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Reviewed, UniProtKB/Swiss-Prot P04058 (ACES_TORCA)

Last modified October 13, 2009. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Acetylcholinesterase
      Short name=AChE
    EC=3.1.1.7
Gene names
Name: ache
OrganismTorpedo californica (Pacific electric ray)
Taxonomic identifier7787 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Chondrichthyes › Elasmobranchii › Squalea › Hypnosqualea › Pristiorajea › Batoidea › Torpediniformes › Torpedinoidei › Torpedinidae › Torpedo

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Protein attributes

Sequence length586 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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 + H2O = choline + acetate.

Enzyme regulation

Inhibited by substrate concentrations above 0.5 mM. Ref.22

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. Ref.11

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.

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Alternative products

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

Note: 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.
Note: GPI-anchored form.
Isoform T (identifier: P04058-2)

The sequence of this isoform differs from the canonical sequence as follows:
     557-586: ACDGELSSSGTSSSKGIIFYVLFSILYLIF → ETIDEAERQWKTEFHRWSSYMMHWKNQFDHYSRHESCAEL
Note: Attached to the membrane through disulfide linkage with the collagenic subunit, itself bound to the membrane.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.3
Chain22 – 564543Acetylcholinesterase
PRO_0000008595
Propeptide565 – 58622Removed in mature form
PRO_0000008596

Sites

Active site2211Acyl-ester intermediate Ref.22 Ref.11
Active site3481Charge relay system Ref.22 Ref.11
Active site4611Charge relay system Ref.22 Ref.11

Amino acid modifications

Lipidation5641GPI-anchor amidated serine Ref.8 Ref.9
Glycosylation801N-linked (GlcNAc...) Ref.22 Ref.18
Glycosylation4371N-linked (GlcNAc...) Ref.22 Ref.11 Ref.18
Glycosylation4781N-linked (GlcNAc...) Ref.18
Glycosylation5541N-linked (GlcNAc...) Ref.18
Disulfide bond88 ↔ 115 Ref.11 Ref.7
Disulfide bond275 ↔ 286 Ref.11 Ref.7
Disulfide bond423 ↔ 542 Ref.11 Ref.7
Disulfide bond558Interchain Ref.11 Ref.7

Natural variations

Alternative sequence557 – 58630ACDGE…LYLIF → ETIDEAERQWKTEFHRWSSY MMHWKNQFDHYSRHESCAEL in isoform T.
VSP_001460

Experimental info

Mutagenesis2201E → H: Loss of activity.
Mutagenesis2201E → Q or D: Decrease in activity.
Mutagenesis2211S → C: Loss of activity.
Mutagenesis2211S → V: Loss of activity.
Mutagenesis4461H → Q: Almost no loss of activity.
Mutagenesis4611H → Q: Loss of activity.

Secondary structure

1 ........................................................................................... 586
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform H (Globular) [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: 731D5F0F3ABA62A8

FASTA58665,906
        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

« Hide

Isoform T.

Checksum: 36D5E9A30F9E6065
Show »

