{"doi":"10.1073/pnas.1220895110","title":"RAC1\n                    <sup>P29S</sup>\n                    is a spontaneously activating cancer-associated GTPase","abstract":"<jats:p>\n                    RAC1 is a small, Ras-related GTPase that was recently reported to harbor a recurrent UV-induced signature mutation in melanoma, resulting in substitution of P29 to serine (RAC1\n                    <jats:sup>P29S</jats:sup>\n                    ), ranking this the third most frequently occurring gain-of-function mutation in melanoma. Although the Ras family GTPases are mutated in about 30% of all cancers, mutations in the Rho family GTPases have rarely been observed. In this study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations that eliminate GTPase activity, the activated melanoma RAC1\n                    <jats:sup>P29S</jats:sup>\n                    protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange. Determination and comparison of crystal structures for activated RAC1 GTPases suggest that RAC1\n                    <jats:sup>F28L</jats:sup>\n                    —a known spontaneously activated RAC1 mutant—and RAC1\n                    <jats:sup>P29S</jats:sup>\n                    are self-activated in distinct fashions. Moreover, the mechanism of RAC1\n                    <jats:sup>P29S</jats:sup>\n                    and RAC1\n                    <jats:sup>F28L</jats:sup>\n                    activation differs from the common oncogenic mutations found in Ras-like GTPases that abrogate GTP hydrolysis. The melanoma RAC1\n                    <jats:sup>P29S</jats:sup>\n                    gain-of-function point mutation therefore represents a previously undescribed class of cancer-related GTPase activity.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2013,"id":648355,"datarank":6.778965619127833,"base_score":5.181783550292085,"endowment":5.181783550292085,"self_citation_contribution":0.7772675325438129,"citation_network_contribution":6.00169808658402,"self_endowment_contribution":0.7772675325438129,"citer_contribution":6.00169808658402,"corpus_percentile":null,"corpus_rank":null,"citation_count":177,"citer_count":169,"citers_with_citation_signal":150,"citers_with_endowment":150,"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":893163,"name":"Byung Hak Ha","orcid":"0000-0001-6594-0835","position":1,"is_corresponding":false},{"id":1689622,"name":"Edna C. Holman","orcid":null,"position":2,"is_corresponding":false},{"id":110550,"name":"Ruth Halaban","orcid":"0000-0001-8451-1964","position":3,"is_corresponding":false},{"id":499484,"name":"Joseph Schlessinger","orcid":"0000-0002-5085-5969","position":4,"is_corresponding":false},{"id":86333,"name":"Titus J. Boggon","orcid":"0000-0003-2862-1637","position":5,"is_corresponding":false},{"id":1175520,"name":"Matthew J. Davis","orcid":"0000-0003-4159-6739","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"RAC1\n                    <sup>P29S</sup>\n                    is a spontaneously activating cancer-associated GTPase","abstract":"<jats:p>\n                    RAC1 is a small, Ras-related GTPase that was recently reported to harbor a recurrent UV-induced signature mutation in melanoma, resulting in substitution of P29 to serine (RAC1\n                    <jats:sup>P29S</jats:sup>\n                    ), ranking this the third most frequently occurring gain-of-function mutation in melanoma. Although the Ras family GTPases are mutated in about 30% of all cancers, mutations in the Rho family GTPases have rarely been observed. In this study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations that eliminate GTPase activity, the activated melanoma RAC1\n                    <jats:sup>P29S</jats:sup>\n                    protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange. Determination and comparison of crystal structures for activated RAC1 GTPases suggest that RAC1\n                    <jats:sup>F28L</jats:sup>\n                    —a known spontaneously activated RAC1 mutant—and RAC1\n                    <jats:sup>P29S</jats:sup>\n                    are self-activated in distinct fashions. Moreover, the mechanism of RAC1\n                    <jats:sup>P29S</jats:sup>\n                    and RAC1\n                    <jats:sup>F28L</jats:sup>\n                    activation differs from the common oncogenic mutations found in Ras-like GTPases that abrogate GTP hydrolysis. The melanoma RAC1\n                    <jats:sup>P29S</jats:sup>\n                    gain-of-function point mutation therefore represents a previously undescribed class of cancer-related GTPase activity.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.181783550292085,"endowment":5.181783550292085,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23284172","pmcid":"PMC3549122","openalex_id":"https://openalex.org/W1982486180","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM102262","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA121974","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P50 CA121974","title":null},{"funder_name":"NIBIB NIH HHS","grant_id":"P30 EB009998","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM102262","title":null}],"total_grants":5,"fwci":5.6386,"citation_percentile":0.96923628,"influential_citations":0,"citation_trend":[{"year":2013,"count":8},{"year":2014,"count":13},{"year":2015,"count":12},{"year":2016,"count":8},{"year":2017,"count":10},{"year":2018,"count":13},{"year":2019,"count":17},{"year":2020,"count":23},{"year":2021,"count":18},{"year":2022,"count":14},{"year":2023,"count":12},{"year":2024,"count":9},{"year":2025,"count":16},{"year":2026,"count":4}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/110/3/912.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/110/3/912.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1220895110","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1220895110","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23284172","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3549122","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3549122","host_type":"repository"}],"fields_of_study":["Melanoma and MAPK Pathways","Protein Kinase Regulation and GTPase Signaling","PI3K/AKT/mTOR signaling in cancer"],"mesh_terms":["Animals","Chlorocebus aethiops","Enzyme Activation","Guanosine Triphosphate","Humans","Hydrolysis","Kinetics","Melanoma","Microscopy, Fluorescence","Models, Molecular","Oncogenes","Recombinant Fusion Proteins","Signal Transduction","Crystallography, X-Ray","COS Cells","Amino Acid Substitution","Mutation, Missense","rac1 GTP-Binding Protein","Cell Surface Extensions","NIH 3T3 Cells","Mice","Static Electricity","Genetic Association Studies"],"keywords":["GTPase","RAC1","GTP'","Mutation","Biology","Melanoma","Mutant","Cell biology","Cancer research","Biochemistry","Signal transduction","Gene","Enzyme"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Decent work and economic growth"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:31:20.544201Z","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":[]}