PUBLICATION
Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters
- Authors
- Byrne, K.L., Szeligowski, R.V., Shen, H.
- ID
- ZDB-PUB-231002-151
- Date
- 2023
- Source
- Biomolecules 13(9): (Journal)
- Registered Authors
- Keywords
- SLC25, deorphanization, metabolite transport, mitochondria, phylogenetic analysis
- MeSH Terms
-
- Animals
- Caenorhabditis elegans/genetics
- Caenorhabditis elegans/metabolism
- Drosophila melanogaster/genetics
- Drosophila melanogaster/metabolism
- Humans
- Mitochondria/genetics
- Mitochondria/metabolism
- Mitochondrial Membrane Transport Proteins/genetics
- Mitochondrial Membrane Transport Proteins/metabolism
- Mitochondrial Proteins*/chemistry
- Mitochondrial Proteins*/genetics
- Mitochondrial Proteins*/metabolism
- Organic Anion Transporters*/chemistry
- Organic Anion Transporters*/genetics
- Organic Anion Transporters*/metabolism
- Phylogeny
- Saccharomyces cerevisiae/genetics
- Saccharomyces cerevisiae/metabolism
- PubMed
- 37759714 Full text @ Biomolecules
Citation
Byrne, K.L., Szeligowski, R.V., Shen, H. (2023) Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters. Biomolecules. 13(9):.
Abstract
Homology search and phylogenetic analysis have commonly been used to annotate gene function, although they are prone to error. We hypothesize that the power of homology search in functional annotation depends on the coupling of sequence variation to functional diversification, and we herein focus on the SoLute Carrier (SLC25) family of mitochondrial metabolite transporters to survey this coupling in a family-wide manner. The SLC25 family is the largest family of mitochondrial metabolite transporters in eukaryotes that translocate ligands of different chemical properties, ranging from nucleotides, amino acids, carboxylic acids and cofactors, presenting adequate experimentally validated functional diversification in ligand transport. Here, we combine phylogenetic analysis to profile SLC25 transporters across common eukaryotic model organisms, from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, to Homo sapiens, and assess their sequence adaptations to the transported ligands within individual subfamilies. Using several recently studied and poorly characterized SLC25 transporters, we discuss the potentials and limitations of phylogenetic analysis in guiding functional characterization.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping