P23141 · EST1_HUMAN
- ProteinLiver carboxylesterase 1
- GeneCES1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids567 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062).
Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062).
Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644).
Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644).
Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644).
Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984).
Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277).
First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277).
Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062).
Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644).
Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644).
Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644).
Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984).
Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277).
First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277).
Catalytic activity
- a carboxylic ester + H2O = a carboxylate + an alcohol + H+
- cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate + cholesterol + H+This reaction proceeds in the forward direction.
- 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H+This reaction proceeds in the forward direction.
- H2O + prostaglandin E2 1-glyceryl ester = glycerol + H+ + prostaglandin E2This reaction proceeds in the forward direction.
- H2O + prostaglandin F2alpha 1-glyceryl ester = glycerol + H+ + prostaglandin F2alphaThis reaction proceeds in the forward direction.
Activity regulation
Activated by CHAPS (PubMed:9490062).
Inhibited by chlorpyrifos oxon (IC50=0.21 nM), paraoxon (IC50=0.29 nM), or methyl paraoxon (IC50=49 nM) (PubMed:18762277).
Inhibited by chlorpyrifos oxon (IC50=0.21 nM), paraoxon (IC50=0.29 nM), or methyl paraoxon (IC50=49 nM) (PubMed:18762277).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
106.6 μM | p-nitrophenyl acetate | |||||
775.7 μM | L-methylphenidate | |||||
663.5 μM | D-methylphenidate | |||||
116 μM | cocaine | |||||
43 mM | ethanol | |||||
0.8 mM | 4-methylumbelliferyl acetate | |||||
6.3 mM | heroin | |||||
8.3 mM | 6-monoacetylmorphine | |||||
49 μM | 2-arachidonoylglycerol | |||||
250 μM | prostaglandin E2 1-glyceryl ester | |||||
93 μM | prostaglandin F2alpha 1-glyceryl ester |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
493.9 nmol/min/mg | with p-nitrophenyl acetate as substrate | ||||
1701.1 pmol/min/mg | with L-methylphenidate as substrate | ||||
177.2 pmol/min/mg | with D-methylphenidate as substrate |
kcat is 59 min-1, 29 min-1, 90 min-1 with 2-arachidonoylglycerol, prostaglandin F2alpha 1-glyceryl ester and prostaglandin E2 1-glyceryl ester as substrates, respectively.
pH Dependence
Optimum pH is 6.5.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 221 | Acyl-ester intermediate | ||||
Sequence: S | ||||||
Active site | 354 | Charge relay system | ||||
Sequence: E | ||||||
Active site | 468 | Charge relay system | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameLiver carboxylesterase 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP23141
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Moves from cytoplasm to lipid droplets upon lipid loading. Associates with lipid droplets independently of triglycerides (TG) content of the droplets and hydrolyzes cholesteryl esters more efficiently from mixed droplets.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_002357 | 18 | ||||
Sequence: G → GA | ||||||
Natural variant | VAR_014314 | 75 | in dbSNP:rs2307240 | |||
Sequence: S → N | ||||||
Mutagenesis | 79 | Abolishes glycosylation. | ||||
Sequence: N → A | ||||||
Natural variant | VAR_046954 | 143 | 5.4-fold decrease in activity with p-nitrophenyl acetate as substrate; no change in affinity for p-nitrophenyl acetate; loss of activity with L- or D-methylphenidate as substrate; dbSNP:rs71647871 | |||
Sequence: G → E | ||||||
Natural variant | VAR_014594 | 199 | in dbSNP:rs2307243 | |||
Sequence: R → H | ||||||
Natural variant | VAR_014595 | 203 | in dbSNP:rs2307227 | |||
Sequence: D → E | ||||||
Mutagenesis | 221 | Loss of activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 354 | Loss of activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 468 | Loss of activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 564-567 | Does not result in secretion. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 826 variants from UniProt as well as other sources including ClinVar and dbSNP.
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 | 1-17 | |||||
Sequence: MWLRAFILATLSASAAW | ||||||
Chain | PRO_0000391359 | 18-567 | Liver carboxylesterase 1 | |||
Sequence: GHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPLGPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWGFFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLFHRAISESGVALTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLKMKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIPMQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDLIADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLKDKEVAFWTNLFAKKAVEKPPQTEHIEL | ||||||
Glycosylation | 79 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 87↔116 | |||||
Sequence: CTQDPKAGQLLSELFTNRKENIPLKLSEDC | ||||||
Disulfide bond | 274↔285 | |||||
Sequence: CKTTTSAVMVHC | ||||||
Modified residue | 380 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Contains sialic acid.
