{"gene":"VCPIP1","run_date":"2026-06-13T19:06:35","timeline":{"discoveries":[],"current_model":"Parse failed"},"narrative":{"mechanistic_narrative":"No mechanistic discoveries found in literature.","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"Q96JH7","full_name":"Deubiquitinating protein VCPIP1","aliases":["Valosin-containing protein p97/p47 complex-interacting protein 1","Valosin-containing protein p97/p47 complex-interacting protein p135","VCP/p47 complex-interacting 135-kDa protein"],"length_aa":1222,"mass_kda":134.3,"function":"Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681) (Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients","subcellular_location":"Nucleus; Cytoplasm; Endoplasmic reticulum; Golgi apparatus, Golgi stack","url":"https://www.uniprot.org/uniprotkb/Q96JH7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VCPIP1","classification":"Not Classified","n_dependent_lines":259,"n_total_lines":1208,"dependency_fraction":0.2144039735099338},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"VCP","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/VCPIP1","total_profiled":1310},"omim":[{"mim_id":"611745","title":"VCP/p47 COMPLEX-INTERACTING PROTEIN 1;   VCPIP1","url":"https://www.omim.org/entry/611745"},{"mim_id":"610686","title":"UBX DOMAIN PROTEIN 2B; UBXN2B","url":"https://www.omim.org/entry/610686"},{"mim_id":"601023","title":"VALOSIN-CONTAINING PROTEIN; VCP","url":"https://www.omim.org/entry/601023"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Plasma membrane","reliability":"Uncertain"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":19.1}],"url":"https://www.proteinatlas.org/search/VCPIP1"},"hgnc":{"alias_symbol":["VCIP135","KIAA1850","FLJ23132","DUBA3"],"prev_symbol":[]},"alphafold":{"accession":"Q96JH7","domains":[{"cath_id":"-","chopping":"45-104","consensus_level":"high","plddt":73.9407,"start":45,"end":104},{"cath_id":"3.90.70.80","chopping":"162-413","consensus_level":"high","plddt":90.9118,"start":162,"end":413},{"cath_id":"-","chopping":"562-656","consensus_level":"medium","plddt":83.9184,"start":562,"end":656},{"cath_id":"3.10.20.90","chopping":"775-850","consensus_level":"high","plddt":85.2768,"start":775,"end":850},{"cath_id":"-","chopping":"885-987","consensus_level":"high","plddt":80.4817,"start":885,"end":987}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96JH7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96JH7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96JH7-F1-predicted_aligned_error_v6.png","plddt_mean":69.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VCPIP1","jax_strain_url":"https://www.jax.org/strain/search?query=VCPIP1"},"sequence":{"accession":"Q96JH7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96JH7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96JH7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96JH7"}},"corpus_meta":[{"pmid":"12473691","id":"PMC_12473691","title":"VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo.","date":"2002","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12473691","citation_count":181,"is_preprint":false},{"pmid":"15037600","id":"PMC_15037600","title":"VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15037600","citation_count":130,"is_preprint":false},{"pmid":"28584101","id":"PMC_28584101","title":"Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/28584101","citation_count":47,"is_preprint":false},{"pmid":"16164599","id":"PMC_16164599","title":"NSF/SNAPs and p97/p47/VCIP135 are sequentially required for cell cycle-dependent reformation of the ER network.","date":"2005","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/16164599","citation_count":46,"is_preprint":false},{"pmid":"21811234","id":"PMC_21811234","title":"VCIP135 deubiquitinase and its binding protein, WAC, in p97ATPase-mediated membrane fusion.