P21836 (ACES_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetylcholinesterase
Short name=AChE
EC=3.1.1.7

Gene names

Name:

Ache

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › 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 + H2O = 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. Ref.4
Subcellular location	Cell junction › synapse. Secreted. Cell membrane; Peripheral membrane protein By 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	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acetylcholine catabolic process Inferred from direct assay PubMed 16434405PubMed 7512968. Source: MGI choline metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome neurotransmitter receptor biosynthetic process Inferred from mutant phenotype PubMed 14645660. Source: MGI osteoblast development Inferred from electronic annotation. Source: Compara protein tetramerization Inferred from direct assay PubMed 8626792. Source: MGI receptor internalization Inferred from mutant phenotype PubMed 14645660. Source: MGI regulation of axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of dendrite morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of receptor recycling Inferred from mutant phenotype PubMed 14645660. Source: MGI retina development in camera-type eye Inferred from mutant phenotype PubMed 15579149. Source: MGI synapse assembly Inferred from Biological aspect of Ancestor. Source: RefGenome synaptic transmission, cholinergic Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW axon Inferred from Biological aspect of Ancestor. Source: RefGenome basal lamina Inferred from direct assay PubMed 7885444. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay PubMed 16434405. Source: MGI dendrite Inferred from Biological aspect of Ancestor. Source: RefGenome endoplasmic reticulum lumen Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular space Inferred from direct assay PubMed 16434405PubMed 8626792. Source: MGI neuromuscular junction Inferred from direct assay PubMed 7885444. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay PubMed 8626792. Source: MGI postsynaptic membrane Inferred from Biological aspect of Ancestor. Source: RefGenome presynaptic membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	acetylcholinesterase activity Inferred from direct assay PubMed 16434405PubMed 7512968. Source: MGI carboxylesterase activity Inferred from Biological aspect of Ancestor. Source: RefGenome serine hydrolase activity Inferred from electronic annotation. Source: Compara
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.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Chain

32 – 614

583

Acetylcholinesterase

PRO_0000008588

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

1

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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

Beta strand

196 – 198

3

Helix

202 – 217

16

Helix

218 – 221

4

Beta strand

223 – 233

11

Helix

235 – 245

11

Helix

247 – 250

4

Beta strand

254 – 260

7

Beta strand

263 – 268

6

Helix

272 – 285

14

Turn

286 – 290

5

Beta strand

291 – 293

3

Helix

297 – 304

8

Beta strand

305 – 307

3

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

Beta strand

379 – 381

3

Helix

387 – 397

11

Helix

403 – 413

11

Beta strand

416 – 418

3

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

523 – 525

3

Beta strand

526 – 528

3

Turn

536 – 538

3

Beta strand

540 – 547

8

Beta strand

550 – 553

4

Helix

557 – 571

15

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 34-573 IN COMPLEX WITH INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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

IPI

IPI00128567.

PIR

JH0314.

RefSeq

NP_033729.1. NM_009599.3.

