{"gene":"DAZAP1","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2001,"finding":"DAZAP1 was originally identified as an interaction partner of DAZ and DAZL via yeast two-hybrid; DAZAP1 contains two RNA-binding domains (RBDs) and a proline-rich C-terminal region; in subcellular fractionation, the majority of DAZAP1 is present in the cytoplasmic fraction but not associated with polyribosomes.","method":"Yeast two-hybrid, Western blot, subcellular fractionation","journal":"BMC genomics","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — yeast two-hybrid plus fractionation; foundational characterization replicated in later work","pmids":["11604102"],"is_preprint":false},{"year":2004,"finding":"Mouse DAZAP1 (mPrrp) undergoes dynamic intranuclear and subcellular localization changes during spermatogenesis; a long stretch spanning the C-terminal half of the protein is required for nuclear import.","method":"Immunohistochemistry with monoclonal antibody, mutagenesis, subcellular localization analysis","journal":"Archives of histology and cytology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — mutagenesis-based domain mapping combined with immunolocalization in a single study","pmids":["15700540"],"is_preprint":false},{"year":2005,"finding":"DAZAP1/MEF2D fusion protein retains sequence-specific RNA-binding activity; MEF2D/DAZAP1 fusion binds DNA in a manner indistinguishable from native MEF2D and is a more potent transcriptional activator than MEF2D.","method":"DNA-binding assay, transcriptional activation assay, leukemia cell line analysis","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and functional assays in a single lab, two orthogonal methods","pmids":["15744350"],"is_preprint":false},{"year":2005,"finding":"DAZAP1 is expressed in ovarian luteal cells and co-immunoprecipitates with DAZL in ovarian tissue, demonstrating an in vivo interaction.","method":"Co-immunoprecipitation, Western blot, immunohistochemistry","journal":"Fertility and sterility","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP result in a single lab without functional follow-up","pmids":["16209998"],"is_preprint":false},{"year":2006,"finding":"DAZAP1 shuttles between the nucleus and cytoplasm via a novel 25 amino acid C-terminal segment (ZNS) that shares no homology with known nuclear localization or export signals; nuclear localization of DAZAP1 is dependent on active RNA Pol II transcription, as its inhibition retains DAZAP1 in the cytoplasm; DAZAP1 colocalizes with hnRNP A1 and hnRNP C1 in the nucleus as part of hnRNP particles.","method":"Immunostaining, heterokaryon formation assay, mutagenesis, RNA Pol II inhibitor treatment","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (heterokaryon, mutagenesis, inhibitor treatment) in single study; ZNS domain findings replicated in later work","pmids":["16772659"],"is_preprint":false},{"year":2006,"finding":"ERK2 phosphorylates DAZAP1 at Thr269 and Thr315 in vitro and in cells; this phosphorylation induces dissociation of DAZAP1 from DAZ; DAZ cannot bind simultaneously to both DAZAP1 and PABP, suggesting phosphorylation-driven DAZAP1 release allows DAZ to interact with PABP and stimulate translation.","method":"In vitro kinase assay, mass spectrometry, site-directed mutagenesis (Thr→Asp), co-immunoprecipitation in HEK-293 cells and RAW 264.7 macrophages","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase reconstitution with mutagenesis, confirmed in multiple cell lines with MKK1 inhibitors","pmids":["16848763"],"is_preprint":false},{"year":2007,"finding":"Both MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins transform NIH 3T3 cells (~20-fold increase in soft agar colony formation); co-expression of both fusion proteins is synergistic; wild-type DAZAP1 expression allows proliferation under low-serum conditions and suppresses apoptosis.","method":"Retroviral gene transfer, soft agar colony formation assay, low-serum proliferation assay, apoptosis assay","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays, single lab","pmids":["17898785"],"is_preprint":false},{"year":2008,"finding":"DAZAP1 binds to a mutant BRCA1 exon 18 sequence created by a G-to-T transversion (+6 position) via RNA pulldown; siRNA-mediated depletion of DAZAP1 rescues exon 18 inclusion, demonstrating that DAZAP1 binding to this exonic splicing silencer causes exon skipping.","method":"RNA pulldown assay, siRNA knockdown, minigene splicing reporter, mutation analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — RNA pulldown plus siRNA functional validation plus extensive mutational analysis in one rigorous study","pmids":["18391021"],"is_preprint":false},{"year":2008,"finding":"DAZAP1 is required for normal mouse development and spermatogenesis; null or hypomorphic Dazap1 mice show growth retardation and spermatogenic arrest before meiotic division (absence of haploid cells by FACS); DAZAP1 localizes to the nucleus excluding the XY body in pachytene spermatocytes, consistent with a role in mRNA transcription and transport.","method":"Mouse knockout/hypomorphic allele generation, FACS analysis, immunostaining","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — defined loss-of-function alleles with specific cellular phenotypic readout confirmed by FACS","pmids":["18669443"],"is_preprint":false},{"year":2009,"finding":"DAZAP1's RNA recognition motifs (RRMs) interact with the C-termini of multiple other RNA-binding proteins (beyond DAZ) in a phosphorylation-independent manner, suggesting DAZAP1 is part of mRNA degradation/silencing complexes in non-germinal cells.","method":"Co-immunoprecipitation, domain-mapping pulldown","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/pulldown study, no functional rescue, single lab","pmids":["19285026"],"is_preprint":false},{"year":2011,"finding":"DAZAP1 (both Xenopus and human) acts as an mRNA-specific activator of translation initiation in a 3'UTR binding-site-number-dependent manner; this activity maps to the C-terminal region; DAZAP1 stimulates translation independently of 5'-cap recognition but is modulated by poly(A) tail status, suggesting a function in end-to-end mRNA complex formation; this activity does not require direct interaction with eIF4G.","method":"In vitro translation assay, IRES reporter mRNA assay, domain mapping, polysome fractionation, Xenopus oocyte injection","journal":"RNA (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstituted in vitro translation plus domain mutagenesis plus IRES reporters, multiple orthogonal methods in single study","pmids":["21576381"],"is_preprint":false},{"year":2011,"finding":"DAZAP1 binds to an Alu-derived intronic splicing enhancer (ISE) in the ATM gene (shown by RNA pulldown); siRNA-mediated knockdown of DAZAP1 reduces ATM cryptic exon activation, demonstrating that DAZAP1 positively promotes ISE-dependent cryptic exon inclusion.","method":"RNA pulldown assay, siRNA knockdown, splicing reporter assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RNA pulldown plus functional siRNA with splicing readout, two orthogonal methods","pmids":["21858080"],"is_preprint":false},{"year":2012,"finding":"An N-terminal 42 amino acid segment (N42) of DAZAP1 is necessary and sufficient for transcription-dependent nuclear localization; SLIRP was identified as an N42-binding protein via yeast two-hybrid, potentially regulating DAZAP1 subcellular localization.","method":"Mutagenesis, nuclear localization assay, yeast two-hybrid","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mutagenesis with localization readout, yeast two-hybrid for interactor, single lab","pmids":["23111326"],"is_preprint":false},{"year":2013,"finding":"DAZAP1 promotes inclusion of Crem exon 4, Crisp2 exon 9, and Pot1a