Reviewed, UniProtKB/Swiss-Prot P21836 (ACES_MOUSE)

Names and origin

Protein names

Recommended name:
    Acetylcholinesterase
      Short name=AChE
    EC=3.1.1.7

Gene names

Name:

Ache

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	614 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.
Catalytic activity	Acetylcholine + H(2)O = choline + acetate.
Subunit structure	Isoform H generates GPI-anchored dimers; disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers By similarity. Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers.
Subcellular location	Cell junction › synapse. Secreted. Cell membrane; Peripheral membrane proteinBy similarity. Isoform H: Cell membrane; Lipid-anchor › GPI-anchor; Extracellular side.
Tissue specificity	Predominates in most expressing tissues except erythrocytes where a glycophospholipid-attached form of ACHE predominates.
Miscellaneous	Synapses usually contain asymmetric molecules of cholinesterase, with a collagen-like part disulfide-bonded to the catalytic part. A different, globular type of cholinesterase occurs on the outer surfaces of cell membranes, including those of erythrocytes. This is the catalytic subunit of an asymmetric or soluble form of ACHE.
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.

Ontologies

Keywords
Biological process	Neurotransmitter degradation
Cellular component	Cell junction Cell membrane Membrane Secreted Synapse
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hydrolase Serine esterase
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	acetylcholine catabolic process Inferred from direct assay. Source: MGI neurotransmitter receptor biosynthetic process Inferred from mutant phenotype. Source: MGI protein tetramerization Inferred from direct assay. Source: MGI receptor internalization Inferred from mutant phenotype. Source: MGI regulation of receptor recycling Inferred from mutant phenotype. Source: MGI retina development in camera-type eye Inferred from mutant phenotype. Source: MGI
Cellular component	cell surface Inferred from direct assay. Source: MGI extracellular space Inferred from direct assay. Source: MGI plasma membrane Inferred from direct assay. Source: MGI synapse Inferred from direct assay. Source: MGI
Molecular function	acetylcholinesterase activity Inferred from direct assay. Source: MGI laminin binding Inferred from physical interaction. Source: MGI protein self-association Inferred from physical interaction. Source: MGI
Complete GO annotation...

Alternative products

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

Isoform T (identifier: P21836-1)

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.

Isoform H (identifier: P21836-2)

The sequence of this isoform is not available.

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 31

31

Chain

32 – 614

583

Acetylcholinesterase

Sites

Active site

234

1

Acyl-ester intermediate

Active site

365

1

Charge relay system

Active site

478

1

Charge relay system

Amino acid modifications

Glycosylation

296

1

N-linked (GlcNAc...) Potential

Glycosylation

381

1

N-linked (GlcNAc...)

Glycosylation

495

1

N-linked (GlcNAc...)

Disulfide bond

100 ↔ 127

Disulfide bond

288 ↔ 303

Disulfide bond

440 ↔ 560

Disulfide bond

611

Interchain By similarity

Secondary structure

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614

Helix Strand Turn

Details...

