The fifth class of Gα proteins

Yuichiro Oka, Luis R. Saraiva, Yen Yen Kwan, Sigrun I. Korsching

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30 Citations (Scopus)


All α-subunits of vertebrate heterotrimeric G proteins have been classified into 4 major classes, Gs, Gi, Gq, and G12, which possess orthologs already in sponges, one of the earliest animal phyla to evolve. Here we report the discovery of the fifth class of Gα protein, Gv, ancient like the other 4 classes, with members already in sponges, and encoded by 1-2 gnav genes per species. Gv is conserved across the animal kingdom including vertebrates, arthropods, mollusks, and annelids, but has been lost in many lineages such as nematodes, fruit fly, jawless fish, and tetrapods, concordant with a birth-and-death mode of evolution. All Gv proteins contain 5 G-box motifs characteristic of GTP-binding proteins and the expected acylation consensus sites in the N- terminal region. Sixty amino acid residues are conserved only among Gv, suggesting that they may constitute interaction sites for Gv-specific partner molecules. Overall Gv homology is high, on average 70% amino acid identity among vertebrate family members. The dN/dS analysis of teleost gnav genes reveals evolution under stringent negative selection. Genomic structure of vertebrate gnav genes is well conserved and different from those of the other 4 classes. The predicted full ORF of zebrafish gnav1 was confirmed by isolation from cDNA. RT-PCR analysis showed broad expression of gnav1 in adult zebrafish and in situ hybridization demonstrated a more restricted expression in larval tissues including the developing inner ear. The discovery of this fifth class of Gα proteins changes our understanding of G protein evolution.

Original languageEnglish
Pages (from-to)1484-1489
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
Publication statusPublished - 3 Feb 2009



  • Birth-and-death mode
  • Danio rerio
  • Evolution
  • Heterotrimeric G protein
  • Metazoan

ASJC Scopus subject areas

  • General

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