{"gene":"ZNF622","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2002,"finding":"ZNF622 (ZPR9) was identified as a binding partner of murine protein serine/threonine kinase MPK38/MELK via yeast two-hybrid and co-expression assays, and is phosphorylated by MPK38 in vivo. Co-expression of ZPR9 with MPK38 caused accumulation of ZPR9 in the nucleus.","method":"Yeast two-hybrid screen, co-immunoprecipitation, in vivo phosphorylation assay, subcellular localization by co-expression","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and in vivo phosphorylation assay in a single lab with two orthogonal methods","pmids":["11802789"],"is_preprint":false},{"year":2003,"finding":"ZNF622 (ZPR9) physically interacts with B-MYB transcription factor through all three functional domains of B-MYB (DNA-binding domain, transactivation domain, and C-terminal conserved region), and co-expression of ZPR9 significantly upregulates B-MYB transcriptional activity in a dose-dependent manner. Co-expression also caused nuclear accumulation of both proteins. Constitutive ZPR9 expression induces apoptosis in neuroblastoma cells in the presence of retinoic acid.","method":"Yeast two-hybrid, co-immunoprecipitation of endogenous and exogenous proteins, deletion analysis, cotransfection/reporter assay, subcellular localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP of endogenous proteins plus functional transcription reporter assay, single lab, multiple orthogonal methods","pmids":["12645566"],"is_preprint":false},{"year":2011,"finding":"ZNF622 (ZPR9) physically interacts with apoptosis signal-regulating kinase 1 (ASK1) through a disulfide linkage involving Cys1351 and Cys1360 of ASK1 and Cys305 and Cys308 of ZPR9. ASK1 directly phosphorylates ZPR9 at Ser314 and Thr318. Wild-type ZPR9, but not S314A/T318A mutant, stimulates ASK1 kinase activity, promotes ASK1-mediated signaling to JNK and p38 by destabilizing ASK1-Trx and ASK1-14-3-3 inhibitory complexes and by increasing ASK1-MKK3 complex formation, and promotes H2O2-mediated apoptosis in a phosphorylation-dependent manner. ZPR9 also inhibits PDK1-mediated signaling through ASK1 activation.","method":"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, reporter assay (AP-1), apoptosis assay, knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro kinase assay with mutagenesis, reciprocal co-IP, functional pathway readouts, multiple orthogonal methods in single lab","pmids":["21771788"],"is_preprint":false},{"year":2016,"finding":"ZNF622 (ZPR9) is a cofactor of DNAJC21 involved in 60S ribosomal subunit maturation. DNAJC21 mutations impair its interaction with ZNF622, PA2G4, and HSPA8. DNAJC21 deficiency results in cytoplasmic accumulation of PA2G4, aberrant ribosome profiles, and increased cell death.","method":"Co-immunoprecipitation, functional interaction studies with patient-derived lymphoblastoid cells, ribosome profiling","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP interaction data with patient-derived cells and ribosome profiling, single lab, multiple methods","pmids":["27346687"],"is_preprint":false},{"year":2016,"finding":"ZNF622 (ZPR9) is a component of a multiprotein complex with MPK38, ASK1, SMADs, and thioredoxin (TRX) that coordinately regulates redox-dependent ASK1 and TGF-β signaling pathways. Adenoviral delivery of ZPR9 in obese mice restored downregulated ASK1 and TGF-β signaling and ameliorated adiposity, hyperglycemia, hyperlipidemia, and impaired ketogenesis.","method":"Co-immunoprecipitation (multiprotein complex), adenoviral overexpression in mice, metabolic phenotyping","journal":"Antioxidants & redox signaling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiprotein complex identified by co-IP plus in vivo functional rescue, single lab","pmids":["26421442"],"is_preprint":false},{"year":2017,"finding":"ZNF622 (ZPR9) functions as an activator of MPK38, with the interaction mediated by cysteine residues (Cys269 and Cys286 of MPK38; Cys305 and Cys308 of ZPR9). MPK38 phosphorylates ZPR9 at Thr252; wild-type ZPR9 but not T252A mutant enhances ASK1, TGF-β, and p53 function by stabilizing MPK38. This was validated using CRISPR/Cas9-mediated ZPR9(T252A) knockin cell lines, haploinsufficient MEF cells, and inducible knockdown systems.","method":"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, CRISPR/Cas9 knockin, haploinsufficient MEF cells, inducible shRNA knockdown","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro kinase assay, CRISPR knockin validation, multiple genetic tools in single lab with orthogonal methods","pmids":["28195154"],"is_preprint":false},{"year":2018,"finding":"Smad proteins differentially regulate MPK38 activity partly through modulating complex formation between MPK38 and ZPR9 (ZNF622): Smads2/3/4 increased while Smad7 decreased MPK38-ZPR9 complex formation. Phosphorylation-defective Smad mutants abolished these effects.","method":"Co-immunoprecipitation, site-directed mutagenesis, adenoviral delivery in HFD mice","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP of MPK38-ZPR9 complex modulation with mutagenesis validation, single lab","pmids":["29700281"],"is_preprint":false},{"year":2019,"finding":"ZNF622 