{"gene":"STEAP2","run_date":"2026-06-10T07:46:42","timeline":{"discoveries":[{"year":2002,"finding":"STEAP2 (STAMP1) protein localizes to the Golgi complex (predominantly trans-Golgi network), plasma membrane, and vesicular tubular structures in the cytosol; it colocalizes with early endosome antigen 1 (EEA1), suggesting involvement in secretory/endocytic pathways.","method":"GFP-fusion construct imaged by quantitative time-lapse and immunofluorescence confocal microscopy; colocalization with EEA1 marker","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct live-imaging and colocalization with organelle markers in two orthogonal microscopy approaches, single lab","pmids":["12095985"],"is_preprint":false},{"year":2002,"finding":"STEAP2 protein localizes mainly to the plasma membrane, as demonstrated by GFP fusion construct.","method":"GFP fusion construct and fluorescence microscopy","journal":"Laboratory investigation; a journal of technical methods and pathology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (GFP localization only), no functional consequence linked","pmids":["12429817"],"is_preprint":false},{"year":2010,"finding":"STEAP2 (STAMP1) promotes prostate cancer cell proliferation and survival: ectopic expression increased proliferation and activated ERK signaling, while siRNA knockdown inhibited growth, induced cell cycle arrest, and increased apoptosis (including TRAIL-induced apoptosis). Knockdown cells showed dramatically reduced xenograft growth in nude mice.","method":"Ectopic overexpression in DU145/COS-7 cells; siRNA knockdown in LNCaP cells; cell cycle analysis; apoptosis assays; ERK activation by Western blot; nude mouse xenograft","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (overexpression, siRNA KD, in vitro proliferation/apoptosis assays, in vivo xenograft, ERK pathway readout), single lab with comprehensive coverage","pmids":["20587517"],"is_preprint":false},{"year":2014,"finding":"STEAP2 overexpression in normal prostate epithelial PNT2 cells conferred the ability to migrate and invade, establishing a direct functional role for STEAP2 in driving invasive behavior.","method":"STEAP2 overexpression in PNT2 cells; migration and invasion assays (transwell)","journal":"Clinical & experimental metastasis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function in normal cells with defined invasive phenotype readout, single lab","pmids":["25248617"],"is_preprint":false},{"year":2018,"finding":"STEAP2 knockdown in PC3 and LNCaP prostate cancer cells significantly decreased invasion; downstream targets identified include MMP3, MMP10, MMP13, FGFR4, IL1β, KiSS1, SERPINE1 (PC3), MMP7 (LNCaP), and CD82 (both lines), indicating STEAP2 regulates invasion-related gene expression programs.","method":"siRNA knockdown; proliferation, migration, and invasion assays; gene expression analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined phenotypic readout and transcriptional pathway mapping, single lab","pmids":["29674723"],"is_preprint":false},{"year":2018,"finding":"STEAP2 undergoes rapid internalization from the cell surface and traffics to the Golgi region and endosome-like puncta; acute inhibition of endocytosis increases detectable STEAP2 at the plasma membrane. Membrane cholesterol content modulates a conformation-sensitive epitope in the second extracellular loop of STEAP2, suggesting cholesterol-dependent conformational regulation during trafficking. STEAP2's metalloreductase activity was not detectable at the plasma membrane (negative finding).","method":"Monoclonal antibody recognizing conformation-sensitive epitope; antibody internalization assay; cholesterol manipulation; endocytosis inhibition; cell-based metalloreductase activity assay using STEAP4 as positive control","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal approaches (antibody epitope mapping, internalization tracking, pharmacological inhibition, functional metalloreductase assay), single lab","pmids":["29940176"],"is_preprint":false},{"year":2019,"finding":"STEAP2 upregulation in breast cancer cells inhibited EMT and suppressed PI3K/AKT/mTOR signaling pathway activity, reducing proliferation and invasion; conversely, STEAP2 downregulation promoted EMT and activated PI3K/AKT/mTOR signaling.","method":"Lentiviral overexpression and shRNA knockdown; Western blot for PI3K/AKT/mTOR phosphorylation; EMT marker profiling; in vitro invasion assays; in vivo xenograft","journal":"Cancer biology & therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — bidirectional (gain and loss of function) with pathway readout, single lab","pmids":["31696760"],"is_preprint":false},{"year":2022,"finding":"METTL3-mediated m6A modification of STEAP2 mRNA stabilizes STEAP2 mRNA and promotes its translation in an m6A-dependent manner via the reader protein YTHDF1; this METTL3-STEAP2 axis suppresses EMT and Hedgehog signaling in papillary thyroid cancer cells.","method":"m6A modification assays; METTL3 overexpression/silencing; YTHDF1 reader identification; rescue experiments; cell