P06276 · CHLE_HUMAN
- ProteinCholinesterase
- GeneBCHE
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids602 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Catalytic activity
- an acylcholine + H2O = a carboxylate + choline + H+
Activity regulation
Inhibited by mercury. Inhibited by Tabun. Tabun forms a covalent adduct with Ser-226 that becomes irreversible upon aging.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
18 μM | butyrylthiocholine | 25 |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 110 | tacrine (UniProtKB | ChEBI); inhibitor | ||||
Sequence: W | ||||||
Binding site | 144-145 | substrate | ||||
Sequence: GG | ||||||
Active site | 226 | Acyl-ester intermediate | ||||
Sequence: S | ||||||
Active site | 353 | Charge relay system | ||||
Sequence: E | ||||||
Active site | 466 | Charge relay system | ||||
Sequence: H | ||||||
Binding site | 466 | tacrine (UniProtKB | ChEBI); inhibitor | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCholinesterase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP06276
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Butyrylcholinesterase deficiency (BCHED)
- Note
- DescriptionAn autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency.
- See alsoMIM:617936
Natural variants in BCHED
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_040011 | 32 | missing | in BCHED | |
VAR_040012 | 52 | T>M | in BCHED; dbSNP:rs56309853 | |
VAR_040013 | 56 | F>I | in BCHED; dbSNP:rs531738678 | |
VAR_040014 | 61 | Y>C | in BCHED; enzymatically inactive in the plasma; dbSNP:rs116097205 | |
VAR_072730 | 62 | A>V | in BCHED; reduced enzyme activity with butyrylthiocholine as substrate; inactive with butyrylthiocholine as substrate in the presence of G-98; 2-fold lower affinity for butyrylthiocholine; 10-fold lower affinity for butyrylthiocholine in the presence of G-98; dbSNP:rs1553778274 | |
VAR_040015 | 65 | P>S | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs148170012 | |
VAR_002360 | 98 | D>G | in BCHED; atypical form; reduced enzyme activity with butyrylthiocholine as substrate; inactive with butyrylthiocholine as substrate in the presence of V-62; 2-fold lower affinity for butyrylthiocholine; 10-fold lower affinity for butyrylthiocholine in the presence of V-62 or at homozygosity; dbSNP:rs1799807 | |
VAR_040016 | 98 | D>H | in BCHED | |
VAR_072095 | 103 | G>R | in BCHED; reduced enzyme activity; dbSNP:rs979653503 | |
VAR_072096 | 118 | E>D | in BCHED; the mutant undergoes rapid degradation; dbSNP:rs1714937947 | |
VAR_040017 | 124 | N>Y | in BCHED; dbSNP:rs1339128583 | |
VAR_040018 | 128 | P>S | in BCHED; dbSNP:rs3732880 | |
VAR_040019 | 143 | G>D | in BCHED; dbSNP:rs201820739 | |
VAR_040020 | 153 | L>F | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs747598704 | |
VAR_040021 | 156 | Y>C | in BCHED; dbSNP:rs121918558 | |
VAR_040022 | 170 | V>M | in BCHED; allele H variant; dbSNP:rs527843566 | |
VAR_040023 | 198 | D>E | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs781368801 | |
VAR_040024 | 226 | S>G | in BCHED; enzymatically inactive in the plasma; dbSNP:rs370077923 | |
VAR_040025 | 227 | A>V | in BCHED | |
VAR_040026 | 229 | A>T | in BCHED; enzymatically inactive in the plasma | |
VAR_072098 | 232 | V>D | in BCHED; dbSNP:rs1714916354 | |
VAR_040027 | 271 | T>M | in BCHED; allele fluoride-1; dbSNP:rs28933389 | |
VAR_040028 | 278 | T>P | in BCHED; dbSNP:rs892642457 | |
VAR_040030 | 295 | K>R | in BCHED; dbSNP:rs115624085 | |
VAR_040031 | 335 | L>P | in BCHED; expressed at very low level; dbSNP:rs104893684 | |
VAR_040032 | 356 | A>D | in BCHED; dbSNP:rs770337031 | |
VAR_002362 | 358 | L>I | in BCHED; BChE variant form; fluoride-resistant; dbSNP:rs121918557 | |
VAR_072100 | 361 | G>C | in BCHED; results in 20% of activity compared to wild-type | |
VAR_040033 | 393 | G>R | in BCHED; dbSNP:rs115129687 | |
VAR_040034 | 414 | R>C | in BCHED; dbSNP:rs745364489 | |
VAR_040035 | 418 | G>V | in BCHED; allele fluoride-2; dbSNP:rs28933390 | |
VAR_040036 | 446 | F>S | in BCHED | |
VAR_040037 | 488 | E>K | in BCHED; dbSNP:rs200998515 | |
VAR_040038 | 499 | W>R | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs1741687748 | |
VAR_040039 | 502 | F>L | in BCHED; dbSNP:rs769316835 | |
VAR_040040 | 525 | E>V | in BCHED; allele J variant; dbSNP:rs121918556 | |
VAR_040041 | 543 | R>C | in BCHED; dbSNP:rs199660374 | |
VAR_040042 | 546 | Q>L | in BCHED; seems to cause reduced expression of the protein | |
VAR_002364 | 567 | A>T | in BCHED; allele K variant; with reduced enzyme activity; dbSNP:rs1803274 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_040011 | 32 | in BCHED | |||
Sequence: Missing | ||||||
Natural variant | VAR_072094 | 40 | does not affect enzymatic activity; dbSNP:rs116047990 | |||
Sequence: K → R | ||||||
Natural variant | VAR_040012 | 52 | in BCHED; dbSNP:rs56309853 | |||
Sequence: T → M | ||||||
Natural variant | VAR_040013 | 56 | in BCHED; dbSNP:rs531738678 | |||
Sequence: F → I | ||||||
Natural variant | VAR_040014 | 61 | in BCHED; enzymatically inactive in the plasma; dbSNP:rs116097205 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_072730 | 62 | in BCHED; reduced enzyme activity with butyrylthiocholine as substrate; inactive with butyrylthiocholine as substrate in the presence of G-98; 2-fold lower affinity for butyrylthiocholine; 10-fold lower affinity for butyrylthiocholine in the presence of G-98; dbSNP:rs1553778274 | |||
Sequence: A → V | ||||||
Natural variant | VAR_040015 | 65 | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs148170012 | |||
Sequence: P → S | ||||||
Natural variant | VAR_002360 | 98 | in BCHED; atypical form; reduced enzyme activity with butyrylthiocholine as substrate; inactive with butyrylthiocholine as substrate in the presence of V-62; 2-fold lower affinity for butyrylthiocholine; 10-fold lower affinity for butyrylthiocholine in the presence of V-62 or at homozygosity; dbSNP:rs1799807 | |||
Sequence: D → G | ||||||
Natural variant | VAR_040016 | 98 | in BCHED | |||
Sequence: D → H | ||||||
Natural variant | VAR_072095 | 103 | in BCHED; reduced enzyme activity; dbSNP:rs979653503 | |||
Sequence: G → R | ||||||
Natural variant | VAR_072096 | 118 | in BCHED; the mutant undergoes rapid degradation; dbSNP:rs1714937947 | |||
Sequence: E → D | ||||||
Natural variant | VAR_040017 | 124 | in BCHED; dbSNP:rs1339128583 | |||
Sequence: N → Y | ||||||
Natural variant | VAR_072097 | 127 | does not affect enzyme activity; dbSNP:rs755600722 | |||
Sequence: I → M | ||||||
Natural variant | VAR_040018 | 128 | in BCHED; dbSNP:rs3732880 | |||
Sequence: P → S | ||||||
Natural variant | VAR_040019 | 143 | in BCHED; dbSNP:rs201820739 | |||
Sequence: G → D | ||||||
Natural variant | VAR_040020 | 153 | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs747598704 | |||
Sequence: L → F | ||||||
Natural variant | VAR_040021 | 156 | in BCHED; dbSNP:rs121918558 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_040022 | 170 | in BCHED; allele H variant; dbSNP:rs527843566 | |||
Sequence: V → M | ||||||
Natural variant | VAR_040023 | 198 | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs781368801 | |||
Sequence: D → E | ||||||
Natural variant | VAR_040024 | 226 | in BCHED; enzymatically inactive in the plasma; dbSNP:rs370077923 | |||
Sequence: S → G | ||||||
Natural variant | VAR_040025 | 227 | in BCHED | |||
Sequence: A → V | ||||||
Natural variant | VAR_040026 | 229 | in BCHED; enzymatically inactive in the plasma | |||
Sequence: A → T | ||||||
