (GlcNAc...)

Glycosylation

478

1

N-linked (GlcNAc...)

Glycosylation

554

1

N-linked (GlcNAc...)

Disulfide bond

88 ↔ 115

Disulfide bond

275 ↔ 286

Disulfide bond

423 ↔ 542

Disulfide bond

558

Interchain

Natural variations

Alternative sequence

557 – 586

30

ACDGE…LYLIF → ETIDEAERQWKTEFHRWSSY MMHWKNQFDHYSRHESCAEL in isoform T.

VSP_001460

Experimental info

Mutagenesis

220

1

E → H: Loss of activity

Mutagenesis

220

1

E → Q or D: Decrease in activity

Mutagenesis

221

1

S → C: Loss of activity

Mutagenesis

221

1

S → V: Loss of activity

Mutagenesis

446

1

H → Q: Almost no loss of activity

Mutagenesis

461

1

H → Q: Loss of activity

Secondary structure

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586

Helix Strand Turn

Details...

Beta strand

28 – 31

4

Beta strand

34 – 37

4

Beta strand

39 – 43

5

Beta strand

46 – 55

10

Helix

62 – 64

3

Beta strand

76 – 80

5

Helix

100 – 103

4

Beta strand

117 – 122

6

Beta strand

128 – 136

9

Turn

140 – 142

3

Helix

149 – 151

3

Helix

154 – 160

7

Beta strand

163 – 166

4

Helix

172 – 176

5

Beta strand

183 – 185

3

Helix

189 – 204

16

Helix

205 – 208

4

Beta strand

210 – 220

11

Helix

222 – 232

11

Turn

234 – 236

3

Helix

237 – 239

3

Beta strand

241 – 247

7

Helix

259 – 272

14

Helix

280 – 289

10

Helix

292 – 296

5

Helix

297 – 302

6

Beta strand

304 – 306

3

Beta strand

319 – 324

6

Helix

326 – 332

7

Beta strand

340 – 345

6

Helix

350 – 356

7

Helix

370 – 380

11

Helix

386 – 396

11

Helix

405 – 420

16

Helix

422 – 435

14

Beta strand

439 – 444

6

Helix

455 – 457

3

Turn

461 – 464

4

Helix

465 – 468

4

Helix

471 – 473

3

Helix

475 – 477

3

Helix

481 – 500

20

Turn

518 – 520

3

Beta strand

522 – 529

8

Beta strand

533 – 536

4

Helix

539 – 546

8

Helix

548 – 555

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform H (Globular) [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 731D5F0F3ABA62A8	FASTA	586	65,906
	10 20 30 40 50 60 MNLLVTSSLG VLLHLVVLCQ ADDHSELLVN TKSGKVMGTR VPVLSSHISA FLGIPFAEPP 70 80 90 100 110 120 VGNMRFRRPE PKKPWSGVWN ASTYPNNCQQ YVDEQFPGFS GSEMWNPNRE MSEDCLYLNI 130 140 150 160 170 180 WVPSPRPKST TVMVWIYGGG FYSGSSTLDV YNGKYLAYTE EVVLVSLSYR VGAFGFLALH 190 200 210 220 230 240 GSQEAPGNVG LLDQRMALQW VHDNIQFFGG DPKTVTIFGE SAGGASVGMH ILSPGSRDLF 250 260 270 280 290 300 RRAILQSGSP NCPWASVSVA EGRRRAVELG RNLNCNLNSD EELIHCLREK KPQELIDVEW 310 320 330 340 350 360 NVLPFDSIFR FSFVPVIDGE FFPTSLESML NSGNFKKTQI LLGVNKDEGS FFLLYGAPGF 370 380 390 400 410 420 SKDSESKISR EDFMSGVKLS VPHANDLGLD AVTLQYTDWM DDNNGIKNRD GLDDIVGDHN 430 440 450 460 470 480 VICPLMHFVN KYTKFGNGTY LYFFNHRASN LVWPEWMGVI HGYEIEFVFG LPLVKELNYT 490 500 510 520 530 540 AEEEALSRRI MHYWATFAKT GNPNEPHSQE SKWPLFTTKE QKFIDLNTEP MKVHQRLRVQ 550 560 570 580 MCVFWNQFLP KLLNATACDG ELSSSGTSSS KGIIFYVLFS ILYLIF