exon 4 in vivo in mouse testes; DAZAP1 binds intronic regions flanking these exons (Crem intron 3, Crisp2 intron 9, Pot1a intron 4) to regulate splicing; aberrant Pot1a splicing may account for the growth retardation in DAZAP1-deficient mice.","method":"Microarray exon-usage profiling of mutant vs. wild-type testes, minigene splicing reporters, DAZAP1 binding assays, mutagenesis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo microarray identification plus minigene reporters plus direct binding assays, multiple orthogonal methods","pmids":["23965306"],"is_preprint":false},{"year":2013,"finding":"DAZL binds specifically to the 3'UTR of the Dazap1-L transcript and stimulates its translation; the two Dazap1 transcripts (generated by alternative polyadenylation) are differentially regulated, with the Dazap1-S transcript undergoing translational repression associated with poly(A) tail elongation during spermatogenesis.","method":"RNA pulldown followed by mass spectrometry, sucrose gradient fractionation, Northern blot, 3' RACE, reporter gene assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA pulldown/MS plus sucrose gradient plus reporter assay, multiple methods in single lab","pmids":["23658607"],"is_preprint":false},{"year":2014,"finding":"DAZAP1 promotes inclusion of weak exons by recognizing diverse cis-elements; its C-terminal proline-rich domain interacts with and neutralizes general splicing inhibitors, is sufficient to activate splicing when tethered to pre-mRNA, and is phosphorylated by the MEK/Erk pathway; this phosphorylation is essential for both splicing regulatory activity and nuclear/cytoplasmic translocation of DAZAP1; DAZAP1 regulates endogenous splicing events involved in cell growth and its knockdown/overexpression causes cell proliferation defects.","method":"mRNA-seq, minigene splicing assay, tethering assay, MEK/Erk inhibitor treatment, phosphomutant analysis, siRNA knockdown, cell proliferation assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (tethering, mutagenesis, mRNA-seq, inhibitor pharmacology) in single rigorous study","pmids":["24452013"],"is_preprint":false},{"year":2018,"finding":"DAZAP1 binds cox6c mRNA in an intron-dependent manner (binding requires the last intron; no binding to intronless cox6c mRNA); DAZAP1 overexpression suppresses pre-mRNA splicing efficiency of cox6c and reduces mature COX6C protein; this regulates mitochondrial complex IV and cell growth.","method":"RNA immunoprecipitation, intronless vs. genomic expression vectors, overexpression and knockdown assays, Western blot","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP with functional vectors and protein readout, single lab","pmids":["29505834"],"is_preprint":false},{"year":2020,"finding":"DAZAP1 binds the 3'UTR of SLC7A11 mRNA and positively regulates its stability, thereby inhibiting ferroptosis; DAZAP1 knockdown reduces SLC7A11 mRNA stability and sensitizes HCC cells to sorafenib-induced ferroptosis.","method":"RNA immunoprecipitation, siRNA knockdown, mRNA stability assay, ferroptosis assay","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus mRNA stability assay plus functional ferroptosis readout, single lab","pmids":["33358859"],"is_preprint":false},{"year":2020,"finding":"DAZAP1 silencing in ESCC cells causes exon skipping of TSC2 exon 26, producing a short TSC2 isoform that cannot be phosphorylated at Ser981 by AKT; this results in continuous TSC2 activation, inhibition of mTOR via RHEB, and sustained autophagy; starvation-induced miR-10b suppresses DAZAP1 to trigger this pathway.","method":"RNAi, RNAseq alternative splicing analysis, phosphorylation assay, mTOR/RHEB signaling assay, miRNA functional assay","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAseq plus phosphorylation assay plus epistasis through RHEB/mTOR signaling, single lab","pmids":["32308763"],"is_preprint":false},{"year":2022,"finding":"DAZAP1 regulates alternative splicing of KITLG mRNA (shown by RIP-seq and RIP-qPCR); DAZAP1-mediated KITLG splicing increases ERK phosphorylation and promotes myeloma cell proliferation.","method":"RIP-seq, RIP-qPCR, siRNA knockdown, lentiviral overexpression, ERK phosphorylation assay, xenograft tumor model","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-seq plus functional signaling assay, in vitro and in vivo, single lab","pmids":["36242590"],"is_preprint":false},{"year":2023,"finding":"DAZAP1 interacts with PXR (pregnane X receptor) as a paraspeckle component; this interaction is dissociated by the PXR ligand rifampicin; DAZAP1 (together with NEAT1_2 lncRNA) negatively regulates PXR-mediated CYP3A4 transcriptional induction by trapping PXR in paraspeckles in the absence of ligand.","method":"Co-immunoprecipitation in PXR-overexpressing HepG2 cells, siRNA knockdown, luciferase reporter assay for PXR response elements","journal":"Drug metabolism and disposition","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — reciprocal Co-IP plus luciferase reporter, two orthogonal methods, single lab","pmids":["37349114"],"is_preprint":false},{"year":2024,"finding":"DAZAP1 undergoes liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhances COX16 expression via regulation of pre-mRNA alternative splicing, thereby promoting mitochondrial respiration and OSCC invasion/metastasis.","method":"RNA sequencing, DAZAP1 knockdown/overexpression, LLPS assay, mouse OSCC model, EMT marker analysis","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — LLPS demonstration plus splicing and functional assays in vitro and in vivo, single lab","pmids":["39120588"],"is_preprint":false},{"year":2025,"finding":"p52-ZER6 promotes DAZAP1 transcription; DAZAP1 then binds the 3'-UTR of SLC7A11 mRNA to enhance its stability, increasing SLC7A11 expression and cellular glutathione levels, thereby reducing lipid peroxide accumulation and conferring ferroptosis resistance in colorectal cancer.","method":"Transcriptional reporter assay, RNA immunoprecipitation, mRNA stability assay, glutathione and lipid peroxide measurement","journal":"Acta pharmaceutica Sinica. B","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus mRNA stability plus biochemical readouts, single lab","pmids":["40486833"],"is_preprint":false},{"year":2025,"finding":"DAZAP1 binds USP34 mRNA and stabilizes it, leading to increased USP34 protein, which deubiquitinates and stabilizes PIN1, activating the MAPK signaling pathway in gastric cancer; DAZAP1 mRNA is itself protected from YTHDF2-mediated degradation by ALKBH5-catalyzed m6A demethylation.","method":"RNA immunoprecipitation, Western blot, ubiquitination assay, siRNA/overexpression, m6A/ALKBH5/YTHDF2 knockdown experiments","journal":"Cell biology and toxicology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RIP plus ubiquitination assay plus m6A pathway perturbation, single lab with multiple readouts","pmids":["41331184"],"is_preprint":false},{"year":2025,"finding":"DAZAP1 regulates splicing and expression of ULK1 via nonsense-mediated mRNA decay control; DAZAP1-dependent ULK1 upregulation promotes mitophagy and OXPHOS to sustain gastric cancer stem cell metabolic demands.","method":"RNA immunoprecipitation, PCR, Seahorse metabolic assay, transmission electron microscopy, immunofluorescence, sphere formation assay, rescue overexpression","journal":"JCI insight","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP plus multiple orthogonal functional assays (Seahorse, TEM, rescue), single lab","pmids":["40401521"],"is_preprint":false},{"year":2025,"finding":"DAZAP1 physically binds NOTCH1 and JAG1 mRNAs (shown by RNA immunoprecipitation and sequencing) to stabilize them, activating NOTCH/JAG1 signaling and promoting EMT, migration, and invasion in gastric