The sequence of a novel cGMP-regulated, tetrameric, K+ selective channel (Sp-tetraKCNG) was discovered in the sea urchin Strongylocentrotus purpuratus. The Sp-tetraKCNG is a single polypeptide made of four KCNG domains similar to voltage-dependent Na+ and Ca2+ channels. Each KCNG domain has six transmembrane segments (S1-S6), the ion pore having the K+ selectivity signature GYGD and a cyclic nucleotide-binding domain (CNBD). This novel channel is evolutionary located between K+-selective and voltage-dependent EAG channels and voltage-independent cationic CNG channels. Bilayer reconstitutions demonstrate such a cGMP-regulated K+ selective channel in sea urchin spermatozoa. (c) 2007 Elsevier Inc. All rights reserved.