acts as a cellular antiviral protein against human adenovirus (HAdV). ZNF622 forms a trimeric complex with viral pVII protein and cellular nucleophosmin 1 (NPM1). Loss of ZNF622 increases pVII binding to viral DNA and pVII levels in purified virions, enhances cell lysis, and increases infectious virion accumulation. ZNF622 accumulated in nuclei of virus-infected cells. ZNF622 mutations and NPM1 deficiency altered pVII's ability to bind viral DNA.","method":"Protein interaction studies (co-IP), ZNF622 knockout cells, virion purification and quantification, cell lysis assay, immunofluorescence localization","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — ZNF622 KO with multiple functional readouts (viral DNA binding, virion accumulation, cell lysis), trimeric complex identified by co-IP, orthogonal methods","pmids":["30429337"],"is_preprint":false},{"year":2021,"finding":"HectD1 E3 ubiquitin ligase ubiquitinates and degrades ZNF622, an assembly factor for the ribosomal 60S subunit. Loss of HectD1 leads to accumulation of ZNF622 and the anti-association factor eIF6 on 60S, causing 60S/40S joining defects and reduced protein synthesis. Depletion of ZNF622 in Hectd1-deficient HSCs restored ribosomal subunit joining, protein synthesis, and HSC reconstitution capacity.","method":"Ubiquitination assay, ribosome fractionation, genetic epistasis (Znf622 depletion in Hectd1 KO), protein synthesis measurement, HSC transplantation assay","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — ubiquitination assay establishing ZNF622 as HectD1 substrate, genetic epistasis rescue, ribosome fractionation, and in vivo functional reconstitution","pmids":["33711283"],"is_preprint":false},{"year":2025,"finding":"DUSP12 interacts with ZNF622 (ZPR9) via its unique zinc-binding domain. DUSP12 overexpression promotes de-phosphorylation of ZNF622 at Ser143. ZNF622 overexpression causes pre-metaphase mitotic defects dependent on Ser143 phosphorylation state (phosphomimetic and phosphorylation-deficient mutants did not). Knockdown of DUSP12 promoted stress-induced apoptosis, while knockdown of ZNF622 suppressed it, placing ZNF622 downstream of DUSP12 in a cell death pathway.","method":"Affinity- and proximity-based biochemical purification coupled to mass spectrometry, in-cell and in-vitro IP assays, phosphoproteomic analysis, ZNF622 overexpression with phosphomutants, siRNA knockdown, apoptosis assay","journal":"Cell death & disease","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — mass spectrometry-identified phosphorylation site, in vitro IP validation, functional phosphomutant analysis, and genetic epistasis via double knockdown","pmids":["41851086","39868293"],"is_preprint":false},{"year":2026,"finding":"In yeast, Rei1 (ZNF622 ortholog) and its paralog Reh1 facilitate loading of ribosomal protein eL24 onto pre-60S particles in the cytoplasm. Pre-60S subunits from rei1Δ reh1Δ cells are specifically deficient in eL24. eL24 overexpression suppresses the growth defect of the double mutant. Suppressors of rei1Δ reh1Δ growth defects (mutations in uL3, Lsg1, Ppq1) partially reverse the eL24 loading defect, establishing that Rei1/Reh1 act upstream of eL24 recruitment during cytoplasmic 60S maturation.","method":"Protein composition analysis of isolated pre-60S particles (MS), genetic suppressor screen, overexpression rescue","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic analysis of pre-60S composition plus genetic suppressor screen in yeast ortholog, single lab, preprint","pmids":["41959095"],"is_preprint":true}],"current_model":"ZNF622 (ZPR9) is a zinc finger protein that functions primarily as a cytoplasmic assembly factor for the 60S ribosomal subunit (facilitating eL24 loading and subunit joining, antagonized by eIF6), is ubiquitinated and degraded by the E3 ligase HectD1 to regulate ribosome assembly and protein synthesis in hematopoietic stem cells, is phosphorylated by MPK38 (at Thr252) and ASK1 (at Ser314/Thr318) to positively regulate their respective signaling pathways (ASK1/JNK/p38, TGF-β, p53), is dephosphorylated at Ser143 by DUSP12 to suppress stress-induced apoptosis, forms a trimeric complex with adenoviral pVII and NPM1 to restrict viral DNA binding and lytic growth, and co-activates B-MYB transcriptional activity through direct interaction."},"narrative":{"mechanistic_narrative":"ZNF622 (ZPR9) is a zinc finger protein that functions as a cytoplasmic 60S ribosomal subunit assembly factor and as a redox-sensitive signaling cofactor. In ribosome biogenesis it acts as a cofactor of DNAJC21 in 60S maturation, with its yeast ortholog Rei1 (and paralog Reh1) promoting loading of ribosomal protein eL24 onto pre-60S particles during cytoplasmic maturation [PMID:27346687, PMID:41959095]. Its level is set by HectD1-mediated ubiquitination and degradation; loss of HectD1 stabilizes ZNF622 and the anti-association factor eIF6 on 60S particles, blocking 60S/40S joining and protein synthesis, and depletion of ZNF622 restores subunit joining and hematopoietic stem cell reconstitution in HectD1-deficient cells [PMID:33711283]. Independently, ZNF622 is a phosphorylation-controlled