cancer.","method":"RNA immunoprecipitation and sequencing (RIP-seq), mRNA stability assay, overexpression and knockdown, migration/invasion assays","journal":"International journal of oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RIP-seq plus mRNA stability, single lab, limited mechanistic depth","pmids":["41789621"],"is_preprint":false}],"current_model":"DAZAP1 is an evolutionarily conserved hnRNP-type RNA-binding protein that uses its two N-terminal RRMs to bind diverse pre-mRNA cis-elements and 3'UTR sequences, and its C-terminal proline-rich domain to interact with and neutralize splicing inhibitors—thereby promoting weak-exon inclusion and acting as a splicing activator; the C-terminal domain is also phosphorylated by ERK1/2 at Thr269 and Thr315, which is essential for its splicing activity, drives its nuclear/cytoplasmic translocation, and disrupts its interaction with DAZ (freeing DAZ to stimulate translation via PABP); DAZAP1 additionally stabilizes specific mRNAs (e.g., SLC7A11, USP34, NOTCH1/JAG1) via 3'UTR binding, activates translation initiation in a cap-independent, poly(A)-sensitive manner, undergoes liquid-liquid phase separation to concentrate nuclear splicing activity, and is required in vivo for spermatogenesis and normal growth as demonstrated by mouse knockout models."},"narrative":{"mechanistic_narrative":"DAZAP1 is an evolutionarily conserved hnRNP-type RNA-binding protein that acts as a splicing activator and post-transcriptional regulator, controlling exon usage and mRNA fate during spermatogenesis and cell growth [PMID:18669443, PMID:24452013]. It carries two N-terminal RNA recognition motifs that bind diverse cis-elements—including exonic splicing silencers, Alu-derived intronic splicing enhancers, and intronic regions flanking weak exons—and a C-terminal proline-rich domain that, when tethered to pre-mRNA, is sufficient to activate splicing by interacting with and neutralizing general splicing inhibitors, thereby promoting inclusion of weak exons [PMID:18391021, PMID:21858080, PMID:23965306, PMID:24452013]. DAZAP1 shuttles between nucleus and cytoplasm through a novel C-terminal segment (ZNS) and an N-terminal N42 segment, with nuclear localization dependent on active RNA Pol II transcription, where it colocalizes with hnRNP A1 and C1 in hnRNP particles [PMID:16772659, PMID:23111326]. The MEK/ERK pathway phosphorylates the C-terminal domain at Thr269 and Thr315; this phosphorylation is essential for splicing activity and nuclear/cytoplasmic translocation, and dissociates DAZAP1 from its original partner DAZ, freeing DAZ to engage PABP and stimulate translation [PMID:16848763, PMID:24452013]. Beyond splicing, DAZAP1 itself activates translation initiation in a 3'UTR-binding-site-number-dependent, cap-independent but poly(A)-sensitive manner, consistent with promoting end-to-end mRNA complex formation [PMID:21576381], and stabilizes specific target mRNAs through 3'UTR binding—including SLC7A11 to suppress ferroptosis and USP34 and NOTCH1/JAG1 to drive tumor signaling [PMID:33358859, PMID:40486833, PMID:41331184, PMID:41789621]. DAZAP1 concentrates its nuclear splicing activity via liquid-liquid phase separation [PMID:39120588]. In vivo, mouse knockout and hypomorphic alleles cause growth retardation and spermatogenic arrest before meiosis, establishing essential roles in development and germ cell differentiation [PMID:18669443].","teleology":[{"year":2001,"claim":"Established DAZAP1 as a DAZ/DAZL-interacting protein with a modular architecture, framing it as a candidate regulator of germ-cell mRNA metabolism.","evidence":"Yeast two-hybrid, Western blot, and subcellular fractionation identifying two RBDs and a proline-rich C-terminus","pmids":["11604102"],"confidence":"Medium","gaps":["RNA targets undefined","Functional consequence of DAZ binding not tested","Cytoplasmic predominance not mechanistically explained"]},{"year":2006,"claim":"Defined how DAZAP1 traffics between compartments, showing a novel ZNS shuttling signal and transcription-coupled nuclear residence within hnRNP particles.","evidence":"Heterokaryon assay, mutagenesis, RNA Pol II inhibitor treatment, and colocalization with hnRNP A1/C1","pmids":["16772659"],"confidence":"High","gaps":["Import/export receptors for ZNS unidentified","Link between transcription dependence and splicing function not yet established"]},{"year":2006,"claim":"Connected DAZAP1 to ERK signaling and revealed phosphorylation as a switch that releases DAZ to engage the translation machinery.","evidence":"In vitro ERK2 kinase assay, mass spectrometry, phosphomimetic mutagenesis, and Co-IP in HEK293 and macrophages","pmids":["16848763"],"confidence":"High","gaps":["Whether phosphorylation alters DAZAP1's own RNA binding not addressed here","In vivo physiological trigger of ERK input unclear"]},{"year":2008,"claim":"Demonstrated DAZAP1 is genetically required for mammalian development and meiotic progression in spermatogenesis.","evidence":"Mouse knockout/hypomorphic alleles with FACS and immunostaining showing pre-meiotic arrest","pmids":["18669443"],"confidence":"High","gaps":["Molecular target mRNAs driving the phenotype not identified in this study","Tissue-specific vs systemic contributions unresolved"]},{"year":2008,"claim":"Provided direct evidence that DAZAP1 acts on splicing by binding an exonic splicing silencer to enforce exon skipping.","evidence":"RNA pulldown, siRNA depletion, and minigene reporter on a mutant BRCA1 exon 18 element","pmids":["18391021"],"confidence":"High","gaps":["Generality of silencer vs enhancer behavior not yet defined","Co-factors mediating skipping unknown"]},{"year":2011,"claim":"Revealed a direct translational activation function distinct from splicing, mapped to the C-terminus and dependent on 3'UTR site number and poly(A) status.","evidence":"In vitro translation, IRES reporters, polysome fractionation, and Xenopus oocyte injection","pmids":["21576381"],"confidence":"High","gaps":["Bridging factor for end-to-end complex unidentified (not eIF4G)","Endogenous mRNA targets of this activity unspecified"]},{"year":2011,"claim":"Showed DAZAP1 can act as a positive splicing regulator through intronic splicing enhancers, broadening its element repertoire.","evidence":"RNA pulldown and siRNA knockdown on an Alu-derived ATM ISE with splicing reporter","pmids":["21858080"],"confidence":"Medium","gaps":["Mechanism reconciling silencer (BRCA1) and enhancer (ATM) outcomes not resolved","Direct vs indirect binding to ISE in vivo not confirmed"]},{"year":2013,"claim":"Identified physiological in vivo splicing targets in testes, linking DAZAP1-dependent exon inclusion to the growth and germ-cell phenotypes.","evidence":"Microarray exon profiling of mutant vs WT testes, minigene reporters, and binding assays for Crem, Crisp2, and Pot1a","pmids":["23965306"],"confidence":"High","gaps":["Whether Pot1a misregulation is sufficient for growth retardation not proven","Full in vivo target set incomplete"]},{"year":2014,"claim":"Integrated the mechanism by showing the proline-rich C-terminus neutralizes general splicing inhibitors and that MEK/ERK phosphorylation is essential for splicing activity and shuttling.","evidence":"mRNA-seq, tethering assay, phosphomutant analysis, MEK/Erk inhibitors, and proliferation assays","pmids":["24452013"],"confidence":"High","gaps":["Identity of the neutralized splicing inhibitors not fully enumerated","Direct structural basis of inhibitor neutralization unknown"]},{"year":2024,"claim":"Showed liquid-liquid phase separation as the biophysical basis for concentrating DAZAP1 splicing activity in the nucleus.","evidence":"LLPS assay with RNA-seq, knockdown/overexpression, and OSCC mouse