Protein Interaction Map of APOBEC3 Enzyme Family Reveals Deamination-Independent Role in Cellular Function.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38548018", "kind": "science-record", "revision": 4, "content_hash": "sha256:b42625538dc49fa9bf811761793e7ea34785df7d31bf7593cce818b77e9618f7", "created_at": "2026-11-01T19:20:30Z", "updated_at": "2026-11-01T22:11:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Protein Interaction Map of APOBEC3 Enzyme Family Reveals Deamination-Independent Role in Cellular Function.", "doi": "10.1016/j.mcpro.2024.100755", "pmid": "38548018", "authors": ["Gwendolyn M Jang", "Arun Kumar Annan Sudarsan", "Arzhang Shayeganmehr", "Erika Prando Munhoz", "Reanna Lao", "Amit Gaba", "Milaid Granadillo Rodríguez", "Robin P Love", "Benjamin J Polacco", "Yuan Zhou", "Nevan J Krogan", "Robyn M Kaake", "Linda Chelico"], "journal": "Molecular & cellular proteomics : MCP", "year": 2024, "abstract": "Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part of the intrinsic immunity against viruses and retroelements. These enzymes deaminate cytosine to form uracil which can functionally inactivate or cause degradation of viral or retroelement genomes. In addition, APOBEC3s have deamination-independent antiviral activity through protein and nucleic acid interactions. If expression levels are misregulated, some APOBEC3 enzymes can access the human genome leading to deamination and mutagenesis, contributing to cancer initiation and evolution. While APOBEC3 enzymes are known to interact with large ribonucleoprotein complexes, the function and RNA dependence are not entirely understood. To further understand their cellular roles, we determined by affinity purification mass spectrometry (AP-MS) the protein interaction network for the human APOBEC3 enzymes and mapped a diverse set of protein-protein and protein-RNA mediated interactions. Our analysis identified novel RNA-mediated interactions between APOBEC3C, APOBEC3H Haplotype I and II, and APOBEC3G with spliceosome proteins, and APOBEC3G and APOBEC3H Haplotype I with proteins involved in tRNA methylation and ncRNA export from the nucleus. In addition, we identified RNA-independent protein-protein interactions with APOBEC3B, APOBEC3D, and APOBEC3F and the prefoldin family of protein-folding chaperones. Interaction between prefoldin 5 (PFD5) and APOBEC3B disrupted the ability of PFD5 to induce degradation of the oncogene cMyc, implicating the APOBEC3B protein interaction network in cancer. Altogether, the results uncover novel functions and interactions of the APOBEC3 family and suggest they may have fundamental roles in cellular RNA biology, their protein-protein interactions are not redundant, and there are protein-protein interactions with tumor suppressors, suggesting a role in cancer biology. Data are available via ProteomeXchange with the identifier PXD044275.", "claims": [{"id": "claim-method", "statement": "Data was searched using MaxQuant (28) (Supplemental Tables S3 and S4), and high-confidence PPIs were differentiated from background using a two-step filtering approach with the SAINTexpress (24) and CompPASS (25) scoring algorithms.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38548018", "locator": "sections[21] \"Global Analysis of A3 Protein-Protein Interactions (PPIs)\" paragraph 2", "quote": "Data was searched using MaxQuant (28) (Supplemental Tables S3 and S4), and high-confidence PPIs were differentiated from background using a two-step filtering approach with the SAINTexpress (24) and CompPASS (25) scoring algorithms."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are contained within the manuscript and are available via ProteomeXchange with identifier PXD044275.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38548018", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All data are contained within the manuscript and are available via ProteomeXchange with identifier PXD044275."}], "state": "complete"}, {"id": "claim-target-result", "statement": "AP-MS identified RNA-dependent and RNA-independent protein interactions for APOBEC3B, APOBEC3D, and APOBEC3F with prefoldin proteins, and showed that APOBEC3B interaction with PFD5 stabilizes cMyc.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38548018", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "We discovered novel APOBEC3-specific and shared interactors that are RNA-dependent and -independent."}, {"asset": "source:pmid:38548018", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Notably, there were stable interactions between prefoldin complex (PFD1-6) subunits and APOBEC3B, APOBEC3D, and APOBEC3F."}, {"asset": "source:pmid:38548018", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Expression of APOBEC3B decreased PFD5 interaction with cMyc and increased cMyc steady-state levels, indicating a potential protein interaction-dependent contribution of APOBEC3B in cancer."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "AP-MS identified RNA-dependent and RNA-independent protein interactions for APOBEC3B, APOBEC3D, and APOBEC3F with prefoldin proteins, and showed that APOBEC3B interaction with PFD5 stabilizes cMyc.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38548018"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Data was searched using MaxQuant (28) (Supp", "oteins were trypsin digested and analyzed by LC-MS/MS. Peptides and proteins were identified by Ma", "deaminase activity (58). Consistent with the proteomics results of the previous study, in our hands"], "order_basis": "paper_text_order:890", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(BioRad; 1:10,000), respectively. Pierce ECL Western Blotting Substrate (Thermo Scientific) was used to de", "tifying PPIs from a purification background. Immunoblotting for co-immunoprecipitation (co-IP) experimen", "lectrophoresis (SDS-PAGE), Silver Stain, and Immunoblot Analysis of Affinity Purified Proteins Prote", "Secondary antibodies were used at 1:10,000. Immunoblots were quantified using Image Studio software."], "order_basis": "paper_text_order:3362", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were performed in triplicate. 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