ACHE

Protein identityUniProt · HPA

UniProt accession

P22303

Gene

ACHE

Ensembl

ENSG00000087085

Chromosome

7

Canonical length

614 aa

Protein class

Blood group antigen proteins, Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Golgi apparatus,Vesicles

Secretome location

Intracellular and membrane

OverviewNCBI Gene

Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion[provided by RefSeq, Sep 2019]

Canonical amino-acid sequenceUniProt

614 residues, UniProt reviewed canonical sequence.

>P22303|ACHE
     1  MRPPQCLLHT PSLASPLLLL LLWLLGGGVG AEGREDAELL VTVRGGRLRG IRLKTPGGPV
    61  SAFLGIPFAE PPMGPRRFLP PEPKQPWSGV VDATTFQSVC YQYVDTLYPG FEGTEMWNPN
   121  RELSEDCLYL NVWTPYPRPT SPTPVLVWIY GGGFYSGASS LDVYDGRFLV QAERTVLVSM
   181  NYRVGAFGFL ALPGSREAPG NVGLLDQRLA LQWVQENVAA FGGDPTSVTL FGESAGAASV
   241  GMHLLSPPSR GLFHRAVLQS GAPNGPWATV GMGEARRRAT QLAHLVGCPP GGTGGNDTEL
   301  VACLRTRPAQ VLVNHEWHVL PQESVFRFSF VPVVDGDFLS DTPEALINAG DFHGLQVLVG
   361  VVKDEGSYFL VYGAPGFSKD NESLISRAEF LAGVRVGVPQ VSDLAAEAVV LHYTDWLHPE
   421  DPARLREALS DVVGDHNVVC PVAQLAGRLA AQGARVYAYV FEHRASTLSW PLWMGVPHGY
   481  EIEFIFGIPL DPSRNYTAEE KIFAQRLMRY WANFARTGDP NEPRDPKAPQ WPPYTAGAQQ
   541  YVSLDLRPLE VRRGLRAQAC AFWNRFLPKL LSATDTLDEA ERQWKAEFHR WSSYMVHWKN
   601  QFDHYSKQDR CSDL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACHE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

153 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACHE.

Disease | AutoantibodyPubMed

Conditions in which antibodies against ACHE are reported. Each links to that disease's full target list.

• Myasthenia Gravis 4
• Graves Disease 3

ReferencesPubMed · IEDB

Publications for ACHE from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

2.75

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acetylcholine catabolic process
• acetylcholine catabolic process in synaptic cleft
• acetylcholine receptor signaling pathway
• amyloid precursor protein metabolic process
• cell adhesion
• negative regulation of synaptic transmission, cholinergic
• nervous system development
• osteoblast development
• positive regulation of cold-induced thermogenesis
• positive regulation of protein secretion
• receptor internalization
• regulation of receptor recycling
• retina development in camera-type eye
• synapse assembly

Molecular functions

• acetylcholine binding
• acetylcholinesterase activity
• amyloid-beta binding
• cholinesterase activity
• collagen binding
• hydrolase activity
• laminin binding
• protein homodimerization activity
• serine hydrolase activity

Cellular components

• basement membrane
• cell surface
• extracellular region
• extracellular space
• Golgi apparatus
• membrane
• neuromuscular junction
• nucleus
• perinuclear region of cytoplasm
• plasma membrane
• side of membrane
• synapse
• synaptic cleft

Protein domainsUniProt · Pfam · InterPro

• Cholinesterase
• Carboxylesterase, type B
• Acetylcholinesterase, tetramerisation domain
• Carboxylesterase type B, conserved site
• Carboxylesterase type B, active site
• Alpha/Beta hydrolase fold
• Acetylcholinesterase-related enzymes
• Carboxylesterase family
• Acetylcholinesterase tetramerisation domain

KeywordsUniProt

• Blood group antigen
• Cell membrane
• Disulfide bond
• Glycoprotein
• GPI-anchor
• Hydrolase
• Lipoprotein
• Membrane
• Neurotransmitter degradation
• Nucleus
• Secreted
• Serine esterase
• Signal
• Synapse

InteractionsUniProt · HPA

Protein binding partners of ACHE in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PRIMA1