activator of stress kinase signaling: it binds MPK38/MELK and ASK1 through cysteine-mediated linkages, is phosphorylated by MPK38 at Thr252 and by ASK1 at Ser314/Thr318, and in its phosphorylated state stimulates ASK1 kinase activity, drives ASK1/JNK/p38, TGF-β, and p53 signaling, and promotes oxidative-stress-induced apoptosis [PMID:21771788, PMID:28195154]. Dephosphorylation at Ser143 by the phosphatase DUSP12 places ZNF622 in a cell-death pathway whose activity depends on its phosphorylation state [PMID:41851086, PMID:39868293]. ZNF622 also co-activates the transcription factor B-MYB through direct interaction [PMID:12645566] and acts as an antiviral restriction factor against human adenovirus by forming a trimeric complex with viral pVII and cellular NPM1 that limits pVII-viral DNA binding and lytic virion production [PMID:30429337].","teleology":[{"year":2002,"claim":"Established the first molecular partner of ZNF622, linking it to a serine/threonine kinase and to regulated nuclear localization.","evidence":"Yeast two-hybrid, co-IP and in vivo phosphorylation with MPK38/MELK","pmids":["11802789"],"confidence":"Medium","gaps":["Functional consequence of MPK38 phosphorylation not defined","Phosphosite not mapped at this stage"]},{"year":2003,"claim":"Showed ZNF622 acts as a transcriptional co-activator, broadening its role beyond kinase binding.","evidence":"Yeast two-hybrid, endogenous/exogenous co-IP, reporter assay and apoptosis in neuroblastoma cells","pmids":["12645566"],"confidence":"Medium","gaps":["Mechanism of B-MYB co-activation unresolved","Relationship between transcriptional and kinase roles unclear"]},{"year":2011,"claim":"Defined ZNF622 as a phosphorylation-dependent activator of ASK1, mapping the binding chemistry and phosphosites that control stress signaling.","evidence":"Co-IP, in vitro kinase assay, site-directed mutagenesis (Cys/Ser/Thr), AP-1 reporter and apoptosis assays","pmids":["21771788"],"confidence":"High","gaps":["In vivo relevance of disulfide-mediated binding not tested","Connection to ribosomal function not addressed"]},{"year":2016,"claim":"Placed ZNF622 in 60S ribosomal subunit maturation as a DNAJC21 cofactor, introducing a function entirely distinct from its signaling roles.","evidence":"Co-IP, patient-derived lymphoblastoid cells, ribosome profiling","pmids":["27346687"],"confidence":"Medium","gaps":["Direct biochemical role of ZNF622 in maturation not defined","Whether ZNF622 is required for normal ribosome assembly not shown"]},{"year":2017,"claim":"Established a reciprocal MPK38-ZNF622 activation loop and identified Thr252 as the functional phosphosite for stabilizing MPK38 and amplifying ASK1/TGF-β/p53 output.","evidence":"In vitro kinase assay, CRISPR/Cas9 T252A knockin, haploinsufficient MEFs, inducible knockdown","pmids":["28195154"],"confidence":"High","gaps":["Tissue contexts where this loop operates not delineated","Integration with ribosomal function not addressed"]},{"year":2018,"claim":"Showed Smad proteins tune signaling output by modulating MPK38-ZNF622 complex assembly, connecting ZNF622 to TGF-β regulation.","evidence":"Co-IP, site-directed mutagenesis, adenoviral delivery in HFD mice","pmids":["29700281"],"confidence":"Medium","gaps":["Direct Smad-ZNF622 contact not established","Mechanism of complex modulation unclear"]},{"year":2019,"claim":"Identified an antiviral function for ZNF622, restricting adenovirus via a pVII-NPM1 trimeric complex that limits viral DNA binding.","evidence":"Co-IP, ZNF622 knockout cells, virion purification, cell lysis and immunofluorescence assays","pmids":["30429337"],"confidence":"High","gaps":["Whether restriction requires ZNF622's ribosomal or signaling activities unknown","Breadth of antiviral activity beyond HAdV untested"]},{"year":2021,"claim":"Defined how ZNF622 levels are controlled and the functional cost of mis-regulation, establishing it as a HectD1 ubiquitination substrate gating 60S/40S joining and protein synthesis.","evidence":"Ubiquitination assay, ribosome fractionation, genetic epistasis (Znf622 depletion in Hectd1 KO), HSC transplantation","pmids":["33711283"],"confidence":"High","gaps":["Direct molecular interaction of ZNF622 with eIF6 on 60S not resolved","How ubiquitination is triggered not defined"]},{"year":2025,"claim":"Identified DUSP12 as a phosphatase acting on ZNF622 Ser143 and placed ZNF622 in a stress-induced cell-death pathway with phosphorylation-state-dependent mitotic effects.","evidence":"Affinity/proximity MS, in-cell and in-vitro IP, phosphoproteomics, phosphomutant overexpression, siRNA epistasis, apoptosis assay","pmids":["41851086","39868293"],"confidence":"High","gaps":["Kinase responsible for Ser143 phosphorylation unidentified","Mechanistic basis of the mitotic defect unresolved"]},{"year":2026,"claim":"Defined the molecular step ZNF622's ortholog performs in ribosome maturation: loading of eL24 onto pre-60S particles upstream of subunit completion.","evidence":"MS composition analysis of pre-60S particles, genetic suppressor screen and overexpression rescue in yeast (preprint)","pmids":["41959095"],"confidence":"Medium","gaps":["Direct conservation of eL24-loading