Cholinesterase (BCHE)

The protein contains 602 amino acids for an estimated molecular weight of 68418 Da.

 

Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 91%
Model score: 99

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VariantDescription
Does not affect enzymatic activity
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED; the mutant undergoes rapid degradation
BCHED
Does not affect enzyme activity
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED
BCHED; enzymatically inactive in the plasma
BCHED
BCHED
BCHED
dbSNP:rs16849700
BCHED
Does not affect enzymatic activity
BCHED
BCHED
BCHED
BCHED; results in 20% of activity compared to wild-type
BCHED
BCHED
BCHED
BCHED
BCHED
Does not affect enzymatic activity
BCHED; seems to cause reduced expression of the protein
BCHED
BCHED
BCHED
BCHED; seems to cause reduced expression of the protein
BCHED

No binding partner found

The reference OMIM entry for this protein is 177400

Butyrylcholinesterase; bche
Pseudocholinesterase e1; che1
Acylcholine acylhydrolase butyrylcholinesterase deficiency, included
Acholinesterasemia, included
Suxamethonium sensitivity, included
Pseudocholinesterase deficiency, included
Apne

CLONING

Lockridge et al. (1987) concluded that the 4 subunits of cholinesterase are identical and that each contains 574 amino acids and 9 carbohydrate chains attached to 9 asparagines. Prody et al. (1987) isolated and characterized full-length cDNA clones for pseudocholinesterase (butyrylcholinesterase) from human fetal tissues. McTiernan et al. (1987) screened a cDNA library from human basal ganglia with oligonucleotide probes corresponding to the amino acid sequence of human serum cholinesterase (EC 3.1.1.8), which is also known as acylcholine acylhydrolase. There were 1,722 basepairs of the coding sequence corresponding to the protein found circulating in human serum. The amino acid sequence deduced from the cDNA exactly matched the 574-amino acid sequence of human serum cholinesterase; therefore, the clones represented cholinesterase rather than acetylcholinesterase (ACHE; 100740). Hybridization of genomic DNA blots suggested that a single gene, or very few genes, code for cholinesterase. The amino acid sequences of cholinesterase in brain and serum are apparently identical. Cholinesterase is present in particularly high levels in embryonic and fetal human brain as well as in nervous system tumors such as glioblastomas, neuroblastomas, and meningiomas. The widespread expression in early differentiation suggests development-related functions for this protein.

MAPPING

On the basis of dosage effects, Arias et al. (1985) suggested that CHE1 is located at 3q25.2 and that ceruloplasmin (CP; 117700) and TF are nearer the centromere. Using a cDNA clone as a probe for in situ hybridization, Soreq et al. (1987) mapped the CHE1 gene to 3q21-q26. Lapidot-Lifson et al. (1989) studied the coamplification of butyrylcholinesterase and acetylcholinesterase (100740) in disorders of platelet production and in leukemia patients. This may indicate that the 2 genes are linked. Gnatt et al. (1990) found that cDNAs made from BCHE mRNA in glioblastoma and nerve blastoma cells map to the same site on 3q where the serum protein polymorphism maps. Furthermore, the asp70-to-gly mutation, which is responsible for the 'atypical' butyrylcholinesterase that is deficient in its capacity to hydrolyze succinylcholine, was identified in an mRNA isolated from glioblastoma tissue. Both Allderdice et al. (1991) and Gaughan et al. (1991) confirmed localization of the BCHE gene on 3q26. For the study of localization by in situ hybridization in a chromosomal rearrangement, Allderdice et al. (1991) used a different cDNA probe from that used by Soreq et al. (1987). Gaughan et al. (1991) used a PCR-derived probe that included the active site region to give a single hybridization signal by in situ hybridization and refined the localization to 3q26.1-q26.2.

CLINICAL FEATURES

Mutant alleles at the CHE1 locus are responsible for suxamethonium sensitivity. Homozygous persons sustain prolonged apnea after administration of the muscle relaxant suxamethonium in connection with surgical anesthesia. The activity of pseudocholinesterase in the serum is low and its substrate behavior is atypical. In the absence of the relaxant, the homozygote is at no known disadvantage. The dibucaine number (percentage inhibition by dibucaine) identifies 3 genotypes (Kalow and Genest, 1957). Two further alleles are a silent gene and an allele identified by fluoride inhibition. Heterogeneity of the 'silent' cholinesterase genes was indicated by the studies of Rubinstein et ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 177400 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).