{"doi":"10.3390/ijms23010143","title":"The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum","abstract":"<jats:p>Looking at the variety of the thousands of different polypeptides that have been focused on in the research on the endoplasmic reticulum from the last five decades taught us one humble lesson: no one size fits all. Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the recently discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. With an emphasis on targeting routes and protein translocases, we will discuss those functional networks that drive efficient protein topogenesis and shed light on their redundant and dynamic nature in health and disease.</jats:p>","journal":"International Journal of Molecular Sciences","year":2021,"id":37256,"datarank":0.8390478602748991,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.32886825302557565,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.32886825302557565,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":24,"citers_with_citation_signal":18,"citers_with_endowment":18,"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":187081,"name":"Mark Sicking","orcid":null,"position":1,"is_corresponding":false},{"id":187082,"name":"Drazena Hadzibeganovic","orcid":null,"position":2,"is_corresponding":false},{"id":187083,"name":"Sarah Haßdenteufel","orcid":null,"position":3,"is_corresponding":false},{"id":187084,"name":"Sven Lang","orcid":"0000-0003-1326-1851","position":4,"is_corresponding":false},{"id":187080,"name":"Andrea Tirincsi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35008565","pmcid":"PMC8745461","openalex_id":"https://openalex.org/W4200471314","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"SFB 894","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"IRTG 1830","title":null},{"funder_name":"Saarland University Medical Center","grant_id":"HOMFORexcellent program","title":null},{"funder_name":"Weizmann Institute of Science","grant_id":"FGS Excellence postdoc fellowship","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"157660137/SFB 894","title":"Ca2+ Signals: Molecular Mechanisms and Integrative Functions"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"}],"total_grants":6,"fwci":2.1607,"citation_percentile":0.87236073,"influential_citations":1,"citation_trend":[{"year":2022,"count":8},{"year":2023,"count":2},{"year":2024,"count":10},{"year":2025,"count":7},{"year":2026,"count":2}],"oa_status":"gold","license":"other-oa","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/23/1/143/pdf?version=1640362964","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/23/1/143/pdf?version=1640362964","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/23/1/143/pdf?version=1640362964","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/23/1/143/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms23010143","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35008565","host_type":"repository"},{"url":"https://doaj.org/article/08b1b82628b749689a325e4ecead66b4","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms23010143","host_type":"repository"},{"url":"http://dx.doi.org/10.22028/D291-35224","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8745461","host_type":"repository"},{"url":"https://doi.org/10.22028/d291-35224","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8745461","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8745461?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.22028/d291-35224","host_type":""},{"url":"http://dx.doi.org/10.3390/ijms23010143","host_type":""}],"fields_of_study":["Endoplasmic Reticulum Stress and Disease","Cellular transport and secretion","RNA and protein synthesis mechanisms","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Cytosol","Endoplasmic Reticulum","Humans","Protein Sorting Signals","Protein Transport","Proteins","Signal Recognition Particle"],"mesh_terms":["Animals","Cytosol","Endoplasmic Reticulum","Humans","Proteins","Signal Recognition Particle","Protein Transport","Protein Sorting Signals"],"keywords":["Endoplasmic reticulum","Signal recognition particle","Protein targeting","Ribosome","Sec61","Transport protein","Cell biology","Signal recognition particle receptor","Cytosol","Protein Sorting Signals","Biology","STIM1","Translocon","Membrane protein","Signal peptide","Biochemistry","Gene","Peptide sequence","Membrane","Hydrophobicity","SRP","Protein transport","Emc","Sec61 Complex","Transmembrane Helix","Snd","Get","Positive-inside Rule","ddc:610","Proteins","610","Review","Animals","Humans"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T18:55:57.479705Z","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":[]}