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Gene_locus Report for: 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 There are 3 isoforms some times called Ces1b, Ces1c they are not as diffiernt as the different genes if CE1 in mice (a,b,c,d,ef) ). 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. Aso called monocyte-specific esterase or macrophage esterase


Relationship
Family|Carb_B_Chordata
Block| C
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> 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
34 mutations: Table (e.g. : A158V, A269S, Asp260GlufsX39_human-CES1 ... more)
19 structures (e.g. : 1MX1, 1MX5, 1MX9... more)
No kinetic


Risk factor: Non-Hodgkin lymphoma (NHL) or B-cell chronic lymphocytic leukemia (CLL) -
Xenobiotic sensitivity: CES-1 deficiency -

53 substrates (e.g. : 2-oxo-clopidogrel, 4-MOMMP, BMBT... more)
17 inhibitors (e.g. : 1-Dodecylindoline-2,3-dione, 76-0079, Benzil... more)
>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 16 more: 8EOR, 5A7G, 5A7H
>3 UniProt links 3 more: P23141, B7Z795, H3BQR4
>3 Interpro links 3 more: P23141, B7Z795, H3BQR4
>3 Pfam links 3 more: P23141, B7Z795, H3BQR4
>3 PIRSF links 3 more: P23141, B7Z795, H3BQR4
>3 SUPERFAM links 3 more: P23141, B7Z795, H3BQR4
1 EntrezGene : 1066
1 SNP : 1066
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


References
158 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


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