Comprehensive Analysis of Non-Synonymous Natural Variants of G Protein-Coupled Receptors
Biomolecules & Therapeutics
;
: 101-108, 2018.
Article
in English
| WPRIM
| ID: wpr-713587
ABSTRACT
G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as β-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Physiology
/
Polymorphism, Genetic
/
Genetic Variation
/
DNA
/
Amino Acid Sequence
/
Receptors, Opioid
/
Vital Signs
Language:
English
Journal:
Biomolecules & Therapeutics
Year:
2018
Type:
Article
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