Natural variant | VAR_072098 | 232 | in BCHED; dbSNP:rs1714916354 | |||
Sequence: V → D | ||||||
Natural variant | VAR_040027 | 271 | in BCHED; allele fluoride-1; dbSNP:rs28933389 | |||
Sequence: T → M | ||||||
Natural variant | VAR_040028 | 278 | in BCHED; dbSNP:rs892642457 | |||
Sequence: T → P | ||||||
Natural variant | VAR_040029 | 283 | in dbSNP:rs16849700 | |||
Sequence: E → D | ||||||
Natural variant | VAR_040030 | 295 | in BCHED; dbSNP:rs115624085 | |||
Sequence: K → R | ||||||
Natural variant | VAR_072099 | 322 | does not affect enzymatic activity; dbSNP:rs754644618 | |||
Sequence: V → M | ||||||
Natural variant | VAR_040031 | 335 | in BCHED; expressed at very low level; dbSNP:rs104893684 | |||
Sequence: L → P | ||||||
Natural variant | VAR_040032 | 356 | in BCHED; dbSNP:rs770337031 | |||
Sequence: A → D | ||||||
Natural variant | VAR_002362 | 358 | in BCHED; BChE variant form; fluoride-resistant; dbSNP:rs121918557 | |||
Sequence: L → I | ||||||
Natural variant | VAR_072100 | 361 | in BCHED; results in 20% of activity compared to wild-type | |||
Sequence: G → C | ||||||
Natural variant | VAR_040033 | 393 | in BCHED; dbSNP:rs115129687 | |||
Sequence: G → R | ||||||
Natural variant | VAR_040034 | 414 | in BCHED; dbSNP:rs745364489 | |||
Sequence: R → C | ||||||
Natural variant | VAR_040035 | 418 | in BCHED; allele fluoride-2; dbSNP:rs28933390 | |||
Sequence: G → V | ||||||
Natural variant | VAR_040036 | 446 | in BCHED | |||
Sequence: F → S | ||||||
Natural variant | VAR_040037 | 488 | in BCHED; dbSNP:rs200998515 | |||
Sequence: E → K | ||||||
Natural variant | VAR_072101 | 498 | does not affect enzymatic activity; dbSNP:rs115017300 | |||
Sequence: R → W | ||||||
Natural variant | VAR_040038 | 499 | in BCHED; seems to cause reduced expression of the protein; dbSNP:rs1741687748 | |||
Sequence: W → R | ||||||
Natural variant | VAR_040039 | 502 | in BCHED; dbSNP:rs769316835 | |||
Sequence: F → L | ||||||
Natural variant | VAR_040040 | 525 | in BCHED; allele J variant; dbSNP:rs121918556 | |||
Sequence: E → V | ||||||
Natural variant | VAR_040041 | 543 | in BCHED; dbSNP:rs199660374 | |||
Sequence: R → C | ||||||
Natural variant | VAR_040042 | 546 | in BCHED; seems to cause reduced expression of the protein | |||
Sequence: Q → L | ||||||
Natural variant | VAR_002364 | 567 | in BCHED; allele K variant; with reduced enzyme activity; dbSNP:rs1803274 | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 968 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-28 | |||||
Sequence: MHSKVTIICIRFLFWFLLLCMLIGKSHT | ||||||
Chain | PRO_0000008613 | 29-602 | Cholinesterase | |||
Sequence: EDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVYGAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCVGL | ||||||
Glycosylation | 45 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 85 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 93↔120 | |||||
Sequence: CCQNIDQSFPGFHGSEMWNPNTDLSEDC | ||||||
Glycosylation | 134 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Modified residue | 226 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 269 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 280↔291 | |||||
Sequence: CSRENETEIIKC | ||||||
Glycosylation | 284 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 369 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 428↔547 | |||||
Sequence: CPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQC | ||||||
Glycosylation | 483 | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 509 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 513 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 514 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 599 | Interchain | ||||
Sequence: C |
Post-translational modification
N-glycosylated. No other PTM detected (PubMed:20946535).