role in human ZNF622 not shown","Preprint, not peer-reviewed","Structural basis of eL24 recruitment unresolved"]},{"year":null,"claim":"How ZNF622's ribosome-assembly function, its kinase-signaling/apoptosis roles, and its antiviral activity are coordinated within a single cell remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model linking cytoplasmic ribosome assembly to nuclear signaling functions","Whether distinct ZNF622 pools serve distinct functions is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,5]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,5,8]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[3,8]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,7]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,8,10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,5]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[2,9]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[8]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[7]}],"complexes":["ZNF622-pVII-NPM1 trimeric complex","MPK38-ASK1-SMAD-TRX-ZNF622 complex"],"partners":["MPK38","ASK1","MYBL2","DNAJC21","NPM1","HECTD1","DUSP12","SMAD4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q969S3","full_name":"Cytoplasmic 60S subunit biogenesis factor ZNF622","aliases":["Zinc finger protein 622","Zinc finger-like protein 9"],"length_aa":477,"mass_kda":54.3,"function":"Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q969S3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF622","classification":"Not Classified","n_dependent_lines":228,"n_total_lines":1208,"dependency_fraction":0.18874172185430463},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NPM1","stoichiometry":0.2},{"gene":"PSPC1","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2},{"gene":"RBM42","stoichiometry":0.2},{"gene":"RBM8A","stoichiometry":0.2},{"gene":"RPS16","stoichiometry":0.2},{"gene":"SRP68","stoichiometry":0.2},{"gene":"SRP72","stoichiometry":0.2},{"gene":"SRP9","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ZNF622","total_profiled":1310},"omim":[{"mim_id":"617048","title":"DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 21; DNAJC21","url":"https://www.omim.org/entry/617048"},{"mim_id":"608694","title":"ZINC FINGER PROTEIN 622; ZNF622","url":"https://www.omim.org/entry/608694"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZNF622"},"hgnc":{"alias_symbol":["MGC2485","MGC17552","ZPR9"],"prev_symbol":[]},"alphafold":{"accession":"Q969S3","domains":[{"cath_id":"-","chopping":"5-64","consensus_level":"high","plddt":87.8137,"start":5,"end":64},{"cath_id":"-","chopping":"248-349","consensus_level":"high","plddt":89.7958,"start":248,"end":349},{"cath_id":"-","chopping":"375-402","consensus_level":"medium","plddt":88.2707,"start":375,"end":402},{"cath_id":"3.30.160","chopping":"65-115","consensus_level":"medium","plddt":83.9704,"start":65,"end":115}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969S3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q969S3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q969S3-F1-predicted_aligned_error_v6.png","plddt_mean":72.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF622","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF622"},"sequence":{"accession":"Q969S3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q969S3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q969S3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969S3"}},"corpus_meta":[{"pmid":"27346687","id":"PMC_27346687","title":"DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation.","date":"2016","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27346687","citation_count":95,"is_preprint":false},{"pmid":"34545074","id":"PMC_34545074","title":"Multi-level inhibition of coronavirus replication by chemical ER stress.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34545074","citation_count":87,"is_preprint":false},{"pmid":"33711283","id":"PMC_33711283","title":"HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis.","date":"2021","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/33711283","citation_count":59,"is_preprint":false},{"pmid":"11802789","id":"PMC_11802789","title":"Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38).","date":"2002","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11802789","citation_count":40,"is_preprint":false},{"pmid":"12645566","id":"PMC_12645566","title":"Enhancement of B-MYB transcriptional activity by ZPR9, a novel zinc finger protein.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12645566","citation_count":36,"is_preprint":false},{"pmid":"29700281","id":"PMC_29700281","title":"Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity.","date":"2018","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/29700281","citation_count":36,"is_preprint":false},{"pmid":"30270343","id":"PMC_30270343","title":"Altered DNA Methylation Sites in Peripheral Blood Leukocytes from Patients with Simple Steatosis and Nonalcoholic Steatohepatitis (NASH).","date":"2018","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/30270343","citation_count":25,"is_preprint":false},{"pmid":"28195154","id":"PMC_28195154","title":"Zinc finger protein ZPR9 functions as an activator of AMPK-related serine/threonine kinase MPK38/MELK involved in ASK1/TGF-β/p53 signaling pathways.