Cleavage of the signal sequence can occur at 2 positions, either between Trp-17 and Gly-18 or between Gly-18 and His-19.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homotrimer and homohexamer. Binds to beta-glucuronidase.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P23141-3 | AHNAK2 Q8IVF2-3 | 3 | EBI-12360993, EBI-12078468 | |
BINARY | P23141-3 | CYSRT1 A8MQ03 | 3 | EBI-12360993, EBI-3867333 | |
BINARY | P23141-3 | EBP Q15125 | 3 | EBI-12360993, EBI-3915253 | |
BINARY | P23141-3 | GORAB Q5T7V8 | 3 | EBI-12360993, EBI-3917143 | |
BINARY | P23141-3 | KPRP Q5T749 | 3 | EBI-12360993, EBI-10981970 | |
BINARY | P23141-3 | PDZK1IP1 Q13113 | 3 | EBI-12360993, EBI-716063 | |
BINARY | P23141-3 | PLSCR4 Q9NRQ2 | 3 | EBI-12360993, EBI-769257 | |
BINARY | P23141-3 | SAR1A Q9NR31 | 3 | EBI-12360993, EBI-3920694 | |
BINARY | P23141-3 | VENTX O95231 | 3 | EBI-12360993, EBI-10191303 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
P23141-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length567
- Mass (Da)62,521
- Last updated1992-08-01 v2
- ChecksumD3A00BDCDC7E5DFF
P23141-2
- Name2
- Differences from canonical
- 17-17: W → WA
P23141-3
- Name3
- Differences from canonical
- 362-362: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H3BSU0 | H3BSU0_HUMAN | CES1 | 84 | ||
H3BQV8 | H3BQV8_HUMAN | CES1 | 131 | ||
H3BQR4 | H3BQR4_HUMAN | CES1 | 44 | ||
A0A140TA63 | A0A140TA63_HUMAN | CES1 | 134 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 5; AAD53175 | ||||
Sequence: W → L | ||||||
Sequence conflict | 4-7 | in Ref. 3; BAA04650, 8; BAC87749/BAC87751, 9; BAF83312/BAF84898 and 11; AAH12418 | ||||
Sequence: RAFI → PALV | ||||||
Sequence conflict | 12 | in Ref. 3; BAA04650, 8; BAC87749/BAC87751, 9; BAF83312/BAF84898 and 11; AAH12418 | ||||
Sequence: S → A | ||||||
Alternative sequence | VSP_021026 | 17 | in isoform 2 | |||
Sequence: W → WA | ||||||
Sequence conflict | 19 | in Ref. 14; AA sequence | ||||
Sequence: H → N | ||||||
Sequence conflict | 19-21 | in Ref. 15; AA sequence | ||||
Sequence: HPS → GPP | ||||||
Sequence conflict | 21-24 | in Ref. 14; AA sequence | ||||
Sequence: SSPP → EAVV | ||||||
Sequence conflict | 27-28 | in Ref. 14; AA sequence | ||||
Sequence: DT → AK | ||||||
Sequence conflict | 28-29 | in Ref. 15; AA sequence | ||||
Sequence: TV → DT | ||||||
Sequence conflict | 56 | in Ref. 2; AAA16036/AAA35711 | ||||
Sequence: A → G | ||||||
Sequence conflict | 64 | in Ref. 18; CAA37147 | ||||
Sequence: R → G | ||||||
Sequence conflict | 65 | in Ref. 6; AAP20868 | ||||
Sequence: F → S | ||||||
Sequence conflict | 75 | in Ref. 14; AA sequence | ||||
Sequence: S → A | ||||||
Sequence conflict | 78 | in Ref. 14; AA sequence | ||||
Sequence: K → I | ||||||
Sequence conflict | 89 | in Ref. 6; AAP20868 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 98 | in Ref. 14; AA sequence | ||||
Sequence: S → F | ||||||
Sequence conflict | 105-107 | in Ref. 14; AA sequence | ||||
Sequence: KEN → PAD | ||||||
Sequence conflict | 115 | in Ref. 19; AAA83932 | ||||
Sequence: D → H | ||||||