The major N-glycan structures are of the complex diantennary type with 1 and 2 N-acetylneuraminic acid molecules (Neu5Ac) making up approximately 33% and 47% of the total N-glycans, respectively. Only low amounts of fucosylated diantennary N-glycans are detected (approximately 2%). Triantennary N-glycans with or without fucose amount to approximately 13%, whereas 5% of the total N-glycans are of the oligomannosidic or hybrid type
The major N-glycan structures are of the complex diantennary type with 1 and 2 N-acetylneuraminic acid molecules (Neu5Ac) making up approximately 33% and 47% of the total N-glycans, respectively. Only low amounts of fucosylated diantennary N-glycans are detected (approximately 2%). Triantennary N-glycans with or without fucose amount to approximately 13%, whereas 5% of the total N-glycans are of the oligomannosidic or hybrid type
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in blood plasma (at protein level). Present in most cells except erythrocytes.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homotetramer; disulfide-linked. Dimer of dimers.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P06276 | ATXN3 P54252 | 3 | EBI-7936069, EBI-946046 | |
BINARY | P06276 | BAG6 P46379-2 | 3 | EBI-7936069, EBI-10988864 | |
BINARY | P06276 | BCHE P06276 | 8 | EBI-7936069, EBI-7936069 | |
BINARY | P06276 | CASP6 P55212 | 3 | EBI-7936069, EBI-718729 | |
BINARY | P06276 | DNAJB6 O75190-2 | 3 | EBI-7936069, EBI-12593112 | |
BINARY | P06276 | KLF11 O14901 | 3 | EBI-7936069, EBI-948266 | |
BINARY | P06276 | LAMP2 P13473-2 | 3 | EBI-7936069, EBI-21591415 | |
BINARY | P06276 | PRPF40A O75400-2 | 3 | EBI-7936069, EBI-5280197 | |
BINARY | P06276 | RAN P62826 | 3 | EBI-7936069, EBI-286642 | |
BINARY | P06276 | SEC11A P67812 | 3 | EBI-7936069, EBI-1042500 | |
BINARY | P06276 | SMR3B P02814 | 2 | EBI-7936069, EBI-738612 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length602
- Mass (Da)68,418
- Last updated1988-08-01 v1
- ChecksumC9836409D9057F27
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M32391 EMBL· GenBank· DDBJ | AAA99296.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M32389 EMBL· GenBank· DDBJ | AAA99296.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M32390 EMBL· GenBank· DDBJ | AAA99296.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M16541 EMBL· GenBank· DDBJ | AAA98113.1 EMBL· GenBank· DDBJ | mRNA | ||
M16474 EMBL· GenBank· DDBJ | AAA52015.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292063 EMBL· GenBank· DDBJ | BAF84752.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018141 EMBL· GenBank· DDBJ | AAH18141.1 EMBL· GenBank· DDBJ | mRNA |