Human Gene ACHE (ENST00000428317.7) Description and Page Index
  Description: Homo sapiens acetylcholinesterase (Cartwright blood group) (ACHE), transcript variant 5, mRNA. (from RefSeq NM_001302622)
RefSeq Summary (NM_001302622): 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].
Gencode Transcript: ENST00000428317.7
Gencode Gene: ENSG00000087085.15
Transcript (Including UTRs)
   Position: hg38 chr7:100,889,994-100,896,129 Size: 6,136 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr7:100,890,214-100,894,232 Size: 4,019 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:100,889,994-100,896,129)mRNA (may differ from genome)Protein (614 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ACES_HUMAN
DESCRIPTION: RecName: Full=Acetylcholinesterase; Short=AChE; EC=3.1.1.7; Flags: Precursor;
FUNCTION: Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
CATALYTIC ACTIVITY: Acetylcholine + H(2)O = choline + acetate.
SUBUNIT: 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.
INTERACTION: Q9Y215:COLQ; NbExp=2; IntAct=EBI-1637793, EBI-1637847; P06733:ENO1; NbExp=2; IntAct=EBI-1637793, EBI-353877; P63244:GNB2L1; NbExp=2; IntAct=EBI-1637793, EBI-296739;
SUBCELLULAR LOCATION: Cell junction, synapse. Secreted (By similarity). Cell membrane; Peripheral membrane protein (By similarity).
SUBCELLULAR LOCATION: Isoform T: Nucleus. Note=Only observed in apoptotic nuclei.
SUBCELLULAR LOCATION: Isoform H: Cell membrane; Lipid-anchor, GPI- anchor; Extracellular side (By similarity).
TISSUE SPECIFICITY: Isoform H is highly expressed in erythrocytes.
POLYMORPHISM: ACHE is responsible for the Yt blood group system [MIM:112100]. The molecular basis of the Yt(a)=Yt1/Yt(b)=Yt2 blood group antigens is a single variation in position 353; His-353 corresponds to Yt(a) and the rare variant with Asn-353 to Yt(b).
SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation database; URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=yt";
WEB RESOURCE: Name=Wikipedia; Note=Acetylcholinesterase entry; URL="http://en.wikipedia.org/wiki/Acetylcholinesterase";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ache/";

-  MalaCards Disease Associations
  MalaCards Gene Search: ACHE
Diseases sorted by gene-association score: colonic pseudo-obstruction (22), primary orthostatic hypotension (18), vascular dementia (16), myasthenic syndrome, congenital, 5 (15), wernicke-korsakoff syndrome (13), agraphia (12), cholinergic urticaria (12), irinotecan toxicity (12), hirschsprung disease 1 (12), myasthenia gravis (12), megacolon (11), amnestic disorder (11), hypoganglionosis (10), congenital myasthenic syndrome (9), tendinosis (9), rem sleep behavior disorder (8), gastroschisis (8), intestinal obstruction (8), rumination disorder (7), autoinflammation with infantile enterocolitis (7), hypohidrosis (7), neuronal intestinal dysplasia (7), epidermolysis bullosa, junctional, herlitz type (6), congenital nephrotic syndrome finnish type (6), polyneuropathy (6), cerebrovascular disease (6), dementia, lewy body (6), orthostatic intolerance (6), ptosis, congenital (6), supranuclear palsy, progressive (6), colonic disease (5), cataract 1, multiple types (5), anencephaly (5), epidermolysis bullosa, junctional, with pyloric stenosis (5), dementia (5), cataract 14, multiple types (5), myopathy, x-linked, with excessive autophagy (5), neuromuscular junction disease (5), binswanger's disease (4), cenani-lenz syndactyly syndrome (4), pure autonomic failure (4), dementia, frontotemporal (4), toxic encephalopathy (4), alzheimer disease (4), aplasia cutis congenita (4), nominal aphasia (3), neural tube defects (3), parkinson disease, late-onset (1), malaria (1), nervous system disease (1), central nervous system disease (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -35.6091-0.391 Picture PostScript Text
3' UTR -65.50220-0.298 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR014788 - AChE_tetra
IPR002018 - CarbesteraseB
IPR019826 - Carboxylesterase_B_AS
IPR019819 - Carboxylesterase_B_CS
IPR000997 - Cholinesterase

Pfam Domains:
PF08674 - Acetylcholinesterase tetramerisation domain
PF00135 - Carboxylesterase family

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1B41
- X-ray MuPIT

1F8U
- X-ray MuPIT

1PUV
- Model
To conserve bandwidth, only the images from the first 3 structures are shown.
1PUW - Model 1VZJ - X-ray 2CLJ - Model
2X8B - X-ray MuPIT 3LII - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P22303
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI     
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001540 beta-amyloid binding
GO:0003990 acetylcholinesterase activity
GO:0004104 cholinesterase activity
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0016787 hydrolase activity
GO:0017171 serine hydrolase activity
GO:0042166 acetylcholine binding
GO:0042803 protein homodimerization activity
GO:0043236 laminin binding
GO:0043621 protein self-association
GO:0052689 carboxylic ester hydrolase activity