Sequence conflict | 186 | in Ref. 18; CAA37147 | ||||
Sequence: R → G | ||||||
Sequence conflict | 247 | in Ref. 14; AA sequence | ||||
Sequence: S → I | ||||||
Sequence conflict | 251 | in Ref. 14; AA sequence | ||||
Sequence: L → K | ||||||
Sequence conflict | 253 | in Ref. 14; AA sequence | ||||
Sequence: S → G | ||||||
Sequence conflict | 255 | in Ref. 9; BAF83312 | ||||
Sequence: L → P | ||||||
Sequence conflict | 258 | in Ref. 14; AA sequence | ||||
Sequence: K → Q | ||||||
Sequence conflict | 281 | in Ref. 19; AAA83932 | ||||
Sequence: V → A | ||||||
Sequence conflict | 298 | in Ref. 14; AA sequence | ||||
Sequence: T → I | ||||||
Sequence conflict | 302 | in Ref. 14; AA sequence | ||||
Sequence: K → A | ||||||
Sequence conflict | 305 | in Ref. 14; AA sequence | ||||
Sequence: S → M | ||||||
Sequence conflict | 337 | in Ref. 19; AAA83932 | ||||
Sequence: A → R | ||||||
Alternative sequence | VSP_047158 | 362 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 417 | in Ref. 19; AAA83932 | ||||
Sequence: F → I | ||||||
Sequence conflict | 512 | in Ref. 19; AAA83932 | ||||
Sequence: E → K | ||||||
Sequence conflict | 536 | in Ref. 2; AAA16036/AAA35711 | ||||
Sequence: A → G | ||||||
Sequence conflict | 563 | in Ref. 19; AAA83932 | ||||
Sequence: E → D |
Polymorphism
Genetic variants in CES1 are associated with clinically significant alterations in pharmacokinetics and drug response of carboxylesterase 1 substrates [MIM:618057].
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M73499 EMBL· GenBank· DDBJ | AAA35649.1 EMBL· GenBank· DDBJ | mRNA | ||
L07764 EMBL· GenBank· DDBJ | AAA16036.1 EMBL· GenBank· DDBJ | mRNA | ||
L07765 EMBL· GenBank· DDBJ | AAA35711.1 EMBL· GenBank· DDBJ | mRNA | ||
D21088 EMBL· GenBank· DDBJ | BAA04650.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S73751 EMBL· GenBank· DDBJ | AAC60631.2 EMBL· GenBank· DDBJ | mRNA | ||
AF177775 EMBL· GenBank· DDBJ | AAD53175.1 EMBL· GenBank· DDBJ | mRNA | ||
AY268104 EMBL· GenBank· DDBJ | AAP20868.1 EMBL· GenBank· DDBJ | mRNA | ||
AB119995 EMBL· GenBank· DDBJ | BAC87748.1 EMBL· GenBank· DDBJ | mRNA | ||
AB119996 EMBL· GenBank· DDBJ | BAC87749.1 EMBL· GenBank· DDBJ | mRNA | ||
AB119997 EMBL· GenBank· DDBJ | BAC87750.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB119998 EMBL· GenBank· DDBJ | BAC87751.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK290623 EMBL· GenBank· DDBJ | BAF83312.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292209 EMBL· GenBank· DDBJ | BAF84898.1 EMBL· GenBank· DDBJ | mRNA | ||
AC147362 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC012418 EMBL· GenBank· DDBJ | AAH12418.1 EMBL· GenBank· DDBJ | mRNA | ||
BC110338 EMBL· GenBank· DDBJ | AAI10339.1 EMBL· GenBank· DDBJ | mRNA | ||
AB025026 EMBL· GenBank· DDBJ | BAA84995.1 EMBL· GenBank· DDBJ | mRNA | ||
M55509 EMBL· GenBank· DDBJ | AAA35650.1 EMBL· GenBank· DDBJ | mRNA | ||
X52973 EMBL· GenBank· DDBJ | CAA37147.1 EMBL· GenBank· DDBJ | mRNA | ||
M65261 EMBL· GenBank· DDBJ | AAA83932.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |