{"doi":"10.1002/1873-3468.13202","title":"Nuclear localization of Hif‐3α requires two redundant <scp>NLS</scp> motifs in its unique C‐terminal region","abstract":"<jats:p>Hif‐3α, a member of the hypoxia‐inducible factor (<jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>) family, enters the nucleus and regulates gene expression in response to hypoxia. The molecular basis of its nuclear localization is not clear. <jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>‐1α and <jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>‐2α use a bipartite nuclear localization signal (<jats:styled-content style=\"fixed-case\">NLS</jats:styled-content>) to enter the nucleus. This motif is not conserved in Hif‐3α. Although there is a conserved Arg/Lys rich motif in the Hif‐3α N‐terminal region, deletion of this region has minimal effect on Hif‐3α nuclear localization. Here, we mapped the functional <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> to the unique C‐terminal region of Hif‐3α and identified two clusters of basic residues critical for its nuclear localization. The two <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> motifs are functionally redundant. Our results, thus, suggest that Hif‐3α nuclear localization is mediated through two redundant <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> motifs located in its unique C‐terminal region.</jats:p>","journal":"FEBS Letters","year":2018,"id":672575,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"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":406991,"name":"Peng Zhang","orcid":"0000-0001-8071-3729","position":1,"is_corresponding":false},{"id":246173,"name":"Ling Lu","orcid":"0000-0001-6693-8665","position":2,"is_corresponding":false},{"id":1757254,"name":"Yunzhang Liu","orcid":null,"position":3,"is_corresponding":false},{"id":603325,"name":"Yun Li","orcid":"0000-0003-0949-6519","position":4,"is_corresponding":false},{"id":807455,"name":"Cunming Duan","orcid":null,"position":5,"is_corresponding":false},{"id":1495595,"name":"Qing Yao","orcid":"0000-0003-1281-8603","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nuclear localization of Hif‐3α requires two redundant <scp>NLS</scp> motifs in its unique C‐terminal region","abstract":"<jats:p>Hif‐3α, a member of the hypoxia‐inducible factor (<jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>) family, enters the nucleus and regulates gene expression in response to hypoxia. The molecular basis of its nuclear localization is not clear. <jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>‐1α and <jats:styled-content style=\"fixed-case\">HIF</jats:styled-content>‐2α use a bipartite nuclear localization signal (<jats:styled-content style=\"fixed-case\">NLS</jats:styled-content>) to enter the nucleus. This motif is not conserved in Hif‐3α. Although there is a conserved Arg/Lys rich motif in the Hif‐3α N‐terminal region, deletion of this region has minimal effect on Hif‐3α nuclear localization. Here, we mapped the functional <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> to the unique C‐terminal region of Hif‐3α and identified two clusters of basic residues critical for its nuclear localization. The two <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> motifs are functionally redundant. Our results, thus, suggest that Hif‐3α nuclear localization is mediated through two redundant <jats:styled-content style=\"fixed-case\">NLS</jats:styled-content> motifs located in its unique C‐terminal region.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30047986","pmcid":null,"openalex_id":"https://openalex.org/W2884371102","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"30970357","title":null}],"total_grants":1,"fwci":0.1366,"citation_percentile":0.40256439,"influential_citations":0,"citation_trend":[{"year":2020,"count":2}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.13202","host_type":"journal"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.13202","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2F1873-3468.13202","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/1873-3468.13202","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/1873-3468.13202","host_type":"publisher"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1873-3468.13202","host_type":"publisher"},{"url":"https://doi.org/10.1002/1873-3468.13202","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30047986","host_type":"repository"},{"url":"https://hdl.handle.net/2027.42/145561","host_type":"repository"}],"fields_of_study":["Cancer, Hypoxia, and Metabolism","Mitochondrial Function and Pathology","ATP Synthase and ATPases Research","Apoptosis Regulatory Proteins","Basic Helix-Loop-Helix Proteins","Cell Hypoxia","Cell Nucleus","Gene Expression Regulation","HeLa Cells","Humans","Nuclear Localization Signals","Protein Domains","Repressor Proteins","Endothelial PAS Domain-Containing Protein 1"],"mesh_terms":["Protein Domains","Endothelial PAS Domain-Containing Protein 1","Cell Nucleus","Gene Expression Regulation","HeLa Cells","Humans","Repressor Proteins","Cell Hypoxia","Nuclear Localization Signals","Apoptosis Regulatory Proteins","Basic Helix-Loop-Helix Proteins","Basic Helix-Loop-Helix Transcription Factors"],"keywords":["NLS","Nuclear localization sequence","Nuclear transport","Nuclear export signal","Nuclear protein","Cell biology","Biology","Nucleus","Cell nucleus","Gene","Molecular biology","Genetics","Transcription factor","hypoxia","hypoxia-inducible factor","nuclear localization signal","zebrafish"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T09:37:29.585491Z","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":[]}