Biological Process:
GO:0001507 acetylcholine catabolic process in synaptic cleft
GO:0001919 regulation of receptor recycling
GO:0002076 osteoblast development
GO:0006260 DNA replication
GO:0006581 acetylcholine catabolic process
GO:0006656 phosphatidylcholine biosynthetic process
GO:0007155 cell adhesion
GO:0007399 nervous system development
GO:0007416 synapse assembly
GO:0007517 muscle organ development
GO:0008283 cell proliferation
GO:0009611 response to wounding
GO:0031623 receptor internalization
GO:0032223 negative regulation of synaptic transmission, cholinergic
GO:0042135 neurotransmitter catabolic process
GO:0042136 neurotransmitter biosynthetic process
GO:0042982 amyloid precursor protein metabolic process
GO:0045212 neurotransmitter receptor biosynthetic process
GO:0050714 positive regulation of protein secretion
GO:0051262 protein tetramerization
GO:0060041 retina development in camera-type eye

Cellular Component:
GO:0005576 extracellular region
GO:0005605 basal lamina
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0030054 cell junction
GO:0031225 anchored component of membrane
GO:0031594 neuromuscular junction
GO:0043083 synaptic cleft
GO:0045202 synapse
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  HV708922 - JP 2012506450-A/20: Methods for treating eye disorders.
AK223443 - Homo sapiens mRNA for acetylcholinesterase isoform E4-E6 precursor variant, clone: FCC112G06.
BC026315 - Homo sapiens acetylcholinesterase (Yt blood group), mRNA (cDNA clone IMAGE:4795048).
HV708921 - JP 2012506450-A/19: Methods for treating eye disorders.
BC094752 - Homo sapiens cDNA clone IMAGE:5312273, containing frame-shift errors.
AK291321 - Homo sapiens cDNA FLJ77135 complete cds, highly similar to Homo sapiens acetylcholinesterase (YT blood group) (ACHE), transcript variant E4-E6, mRNA.
M55040 - Human acetylcholinesterase (ACHE) mRNA, complete cds.
AF334270 - Homo sapiens apoptosis-related acetylcholinesterase (ARACHE) mRNA, complete cds, alternatively spliced.
JC046429 - Sequence 60 from Patent WO2013168162.
JD173702 - Sequence 154726 from Patent EP1572962.
JC046421 - Sequence 52 from Patent WO2013168162.
AB463388 - Synthetic construct DNA, clone: pF1KB8379, Homo sapiens ACHE gene for acetylcholinesterase, without stop codon, in Flexi system.
JD158046 - Sequence 139070 from Patent EP1572962.
JD394441 - Sequence 375465 from Patent EP1572962.
JD044942 - Sequence 25966 from Patent EP1572962.
BC105060 - Homo sapiens acetylcholinesterase (Yt blood group), mRNA (cDNA clone MGC:132720 IMAGE:8144063), complete cds.
BC143469 - Homo sapiens acetylcholinesterase (Yt blood group), mRNA (cDNA clone MGC:176994 IMAGE:9051977), complete cds.
BC105062 - Homo sapiens acetylcholinesterase (Yt blood group), transcript variant E4-E5, mRNA (cDNA clone MGC:132722 IMAGE:8144065), complete cds.
BC001541 - Homo sapiens acetylcholinesterase (Yt blood group), mRNA (cDNA clone IMAGE:3453362), with apparent retained intron.
BC036813 - Homo sapiens acetylcholinesterase (Yt blood group), mRNA (cDNA clone IMAGE:5732482), partial cds.
LF211990 - JP 2014500723-A/19493: Polycomb-Associated Non-Coding RNAs.
MA447567 - JP 2018138019-A/19493: Polycomb-Associated Non-Coding RNAs.
AY389977 - Homo sapiens N-terminal extended acetylcholinesterase (ACHE) mRNA, exon E1d and partial cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00564 - Glycerophospholipid metabolism

Reactome (by CSHL, EBI, and GO)

Protein P22303 (Reactome details) participates in the following event(s):

R-HSA-9023617 Butyrylcholinesterase hydrolyzes acyl Ghrelin
R-HSA-372519 AcCho is hydrolyzed to Cho and acetate by ACHE
R-HSA-422085 Synthesis, secretion, and deacylation of Ghrelin
R-HSA-112311 Neurotransmitter clearance
R-HSA-1483191 Synthesis of PC
R-HSA-2980736 Peptide hormone metabolism
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-1483206 Glycerophospholipid biosynthesis
R-HSA-392499 Metabolism of proteins
R-HSA-112316 Neuronal System
R-HSA-1483257 Phospholipid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A4D2E2, ACES_HUMAN, B7ZKZ0, D6W5X7, NM_001302622, P22303, Q16169, Q29S23, Q2M324, Q504V3, Q53F46, Q86TM9, Q86YX9, Q9BXP7, uc003uxi.1, uc003uxi.2, uc003uxi.3, uc003uxi.4, uc003uxi.5, uc003uxi.6
UCSC ID: uc003uxi.6
RefSeq Accession: NM_001302622
Protein: P22303 (aka ACES_HUMAN)
CCDS: CCDS5709.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.