model","pmids":["39120588"],"confidence":"Medium","gaps":["Domains/residues driving phase separation not mapped","Relationship between LLPS and ERK phosphorylation untested"]},{"year":2025,"claim":"Extended DAZAP1's role to 3'UTR-mediated mRNA stabilization across cancers, controlling ferroptosis resistance and oncogenic signaling.","evidence":"RIP, mRNA stability assays, and functional readouts for SLC7A11, USP34/PIN1/MAPK, and NOTCH1/JAG1 targets","pmids":["33358859","40486833","41331184","41789621"],"confidence":"Medium","gaps":["Binding-site definitions within 3'UTRs incomplete","Mechanism of stabilization (decay factor displacement) not resolved","NOTCH1/JAG1 link rests on a single low-confidence study"]},{"year":null,"claim":"How DAZAP1 selects between splicing activation, mRNA stabilization, and translational control on a given transcript, and how phosphorylation and phase separation coordinate these outputs, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking RRM target choice to functional outcome","Structural basis of inhibitor neutralization and LLPS unmapped","Direct nuclear import/export machinery for ZNS/N42 unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,7,10,11,13,17]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[7,11,13,15]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[5,15,20]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4,8,21]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,4]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[4,20]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[7,11,13,15,17]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[4,13,15]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[8,13]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,19,23]}],"complexes":["hnRNP particle","paraspeckle"],"partners":["DAZ","DAZL","PABP","HNRNP A1","HNRNP C1","SLIRP","PXR"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96EP5","full_name":"DAZ-associated protein 1","aliases":["Deleted in azoospermia-associated protein 1"],"length_aa":407,"mass_kda":43.4,"function":"RNA-binding protein, which may be required during spermatogenesis","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q96EP5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DAZAP1","classification":"Not Classified","n_dependent_lines":198,"n_total_lines":1208,"dependency_fraction":0.16390728476821192},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DAZAP1","total_profiled":1310},"omim":[{"mim_id":"607431","title":"DAZ-ASSOCIATED PROTEIN 2; DAZAP2","url":"https://www.omim.org/entry/607431"},{"mim_id":"607430","title":"DAZ-ASSOCIATED PROTEIN 1; DAZAP1","url":"https://www.omim.org/entry/607430"},{"mim_id":"601486","title":"DELETED IN AZOOSPERMIA-LIKE; DAZL","url":"https://www.omim.org/entry/601486"},{"mim_id":"400003","title":"DELETED IN AZOOSPERMIA 1; DAZ1","url":"https://www.omim.org/entry/400003"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Midbody","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DAZAP1"},"hgnc":{"alias_symbol":["MGC19907"],"prev_symbol":[]},"alphafold":{"accession":"Q96EP5","domains":[{"cath_id":"3.30.70.330","chopping":"5-83","consensus_level":"high","plddt":89.9368,"start":5,"end":83},{"cath_id":"3.30.70.330","chopping":"113-186","consensus_level":"high","plddt":88.4915,"start":113,"end":186}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EP5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EP5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96EP5-F1-predicted_aligned_error_v6.png","plddt_mean":64.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DAZAP1","jax_strain_url":"https://www.jax.org/strain/search?query=DAZAP1"},"sequence":{"accession":"Q96EP5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96EP5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96EP5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96EP5"}},"corpus_meta":[{"pmid":"33358859","id":"PMC_33358859","title":"RNA binding protein DAZAP1 promotes HCC progression and regulates ferroptosis by interacting with SLC7A11 mRNA.","date":"2020","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/33358859","citation_count":81,"is_preprint":false},{"pmid":"18391021","id":"PMC_18391021","title":"Binding of DAZAP1 and hnRNPA1/A2 to an exonic splicing silencer in a natural BRCA1 exon 18 mutant.","date":"2008","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/18391021","citation_count":71,"is_preprint":false},{"pmid":"24452013","id":"PMC_24452013","title":"The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/24452013","citation_count":51,"is_preprint":false},{"pmid":"15744350","id":"PMC_15744350","title":"Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia.","date":"2005","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/15744350","citation_count":47,"is_preprint":false},{"pmid":"18669443","id":"PMC_18669443","title":"DAZAP1, an hnRNP protein, is required for normal growth and spermatogenesis in mice.","date":"2008","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/18669443","citation_count":42,"is_preprint":false},{"pmid":"21576381","id":"PMC_21576381","title":"DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation.","date":"2011","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/21576381","citation_count":41,"is_preprint":false},{"pmid":"16772659","id":"PMC_16772659","title":"A novel nucleocytoplasmic shuttling sequence of DAZAP1, a testis-abundant RNA-binding protein.","date":"2006","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/16772659","citation_count":40,"is_preprint":false},{"pmid":"32308763","id":"PMC_32308763","title":"Starvation-induced suppression of DAZAP1 by miR-10b integrates splicing control into TSC2-regulated oncogenic autophagy in esophageal squamous cell carcinoma.","date":"2020","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/32308763","citation_count":33,"is_preprint":false},{"pmid":"17898785","id":"PMC_17898785","title":"Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia.","date":"2007","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/17898785","citation_count":30,"is_preprint":false},{"pmid":"21858080","id":"PMC_21858080","title":"Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-derived intronic splicing enhancer regulates ATM aberrant splicing.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21858080","citation_count":28,"is_preprint":false},{"pmid":"11604102","id":"PMC_11604102","title":"Characterization of the mouse Dazap1 gene encoding an RNA-binding protein that interacts with infertility factors DAZ and DAZL.","date":"2001","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/11604102","citation_count":27,"is_preprint":false},{"pmid":"16848763","id":"PMC_16848763","title":"Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ.","date":"2006","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/16848763","citation_count":26,"is_preprint":false},{"pmid":"39120588","id":"PMC_39120588","title":"DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma.","date":"2024","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/39120588","citation_count":24,"is_preprint":false},{"pmid":"19285026","id":"PMC_19285026","title":"DAZAP1 interacts via its RNA-recognition motifs with the C-termini of other RNA-binding proteins.","date":"2009","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/19285026","citation_count":20,"is_preprint":false},{"pmid":"23965306","id":"PMC_23965306","title":"DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts.","date":"2013","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/23965306","citation_count":19,"is_preprint":false},{"pmid":"29505834","id":"PMC_29505834","title":"Specific intron-dependent loading of DAZAP1 onto the cox6c transcript suppresses pre-mRNA splicing efficacy and induces cell growth retardation.","date":"2018","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/29505834","citation_count":13,"is_preprint":false},{"pmid":"15700540","id":"PMC_15700540","title":"Dynamic changes in intranuclear and subcellular localizations of mouse Prrp/DAZAP1 during spermatogenesis: the necessity of the C-terminal proline-rich region for nuclear import and localization.","date":"2004","source":"Archives of histology and cytology","url":"https://pubmed.ncbi.nlm.nih.gov/15700540","citation_count":13,"is_preprint":false},{"pmid":"16209998","id":"PMC_16209998","title":"Expression patterns of the DAZ-associated protein DAZAP1 in rat and human ovaries.","date":"2005","source":"Fertility and sterility","url":"https://pubmed.ncbi.nlm.nih.gov/16209998","citation_count":10,"is_preprint":false},{"pmid":"37507717","id":"PMC_37507717","title":"MiR-320a upregulation improves IL-1β-induced osteoarthritis via targeting the DAZAP1 and MAPK pathways.","date":"2023","source":"Journal of orthopaedic surgery and research","url":"https://pubmed.ncbi.nlm.nih.gov/37507717","citation_count":10,"is_preprint":false},{"pmid":"23658607","id":"PMC_23658607","title":"Differential translation of Dazap1 transcripts during spermatogenesis.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23658607","citation_count":10,"is_preprint":false},{"pmid":"36242590","id":"PMC_36242590","title":"DAZAP1 facilitates the alternative splicing of KITLG to promote multiple myeloma cell proliferation via ERK signaling pathway.","date":"2022","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/36242590","citation_count":9,"is_preprint":false},{"pmid":"35091997","id":"PMC_35091997","title":"DAZAP1 overexpression promotes growth of HCC cell lines: a primary study using CEUS.","date":"2022","source":"Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico","url":"https://pubmed.ncbi.nlm.nih.gov/35091997","citation_count":8,"is_preprint":false},{"pmid":"40486833","id":"PMC_40486833","title":"p52-ZER6/DAZAP1 axis promotes ferroptosis resistance and colorectal cancer progression via regulating SLC7A11 mRNA stabilization.","date":"2025","source":"Acta pharmaceutica Sinica. B","url":"https://pubmed.ncbi.nlm.nih.gov/40486833","citation_count":7,"is_preprint":false},{"pmid":"37349114","id":"PMC_37349114","title":"NEAT1_2 and DAZAP1, Paraspeckle Components, Interact with PXR to Negatively Regulate CYP3A4 Induction.","date":"2023","source":"Drug metabolism and disposition: the biological fate of chemicals","url":"https://pubmed.ncbi.nlm.nih.gov/37349114","citation_count":5,"is_preprint":false},{"pmid":"40401521","id":"PMC_40401521","title":"DAZAP1 maintains gastric cancer stemness by inducing mitophagy.","date":"2025","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/40401521","citation_count":4,"is_preprint":false},{"pmid":"23111326","id":"PMC_23111326","title":"Transcription-dependent nuclear localization of DAZAP1 requires an N-terminal signal.","date":"2012","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/23111326","citation_count":3,"is_preprint":false},{"pmid":"41331184","id":"PMC_41331184","title":"DAZAP1 promotes cancer progression and chemotherapy resistance by stabilizing PIN1 protein in gastric cancer.","date":"2025","source":"Cell biology and toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/41331184","citation_count":1,"is_preprint":false},{"pmid":"41789621","id":"PMC_41789621","title":"RNA‑binding protein DAZAP1 promotes gastric cancer metastasis by enhancing NOTCH1 and JAG1 mRNA stability.","date":"2026","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41789621","citation_count":1,"is_preprint":false},{"pmid":"39754243","id":"PMC_39754243","title":"RNA-binding protein DAZAP1 accelerates the advancement of pancreatic cancer by inhibiting ferroptosis.","date":"2025","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/39754243","citation_count":1,"is_preprint":false},{"pmid":"40584277","id":"PMC_40584277","title":"An integrated analysis of second- and third-generation transcriptome sequencing technologies reveals the DAZAP1 function in pig testis.","date":"2025","source":"Animal reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/40584277","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16530,"output_tokens":6091,"usd":0.070477,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14803,"output_tokens":3891,"usd":0.085645,"stage2_stop_reason":"end_turn"},"total_usd":0.156122,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"DAZAP1 was originally identified as an interaction partner of DAZ and DAZL via yeast two-hybrid; DAZAP1 contains two RNA-binding domains (RBDs) and a proline-rich C-terminal region; in subcellular fractionation, the majority of DAZAP1 is present in the cytoplasmic fraction but not associated with polyribosomes.\",\n      \"method\": \"Yeast two-hybrid, Western blot, subcellular fractionation\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — yeast two-hybrid plus fractionation; foundational characterization replicated in later work\",\n      \"pmids\": [\"11604102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Mouse DAZAP1 (mPrrp) undergoes dynamic intranuclear and subcellular localization changes during spermatogenesis; a long stretch spanning the C-terminal half of the protein is required for nuclear import.\",\n      \"method\": \"Immunohistochemistry with monoclonal antibody, mutagenesis, subcellular localization analysis\",\n      \"journal\": \"Archives of histology and cytology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — mutagenesis-based domain mapping combined with immunolocalization in a single study\",\n      \"pmids\": [\"15700540\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"DAZAP1/MEF2D fusion protein retains sequence-specific RNA-binding activity; MEF2D/DAZAP1 fusion binds DNA in a manner indistinguishable from native MEF2D and is a more potent transcriptional activator than MEF2D.\",\n      \"method\": \"DNA-binding assay, transcriptional activation assay, leukemia cell line analysis\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and functional assays in a single lab, two orthogonal methods\",\n      \"pmids\": [\"15744350\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"DAZAP1 is expressed in ovarian luteal cells and co-immunoprecipitates with DAZL in ovarian tissue, demonstrating an in vivo interaction.\",\n      \"method\": \"Co-immunoprecipitation, Western blot, immunohistochemistry\",\n      \"journal\": \"Fertility and sterility\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP result in a single lab without functional follow-up\",\n      \"pmids\": [\"16209998\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"DAZAP1 shuttles between the nucleus and cytoplasm via a novel 25 amino acid C-terminal segment (ZNS) that shares no homology with known nuclear localization or export signals; nuclear localization of DAZAP1 is dependent on active RNA Pol II transcription, as its inhibition retains DAZAP1 in the cytoplasm; DAZAP1 colocalizes with hnRNP A1 and hnRNP C1 in the nucleus as part of hnRNP particles.\",\n      \"method\": \"Immunostaining, heterokaryon formation assay, mutagenesis, RNA Pol II inhibitor treatment\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (heterokaryon, mutagenesis, inhibitor treatment) in single study; ZNS domain findings replicated in later work\",\n      \"pmids\": [\"16772659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"ERK2 phosphorylates DAZAP1 at Thr269 and Thr315 in vitro and in cells; this phosphorylation induces dissociation of DAZAP1 from DAZ; DAZ cannot bind simultaneously to both DAZAP1 and PABP, suggesting phosphorylation-driven DAZAP1 release allows DAZ to interact with PABP and stimulate translation.