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28195154","citation_count":23,"is_preprint":false},{"pmid":"25485581","id":"PMC_25485581","title":"A crucial role for the phosphorylation of STRAP at Ser(188) by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways.","date":"2014","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/25485581","citation_count":23,"is_preprint":false},{"pmid":"32510676","id":"PMC_32510676","title":"Genome-wide detection of copy number variants in European autochthonous and commercial pig breeds by whole-genome sequencing of DNA pools identified breed-characterising copy number states.","date":"2020","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32510676","citation_count":21,"is_preprint":false},{"pmid":"26421442","id":"PMC_26421442","title":"Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice.","date":"2016","source":"Antioxidants & redox signaling","url":"https://pubmed.ncbi.nlm.nih.gov/26421442","citation_count":18,"is_preprint":false},{"pmid":"21771788","id":"PMC_21771788","title":"Positive regulation of apoptosis signal-regulating kinase 1 signaling by ZPR9 protein, a zinc finger protein.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21771788","citation_count":17,"is_preprint":false},{"pmid":"30429337","id":"PMC_30429337","title":"Cellular Zinc Finger Protein 622 Hinders Human Adenovirus Lytic Growth and Limits Binding of the Viral pVII Protein to Virus DNA.","date":"2019","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/30429337","citation_count":12,"is_preprint":false},{"pmid":"39325823","id":"PMC_39325823","title":"Human cells contain myriad excised linear intron RNAs with links to gene regulation and potential utility as biomarkers.","date":"2024","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39325823","citation_count":7,"is_preprint":false},{"pmid":"39868293","id":"PMC_39868293","title":"DUSP12 promotes cell cycle progression and protects cells from cell death by regulating ZPR9.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39868293","citation_count":1,"is_preprint":false},{"pmid":"41851086","id":"PMC_41851086","title":"DUSP12 promotes cell cycle progression and protects cells from ZNF622 mediated apoptosis.","date":"2026","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41851086","citation_count":1,"is_preprint":false},{"pmid":"34214436","id":"PMC_34214436","title":"Releasing the brake on protein synthesis in hematopoietic stem cells.","date":"2021","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/34214436","citation_count":0,"is_preprint":false},{"pmid":"41959095","id":"PMC_41959095","title":"Rei1 and Reh1 facilitate the loading of eL24.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41959095","citation_count":0,"is_preprint":false},{"pmid":"40694934","id":"PMC_40694934","title":"Gonadal sex differentiation in Eleutheronema tetradactylum: Histological features and transcriptomic insights from mature gonads.","date":"2025","source":"Comparative biochemistry and physiology. Part D, Genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/40694934","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11794,"output_tokens":3458,"usd":0.043626,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10928,"output_tokens":3537,"usd":0.071532,"stage2_stop_reason":"end_turn"},"total_usd":0.115158,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"ZNF622 (ZPR9) was identified as a binding partner of murine protein serine/threonine kinase MPK38/MELK via yeast two-hybrid and co-expression assays, and is phosphorylated by MPK38 in vivo. Co-expression of ZPR9 with MPK38 caused accumulation of ZPR9 in the nucleus.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, in vivo phosphorylation assay, subcellular localization by co-expression\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and in vivo phosphorylation assay in a single lab with two orthogonal methods\",\n      \"pmids\": [\"11802789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"ZNF622 (ZPR9) physically interacts with B-MYB transcription factor through all three functional domains of B-MYB (DNA-binding domain, transactivation domain, and C-terminal conserved region), and co-expression of ZPR9 significantly upregulates B-MYB transcriptional activity in a dose-dependent manner. Co-expression also caused nuclear accumulation of both proteins. Constitutive ZPR9 expression induces apoptosis in neuroblastoma cells in the presence of retinoic acid.