proliferation, migration and invasion assays; in vivo xenograft","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple experimental approaches linking writer (METTL3), reader (YTHDF1), and target (STEAP2 mRNA stability/translation) with rescue validation, single lab","pmids":["35436987"],"is_preprint":false},{"year":2022,"finding":"STEAP2 promotes osteosarcoma cell EMT, invasion, and migration via the PI3K/AKT/mTOR signaling axis; EFEMP2 overexpression reduces invasiveness and EMT partly by targeting STEAP2, and EFEMP2-induced PI3K/AKT/mTOR activation and EMT are abrogated when STEAP2 or Akt is knocked down, placing STEAP2 downstream of EFEMP2 in this pathway.","method":"STEAP2 and EFEMP2 overexpression/knockdown; Western blot for PI3K/AKT/mTOR; EMT markers; invasion/migration assays; epistasis via double KD; in vivo assays","journal":"Cancer biology & therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis (double KD placing STEAP2 downstream of EFEMP2) with multiple functional readouts, single lab","pmids":["36316642"],"is_preprint":false},{"year":2024,"finding":"STEAP2 functions as a metalloreductase that drives HCC cell migration and invasion by increasing intracellular copper levels and activating stress-activated MAP kinases p38 and JNK; copper supplementation rescued migration defects caused by STEAP2 knockdown, and p38 or JNK inhibitors blocked copper-mediated migration rescue.","method":"Stable STEAP2 KD and overexpression in HCC cell lines; intracellular copper measurement; Western blot for p38 and JNK activation; copper rescue experiment; p38/JNK pharmacological inhibition; in vitro migration/invasion; in vivo tumor growth","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — mechanistic pathway established by bidirectional manipulation, copper measurement, chemical rescue and pharmacological epistasis in multiple orthogonal experiments, single lab with comprehensive validation","pmids":["38830975"],"is_preprint":false},{"year":2025,"finding":"High-resolution crystal structures of the STEAP2 N-terminal cytosolic oxidoreductase domain (OxRD) bound to NADPH were solved; single-crystal spectroscopy directly validated the redox state of bound NADPH. Comparison with cryo-EM structure revealed conformational differences in the FAD-binding region, suggesting domain reorientation between OxRD and the transmembrane domain facilitates FADH2 loading and FAD release as part of the electron transfer pathway (NADPH→FAD→heme→extracellular metal ions).","method":"High-resolution X-ray crystallography; single-crystal UV-visible spectroscopy for redox-state validation; comparison with cryo-EM structure","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with direct spectroscopic validation of cofactor redox state; orthogonal structural methods (X-ray + cryo-EM comparison) establishing mechanistic electron transfer model","pmids":["41101505"],"is_preprint":false},{"year":2026,"finding":"ETV1 transcriptionally activates miR-3175 through direct promoter binding; miR-3175 directly suppresses STEAP2 expression via conserved 3'UTR binding sites; STEAP2 functions as a tumor suppressor in glioma such that its overexpression inhibits malignant phenotypes. This ETV1/miR-3175/STEAP2 axis was confirmed by rescue experiments.","method":"Chromatin immunoprecipitation (ChIP); luciferase reporter assays; biotin-streptavidin pulldown; RNA immunoprecipitation; gain/loss-of-function studies; rescue experiments; in vivo xenograft","journal":"BioFactors (Oxford, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal molecular methods (ChIP, luciferase, RIP, pulldown) establishing regulatory axis with rescue validation, single lab","pmids":["41856673"],"is_preprint":false}],"current_model":"STEAP2 is a six-transmembrane metalloreductase that transfers electrons from cytosolic NADPH through FAD and heme to extracellular ferric and cupric ions (structurally validated by crystal structure with spectroscopic redox confirmation); it localizes to the trans-Golgi network, plasma membrane, and endosomes via cholesterol-modulated conformational changes during dynamic trafficking, with metalloreductase activity suppressed at the plasma membrane; functionally, STEAP2 promotes cell proliferation, migration, and invasion in multiple cancer contexts by activating ERK and PI3K/AKT/mTOR signaling and, in hepatocellular carcinoma, by elevating intracellular copper levels to activate p38 and JNK MAP kinases; its expression is post-transcriptionally regulated by METTL3-mediated m6A modification read by YTHDF1, and transcriptionally repressed by the ETV1/miR-3175 axis in glioma."