FASTA59667,818

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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 bonds in acetylcholinesterase."
McPhee-Quigley K., Vedvick T.S., Taylor P., Taylor S.S.
J. Biol. Chem. 261:13565-13570(1986) [PubMed: 3759980] [Abstract]
Cited for: DISULFIDE BONDS.
[8]"Structure of the glycosyl-phosphatidylinositol membrane anchor of acetylcholinesterase from the electric organ of the electric-fish, Torpedo californica."
Mehlert A., Varon L., Silman I., Homans S.W., Ferguson M.A.
Biochem. J. 296:473-479(1993) [PubMed: 8257440] [Abstract]
Cited for: STRUCTURE OF THE GPI-ANCHOR.
[9]"Residues in Torpedo californica acetylcholinesterase necessary for processing to a glycosyl phosphatidylinositol-anchored form."
Bucht G., Hjalmarsson K.
Biochim. Biophys. Acta 1292:223-232(1996) [PubMed: 8597567] [Abstract]
Cited for: GPI-ANCHOR AT SER-564.
[10]"Mutagenesis of essential functional residues in acetylcholinesterase."
Gibney G., Camp S., Dionne M., McPhee-Quigley K., Taylor P.
Proc. Natl. Acad. Sci. U.S.A. 87:7546-7550(1990) [PubMed: 2217185] [Abstract]
Cited for: MUTAGENESIS.
[11]"Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein."
Sussman J.L., Harel M., Frolow F., Oefner C., Goldman A., Toker L., Silman I.
Science 253:872-879(1991) [PubMed: 1678899] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-558, ACTIVE SITE, GLYCOSYLATION AT ASN-437, DISULFIDE BONDS, SUBUNIT.
[12]"Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase."
Harel M., Schalk I., Ehret-Sabatier L., Bouet F., Goeldner M., Hirth C., Axelsen P.H., Silman I., Sussman J.L.
Proc. Natl. Acad. Sci. U.S.A. 90:9031-9035(1993) [PubMed: 8415649] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-556 IN COMPLEX WITH SUBSTRATE ANALOGS.
[13]"Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target."
Harel M., Kleywegt G.J., Ravelli R.B., Silman I., Sussman J.L.
Structure 3:1355-1366(1995) [PubMed: 8747462] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 22-558 IN COMPLEX WITH FASCICULIN.
[14]"Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A."
Raves M.L., Harel M., Pang Y.P., Silman I., Kozikowski A.P., Sussman J.L.
Nat. Struct. Biol. 4:57-63(1997) [PubMed: 8989325] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 22-558 IN COMPLEX WITH THE INHIBITOR HUPERZINE A.
[15]"'Back door' opening implied by the crystal structure of a carbamoylated acetylcholinesterase."
Bartolucci C., Perola E., Cellai L., Brufani M., Lamba D.
Biochemistry 38:5714-5719(1999) [PubMed: 10231521] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 22-558.
[16]"Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level."
Millard C.B., Kryger G., Ordentlich A., Greenblatt H.M., Harel M., Raves M.L., Segall Y., Barak D., Shafferman A., Silman I., Sussman J.L.
Biochemistry 38:7032-7039(1999) [PubMed: 10353814] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 22-558.
[17]"Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3-A resolution."
Greenblatt H.M., Kryger G., Lewis T., Silman I., Sussman J.L.
FEBS Lett. 463:321-326(1999) [PubMed: 10606746] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 22-564 IN COMPLEX WITH GALANTHAMINE.
[18]"Structure of acetylcholinesterase complexed with E2020 (Aricept(R)): implications for the design of new anti-Alzheimer drugs."
Kryger G., Silman I., Sussman J.L.
Structure 7:297-307(1999) [PubMed: 10368299] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 22-564 IN COMPLEX WITH THE SYNTHETIC INHIBITOR ARICEPT, GLYCOSYLATION AT ASN-80; ASN-437; ASN-478 AND ASN-554.
[19]"3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates."
Dvir H., Wong D.M., Harel M., Barril X., Orozco M., Luque F.J., Munoz-Torrero D., Camps P., Rosenberry T.L., Silman I., Sussman J.L.
Biochemistry 41:2970-2981(2002) [PubMed: 11863435] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 22-564 IN COMPLEX WITH THE SYNTHETIC INHIBITOR HUPRINE.
[20]"Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine."
Bar-On P., Millard C.B., Harel M., Dvir H., Enz A., Sussman J.L., Silman I.