\",\n      \"method\": \"In vitro kinase assay, mass spectrometry, site-directed mutagenesis (Thr→Asp), co-immunoprecipitation in HEK-293 cells and RAW 264.7 macrophages\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase reconstitution with mutagenesis, confirmed in multiple cell lines with MKK1 inhibitors\",\n      \"pmids\": [\"16848763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Both MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins transform NIH 3T3 cells (~20-fold increase in soft agar colony formation); co-expression of both fusion proteins is synergistic; wild-type DAZAP1 expression allows proliferation under low-serum conditions and suppresses apoptosis.\",\n      \"method\": \"Retroviral gene transfer, soft agar colony formation assay, low-serum proliferation assay, apoptosis assay\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays, single lab\",\n      \"pmids\": [\"17898785\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"DAZAP1 binds to a mutant BRCA1 exon 18 sequence created by a G-to-T transversion (+6 position) via RNA pulldown; siRNA-mediated depletion of DAZAP1 rescues exon 18 inclusion, demonstrating that DAZAP1 binding to this exonic splicing silencer causes exon skipping.\",\n      \"method\": \"RNA pulldown assay, siRNA knockdown, minigene splicing reporter, mutation analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — RNA pulldown plus siRNA functional validation plus extensive mutational analysis in one rigorous study\",\n      \"pmids\": [\"18391021\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"DAZAP1 is required for normal mouse development and spermatogenesis; null or hypomorphic Dazap1 mice show growth retardation and spermatogenic arrest before meiotic division (absence of haploid cells by FACS); DAZAP1 localizes to the nucleus excluding the XY body in pachytene spermatocytes, consistent with a role in mRNA transcription and transport.\",\n      \"method\": \"Mouse knockout/hypomorphic allele generation, FACS analysis, immunostaining\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — defined loss-of-function alleles with specific cellular phenotypic readout confirmed by FACS\",\n      \"pmids\": [\"18669443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"DAZAP1's RNA recognition motifs (RRMs) interact with the C-termini of multiple other RNA-binding proteins (beyond DAZ) in a phosphorylation-independent manner, suggesting DAZAP1 is part of mRNA degradation/silencing complexes in non-germinal cells.\",\n      \"method\": \"Co-immunoprecipitation, domain-mapping pulldown\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/pulldown study, no functional rescue, single lab\",\n      \"pmids\": [\"19285026\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DAZAP1 (both Xenopus and human) acts as an mRNA-specific activator of translation initiation in a 3'UTR binding-site-number-dependent manner; this activity maps to the C-terminal region; DAZAP1 stimulates translation independently of 5'-cap recognition but is modulated by poly(A) tail status, suggesting a function in end-to-end mRNA complex formation; this activity does not require direct interaction with eIF4G.\",\n      \"method\": \"In vitro translation assay, IRES reporter mRNA assay, domain mapping, polysome fractionation, Xenopus oocyte injection\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted in vitro translation plus domain mutagenesis plus IRES reporters, multiple orthogonal methods in single study\",\n      \"pmids\": [\"21576381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DAZAP1 binds to an Alu-derived intronic splicing enhancer (ISE) in the ATM gene (shown by RNA pulldown); siRNA-mediated knockdown of DAZAP1 reduces ATM cryptic exon activation, demonstrating that DAZAP1 positively promotes ISE-dependent cryptic exon inclusion.\",\n      \"method\": \"RNA pulldown assay, siRNA knockdown, splicing reporter assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RNA pulldown plus functional siRNA with splicing readout, two orthogonal methods\",\n      \"pmids\": [\"21858080\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"An N-terminal 42 amino acid segment (N42) of DAZAP1 is necessary and sufficient for transcription-dependent nuclear localization; SLIRP was identified as an N42-binding protein via yeast two-hybrid, potentially regulating DAZAP1 subcellular localization.\",\n      \"method\": \"Mutagenesis, nuclear localization assay, yeast two-hybrid\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mutagenesis with localization readout, yeast two-hybrid for interactor, single lab\",\n      \"pmids\": [\"23111326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"DAZAP1 promotes inclusion of Crem exon 4, Crisp2 exon 9, and Pot1a exon 4 in vivo in mouse testes; DAZAP1 binds intronic regions flanking these exons (Crem intron 3, Crisp2 intron 9, Pot1a intron 4) to regulate splicing; aberrant Pot1a splicing may account for the growth retardation in DAZAP1-deficient mice.\",\n      \"method\": \"Microarray exon-usage profiling of mutant vs. wild-type testes, minigene splicing reporters, DAZAP1 binding assays, mutagenesis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo microarray identification plus minigene reporters plus direct binding assays, multiple orthogonal methods\",\n      \"pmids\": [\"23965306\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"DAZL binds specifically to the 3'UTR of the Dazap1-L transcript and stimulates its translation; the two Dazap1 transcripts (generated by alternative polyadenylation) are differentially regulated, with the Dazap1-S transcript undergoing translational repression associated with poly(A) tail elongation during spermatogenesis.\",\n      \"method\": \"RNA pulldown followed by mass spectrometry, sucrose gradient fractionation, Northern blot, 3' RACE, reporter gene assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA pulldown/MS plus sucrose gradient plus reporter assay, multiple methods in single lab\",\n      \"pmids\": [\"23658607\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DAZAP1 promotes inclusion of weak exons by recognizing diverse cis-elements; its C-terminal proline-rich domain interacts with and neutralizes general splicing inhibitors, is sufficient to activate splicing when tethered to pre-mRNA, and is phosphorylated by the MEK/Erk pathway; this phosphorylation is essential for both splicing regulatory activity and nuclear/cytoplasmic translocation of DAZAP1; DAZAP1 regulates endogenous splicing events involved in cell growth and its knockdown/overexpression causes cell proliferation defects.\",\n      \"method\": \"mRNA-seq, minigene splicing assay, tethering assay, MEK/Erk inhibitor treatment, phosphomutant analysis, siRNA knockdown, cell proliferation assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (tethering, mutagenesis, mRNA-seq, inhibitor pharmacology) in single rigorous study\",\n      \"pmids\": [\"24452013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DAZAP1 binds cox6c mRNA in an intron-dependent manner (binding requires the last intron; no binding to intronless cox6c mRNA); DAZAP1 overexpression suppresses pre-mRNA splicing efficiency of cox6c and reduces mature COX6C protein; this regulates mitochondrial complex IV and cell growth.\",\n      \"method\": \"RNA immunoprecipitation, intronless vs. genomic expression vectors, overexpression and knockdown assays, Western blot\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP with functional vectors and protein readout, single lab\",\n      \"pmids\": [\"29505834\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DAZAP1 binds the 3'UTR of SLC7A11 mRNA and positively regulates its stability, thereby inhibiting ferroptosis; DAZAP1 knockdown reduces SLC7A11 mRNA stability and sensitizes HCC cells to sorafenib-induced ferroptosis.