Human phospholipases A2: a functional and evolutionary analysis
Phospholipases A2 (PLA2) are capable of hydrolyzing the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids. The PLA2 superfamily enzymes are widespread and present in most mammalian cells and tissues, regulating metabolism, remodeling the membrane and maintaining its...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2023-01-01
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| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/3580 |
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| author | I. I. Turnaev M. E. Bocharnikova D. A. Afonnikov |
| author_facet | I. I. Turnaev M. E. Bocharnikova D. A. Afonnikov |
| author_sort | I. I. Turnaev |
| collection | DOAJ |
| description | Phospholipases A2 (PLA2) are capable of hydrolyzing the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids. The PLA2 superfamily enzymes are widespread and present in most mammalian cells and tissues, regulating metabolism, remodeling the membrane and maintaining its homeostasis, producing lipid mediators and activating inflammatory reactions, so disruption of PLA2-regulated lipid metabolism often leads to various diseases. In this study, 29 PLA2 genes in the human genome were systematically collected and described based on literature and sequence analyses. Localization of the PLA2 genes in human genome showed they are placed on 12 human chromosomes, some of them forming clusters. Their RVI scores estimating gene tolerance to the mutations that accumulate in the human population demonstrated that the G4-type PLA2 genes belonging to one of the two largest clusters (4 genes) were most tolerant. On the contrary, the genes encoding G6-type PLA2s (G6B, G6F, G6C, G6A) localized outside the clusters had a reduced tolerance to mutations. Analysis of the association between PLA2 genes and human diseases found in the literature showed 24 such genes were associated with 119 diseases belonging to 18 groups, so in total 229 disease/PLA2 gene relationships were described to reveal that G4, G2 and G7-type PLA2 proteins were involved in the largest number of diseases if compared to other PLA2 types. Three groups of diseases turned out to be associated with the greatest number of PLA2 types: neoplasms, circulatory and endocrine system diseases. Phylogenetic analysis showed that a common origin can be established only for secretory PLA2s (G1, G2, G3, G5, G10 and G12). The remaining PLA2 types (G4, G6, G7, G8, G15 and G16) could be considered evolutionarily independent. Our study has found that the genes most tolerant to PLA2 mutations in humans (G4, G2, and G7 types) belong to the largest number of disease groups. |
| first_indexed | 2024-03-07T16:05:10Z |
| format | Article |
| id | doaj.art-81d4b49fd72c460e8982b73764843d76 |
| institution | Directory Open Access Journal |
| issn | 2500-3259 |
| language | English |
| last_indexed | 2024-04-24T11:06:27Z |
| publishDate | 2023-01-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj.art-81d4b49fd72c460e8982b73764843d762024-04-11T15:31:05ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-01-0126878779710.18699/VJGB-22-951317Human phospholipases A2: a functional and evolutionary analysisI. I. Turnaev0M. E. Bocharnikova1D. A. Afonnikov2Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASNovosibirsk State University; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASPhospholipases A2 (PLA2) are capable of hydrolyzing the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids. The PLA2 superfamily enzymes are widespread and present in most mammalian cells and tissues, regulating metabolism, remodeling the membrane and maintaining its homeostasis, producing lipid mediators and activating inflammatory reactions, so disruption of PLA2-regulated lipid metabolism often leads to various diseases. In this study, 29 PLA2 genes in the human genome were systematically collected and described based on literature and sequence analyses. Localization of the PLA2 genes in human genome showed they are placed on 12 human chromosomes, some of them forming clusters. Their RVI scores estimating gene tolerance to the mutations that accumulate in the human population demonstrated that the G4-type PLA2 genes belonging to one of the two largest clusters (4 genes) were most tolerant. On the contrary, the genes encoding G6-type PLA2s (G6B, G6F, G6C, G6A) localized outside the clusters had a reduced tolerance to mutations. Analysis of the association between PLA2 genes and human diseases found in the literature showed 24 such genes were associated with 119 diseases belonging to 18 groups, so in total 229 disease/PLA2 gene relationships were described to reveal that G4, G2 and G7-type PLA2 proteins were involved in the largest number of diseases if compared to other PLA2 types. Three groups of diseases turned out to be associated with the greatest number of PLA2 types: neoplasms, circulatory and endocrine system diseases. Phylogenetic analysis showed that a common origin can be established only for secretory PLA2s (G1, G2, G3, G5, G10 and G12). The remaining PLA2 types (G4, G6, G7, G8, G15 and G16) could be considered evolutionarily independent. Our study has found that the genes most tolerant to PLA2 mutations in humans (G4, G2, and G7 types) belong to the largest number of disease groups.https://vavilov.elpub.ru/jour/article/view/3580phospholipase a2glycerophospholipidshuman diseases |
| spellingShingle | I. I. Turnaev M. E. Bocharnikova D. A. Afonnikov Human phospholipases A2: a functional and evolutionary analysis Вавиловский журнал генетики и селекции phospholipase a2 glycerophospholipids human diseases |
| title | Human phospholipases A2: a functional and evolutionary analysis |
| title_full | Human phospholipases A2: a functional and evolutionary analysis |
| title_fullStr | Human phospholipases A2: a functional and evolutionary analysis |
| title_full_unstemmed | Human phospholipases A2: a functional and evolutionary analysis |
| title_short | Human phospholipases A2: a functional and evolutionary analysis |
| title_sort | human phospholipases a2 a functional and evolutionary analysis |
| topic | phospholipase a2 glycerophospholipids human diseases |
| url | https://vavilov.elpub.ru/jour/article/view/3580 |
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