UniGene

Mm.255464.
Mm.489229.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
1J07	X-ray	2.35	A/B	32-574	[»]
1KU6	X-ray	2.50	A	32-580	[»]
1MAA	X-ray	2.90	A/B/C/D	32-578	[»]
1MAH	X-ray	3.20	A	32-574	[»]
1N5M	X-ray	2.20	A/B	32-572	[»]
1N5R	X-ray	2.25	A/B	32-574	[»]
1Q83	X-ray	2.65	A/B	1-580	[»]
1Q84	X-ray	2.45	A/B	1-580	[»]
2C0P	X-ray	2.50	A/B	32-574	[»]
2C0Q	X-ray	2.50	A/B	32-574	[»]
2GYU	X-ray	2.20	A/B	32-574	[»]
2GYV	X-ray	2.50	A/B	32-574	[»]
2GYW	X-ray	2.40	A/B	32-574	[»]
2H9Y	X-ray	2.40	A/B	32-574	[»]
2HA0	X-ray	2.20	A/B	32-574	[»]
2HA2	X-ray	2.05	A/B	32-574	[»]
2HA3	X-ray	2.25	A/B	32-574	[»]
2HA4	X-ray	2.56	A/B	32-574	[»]
2HA5	X-ray	2.15	A/B	32-574	[»]
2HA6	X-ray	2.25	A/B	32-574	[»]
2HA7	X-ray	2.66	A/B	32-574	[»]
2JEY	X-ray	2.70	A/B	32-574	[»]
2JEZ	X-ray	2.60	A/B	32-574	[»]
2JF0	X-ray	2.50	A/B	32-574	[»]
2JGE	X-ray	2.60	A/B	32-574	[»]
2JGF	X-ray	2.50	A/B	32-574	[»]
2JGI	X-ray	2.90	A/B	32-574	[»]
2JGJ	X-ray	2.50	A/B	32-574	[»]
2JGK	X-ray	2.90	A/B	32-574	[»]
2JGL	X-ray	2.60	A/B	32-574	[»]
2JGM	X-ray	2.90	A/B	32-574	[»]
2WHP	X-ray	2.20	A/B	32-573	[»]
2WHQ	X-ray	2.15	A/B	32-574	[»]
2WHR	X-ray	2.54	A/B	32-574	[»]
2WLS	X-ray	2.60	A/B	32-574	[»]
2WU3	X-ray	2.70	A/B	32-574	[»]
2WU4	X-ray	2.40	A/B	32-574	[»]
2XUD	X-ray	2.65	A/B	32-574	[»]
2XUF	X-ray	2.55	A/B	32-574	[»]
2XUG	X-ray	2.60	A/B	32-574	[»]
2XUH	X-ray	2.65	A/B	32-574	[»]
2XUI	X-ray	2.60	A/B	32-574	[»]
2XUJ	X-ray	2.65	A/B	32-574	[»]
2XUK	X-ray	2.75	A/B	32-574	[»]
2XUO	X-ray	2.80	A/B	32-574	[»]
2XUP	X-ray	2.70	A/B	32-574	[»]
2XUQ	X-ray	2.70	A/B	32-574	[»]
2Y2U	X-ray	2.60	A/B	32-574	[»]
2Y2V	X-ray	2.45	A/B	32-574	[»]
3DL4	X-ray	2.50	A/B	32-574	[»]
3DL7	X-ray	2.50	A/B	32-574	[»]
4A16	X-ray	2.65	A/B/C/D	35-574	[»]
4A23	X-ray	2.40	A/B	32-574	[»]
4ARA	X-ray	2.50	A/B	32-574	[»]
4ARB	X-ray	2.25	A/B	32-574	[»]
4BC0	X-ray	3.35	A/B/C/D	32-574	[»]
4BC1	X-ray	2.95	A/B/C/D	32-574	[»]

ProteinModelPortal

P21836.

SMR

P21836. Positions 35-608.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1206315.

Protein family/group databases

MEROPS

S09.979.

PTM databases

PhosphoSite

P21836.

Proteomic databases

PaxDb

P21836.

PRIDE

P21836.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000024099; ENSMUSP00000024099; ENSMUSG00000023328.
ENSMUST00000085934; ENSMUSP00000083097; ENSMUSG00000023328.

GeneID

11423.

KEGG

mmu:11423.

Organism-specific databases

CTD

43.

MGI

MGI:87876. Ache.

Phylogenomic databases

eggNOG

COG2272.

HOGENOM

HOG000091866.

HOVERGEN

HBG008839.

InParanoid

P21836.

KO

K01049.

OMA

QYVSLNL.

OrthoDB

EOG46WZ86.

Enzyme and pathway databases

SABIO-RK

P21836.

Gene expression databases

ArrayExpress

P21836.

Bgee

P21836.

CleanEx

MM_ACHE.

Genevestigator

P21836.

GermOnline

ENSMUSG00000023328. Mus musculus.

Family and domain databases

InterPro

IPR014788. AChE_tetra.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
IPR000997. Cholinesterase.
[Graphical view]

Pfam

PF08674. AChE_tetra. 1 hit.
PF00135. COesterase. 1 hit.
[Graphical view]

PRINTS

PR00878. CHOLNESTRASE.

ProDom

PD415333. AChE_tetra. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

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

ProtoNet

Search...

Other

BindingDB

P21836.

ChEMBL

CHEMBL3198.

EvolutionaryTrace

P21836.

NextBio

278674.

SOURCE

Search...

Entry information

Entry name

ACES_MOUSE

Accession

Primary (citable) accession number: P21836

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program