\",\n      \"method\": \"RNA immunoprecipitation, siRNA knockdown, mRNA stability assay, ferroptosis assay\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus mRNA stability assay plus functional ferroptosis readout, single lab\",\n      \"pmids\": [\"33358859\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DAZAP1 silencing in ESCC cells causes exon skipping of TSC2 exon 26, producing a short TSC2 isoform that cannot be phosphorylated at Ser981 by AKT; this results in continuous TSC2 activation, inhibition of mTOR via RHEB, and sustained autophagy; starvation-induced miR-10b suppresses DAZAP1 to trigger this pathway.\",\n      \"method\": \"RNAi, RNAseq alternative splicing analysis, phosphorylation assay, mTOR/RHEB signaling assay, miRNA functional assay\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAseq plus phosphorylation assay plus epistasis through RHEB/mTOR signaling, single lab\",\n      \"pmids\": [\"32308763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DAZAP1 regulates alternative splicing of KITLG mRNA (shown by RIP-seq and RIP-qPCR); DAZAP1-mediated KITLG splicing increases ERK phosphorylation and promotes myeloma cell proliferation.\",\n      \"method\": \"RIP-seq, RIP-qPCR, siRNA knockdown, lentiviral overexpression, ERK phosphorylation assay, xenograft tumor model\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-seq plus functional signaling assay, in vitro and in vivo, single lab\",\n      \"pmids\": [\"36242590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DAZAP1 interacts with PXR (pregnane X receptor) as a paraspeckle component; this interaction is dissociated by the PXR ligand rifampicin; DAZAP1 (together with NEAT1_2 lncRNA) negatively regulates PXR-mediated CYP3A4 transcriptional induction by trapping PXR in paraspeckles in the absence of ligand.\",\n      \"method\": \"Co-immunoprecipitation in PXR-overexpressing HepG2 cells, siRNA knockdown, luciferase reporter assay for PXR response elements\",\n      \"journal\": \"Drug metabolism and disposition\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — reciprocal Co-IP plus luciferase reporter, two orthogonal methods, single lab\",\n      \"pmids\": [\"37349114\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DAZAP1 undergoes liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhances COX16 expression via regulation of pre-mRNA alternative splicing, thereby promoting mitochondrial respiration and OSCC invasion/metastasis.\",\n      \"method\": \"RNA sequencing, DAZAP1 knockdown/overexpression, LLPS assay, mouse OSCC model, EMT marker analysis\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — LLPS demonstration plus splicing and functional assays in vitro and in vivo, single lab\",\n      \"pmids\": [\"39120588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"p52-ZER6 promotes DAZAP1 transcription; DAZAP1 then binds the 3'-UTR of SLC7A11 mRNA to enhance its stability, increasing SLC7A11 expression and cellular glutathione levels, thereby reducing lipid peroxide accumulation and conferring ferroptosis resistance in colorectal cancer.\",\n      \"method\": \"Transcriptional reporter assay, RNA immunoprecipitation, mRNA stability assay, glutathione and lipid peroxide measurement\",\n      \"journal\": \"Acta pharmaceutica Sinica. B\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus mRNA stability plus biochemical readouts, single lab\",\n      \"pmids\": [\"40486833\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DAZAP1 binds USP34 mRNA and stabilizes it, leading to increased USP34 protein, which deubiquitinates and stabilizes PIN1, activating the MAPK signaling pathway in gastric cancer; DAZAP1 mRNA is itself protected from YTHDF2-mediated degradation by ALKBH5-catalyzed m6A demethylation.\",\n      \"method\": \"RNA immunoprecipitation, Western blot, ubiquitination assay, siRNA/overexpression, m6A/ALKBH5/YTHDF2 knockdown experiments\",\n      \"journal\": \"Cell biology and toxicology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RIP plus ubiquitination assay plus m6A pathway perturbation, single lab with multiple readouts\",\n      \"pmids\": [\"41331184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DAZAP1 regulates splicing and expression of ULK1 via nonsense-mediated mRNA decay control; DAZAP1-dependent ULK1 upregulation promotes mitophagy and OXPHOS to sustain gastric cancer stem cell metabolic demands.\",\n      \"method\": \"RNA immunoprecipitation, PCR, Seahorse metabolic assay, transmission electron microscopy, immunofluorescence, sphere formation assay, rescue overexpression\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP plus multiple orthogonal functional assays (Seahorse, TEM, rescue), single lab\",\n      \"pmids\": [\"40401521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DAZAP1 physically binds NOTCH1 and JAG1 mRNAs (shown by RNA immunoprecipitation and sequencing) to stabilize them, activating NOTCH/JAG1 signaling and promoting EMT, migration, and invasion in gastric cancer.\",\n      \"method\": \"RNA immunoprecipitation and sequencing (RIP-seq), mRNA stability assay, overexpression and knockdown, migration/invasion assays\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RIP-seq plus mRNA stability, single lab, limited mechanistic depth\",\n      \"pmids\": [\"41789621\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DAZAP1 is an evolutionarily conserved hnRNP-type RNA-binding protein that uses its two N-terminal RRMs to bind diverse pre-mRNA cis-elements and 3'UTR sequences, and its C-terminal proline-rich domain to interact with and neutralize splicing inhibitors—thereby promoting weak-exon inclusion and acting as a splicing activator; the C-terminal domain is also phosphorylated by ERK1/2 at Thr269 and Thr315, which is essential for its splicing activity, drives its nuclear/cytoplasmic translocation, and disrupts its interaction with DAZ (freeing DAZ to stimulate translation via PABP); DAZAP1 additionally stabilizes specific mRNAs (e.g., SLC7A11, USP34, NOTCH1/JAG1) via 3'UTR binding, activates translation initiation in a cap-independent, poly(A)-sensitive manner, undergoes liquid-liquid phase separation to concentrate nuclear splicing activity, and is required in vivo for spermatogenesis and normal growth as demonstrated by mouse knockout models.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DAZAP1 is an evolutionarily conserved hnRNP-type RNA-binding protein that acts as a splicing activator and post-transcriptional regulator, controlling exon usage and mRNA fate during spermatogenesis and cell growth [#8, #15]. It carries two N-terminal RNA recognition motifs that bind diverse cis-elements—including exonic splicing silencers, Alu-derived intronic splicing enhancers, and intronic regions flanking weak exons—and a C-terminal proline-rich domain that, when tethered to pre-mRNA, is sufficient to activate splicing by interacting with and neutralizing general splicing inhibitors, thereby promoting inclusion of weak exons [#7, #11, #13, #15]. DAZAP1 shuttles between nucleus and cytoplasm through a novel C-terminal segment (ZNS) and an N-terminal N42 segment, with nuclear localization dependent on active RNA Pol II transcription, where it colocalizes with hnRNP A1 and C1 in hnRNP particles [#4, #12]. The MEK/ERK pathway phosphorylates the C-terminal domain at Thr269 and Thr315; this phosphorylation is essential for splicing activity and nuclear/cytoplasmic translocation, and dissociates DAZAP1 from its original partner DAZ, freeing DAZ to engage PABP and stimulate translation [#5, #15]. Beyond splicing, DAZAP1 itself activates translation initiation in a 3'UTR-binding-site-number-dependent, cap-independent but poly(A)-sensitive manner, consistent with promoting end-to-end mRNA complex formation [#10], and stabilizes specific target mRNAs through 3'UTR binding—including SLC7A11 to suppress ferroptosis and USP34 and NOTCH1/JAG1 to drive tumor signaling [#17, #22, #23, #25]. DAZAP1 concentrates its nuclear splicing activity via liquid-liquid phase separation [#21]. In vivo, mouse knockout and hypomorphic alleles cause growth retardation and spermatogenic arrest before meiosis, establishing essential roles in development and germ cell differentiation [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established DAZAP1 as a DAZ/DAZL-interacting protein with a modular architecture, framing it as a candidate regulator of germ-cell mRNA metabolism.