Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ACHE (P22303) - Overview - Molecular Target Synopsis

Protein


ACHE, Acetylcholinesterase
Enzyme Classification 3.1.1.7
UniProt P22303

Also Known as ACES_HUMAN, ACHE

Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis. Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers (By similarity). 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. Isoform R may be monomeric.

6O4W
BINARY COMPLEX OF NATIVE HACHE WITH DONEPEZIL
RCSB/PDB
Inspect Structure
See all 3D Structures for ACHE

Isoforms / Transcripts (Protein Coding)


Drugs


ACHE is targeted by Approved Drugs Donepezil, Rivastigmine, Isoflurophate, Ambenonium, Pyridostigmine, Neostigmine, Demecarium, Pralidoxime, Hexafluorenium, Echothiophate, Edrophonium, Tacrine, Galantamine. (see details)
Donepezil
Rivastigmine
Isoflurophate
Ambenonium
Pyridostigmine
Neostigmine
Demecarium
Pralidoxime
Hexafluorenium
Echothiophate
Edrophonium
Tacrine
Galantamine

Sub-cellular localization


UniProt: ACHE is active in the following subcellular-locations: cell junction, cell membrane, nucleus, secreted, synapse.
GO terms: ACHE is active in the following subcellular-locations: anchored component of membrane, basement membrane, cell junction, cell surface, extracellular region, extracellular space, Golgi apparatus, membrane, neuromuscular junction, nucleus, perinuclear region of cytoplasm, plasma membrane, synapse, synaptic cleft.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ACHE has gain in 7 cell-lines, loss in 1 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, HL_60, NCI_H460

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-1, CAL 54, ABC-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HMEC, HSMM

(see details)

3D Structures


For ACHE there are:
38 structures (75 chains) solved
36 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

ACHE is solved in complex with the approved drug(s):

GNT/GALANTAMINE (4EY6_A, 4EY6_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ACHE has been screened with 7177 compounds (13484 bioactivities), 1863 compounds have bioactivities that show binding affinity of <= 500nM (2927 bioactivities). (see details)