	Isoform T [UniParc]. Checksum: 36D5E9A30F9E6065		596	67,818
	10 20 30 40 50 60 MNLLVTSSLG VLLHLVVLCQ ADDHSELLVN TKSGKVMGTR VPVLSSHISA FLGIPFAEPP 70 80 90 100 110 120 VGNMRFRRPE PKKPWSGVWN ASTYPNNCQQ YVDEQFPGFS GSEMWNPNRE MSEDCLYLNI 130 140 150 160 170 180 WVPSPRPKST TVMVWIYGGG FYSGSSTLDV YNGKYLAYTE EVVLVSLSYR VGAFGFLALH 190 200 210 220 230 240 GSQEAPGNVG LLDQRMALQW VHDNIQFFGG DPKTVTIFGE SAGGASVGMH ILSPGSRDLF 250 260 270 280 290 300 RRAILQSGSP NCPWASVSVA EGRRRAVELG RNLNCNLNSD EELIHCLREK KPQELIDVEW 310 320 330 340 350 360 NVLPFDSIFR FSFVPVIDGE FFPTSLESML NSGNFKKTQI LLGVNKDEGS FFLLYGAPGF 370 380 390 400 410 420 SKDSESKISR EDFMSGVKLS VPHANDLGLD AVTLQYTDWM DDNNGIKNRD GLDDIVGDHN 430 440 450 460 470 480 VICPLMHFVN KYTKFGNGTY LYFFNHRASN LVWPEWMGVI HGYEIEFVFG LPLVKELNYT 490 500 510 520 530 540 AEEEALSRRI MHYWATFAKT GNPNEPHSQE SKWPLFTTKE QKFIDLNTEP MKVHQRLRVQ 550 560 570 580 590 MCVFWNQFLP KLLNATETID EAERQWKTEF HRWSSYMMHW KNQFDHYSRH ESCAEL

References

[1]	"Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence." Schumacher M., Camp S., Maulet Y., Newton M., McPhee-Quigley K., Taylor S.S., Friedmann T., Taylor P. Nature 319:407-409(1986) [PubMed: 3753747] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-586.
[2]	"Multiple messenger RNA species give rise to the structural diversity in acetylcholinesterase." Schumacher M. J. Biol. Chem. 263:18979-18987(1988) [PubMed: 3198606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[3]	"Primary structures of the catalytic subunits from two molecular forms of acetylcholinesterase. A comparison of NH2-terminal and active center sequences." MacPhee-Quigley K., Taylor P., Taylor S. J. Biol. Chem. 260:12185-12189(1985) [PubMed: 3900071] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-45 AND 214-237.
[4]	"Anionic subsites of the catalytic center of acetylcholinesterase from Torpedo and from cobra venom." Kreienkamp H.J., Weise C., Raba R., Aaviksaar A., Hucho F. Proc. Natl. Acad. Sci. U.S.A. 88:6117-6121(1991) [PubMed: 2068091] [Abstract] Cited for: PROTEIN SEQUENCE OF 100-108.
[5]	"Divergence in primary structure between the molecular forms of acetylcholinesterase." Gibney G., Macphee-Quigley K., Thompson B., Vedvick T., Low M.G., Taylor S.S., Taylor P. J. Biol. Chem. 263:1140-1145(1988) [PubMed: 3335534] [Abstract] Cited for: PROTEIN SEQUENCE OF 552-558.
[6]	"Single gene encodes glycophospholipid-anchored and asymmetric acetylcholinesterase forms: alternative coding exons contain inverted repeat sequences." Maulet Y., Camp S., Gibney G., Rachinsky T.L., Ekstroem T.J., Taylor P. Neuron 4:289-301(1990) [PubMed: 2306366] [Abstract] Cited for: ALTERNATIVE SPLICING.
[7]	"Profile of the disulfide bon