{"doi":"10.1371/journal.pone.0026234","title":"Pigment Epithelium-Derived Factor (PEDF) Interacts with Transportin SR2, and Active Nuclear Import Is Facilitated by a Novel Nuclear Localization Motif","abstract":null,"journal":"PLoS ONE","year":2011,"id":640762,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"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":1665492,"name":"William J. McCormack","orcid":null,"position":1,"is_corresponding":false},{"id":1665494,"name":"Michelle A. Morrin","orcid":null,"position":2,"is_corresponding":false},{"id":1665497,"name":"Wayne J. Higgins","orcid":null,"position":3,"is_corresponding":false},{"id":1665500,"name":"Denise M. Fox","orcid":null,"position":4,"is_corresponding":false},{"id":1665503,"name":"D. Margaret Worrall","orcid":null,"position":5,"is_corresponding":false},{"id":1665490,"name":"Sergio Anguissola","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pigment Epithelium-Derived Factor (PEDF) Interacts with Transportin SR2, and Active Nuclear Import Is Facilitated by a Novel Nuclear Localization Motif","abstract":"PEDF (Pigment epithelium-derived factor) is a non-inhibitory member of the serpin gene family (serpinF1) that displays neurotrophic and anti-angiogenic properties. PEDF contains a secretion signal sequence, but although originally regarded as a secreted extracellular protein, endogenous PEDF is found in the cytoplasm and nucleus of several mammalian cell types. In this study we employed a yeast two-hybrid interaction trap screen to identify transportin-SR2, a member of the importin-β family of nuclear transport karyopherins, as a putative PEDF binding partner. The interaction was supported in vitro by GST-pulldown and co-immunoprecipitation. Following transfection of HEK293 cells with GFP-tagged PEDF the protein was predominantly localised to the nucleus, suggesting that active import of PEDF occurs. A motif (YxxYRVRS) shared by PEDF and the unrelated transportin-SR2 substrate, RNA binding motif protein 4b, was identified and we investigated its potential as a nuclear localization signal (NLS) sequence. Site-directed mutagenesis of this helix A motif in PEDF resulted in a GFP-tagged mutant protein being excluded from the nucleus, and mutation of two arginine residues (R67, R69) was sufficient to abolish nuclear import and PEDF interaction with transportin-SR2. These results suggest a novel NLS and mechanism for serpinF1 nuclear import, which may be critical for anti-angiogenic and neurotrophic function.","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22028839","pmcid":null,"openalex_id":"https://openalex.org/W2133511249","authors":[],"funders":[],"total_grants":0,"fwci":1.5738,"citation_percentile":0.82767987,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":8},{"year":2014,"count":2},{"year":2015,"count":3},{"year":2017,"count":5},{"year":2018,"count":2},{"year":2019,"count":4},{"year":2021,"count":4},{"year":2022,"count":6},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0026234&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0026234&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0026234","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0026234","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22028839","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.290.2012","host_type":""},{"url":"https://doaj.org/article/614c246c36bb415cb6c5686363351eaf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3196545","host_type":"repository"}],"fields_of_study":["Nuclear Structure and Function","RNA Research and Splicing","Biotin and Related Studies","Active Transport, Cell Nucleus","Amino Acid Motifs","Amino Acid Sequence","Cell Nucleus","Eye Proteins","HEK293 Cells","Humans","Models, Molecular","Molecular Sequence Data","Mutagenesis, Site-Directed","Nerve Growth Factors","Nuclear Localization Signals","Peptide Fragments","Protein Binding","Protein Structure, Secondary","Serpins","Two-Hybrid System Techniques","beta Karyopherins","Pigment Epithelium-Derived Factor"],"mesh_terms":["Pigment Epithelium-Derived Factor","Amino Acid Sequence","Cell Nucleus","Eye Proteins","Humans","Models, Molecular","Molecular Sequence Data","Nerve Growth Factors","Peptide Fragments","Protein Binding","Serpins","Mutagenesis, Site-Directed","Protein Structure, Secondary","Nuclear Localization Signals","Two-Hybrid System Techniques","Amino Acid Motifs","Active Transport, Cell Nucleus","beta Karyopherins","HEK293 Cells"],"keywords":["Nuclear transport","Nuclear localization sequence","PEDF","Importin","Nuclear protein","Cell biology","Biology","Nuclear export signal","Green fluorescent protein","HEK 293 cells","Molecular biology","Cell nucleus","Cytoplasm","Biochemistry","Transcription factor","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T13:43:36.577364Z","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":[]}