},"narrative":{"mechanistic_narrative":"STEAP2 is a six-transmembrane metalloreductase that transfers electrons from cytosolic NADPH through FAD and heme cofactors to reduce extracellular metal ions, a mechanism resolved by crystal structures of its NADPH-bound N-terminal oxidoreductase domain with spectroscopic validation of the cofactor redox state [PMID:41101505]. The protein traffics dynamically among the trans-Golgi network, plasma membrane, and endosomes, undergoing rapid surface internalization, and its second extracellular loop adopts a cholesterol-modulated conformation; notably, its metalloreductase activity is not detectable at the plasma membrane [PMID:12095985, PMID:29940176]. Functionally, STEAP2 acts as a metal-handling driver of cancer cell behavior, but with context-dependent and opposing outcomes across tissues: in prostate cancer it promotes proliferation, survival, migration, and invasion through ERK activation and regulation of invasion-associated gene programs [PMID:20587517, PMID:29674723], whereas in hepatocellular carcinoma it elevates intracellular copper to activate the stress kinases p38 and JNK and thereby drive migration and invasion [PMID:38830975]. In breast cancer, thyroid cancer, and glioma, by contrast, STEAP2 suppresses malignant phenotypes—inhibiting EMT and PI3K/AKT/mTOR signaling [PMID:31696760] and acting as a tumor suppressor [PMID:41856673]. STEAP2 expression is post-transcriptionally controlled by METTL3-deposited m6A marks read by YTHDF1, which stabilize and promote translation of STEAP2 mRNA [PMID:35436987], and transcriptionally repressed through an ETV1-driven miR-3175 axis [PMID:41856673].","teleology":[{"year":2002,"claim":"Established the subcellular distribution of STEAP2, framing it as a protein of the secretory and endocytic system rather than a static surface marker.","evidence":"GFP-fusion live imaging and immunofluorescence with EEA1 colocalization in cultured cells","pmids":["12095985","12429817"],"confidence":"Medium","gaps":["Localization studies alone did not assign a molecular activity","Relative steady-state distribution between Golgi and plasma membrane unresolved across the two reports"]},{"year":2010,"claim":"Provided the first functional link between STEAP2 and cancer, showing it drives prostate cancer proliferation and survival via ERK.","evidence":"Ectopic overexpression and siRNA knockdown with cell cycle/apoptosis assays, ERK Western blot, and nude mouse xenograft","pmids":["20587517"],"confidence":"High","gaps":["Did not connect the proliferative phenotype to STEAP2's enzymatic metalloreductase activity","Mechanism of ERK activation downstream of STEAP2 not defined"]},{"year":2014,"claim":"Demonstrated that STEAP2 is sufficient to confer invasive/migratory capacity, extending its role beyond proliferation to metastatic behavior.","evidence":"Gain-of-function overexpression in normal PNT2 prostate epithelial cells with transwell migration/invasion assays","pmids":["25248617"],"confidence":"Medium","gaps":["No molecular effectors of the invasive phenotype identified","Gain-of-function in a single normal cell line"]},{"year":2018,"claim":"Mapped invasion-related transcriptional targets of STEAP2 and clarified its trafficking and the spatial restriction of its enzymatic activity.","evidence":"siRNA knockdown with invasion assays and gene-expression analysis (MMPs, CD82 etc.); conformation-sensitive antibody internalization, cholesterol manipulation, and cell-based metalloreductase assay","pmids":["29674723","29940176"],"confidence":"Medium","gaps":["Whether the identified invasion genes are direct or indirect targets unresolved","Why metalloreductase activity is undetectable at the plasma membrane mechanistically unexplained","Functional role of cholesterol-dependent conformational change not established"]},{"year":2019,"claim":"Revealed that STEAP2 can act as a suppressor of EMT and PI3K/AKT/mTOR signaling, introducing tissue-dependent directionality to its function.","evidence":"Bidirectional lentiviral overexpression/shRNA in breast cancer cells with PI3K/AKT/mTOR Western blots, EMT profiling, invasion assays, and xenograft","pmids":["31696760"],"confidence":"Medium","gaps":["Does not explain why STEAP2 is oncogenic in prostate but suppressive in breast","Link between metalloreductase activity and PI3K/AKT/mTOR not made"]},{"year":2022,"claim":"Defined upstream regulatory inputs to STEAP2 and placed it within signaling epistasis, identifying m6A control and an EFEMP2 axis.","evidence":"m6A assays with METTL3/YTHDF1 manipulation and rescue in thyroid cancer; STEAP2/EFEMP2 double-knockdown epistasis with PI3K/AKT/mTOR readouts in osteosarcoma","pmids":["35436987","36316642"],"confidence":"Medium","gaps":["Direct binding of YTHDF1 to STEAP2 transcript versus indirect effect not fully separated","How EFEMP2 connects mechanistically to STEAP2 unresolved"]},{"year":2024,"claim":"Linked STEAP2's enzymatic identity to a downstream signaling output by showing it raises intracellular copper to activate p38/JNK.","evidence":"Bidirectional knockdown/overexpression in HCC cells with copper measurement, p38/JNK Western blots, copper rescue, pharmacological kinase inhibition, and in vivo growth","pmids":["38830975"],"confidence":"High","gaps":["Whether copper elevation reflects direct cupric reductase activity of STEAP2 not structurally confirmed in this context","Mechanism connecting copper to p38/JNK activation undefined"]},{"year":2025,"claim":"Resolved the structural