human-CES1

 
Homo sapiens (Human) carboxylesterase CES1 hCE1 & for monocyte/macrophage serine-esterase 1 egasyn

Comment
Mammalian liver carboxylesterases (CESs; EC 3.1.1.1) hydrolyze various xenobiotics and endogenous substrates with ester, thioester, or amide bonds and are thought to function mainly in drug metabolism and detoxication of harmful chemicals. CES1 is also responsible for hydrolysis of stored cholesterol esters in macrophage foam cells and release of free cholesterol for high density lipoprotein-mediated cholesterol efflux. Alternative names: Acyl-coenzyme A:cholesterol acyltransferase (ACAT) Monocyte/macrophage serine esterase (HMSE) Serine esterase 1 Brain carboxylesterase hBr1 Triacylglycerol hydrolase (TGH) Egasyn Retinyl ester hydrolase (REH) Cocaine carboxylesterase.(Also named before human-cxesl human-cxest, -mmse, CES, hCES1,CES1A, hBr1 brain carboxylesterase hBr1 on chromosome 16). The region is complex with pseudogene localized head to head with CES1. There are different haplotype and in some the pseudogene is replaced by a complete copy of CES1A1. see Rasmussen et al. 2018 for recent evaluation of genotyping procedures


Relationship
Block C
Homo sapiens position in NCBI Life Tree :
N link to NCBI taxonomic web page and E link to ESTHER gene locus found in this strain.
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

Molecular evidence
Database
33 mutations: Table (ordered Natural and SD mutagenesis) (e.g. : L40stop, S75N, G142E ... more)
18 structures (e.g. : 5A7G, 5A7H, 5A7F... more)
No kinetic

Substrate: Prostaglandin-D2-Glyceryl-Ester , MGS0274 , Tenofovir-alafenamide , Cannabinoid-PB-22 , Imidapril , Remdesivir , CurDD , Prasugrel , Eslicarbazepine-acetate , PGE2-glyceryl-ester , BMBT , Trandolapril , D-luciferin-methyl-ester , Simvastatin , Selexipag , Ciclesonide , 2-oxo-clopidogrel , 4-MOMMP , CES1-BODIPY-probe , Homatropine , Coenzyme-A , Enalapril , Dabigatran-etexilate , Clopidogrel , Methylphenidate , Oseltamivir , Irinotecan , N-Methylnaloxonium , Cocaine , Methylparaben , Ethylparaben , Propylparaben , Heptylparaben , Ethylacetate ,
Inhibitor: Nevadensin , Betulinic-acid , Tanshinone-IIA , Palmitate , ZINC02141756 , JZL195 , Soman , Tacrine , Tamoxifen , Benzil , Mevastatin ,
>3 Genbank links 30 more: NP_001020366, AB119998, AB119996
>3 UniProt links 2 more: P23141, B7Z795, H3BQR4
>3 Ncbi-nid links 10 more: 187028, 179927, 179929
>3 Ncbi-pid links 9 more: 187029, 5823472, 179928
>3 Structure links 15 more: 5A7G, 5A7H, 5A7F
>3 UniProtTrembl links 2 more: P23141, B7Z795, H3BQR4
>3 Interpro links 2 more: P23141, B7Z795, H3BQR4
>3 Prodom links 2 more: P23141, B7Z795, H3BQR4
>3 Pfam links 2 more: P23141, B7Z795, H3BQR4
>3 PIRSF links 2 more: P23141, B7Z795, H3BQR4
>3 SUPERFAM links 2 more: P23141, B7Z795, H3BQR4
>3 QuickSwissBlast links 2 more: P23141, B7Z795, H3BQR4
1 EntrezGene : 1066
1 SNP : 1066
1 UniGene : 558865
1 HUGO HGNC : 1863
1 IUPHAR : 2592
1 OMIM : 114835
1 Ensembl : ENSG00000198848
 
Sequence
Graphical view for this peptide sequence: human-CES1
Colored MSA for Carb_B_Chordata (raw)
MWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIF
LGIPFAKPPLGPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSEL
FTNRKENIPLKLSEDCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAAS
TYDGLALAAHENVVVVTIQYRLGIWGFFSTGDEHSRGNWGHLDQVAALRW
VQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLFHRAISESGVA
LTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLK
MKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGI
NKQEFGWLIPMQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEAT
EKYLGGTDDTVKKKDLFLDLIADVMFGVPSVIVARNHRDAGAPTYMYEFQ
YRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIRLSKMVMKFW
ANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLKDKEVAFWTNL
FAKKAVEKPPQTEHIEL
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIF
LGIPFAKPPLGPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSEL
FTNRKENIPLKLSEDCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAAS
TYDGLALAAHENVVVVTIQYRLGIWGFFSTGDEHSRGNWGHLDQVAALRW
VQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLFHRAISESGVA
LTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLK
MKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGI
NKQEFGWLIPMQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEAT
EKYLGGTDDTVKKKDLFLDLIADVMFGVPSVIVARNHRDAGAPTYMYEFQ
YRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIRLSKMVMKFW
ANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLKDKEVAFWTNL
FAKKAVEKPPQTEHIEL

Graphical view for this nucleotide DNA sequence (1814 bp): human-CES1



References
95 more
    Title: The Influence of the CES1 Genotype on the Pharmacokinetics of Enalapril in Patients with Arterial Hypertension
    Ikonnikova A, Rodina T, Dmitriev A, Melnikov E, Kazakov R, Nasedkina T
    Ref: J Pers Med, 12:, 2022 : PubMed

            

    Title: Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans
    Zhang F, Li HX, Zhang TT, Xiong Y, Wang HN, Lu ZH, Xiong L, He YQ, Ge GB
    Ref: Chemico-Biological Interactions, 351:109744, 2021 : PubMed

            

    Title: Extremely sensitive biomarker of acute organophosphorus insecticide exposure
    Fujikawa Y, Satoh T, Suganuma A, Suzuki S, Niikura Y, Yui S, Yamaura Y
    Ref: Hum Exp Toxicol, 24:333, 2005 : PubMed

            


Other Papers


Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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