human-PLA2G7

 
Homo sapiens (Human) plasma PAF acetylhydrolase Phospholipase A2 groupe 7 PLA2G7 PAFAH PAF-AH

Comment
The PLA2G7 (PAFAH) gene encodes platelet-activating factor (PAF) (Lipoprotein-associated phospholipase A2) acetylhydrolase (EC 3.1.1.47), a secreted enzyme that catalyzes the degradation of PAF to inactive products by hydrolysis of the acetyl group at the sn-2 position, producing the biologically inactive products LYSO-PAF and acetate. Plasma platelet-activating factor acetylhydrolase deficiency is inherited in an autosomal recessive manner (Stafforini et al., 1996) due to mutation of PLA2G7. Kruse et al. (2000) identified PLA2G7 variants on Chromosome 6p21.2 associated with atopy and asthma in a Caucasian population: the variant thr198 allele (I198T; 601690.0002) was highly associated with total IgE (147050) concentrations in an atopic population and with asthma in an asthmatic population; and the variant val379 allele (A379V; 601690.0003) was found to be highly associated with specific sensitization in the atopic population and with asthma in an asthmatic population. (Previously named human-pafa. Other names: 1-alkyl-2-acetylglycerophosphocholine esterase 2-acetyl-1-alkylglycerophosphocholine esterase Group-VIIA phospholipase A2, gVIIA-PLA2, LDL-associated phospholipase A2, LDL-PLA(2), Lp-PLA2). A rationally designed mutant (W298H) of plasma platelet-activating factor acetylhydrolase PLA2G7, which hydrolyzes the organophosphorus nerve agent soman is published by Kirby et al. A positive correlation with PLA2G7 levels has been found in certain disease states, including cardiovascular disorders, dementia,4 diabetic macular edema5 and prostate cancer. Consequently, inhibitors of PLA2G7 have been clinically investigated in atherosclerosis and Alzheimers disease


Relationship
Block X
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
11 mutations: Table (ordered Natural and SD mutagenesis) (e.g. : V279F_human-PLA2G7, I198T_human-PLA2G7, V379A_human-PLA2G7 ... more)
30 structures (e.g. : 5LP1, 5YEA, 5YE9... more)
No kinetic
Disease: Suceptibility to asthma and atopy, Platelet-activating factor acetylhydrolase (PLA2G7) deficiency (PAFAD) -
Substrate: Tween-80 , 4-nitro-3-(octanoyloxy)benzoic-acid ,
Inhibitor: CHEMBL4069230 , CHEMBL4076637 , CHEMBL4075815 , CHEMBL4076292 , 5LP1-71H , Darapladib , CHEMBL3792924 , 5LZ9-7BR , GTPL9797 , Rilapladib , DFP , Paraoxon , Soman ,
>3 Genbank links 4 more: U20157, U24577, BC038452
>3 UniProt links 1 more: Q13093, B4DLM5, B4DG88
1 Ncbi-nid : 780132
2 Ncbi-pid : 780133, 2497687
>3 Structure links 27 more: 5LP1, 5YEA, 5YE9
>3 UniProtTrembl links 1 more: Q13093, B4DLM5, B4DG88
>3 Interpro links 1 more: Q13093, B4DLM5, B4DG88
>3 Prodom links 1 more: Q13093, B4DLM5, B4DG88
>3 Pfam links 1 more: Q13093, B4DLM5, B4DG88
>3 PIRSF links 1 more: Q13093, B4DLM5, B4DG88
>3 SUPERFAM links 1 more: Q13093, B4DLM5, B4DG88
>3 QuickSwissBlast links 1 more: Q13093, B4DLM5, B4DG88
1 EntrezGene : 7941
1 SNP : 7941
1 UniGene : 584823
1 HUGO HGNC : 9040
1 IUPHAR : 1432
1 OMIM : 601690
1 Ensembl : ENSG00000146070
 
Sequence
Graphical view for this peptide sequence: human-PLA2G7
Colored MSA for PAF-Acetylhydrolase (raw)
MVPPKLHVLFCLCGCLAVVYPFDWQYINPVAHMKSSAWVNKIQVLMAAAS
FGQTKIPRGNGPYSVGCTDLMFDHTNKGTFLRLYYPSQDNDRLDTLWIPN
KEYFWGLSKFLGTHWLMGNILRLLFGSMTTPANWNSPLRPGEKYPLVVFS
HGLGAFRTLYSAIGIDLASHGFIVAAVEHRDRSASATYYFKDQSAAEIGD
KSWLYLRTLKQEEETHIRNEQVRQRAKECSQALSLILDIDHGKPVKNALD
LKFDMEQLKDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWMF
PLGDEVYSRIPQPLFFINSEYFQYPANIIKMKKCYSPDKERKMITIRGSV
HQNFADFTFATGKIIGHMLKLKGDIDSNVAIDLSNKASLAFLQKHLGLHK
DFDQWDCLIEGDDENLIPGTNINTTNQHIMLQNSSGIEKYN
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

MVPPKLHVLFCLCGCLAVVYPFDWQYINPVAHMKSSAWVNKIQVLMAAAS
FGQTKIPRGNGPYSVGCTDLMFDHTNKGTFLRLYYPSQDNDRLDTLWIPN
KEYFWGLSKFLGTHWLMGNILRLLFGSMTTPANWNSPLRPGEKYPLVVFS
HGLGAFRTLYSAIGIDLASHGFIVAAVEHRDRSASATYYFKDQSAAEIGD
KSWLYLRTLKQEEETHIRNEQVRQRAKECSQALSLILDIDHGKPVKNALD
LKFDMEQLKDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWMF
PLGDEVYSRIPQPLFFINSEYFQYPANIIKMKKCYSPDKERKMITIRGSV
HQNFADFTFATGKIIGHMLKLKGDIDSNVAIDLSNKASLAFLQKHLGLHK
DFDQWDCLIEGDDENLIPGTNINTTNQHIMLQNSSGIEKYN

Graphical view for this nucleotide DNA sequence (1550 bp): human-PLA2G7



References
49 more
    Title: Profiling Active Enzymes for Polysorbate Degradation in Biotherapeutics by Activity-Based Protein Profiling
    Li X, Chandra D, Letarte S, Adam GC, Welch J, Yang RS, Rivera S, Bodea S, Dow A and Richardson DD <2 more author(s)>
    Ref: Analytical Chemistry, 93:8161, 2021 : PubMed

            

    Title: Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2
    Liu Q, Huang F, Yuan X, Wang K, Zou Y, Shen J, Xu Y
    Ref: Journal of Medicinal Chemistry, 60:10231, 2017 : PubMed

            

    Title: Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
    Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY and Zhang X <11 more author(s)>
    Ref: Journal of Medicinal Chemistry, 59:10738, 2016 : PubMed

            


Other Papers
Svetlov 1996 Arch.Biochem.Biophys 327 113


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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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