basis of the electron-transfer mechanism, validating NADPH→FAD→heme→metal flux through the oxidoreductase domain.","evidence":"High-resolution X-ray crystallography of the NADPH-bound OxRD with single-crystal UV-visible spectroscopy and cryo-EM comparison","pmids":["41101505"],"confidence":"High","gaps":["Dynamics of OxRD-transmembrane domain reorientation not directly observed in real time","Structure does not address physiological metal-substrate selectivity in cells"]},{"year":2026,"claim":"Established a transcriptional repression circuit and reinforced STEAP2's tumor-suppressive role in glioma.","evidence":"ChIP, luciferase reporters, biotin-streptavidin pulldown, RNA immunoprecipitation, gain/loss-of-function, and rescue with xenograft","pmids":["41856673"],"confidence":"Medium","gaps":["Does not reconcile tumor-suppressive role with oncogenic roles in other tissues","Whether suppression depends on STEAP2 metalloreductase activity untested"]},{"year":null,"claim":"It remains unresolved how STEAP2's metalloreductase electron-transfer activity is mechanistically coupled to its opposing oncogenic versus tumor-suppressive signaling outcomes across tissues.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model linking metal reduction to context-dependent ERK/AKT/p38/JNK outcomes","Catalytically inactive mutants not used to test whether signaling roles require enzymatic activity","Physiological (non-cancer) function not characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016491","term_label":"oxidoreductase activity","supporting_discovery_ids":[9,10]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[10]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,5]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,5]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,6,9]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[9]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NFT2","full_name":"Metalloreductase STEAP2","aliases":["Prostate cancer-associated protein 1","Protein up-regulated in metastatic prostate cancer","PUMPCn","Six-transmembrane epithelial antigen of prostate 2","SixTransMembrane protein of prostate 1"],"length_aa":490,"mass_kda":56.1,"function":"Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (By similarity). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (By similarity)","subcellular_location":"Endosome membrane; Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q8NFT2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STEAP2","classification":"Not Classified","n_dependent_lines":54,"n_total_lines":1208,"dependency_fraction":0.04470198675496689},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/STEAP2","total_profiled":1310},"omim":[{"mim_id":"611098","title":"STEAP4 METALLOREDUCTASE; STEAP4","url":"https://www.omim.org/entry/611098"},{"mim_id":"605094","title":"STEAP2 METALLOREDUCTASE; STEAP2","url":"https://www.omim.org/entry/605094"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"prostate","ntpm":119.9}],"url":"https://www.proteinatlas.org/search/STEAP2"},"hgnc":{"alias_symbol":["IPCA-1","STAMP1","STMP"],"prev_symbol":["PCANAP1"]},"alphafold":{"accession":"Q8NFT2","domains":[{"cath_id":"3.40.50.720","chopping":"33-207","consensus_level":"high","plddt":94.4327,"start":33,"end":207},{"cath_id":"1.20.120","chopping":"211-467","consensus_level":"high","plddt":94.9863,"start":211,"end":467}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NFT2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NFT2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NFT2-F1-predicted_aligned_error_v6.png","plddt_mean":88.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STEAP2","jax_strain_url":"https://www.jax.org/strain/search?query=STEAP2"},"sequence":{"accession":"Q8NFT2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NFT2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NFT2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NFT2"}},"corpus_meta":[{"pmid":"35436987","id":"PMC_35436987","title":"METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/35436987","citation_count":78,"is_preprint":false},{"pmid":"12095985","id":"PMC_12095985","title":"Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12095985","citation_count":71,"is_preprint":false},{"pmid":"12429817","id":"PMC_12429817","title":"Cloning and characterization of a novel six-transmembrane protein STEAP2, expressed in normal and malignant prostate.","date":"2002","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/12429817","citation_count":50,"is_preprint":false},{"pmid":"37966111","id":"PMC_37966111","title":"Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer.","date":"2023","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/37966111","citation_count":44,"is_preprint":false},{"pmid":"20587517","id":"PMC_20587517","title":"STAMP1 is both a proliferative and an antiapoptotic factor in prostate cancer.","date":"2010","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/20587517","citation_count":43,"is_preprint":false},{"pmid":"25248617","id":"PMC_25248617","title":"A