{"doi":"10.1146/annurev.biochem.69.1.795","title":"GTPase-Activating Proteins for Heterotrimeric G Proteins: Regulators of G Protein Signaling (RGS) and RGS-Like Proteins","abstract":"<jats:p>▪ Abstract  GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their α subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on Gα subunits, in contrast to GAPs for the Ras-like monomeric GTP-binding proteins. Although they do not contribute directly to the chemistry of GTP hydrolysis, G protein GAPs can accelerate hydrolysis &gt;2000-fold. G protein GAPs include both effector proteins (phospholipase C-β, p115RhoGEF) and a growing family of regulators of G protein signaling (RGS proteins) that are found throughout the animal and fungal kingdoms. GAP activity can sharpen the termination of a signal upon removal of stimulus, attenuate a signal either as a feedback inhibitor or in response to a second input, promote regulatory association of other proteins, or redirect signaling within a G protein signaling network. GAPs are regulated by various controls of their cellular concentrations, by complex interactions with Gβγ or with Gβ5 through an endogenous Gγ-like domain, and by interaction with multiple other proteins.</jats:p>","journal":"Annual Review of Biochemistry","year":2000,"id":637854,"datarank":1.0588137228777998,"base_score":7.0587581525186645,"endowment":7.0587581525186645,"self_citation_contribution":1.0588137228777998,"citation_network_contribution":0.0,"self_endowment_contribution":1.0588137228777998,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1162,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":532242,"name":"Thomas M. 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G protein GAPs include both effector proteins (phospholipase C-β, p115RhoGEF) and a growing family of regulators of G protein signaling (RGS proteins) that are found throughout the animal and fungal kingdoms. GAP activity can sharpen the termination of a signal upon removal of stimulus, attenuate a signal either as a feedback inhibitor or in response to a second input, promote regulatory association of other proteins, or redirect signaling within a G protein signaling network. GAPs are regulated by various controls of their cellular concentrations, by complex interactions with Gβγ or with Gβ5 through an endogenous Gγ-like domain, and by interaction with multiple other proteins.</jats:p>","is_dataset_classified":null,"base_score":7.0587581525186645,"endowment":7.0587581525186645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10966476","pmcid":null,"openalex_id":"https://openalex.org/W1953109900","authors":[],"funders":[],"total_grants":0,"fwci":22.1422,"citation_percentile":0.99786193,"influential_citations":0,"citation_trend":[{"year":2012,"count":62},{"year":2013,"count":35},{"year":2014,"count":42},{"year":2015,"count":40},{"year":2016,"count":34},{"year":2017,"count":38},{"year":2018,"count":24},{"year":2019,"count":32},{"year":2020,"count":22},{"year":2021,"count":45},{"year":2022,"count":19},{"year":2023,"count":27},{"year":2024,"count":26},{"year":2025,"count":13},{"year":2026,"count":7}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.annualreviews.org/doi/pdf/10.1146/annurev.biochem.69.1.795","host_type":"publisher"},{"url":"https://doi.org/10.1146/annurev.biochem.69.1.795","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10966476","host_type":"repository"}],"fields_of_study":["Protein Kinase Regulation and GTPase Signaling","Cellular transport and secretion","Receptor Mechanisms and Signaling"],"mesh_terms":["Amino Acid Sequence","Animals","Humans","Models, Biological","Models, Molecular","Molecular Sequence Data","Phylogeny","Potassium Channels","Signal Transduction","Conserved Sequence","Caenorhabditis elegans","Sequence Homology, Amino Acid","Protein Structure, Tertiary","GTPase-Activating Proteins","RGS Proteins","Heterotrimeric GTP-Binding Proteins"],"keywords":["Heterotrimeric G protein","GTPase-activating protein","G protein","G beta-gamma complex","GTPase","Cell biology","Regulator of G protein signaling","GTP-binding protein regulators","RGS2","Biochemistry","Biology","Signal transduction","Chemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:38:49.670913Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}