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation of endogenous and exogenous proteins, deletion analysis, cotransfection/reporter assay, subcellular localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP of endogenous proteins plus functional transcription reporter assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"12645566\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ZNF622 (ZPR9) physically interacts with apoptosis signal-regulating kinase 1 (ASK1) through a disulfide linkage involving Cys1351 and Cys1360 of ASK1 and Cys305 and Cys308 of ZPR9. ASK1 directly phosphorylates ZPR9 at Ser314 and Thr318. Wild-type ZPR9, but not S314A/T318A mutant, stimulates ASK1 kinase activity, promotes ASK1-mediated signaling to JNK and p38 by destabilizing ASK1-Trx and ASK1-14-3-3 inhibitory complexes and by increasing ASK1-MKK3 complex formation, and promotes H2O2-mediated apoptosis in a phosphorylation-dependent manner. ZPR9 also inhibits PDK1-mediated signaling through ASK1 activation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, reporter assay (AP-1), apoptosis assay, knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro kinase assay with mutagenesis, reciprocal co-IP, functional pathway readouts, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"21771788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ZNF622 (ZPR9) is a cofactor of DNAJC21 involved in 60S ribosomal subunit maturation. DNAJC21 mutations impair its interaction with ZNF622, PA2G4, and HSPA8. DNAJC21 deficiency results in cytoplasmic accumulation of PA2G4, aberrant ribosome profiles, and increased cell death.\",\n      \"method\": \"Co-immunoprecipitation, functional interaction studies with patient-derived lymphoblastoid cells, ribosome profiling\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP interaction data with patient-derived cells and ribosome profiling, single lab, multiple methods\",\n      \"pmids\": [\"27346687\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ZNF622 (ZPR9) is a component of a multiprotein complex with MPK38, ASK1, SMADs, and thioredoxin (TRX) that coordinately regulates redox-dependent ASK1 and TGF-β signaling pathways. Adenoviral delivery of ZPR9 in obese mice restored downregulated ASK1 and TGF-β signaling and ameliorated adiposity, hyperglycemia, hyperlipidemia, and impaired ketogenesis.\",\n      \"method\": \"Co-immunoprecipitation (multiprotein complex), adenoviral overexpression in mice, metabolic phenotyping\",\n      \"journal\": \"Antioxidants & redox signaling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiprotein complex identified by co-IP plus in vivo functional rescue, single lab\",\n      \"pmids\": [\"26421442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ZNF622 (ZPR9) functions as an activator of MPK38, with the interaction mediated by cysteine residues (Cys269 and Cys286 of MPK38; Cys305 and Cys308 of ZPR9). MPK38 phosphorylates ZPR9 at Thr252; wild-type ZPR9 but not T252A mutant enhances ASK1, TGF-β, and p53 function by stabilizing MPK38. This was validated using CRISPR/Cas9-mediated ZPR9(T252A) knockin cell lines, haploinsufficient MEF cells, and inducible knockdown systems.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, CRISPR/Cas9 knockin, haploinsufficient MEF cells, inducible shRNA knockdown\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro kinase assay, CRISPR knockin validation, multiple genetic tools in single lab with orthogonal methods\",\n      \"pmids\": [\"28195154\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Smad proteins differentially regulate MPK38 activity partly through modulating complex formation between MPK38 and ZPR9 (ZNF622): Smads2/3/4 increased while Smad7 decreased MPK38-ZPR9 complex formation. Phosphorylation-defective Smad mutants abolished these effects.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis, adenoviral delivery in HFD mice\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP of MPK38-ZPR9 complex modulation with mutagenesis validation, single lab\",\n      \"pmids\": [\"29700281\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ZNF622 acts as a cellular antiviral protein against human adenovirus (HAdV). ZNF622 forms a trimeric complex with viral pVII protein and cellular nucleophosmin 1 (NPM1). Loss of ZNF622 increases pVII binding to viral DNA and pVII levels in purified virions, enhances cell lysis, and increases infectious virion accumulation. ZNF622 accumulated in nuclei of virus-infected cells. ZNF622 mutations and NPM1 deficiency altered pVII's ability to bind viral DNA.\",\n      \"method\": \"Protein interaction studies (co-IP), ZNF622 knockout cells, virion purification and quantification, cell lysis assay, immunofluorescence localization\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ZNF622 KO with multiple functional readouts (viral DNA binding, virion accumulation, cell lysis), trimeric complex identified by co-IP, orthogonal methods\",\n      \"pmids\": [\"30429337\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"HectD1 E3 ubiquitin ligase ubiquitinates and degrades ZNF622, an assembly factor for the ribosomal 60S subunit. Loss of HectD1 leads to accumulation of ZNF622 and the anti-association factor eIF6 on 60S, causing 60S/40S joining defects and reduced protein synthesis. Depletion of ZNF622 in Hectd1-deficient HSCs restored ribosomal subunit joining, protein synthesis, and HSC reconstitution capacity.