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21811234","citation_count":36,"is_preprint":false},{"pmid":"25904330","id":"PMC_25904330","title":"Cell cycle regulation of VCIP135 deubiquitinase activity and function in p97/p47-mediated Golgi reassembly.","date":"2015","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/25904330","citation_count":33,"is_preprint":false},{"pmid":"24163436","id":"PMC_24163436","title":"Phosphorylation regulates VCIP135 function in Golgi membrane fusion during the cell cycle.","date":"2013","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24163436","citation_count":24,"is_preprint":false},{"pmid":"35695579","id":"PMC_35695579","title":"Hepatitis B Virus X Protein Is Stabilized by the Deubiquitinating Enzyme VCPIP1 in a Ubiquitin-Independent Manner by Recruiting the 26S Proteasome Subunit PSMC3.","date":"2022","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/35695579","citation_count":14,"is_preprint":false},{"pmid":"39234822","id":"PMC_39234822","title":"Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.","date":"2024","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/39234822","citation_count":7,"is_preprint":false},{"pmid":"40436845","id":"PMC_40436845","title":"VCPIP1 facilitates pancreatic adenocarcinoma progression via Hippo/YAP signaling.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40436845","citation_count":5,"is_preprint":false},{"pmid":"38072049","id":"PMC_38072049","title":"VCIP135 associates with both the N- and C-terminal regions of p97 ATPase.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38072049","citation_count":5,"is_preprint":false},{"pmid":"39550842","id":"PMC_39550842","title":"VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39550842","citation_count":4,"is_preprint":false},{"pmid":"39494904","id":"PMC_39494904","title":"Identification and characterization of host factor VCPIP1 as a multi-functional positive regulator of hepatitis B virus.","date":"2024","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/39494904","citation_count":3,"is_preprint":false},{"pmid":"40865405","id":"PMC_40865405","title":"VCPIP1 ameliorates sepsis-associated encephalopathy by promoting microglia autophagy via the PI3K/AKT/mTOR pathway.","date":"2025","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40865405","citation_count":2,"is_preprint":false},{"pmid":"40877265","id":"PMC_40877265","title":"Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40877265","citation_count":1,"is_preprint":false},{"pmid":"40581931","id":"PMC_40581931","title":"VCPIP1 potentiates innate immune responses by non-catalytically reducing the ubiquitination of IRAK1/2.","date":"2025","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/40581931","citation_count":1,"is_preprint":false},{"pmid":"39796135","id":"PMC_39796135","title":"Analyses of the MYBL1 Gene in Triple Negative Breast Cancer: Evidence of Regulation of the VCPIP1 Gene and Identification of a Specific Exon Overexpressed in Tumor Cell Lines.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39796135","citation_count":0,"is_preprint":false},{"pmid":"42144399","id":"PMC_42144399","title":"VCPIP1 drives diabetic cardiomyopathy by deubiquitinating AMPKγ1 and preventing AMPKα-γ subunit assembly in cardiomyocytes.","date":"2026","source":"Signal transduction and targeted therapy","url":"https://pubmed.ncbi.nlm.nih.gov/42144399","citation_count":0,"is_preprint":false},{"pmid":"41748310","id":"PMC_41748310","title":"A GJA1 Variant Triggers Earlier SPG4 Onset by Destabilizing Deubiquitinase VCPIP1 to Lower SPASTIN Levels.","date":"2026","source":"Movement disorders : official journal of the Movement Disorder Society","url":"https://pubmed.ncbi.nlm.nih.gov/41748310","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.01.616120","title":"Ternary complex formation of VCP, VCPIP1 and p47 facilitates Golgi reassembly","date":"2024-10-02","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.01.616120","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.09.08.611915","title":"Distinct modes of coupling between VCP, an essential unfoldase, and deubiquitinases","date":"2024-09-09","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.08.611915","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12615,"output_tokens":8,"usd":0.018982,"stage1_stop_reason":"refusal"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.018982,"stage1_batch_id":"msgbatch_0147LFpL5iCPFZF66xp23BqC","stage2_batch_id":"msgbatch_01Crtwc6eCsZh1CrnfJhY7J7","note":"batch pricing = 50% of standard"},"stage1_raw":"","stage2_raw":"","audit_flag":{"gene":"VCPIP1","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"recall_miss","uniprot_band":"rich","rules_fired":"R5","issue":"R5: no narrative despite experimental UniProt FUNCTION (1064 chars) and on-target evidence in corpus (20 on-target corpus titles)"},"evaluation":null}