\",\n      \"evidence\": \"Yeast two-hybrid, Western blot, and subcellular fractionation identifying two RBDs and a proline-rich C-terminus\",\n      \"pmids\": [\"11604102\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"RNA targets undefined\", \"Functional consequence of DAZ binding not tested\", \"Cytoplasmic predominance not mechanistically explained\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined how DAZAP1 traffics between compartments, showing a novel ZNS shuttling signal and transcription-coupled nuclear residence within hnRNP particles.\",\n      \"evidence\": \"Heterokaryon assay, mutagenesis, RNA Pol II inhibitor treatment, and colocalization with hnRNP A1/C1\",\n      \"pmids\": [\"16772659\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Import/export receptors for ZNS unidentified\", \"Link between transcription dependence and splicing function not yet established\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Connected DAZAP1 to ERK signaling and revealed phosphorylation as a switch that releases DAZ to engage the translation machinery.\",\n      \"evidence\": \"In vitro ERK2 kinase assay, mass spectrometry, phosphomimetic mutagenesis, and Co-IP in HEK293 and macrophages\",\n      \"pmids\": [\"16848763\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether phosphorylation alters DAZAP1's own RNA binding not addressed here\", \"In vivo physiological trigger of ERK input unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrated DAZAP1 is genetically required for mammalian development and meiotic progression in spermatogenesis.\",\n      \"evidence\": \"Mouse knockout/hypomorphic alleles with FACS and immunostaining showing pre-meiotic arrest\",\n      \"pmids\": [\"18669443\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular target mRNAs driving the phenotype not identified in this study\", \"Tissue-specific vs systemic contributions unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Provided direct evidence that DAZAP1 acts on splicing by binding an exonic splicing silencer to enforce exon skipping.\",\n      \"evidence\": \"RNA pulldown, siRNA depletion, and minigene reporter on a mutant BRCA1 exon 18 element\",\n      \"pmids\": [\"18391021\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of silencer vs enhancer behavior not yet defined\", \"Co-factors mediating skipping unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Revealed a direct translational activation function distinct from splicing, mapped to the C-terminus and dependent on 3'UTR site number and poly(A) status.\",\n      \"evidence\": \"In vitro translation, IRES reporters, polysome fractionation, and Xenopus oocyte injection\",\n      \"pmids\": [\"21576381\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Bridging factor for end-to-end complex unidentified (not eIF4G)\", \"Endogenous mRNA targets of this activity unspecified\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed DAZAP1 can act as a positive splicing regulator through intronic splicing enhancers, broadening its element repertoire.\",\n      \"evidence\": \"RNA pulldown and siRNA knockdown on an Alu-derived ATM ISE with splicing reporter\",\n      \"pmids\": [\"21858080\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism reconciling silencer (BRCA1) and enhancer (ATM) outcomes not resolved\", \"Direct vs indirect binding to ISE in vivo not confirmed\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified physiological in vivo splicing targets in testes, linking DAZAP1-dependent exon inclusion to the growth and germ-cell phenotypes.\",\n      \"evidence\": \"Microarray exon profiling of mutant vs WT testes, minigene reporters, and binding assays for Crem, Crisp2, and Pot1a\",\n      \"pmids\": [\"23965306\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Pot1a misregulation is sufficient for growth retardation not proven\", \"Full in vivo target set incomplete\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Integrated the mechanism by showing the proline-rich C-terminus neutralizes general splicing inhibitors and that MEK/ERK phosphorylation is essential for splicing activity and shuttling.\",\n      \"evidence\": \"mRNA-seq, tethering assay, phosphomutant analysis, MEK/Erk inhibitors, and proliferation assays\",\n      \"pmids\": [\"24452013\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the neutralized splicing inhibitors not fully enumerated\", \"Direct structural basis of inhibitor neutralization unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed liquid-liquid phase separation as the biophysical basis for concentrating DAZAP1 splicing activity in the nucleus.\",\n      \"evidence\": \"LLPS assay with RNA-seq, knockdown/overexpression, and OSCC mouse model\",\n      \"pmids\": [\"39120588\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Domains/residues driving phase separation not mapped\", \"Relationship between LLPS and ERK phosphorylation untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended DAZAP1's role to 3'UTR-mediated mRNA stabilization across cancers, controlling ferroptosis resistance and oncogenic signaling.\",\n      \"evidence\": \"RIP, mRNA stability assays, and functional readouts for SLC7A11, USP34/PIN1/MAPK, and NOTCH1/JAG1 targets\",\n      \"pmids\": [\"33358859\", \"40486833\", \"41331184\", \"41789621\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding-site definitions within 3'UTRs incomplete\", \"Mechanism of stabilization (decay factor displacement) not resolved\", \"NOTCH1/JAG1 link rests on a single low-confidence study\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DAZAP1 selects between splicing activation, mRNA stabilization, and translational control on a given transcript, and how phosphorylation and phase separation coordinate these outputs, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking RRM target choice to functional outcome\", \"Structural basis of inhibitor neutralization and LLPS unmapped\", \"Direct nuclear import/export machinery for ZNS/N42 unidentified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 7, 10, 11, 13, 17]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [7, 11, 13, 15]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [5, 15, 20]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4, 8, 21]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [4, 20]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [7, 11, 13, 15, 17]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [4, 13, 15]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [8, 13]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 19, 23]}\n    ],\n    \"complexes\": [\"hnRNP particle\", \"paraspeckle\"],\n    \"partners\": [\"DAZ\", \"DAZL\", \"PABP\", \"hnRNP A1\", \"hnRNP C1\", \"SLIRP\", \"PXR\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}