\",\n      \"method\": \"Ubiquitination assay, ribosome fractionation, genetic epistasis (Znf622 depletion in Hectd1 KO), protein synthesis measurement, HSC transplantation assay\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — ubiquitination assay establishing ZNF622 as HectD1 substrate, genetic epistasis rescue, ribosome fractionation, and in vivo functional reconstitution\",\n      \"pmids\": [\"33711283\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DUSP12 interacts with ZNF622 (ZPR9) via its unique zinc-binding domain. DUSP12 overexpression promotes de-phosphorylation of ZNF622 at Ser143. ZNF622 overexpression causes pre-metaphase mitotic defects dependent on Ser143 phosphorylation state (phosphomimetic and phosphorylation-deficient mutants did not). Knockdown of DUSP12 promoted stress-induced apoptosis, while knockdown of ZNF622 suppressed it, placing ZNF622 downstream of DUSP12 in a cell death pathway.\",\n      \"method\": \"Affinity- and proximity-based biochemical purification coupled to mass spectrometry, in-cell and in-vitro IP assays, phosphoproteomic analysis, ZNF622 overexpression with phosphomutants, siRNA knockdown, apoptosis assay\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — mass spectrometry-identified phosphorylation site, in vitro IP validation, functional phosphomutant analysis, and genetic epistasis via double knockdown\",\n      \"pmids\": [\"41851086\", \"39868293\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In yeast, Rei1 (ZNF622 ortholog) and its paralog Reh1 facilitate loading of ribosomal protein eL24 onto pre-60S particles in the cytoplasm. Pre-60S subunits from rei1Δ reh1Δ cells are specifically deficient in eL24. eL24 overexpression suppresses the growth defect of the double mutant. Suppressors of rei1Δ reh1Δ growth defects (mutations in uL3, Lsg1, Ppq1) partially reverse the eL24 loading defect, establishing that Rei1/Reh1 act upstream of eL24 recruitment during cytoplasmic 60S maturation.\",\n      \"method\": \"Protein composition analysis of isolated pre-60S particles (MS), genetic suppressor screen, overexpression rescue\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic analysis of pre-60S composition plus genetic suppressor screen in yeast ortholog, single lab, preprint\",\n      \"pmids\": [\"41959095\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"ZNF622 (ZPR9) is a zinc finger protein that functions primarily as a cytoplasmic assembly factor for the 60S ribosomal subunit (facilitating eL24 loading and subunit joining, antagonized by eIF6), is ubiquitinated and degraded by the E3 ligase HectD1 to regulate ribosome assembly and protein synthesis in hematopoietic stem cells, is phosphorylated by MPK38 (at Thr252) and ASK1 (at Ser314/Thr318) to positively regulate their respective signaling pathways (ASK1/JNK/p38, TGF-β, p53), is dephosphorylated at Ser143 by DUSP12 to suppress stress-induced apoptosis, forms a trimeric complex with adenoviral pVII and NPM1 to restrict viral DNA binding and lytic growth, and co-activates B-MYB transcriptional activity through direct interaction.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF622 (ZPR9) is a zinc finger protein that functions as a cytoplasmic 60S ribosomal subunit assembly factor and as a redox-sensitive signaling cofactor. In ribosome biogenesis it acts as a cofactor of DNAJC21 in 60S maturation, with its yeast ortholog Rei1 (and paralog Reh1) promoting loading of ribosomal protein eL24 onto pre-60S particles during cytoplasmic maturation [#3, #10]. Its level is set by HectD1-mediated ubiquitination and degradation; loss of HectD1 stabilizes ZNF622 and the anti-association factor eIF6 on 60S particles, blocking 60S/40S joining and protein synthesis, and depletion of ZNF622 restores subunit joining and hematopoietic stem cell reconstitution in HectD1-deficient cells [#8]. Independently, ZNF622 is a phosphorylation-controlled activator of stress kinase signaling: it binds MPK38/MELK and ASK1 through cysteine-mediated linkages, is phosphorylated by MPK38 at Thr252 and by ASK1 at Ser314/Thr318, and in its phosphorylated state stimulates ASK1 kinase activity, drives ASK1/JNK/p38, TGF-\\u03b2, and p53 signaling, and promotes oxidative-stress-induced apoptosis [#2, #5]. Dephosphorylation at Ser143 by the phosphatase DUSP12 places ZNF622 in a cell-death pathway whose activity depends on its phosphorylation state [#9]. ZNF622 also co-activates the transcription factor B-MYB through direct interaction [#1] and acts as an antiviral restriction factor against human adenovirus by forming a trimeric complex with viral pVII and cellular NPM1 that limits pVII-viral DNA binding and lytic virion production [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the first molecular partner of ZNF622, linking it to a serine/threonine kinase and to regulated nuclear localization.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP and in vivo phosphorylation with MPK38/MELK\",\n      \"pmids\": [\"11802789\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of MPK38 phosphorylation not defined\", \"Phosphosite not mapped at this stage\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Showed ZNF622 acts as a transcriptional co-activator, broadening its role beyond kinase binding.