Helix

37 – 39

3

Beta strand

40 – 43

4

Beta strand

46 – 49

4

Beta strand

51 – 55

5

Beta strand

58 – 67

10

Helix

74 – 76

3

Beta strand

88 – 92

5

Beta strand

99 – 101

3

Helix

112 – 115

4

Beta strand

123 – 125

3

Beta strand

129 – 137

9

Beta strand

143 – 149

7

Turn

153 – 155

3

Helix

162 – 164

3

Helix

167 – 173

7

Beta strand

176 – 180

5

Helix

185 – 189

5

Helix

202 – 217

16

Helix

218 – 221

4

Beta strand

223 – 233

11

Helix

235 – 244

10

Helix

247 – 250

4

Beta strand

254 – 260

7

Beta strand

263 – 268

6

Helix

272 – 285

14

Helix

297 – 306

10

Helix

309 – 315

7

Helix

316 – 319

4

Beta strand

321 – 323

3

Beta strand

336 – 341

6

Helix

343 – 349

7

Beta strand

356 – 362

7

Beta strand

364 – 366

3

Helix

367 – 370

4

Turn

371 – 373

3

Helix

387 – 397

11

Helix

403 – 413

11

Helix

422 – 437

16

Helix

439 – 451

13

Beta strand

455 – 461

7

Helix

472 – 474

3

Turn

478 – 481

4

Helix

482 – 485

4

Helix

488 – 490

3

Helix

492 – 494

3

Helix

498 – 517

20

Turn

536 – 538

3

Beta strand

540 – 547

8

Beta strand

550 – 553

4

Helix

557 – 564

8

Helix

566 – 571

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform T [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 66E2512463C21172	FASTA	614	68,169
	10 20 30 40 50 60 MRPPWYPLHT PSLAFPLLFL LLSLLGGGAR AEGREDPQLL VRVRGGQLRG IRLKAPGGPV 70 80 90 100 110 120 SAFLGIPFAE PPVGSRRFMP PEPKRPWSGV LDATTFQNVC YQYVDTLYPG FEGTEMWNPN 130 140 150 160 170 180 RELSEDCLYL NVWTPYPRPA SPTPVLIWIY GGGFYSGAAS LDVYDGRFLA QVEGAVLVSM 190 200 210 220 230 240 NYRVGTFGFL ALPGSREAPG NVGLLDQRLA LQWVQENIAA FGGDPMSVTL FGESAGAASV 250 260 270 280 290 300 GMHILSLPSR SLFHRAVLQS GTPNGPWATV SAGEARRRAT LLARLVGCPP GGAGGNDTEL 310 320 330 340 350 360 IACLRTRPAQ DLVDHEWHVL PQESIFRFSF VPVVDGDFLS DTPEALINTG DFQDLQVLVG 370 380 390 400 410 420 VVKDEGSYFL VYGVPGFSKD NESLISRAQF LAGVRIGVPQ ASDLAAEAVV LHYTDWLHPE 430 440 450 460 470 480 DPTHLRDAMS AVVGDHNVVC PVAQLAGRLA AQGARVYAYI FEHRASTLTW PLWMGVPHGY 490 500 510 520 530 540 EIEFIFGLPL DPSLNYTTEE RIFAQRLMKY WTNFARTGDP NDPRDSKSPQ WPPYTTAAQQ 550 560 570 580 590 600 YVSLNLKPLE VRRGLRAQTC AFWNRFLPKL LSATDTLDEA ERQWKAEFHR WSSYMVHWKN 610 QFDHYSKQER CSDL
	Isoform H (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of mouse acetylcholinesterase: tissue distribution of alternatively spliced mRNA species." Rachinsky T.L., Camp S., Li Y., Ekstroem T.J., Newton M., Taylor P. Neuron 5:317-327(1990) [PubMed: 2400605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5." Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P., Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W., Koop B.F. Nucleic Acids Res. 29:1352-1365(2001) [PubMed: 11239002] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Retina.
[4]	"PRiMA: the membrane anchor of acetylcholinesterase in the brain." Perrier A.L., Massoulie J., Krejci E. Neuron 33:275-285(2002) [PubMed: 11804574] [Abstract] Cited for: INTERACTION WITH PRIMA1.
[5]	"Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex." Bourne Y., Taylor P., Marchot P. Cell 83:503-512(1995) [PubMed: 8521480] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF COMPLEX WITH FASCICULIN.
[6]	"Crystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop in a tetrameric assembly." Bourne Y., Taylor P., Bougis P.E., Marchot P. J. Biol. Chem. 274:2963-2970(1999) [PubMed: 9915834] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[7]	"Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site." Bourne Y., Taylor P., Radic Z., Marchot P. EMBO J. 22:1-12(2003) [PubMed: 12505979] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 34-573 IN COMPLEX WITH INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X56518 mRNA. Translation: CAA39867.1.
AF312033 Genomic DNA. Translation: AAK28816.1.
BC046327 mRNA. Translation: AAH46327.1.

PIR

JH0314.

RefSeq

NP_033729.1.

UniGene

Mm.255464

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C2B	X-ray	4.50	A	35-574	[»]
1C2O	X-ray	4.20	A/B/C/D	36-574	[»]
1J06	X-ray	2.35	A/B	32-574	[»]