Biochemistry 41:3555-3564(2002) [PubMed: 11888271] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-556 IN COMPLEX WITH THE SYNTHETIC INHIBITOR RIVASTIGMINE.
[21]"The crystal structure of the complex of the anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) with Torpedo californica acetylcholinesterase provides a molecular explanation for its cholinergic action."
Harel M., Hyatt J.L., Brumshtein B., Morton C.L., Yoon K.J., Wadkins R.M., Silman I., Sussman J.L., Potter P.M.
Mol. Pharmacol. 67:1874-1881(2005) [PubMed: 15772291] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 22-564 IN COMPLEX WITH THE SYNTHETIC INHIBITOR CPT-11.
[22]"Structural insights into substrate traffic and inhibition in acetylcholinesterase."
Colletier J.-P., Fournier D., Greenblatt H.M., Stojan J., Sussman J.L., Zaccai G., Silman I., Weik M.
EMBO J. 25:2746-2756(2006) [PubMed: 16763558] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 22-558 IN COMPLEXES WITH SUBSTRATE AND SUBSTRATE ANALOGS, GLYCOSYLATION AT ASN-80 AND ASN-437, ACTIVE SITE, ENZYME REGULATION.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X03439 mRNA. Translation: CAA27169.1.
X56516 Genomic DNA. No translation available.
X56517 Genomic DNA. No translation available.
PIRACRYE. A00773.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ACJX-ray2.80A22-556[»]
1ACLX-ray2.80A22-556[»]
1AMNX-ray2.80A22-558[»]
1AX9X-ray2.80A22-558[»]
1CFJX-ray2.60A22-558[»]
1DX6X-ray2.30A22-564[»]
1E3QX-ray2.85A22-564[»]
1E66X-ray2.10A22-564[»]
1EA5X-ray1.80A22-558[»]
1EEAX-ray4.50A22-555[»]
1EVEX-ray2.50A22-564[»]
1FSSX-ray3.00A22-558[»]
1GPKX-ray2.10A22-558[»]
1GPNX-ray2.35A22-558[»]
1GQRX-ray2.20A25-556[»]
1GQSX-ray3.00A25-556[»]
1H22X-ray2.15A22-564[»]
1H23X-ray2.15A22-564[»]
1HBJX-ray2.50A22-564[»]
1JGAmodel-A1-586[»]
1JGBmodel-A1-586[»]
1JJBX-ray2.30A25-556[»]
1OCEX-ray2.70A22-558[»]
1ODCX-ray2.20A22-564[»]
1QIDX-ray2.05A22-558[»]
1QIEX-ray2.10A22-558[»]
1QIFX-ray2.10A22-558[»]
1QIGX-ray2.30A22-558[»]
1QIHX-ray2.50A22-558[»]
1QIIX-ray2.65A22-558[»]
1QIJX-ray2.80A22-558[»]
1QIKX-ray2.90A22-558[»]
1QIMX-ray3.00A22-558[»]
1QTIX-ray2.50A22-537[»]
1SOMX-ray2.20A22-564[»]
1U65X-ray2.61A22-564[»]
1UT6X-ray2.40A22-556[»]
1VOTX-ray2.50A22-558[»]
1VXOX-ray2.40A22-558[»]
1VXRX-ray2.20A22-558[»]
1W4LX-ray2.16A22-564[»]
1W6RX-ray2.05A22-564[»]
1W75X-ray2.40A/B22-564[»]
1W76X-ray2.30A/B22-564[»]
1ZGBX-ray2.30A22-564[»]
1ZGCX-ray2.10A/B22-564[»]
2ACEX-ray2.50A22-558[»]
2ACKX-ray2.40A22-558[»]
2BAGX-ray2.40A22-564[»]
2C4HX-ray2.15A22-558[»]
2C58X-ray2.30A22-558[»]
2C5FX-ray2.60A22-558[»]
2C5GX-ray1.95A22-558[»]
2CEKX-ray2.20A22-556[»]
2CKMX-ray2.15A22-564[»]
2CMFX-ray2.50A22-564[»]
2DFPX-ray2.30A23-556[»]
2J3DX-ray2.60A22-564[»]
2J3QX-ray2.80A22-564[»]
2J4FX-ray2.80A22-564[»]
2V96X-ray2.40A/B22-558[»]
2V97X-ray2.40A/B22-558[»]
2V98X-ray3.00A/B22-558[»]
2VA9X-ray2.40A/B22-558[»]
2VJAX-ray2.30A/B22-558[»]
2VJBX-ray2.39A/B22-558[»]
2VJCX-ray2.20A/B22-558[»]
2VJDX-ray2.30A/B22-558[»]
2VQ6X-ray2.71A22-564[»]
2VT6X-ray2.40A/B22-558[»]
2VT7X-ray2.20A/B22-558[»]
2W6CX-ray2.69X1-586[»]
2WFZX-ray1.95A22-558[»]
2WG0X-ray2.20A22-558[»]
2WG1X-ray2.20A22-558[»]
3ACEmodel-A22-558[»]
4ACEmodel-A22-558[»]
ModBaseSearch...

Protein family/group databases

MEROPSS09.979.

Phylogenomic databases

HOVERGENP04058.

Enzyme and pathway databases

BRENDA3.1.1.7. 74507.

Family and domain databases

InterProIPR000908. Acylcholinesterase_fish/snake.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
IPR000997. Cholinesterase.
[Graphical view]
PANTHERPTHR11559. CarbesteraseB. 1 hit.
PfamPF00135. COesterase. 1 hit.
[Graphical view]
PRINTSPR00879. ACHEFISH.
PR00878. CHOLNESTRASE.
PROSITEPS00122. CARBOXYLESTERASE_B_1. 1 hit.
PS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00674. Galantamine.

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Entry information

Entry nameACES_TORCA
AccessionPrimary (citable) accession number: P04058
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: June 1, 1994
Last modified: October 13, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents