Premium
Revisiting the classification of adhesion GPCRs
Author(s) -
Scholz Nicole,
Langenhan Tobias,
Schöneberg Torsten
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14192
Subject(s) - phylogenetic tree , subfamily , vertebrate , g protein coupled receptor , biology , evolutionary biology , phylogenetics , computational biology , genome , classification scheme , gene , genetics , receptor , computer science , data science
G protein–coupled receptors (GPCRs) are encoded by over 800 genes in the human genome. Motivated by different scientific rationales, the two classification systems that are mainly in use, the ABC and GRAFS systems, organize GPCRs according to their pharmacological features and phylogenetic relations, respectively. Within those systems, adhesion GPCRs (aGPCRs) constitute a group of over 30 mammalian homologs, most of which are still orphans with undefined activating signals and signal transduction properties. Previous efforts have further subdivided mammalian aGPCRs into nine subfamilies to indicate phylogenetic relationships. However, this subclassification scheme has shortcomings and inconsistencies that require attention. Here, we have reassessed the phylogenetic relationships of aGPCRs from vertebrate and invertebrate species. Our findings confirm that secretin receptor–like GPCRs most probably emerged from ancestral aGPCRs. We show that reassignment of several aGPCRs to families essentially requires input from functional data. Our analyses establish the need for introducing novel aGPCR subfamilies due to aGPCR sequences from invertebrate species that are not readily assignable to any existing subfamily. We conclude that the current classification systems ought to be updated to consider an unambiguous taxonomy of a hierarchically organized classification and pharmacological properties, and to accommodate phylogenetic affiliations between aGPCR genes within mammals and across the animal kingdom.