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Functional consequences of naturally occurring DRY motif variants in the mammalian chemoattractant receptor GPR33.

Abstract：

:Most members of the large family of rhodopsin-like G-protein-coupled receptors possess an evolutionarily conserved Asp-Arg-Tyr (DRY) motif in the C-terminal region of the third transmembrane domain. Mutations of residues within this motif usually abolish receptor function and, when they occur naturally, can even cause human diseases. By analyzing over 100 mammalian orthologs of the chemoattractant receptor GPR33 we identified several polymorphic and fixed sequence variations within the DRY motif. Unexpectedly, the naturally occurring mutation of Arg(3.50) to His in mouse GPR33 showed no difference from the wild-type receptor in several functional tests. Sequence analysis of GPR33 from Asian house mice revealed the polymorphic existence of Arg(3.50) and His(3.50) alleles in wild-trapped populations, further supporting the functional equivalence of both allelic variants. In contrast, the Arg(3.50) to Gly mutation found in hamster GPR33 inactivates the receptor and may have contributed to pseudogenization of this gene in this species. Functional data with GPR33 variants indicate different receptor- and context-specific consequences of DRY mutations. Our study also reveals GPR33 as a new example illustrating missense mutations as a first step in the pseudogenization process.

journal_name

Genomics

journal_title

Genomics

authors

Römpler H,Yu HT,Arnold A,Orth A,Schöneberg T

doi

10.1016/j.ygeno.2006.02.009

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

724-32

issue

6

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(06)00051-6

journal_volume

87

pub_type

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