<p>Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (<db_xref db="INTERPRO" dbkey="IPR001019"/>), beta (<db_xref db="INTERPRO" dbkey="IPR001632"/>) and gamma (<db_xref db="INTERPRO" dbkey="IPR001770"/>) [<cite idref="PUB00015168"/>]. G proteins act as signal transducers, relaying a signal from a ligand-activated GPCR (G protein-coupled receptor) to an enzyme or ion channel effector. The activated GPCR promotes the exchange of GDP for GTP on the G protein alpha subunit, allowing the trimeric G protein to be released from the receptor and to dissociate into active (GTP-bound) alpha subunit and beta/gamma dimer, both of which activate distinct downstream effectors. There are several isoforms of each subunit, which together can makeup hundreds of combinations of G proteins, each one linking a specific receptor to a certain effector.</p><p>The heterotrimeric G protein alpha subunit is composed of two domains: a GTP-binding domain and a helical insertion domain. The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The helical insertion domain is inserted into the GTP-binding domain before switch region I, and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation [<cite idref="PUB00015232"/>]. This entry represents the G protein alpha subunit helical insertion domain.</p>