\",\n      \"evidence\": \"Yeast two-hybrid, endogenous/exogenous co-IP, reporter assay and apoptosis in neuroblastoma cells\",\n      \"pmids\": [\"12645566\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of B-MYB co-activation unresolved\", \"Relationship between transcriptional and kinase roles unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined ZNF622 as a phosphorylation-dependent activator of ASK1, mapping the binding chemistry and phosphosites that control stress signaling.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, site-directed mutagenesis (Cys/Ser/Thr), AP-1 reporter and apoptosis assays\",\n      \"pmids\": [\"21771788\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo relevance of disulfide-mediated binding not tested\", \"Connection to ribosomal function not addressed\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Placed ZNF622 in 60S ribosomal subunit maturation as a DNAJC21 cofactor, introducing a function entirely distinct from its signaling roles.\",\n      \"evidence\": \"Co-IP, patient-derived lymphoblastoid cells, ribosome profiling\",\n      \"pmids\": [\"27346687\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical role of ZNF622 in maturation not defined\", \"Whether ZNF622 is required for normal ribosome assembly not shown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Established a reciprocal MPK38-ZNF622 activation loop and identified Thr252 as the functional phosphosite for stabilizing MPK38 and amplifying ASK1/TGF-\\u03b2/p53 output.\",\n      \"evidence\": \"In vitro kinase assay, CRISPR/Cas9 T252A knockin, haploinsufficient MEFs, inducible knockdown\",\n      \"pmids\": [\"28195154\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue contexts where this loop operates not delineated\", \"Integration with ribosomal function not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed Smad proteins tune signaling output by modulating MPK38-ZNF622 complex assembly, connecting ZNF622 to TGF-\\u03b2 regulation.\",\n      \"evidence\": \"Co-IP, site-directed mutagenesis, adenoviral delivery in HFD mice\",\n      \"pmids\": [\"29700281\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct Smad-ZNF622 contact not established\", \"Mechanism of complex modulation unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified an antiviral function for ZNF622, restricting adenovirus via a pVII-NPM1 trimeric complex that limits viral DNA binding.\",\n      \"evidence\": \"Co-IP, ZNF622 knockout cells, virion purification, cell lysis and immunofluorescence assays\",\n      \"pmids\": [\"30429337\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether restriction requires ZNF622's ribosomal or signaling activities unknown\", \"Breadth of antiviral activity beyond HAdV untested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined how ZNF622 levels are controlled and the functional cost of mis-regulation, establishing it as a HectD1 ubiquitination substrate gating 60S/40S joining and protein synthesis.\",\n      \"evidence\": \"Ubiquitination assay, ribosome fractionation, genetic epistasis (Znf622 depletion in Hectd1 KO), HSC transplantation\",\n      \"pmids\": [\"33711283\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular interaction of ZNF622 with eIF6 on 60S not resolved\", \"How ubiquitination is triggered not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified DUSP12 as a phosphatase acting on ZNF622 Ser143 and placed ZNF622 in a stress-induced cell-death pathway with phosphorylation-state-dependent mitotic effects.\",\n      \"evidence\": \"Affinity/proximity MS, in-cell and in-vitro IP, phosphoproteomics, phosphomutant overexpression, siRNA epistasis, apoptosis assay\",\n      \"pmids\": [\"41851086\", \"39868293\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for Ser143 phosphorylation unidentified\", \"Mechanistic basis of the mitotic defect unresolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined the molecular step ZNF622's ortholog performs in ribosome maturation: loading of eL24 onto pre-60S particles upstream of subunit completion.\",\n      \"evidence\": \"MS composition analysis of pre-60S particles, genetic suppressor screen and overexpression rescue in yeast (preprint)\",\n      \"pmids\": [\"41959095\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct conservation of eL24-loading role in human ZNF622 not shown\", \"Preprint, not peer-reviewed\", \"Structural basis of eL24 recruitment unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ZNF622's ribosome-assembly function, its kinase-signaling/apoptosis roles, and its antiviral activity are coordinated within a single cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model linking cytoplasmic ribosome assembly to nuclear signaling functions\", \"Whether distinct ZNF622 pools serve distinct functions is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 5, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3, 8]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 8, 10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [2, 9]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\"ZNF622-pVII-NPM1 trimeric complex\", \"MPK38-ASK1-SMAD-TRX-ZNF622 complex\"],\n    \"partners\": [\"MPK38\", \"ASK1\", \"MYBL2\", \"DNAJC21\", \"NPM1\", \"HECTD1\", \"DUSP12\", \"SMAD4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}