Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene
Abstract Background Frizzled family members belong to G-protein coupled receptors and encode proteins accountable for cell signal transduction, cell proliferation and cell death. Members of Frizzled receptor family are considered to have critical roles in causing various forms of cancer, cardiac hyp...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Evolutionary Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12862-019-1400-9 |
| _version_ | 1818363848211562496 |
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| author | Suman Seemab Nashaiman Pervaiz Rabail Zehra Saneela Anwar Yiming Bao Amir Ali Abbasi |
| author_facet | Suman Seemab Nashaiman Pervaiz Rabail Zehra Saneela Anwar Yiming Bao Amir Ali Abbasi |
| author_sort | Suman Seemab |
| collection | DOAJ |
| description | Abstract Background Frizzled family members belong to G-protein coupled receptors and encode proteins accountable for cell signal transduction, cell proliferation and cell death. Members of Frizzled receptor family are considered to have critical roles in causing various forms of cancer, cardiac hypertrophy, familial exudative vitreoretinopathy (FEVR) and schizophrenia. Results This study investigates the evolutionary and structural aspects of Frizzled receptors, with particular focus on FEVR associated FZD4 gene. The phylogenetic tree topology suggests the diversification of Frizzled receptors at the root of metazoans history. Moreover, comparative structural data reveals that FEVR associated missense mutations in FZD4 effect the common protein region (amino acids 495–537) through a well-known phenomenon called epistasis. This critical protein region is present at the carboxyl-terminal domain and encompasses the K-T/S-XXX-W, a PDZ binding motif and S/T-X-V PDZ recognition motif. Conclusion Taken together these results demonstrate that during the course of evolution, FZD4 has acquired new functions or epistasis via complex patter of gene duplications, sequence divergence and conformational remodeling. In particular, amino acids 495–537 at the C-terminus region of FZD4 protein might be crucial in its normal function and/or pathophysiology. This critical region of FZD4 protein may offer opportunities for the development of novel therapeutics approaches for human retinal vascular disease. |
| first_indexed | 2024-12-13T21:54:59Z |
| format | Article |
| id | doaj.art-02c94dbd1fbd4785bc77abbeed166d3c |
| institution | Directory Open Access Journal |
| issn | 1471-2148 |
| language | English |
| last_indexed | 2024-12-13T21:54:59Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Evolutionary Biology |
| spelling | doaj.art-02c94dbd1fbd4785bc77abbeed166d3c2022-12-21T23:30:10ZengBMCBMC Evolutionary Biology1471-21482019-03-0119111010.1186/s12862-019-1400-9Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 geneSuman Seemab0Nashaiman Pervaiz1Rabail Zehra2Saneela Anwar3Yiming Bao4Amir Ali Abbasi5National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam UniversityNational Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam UniversityNational Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam UniversityNational Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam UniversityBIG Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of SciencesNational Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam UniversityAbstract Background Frizzled family members belong to G-protein coupled receptors and encode proteins accountable for cell signal transduction, cell proliferation and cell death. Members of Frizzled receptor family are considered to have critical roles in causing various forms of cancer, cardiac hypertrophy, familial exudative vitreoretinopathy (FEVR) and schizophrenia. Results This study investigates the evolutionary and structural aspects of Frizzled receptors, with particular focus on FEVR associated FZD4 gene. The phylogenetic tree topology suggests the diversification of Frizzled receptors at the root of metazoans history. Moreover, comparative structural data reveals that FEVR associated missense mutations in FZD4 effect the common protein region (amino acids 495–537) through a well-known phenomenon called epistasis. This critical protein region is present at the carboxyl-terminal domain and encompasses the K-T/S-XXX-W, a PDZ binding motif and S/T-X-V PDZ recognition motif. Conclusion Taken together these results demonstrate that during the course of evolution, FZD4 has acquired new functions or epistasis via complex patter of gene duplications, sequence divergence and conformational remodeling. In particular, amino acids 495–537 at the C-terminus region of FZD4 protein might be crucial in its normal function and/or pathophysiology. This critical region of FZD4 protein may offer opportunities for the development of novel therapeutics approaches for human retinal vascular disease.http://link.springer.com/article/10.1186/s12862-019-1400-9Multigene familyG-protein coupled receptorsFrizzledFZD4MetazoansPhylogenetic analysis |
| spellingShingle | Suman Seemab Nashaiman Pervaiz Rabail Zehra Saneela Anwar Yiming Bao Amir Ali Abbasi Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene BMC Evolutionary Biology Multigene family G-protein coupled receptors Frizzled FZD4 Metazoans Phylogenetic analysis |
| title | Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene |
| title_full | Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene |
| title_fullStr | Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene |
| title_full_unstemmed | Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene |
| title_short | Molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated FZD4 gene |
| title_sort | molecular evolutionary and structural analysis of familial exudative vitreoretinopathy associated fzd4 gene |
| topic | Multigene family G-protein coupled receptors Frizzled FZD4 Metazoans Phylogenetic analysis |
| url | http://link.springer.com/article/10.1186/s12862-019-1400-9 |
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