role for STEAP2 in prostate cancer progression.","date":"2014","source":"Clinical & experimental metastasis","url":"https://pubmed.ncbi.nlm.nih.gov/25248617","citation_count":41,"is_preprint":false},{"pmid":"29699673","id":"PMC_29699673","title":"Phosphoesterification of soybean and peanut proteins with sodium trimetaphosphate (STMP): Changes in structure to improve functionality for food applications.","date":"2018","source":"Food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29699673","citation_count":38,"is_preprint":false},{"pmid":"29674723","id":"PMC_29674723","title":"STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29674723","citation_count":35,"is_preprint":false},{"pmid":"31696760","id":"PMC_31696760","title":"STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo.","date":"2019","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/31696760","citation_count":25,"is_preprint":false},{"pmid":"36316642","id":"PMC_36316642","title":"STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2.","date":"2022","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/36316642","citation_count":18,"is_preprint":false},{"pmid":"11292857","id":"PMC_11292857","title":"Sequence-tagged microsatellite profiling (STMP): a rapid technique for developing SSR markers.","date":"2001","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/11292857","citation_count":15,"is_preprint":false},{"pmid":"19196137","id":"PMC_19196137","title":"Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells.","date":"2009","source":"Tissue engineering. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/19196137","citation_count":14,"is_preprint":false},{"pmid":"38830975","id":"PMC_38830975","title":"STEAP2 promotes hepatocellular carcinoma progression via increased copper levels and stress-activated MAP kinase activity.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38830975","citation_count":8,"is_preprint":false},{"pmid":"12466561","id":"PMC_12466561","title":"Sequence tagged microsatellite profiling (STMP): improved isolation of DNA sequence flanking target SSRs.","date":"2002","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/12466561","citation_count":7,"is_preprint":false},{"pmid":"38872435","id":"PMC_38872435","title":"Unveiling the role of copper metabolism and STEAP2 in idiopathic pulmonary fibrosis molecular landscape.","date":"2024","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38872435","citation_count":6,"is_preprint":false},{"pmid":"29940176","id":"PMC_29940176","title":"Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular trafficking processes leading to broad subcellular distribution.","date":"2018","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/29940176","citation_count":6,"is_preprint":false},{"pmid":"36304279","id":"PMC_36304279","title":"A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates.","date":"2022","source":"Frontiers in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/36304279","citation_count":4,"is_preprint":false},{"pmid":"37329528","id":"PMC_37329528","title":"Investigating STEAP2 as a potential therapeutic target for the treatment of aggressive prostate cancer.","date":"2023","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/37329528","citation_count":2,"is_preprint":false},{"pmid":"41101505","id":"PMC_41101505","title":"Structural and spectroscopic resolution of the NADPH redox state in the STEAP2 cytosolic oxidoreductase domain.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41101505","citation_count":0,"is_preprint":false},{"pmid":"41856673","id":"PMC_41856673","title":"ETV1 Promotes Glioma Progression via miR-3175/STEAP2 Axis.","date":"2026","source":"BioFactors (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/41856673","citation_count":0,"is_preprint":false},{"pmid":"42067902","id":"PMC_42067902","title":"STEAP2-associated modulation of PI3K/AKT/mTOR signaling contributes to ginkgetin-induced apoptosis in bladder cancer cells.","date":"2026","source":"Hereditas","url":"https://pubmed.ncbi.nlm.nih.gov/42067902","citation_count":0,"is_preprint":false},{"pmid":"41997331","id":"PMC_41997331","title":"Strong STMP-crosslinked lignin/chitosan hydrogel films with enhanced aqueous stability and bioactivity for active food packaging.","date":"2026","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/41997331","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13150,"output_tokens":3166,"usd":0.04347,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10725,"output_tokens":3277,"usd":0.067775,"stage2_stop_reason":"end_turn"},"total_usd":0.111245,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"STEAP2 (STAMP1) protein localizes to the Golgi complex (predominantly trans-Golgi network), plasma membrane, and vesicular tubular structures in the cytosol; it colocalizes with early endosome antigen 1 (EEA1), suggesting involvement in secretory/endocytic pathways.\",\n      \"method\": \"GFP-fusion construct imaged by quantitative time-lapse and immunofluorescence confocal microscopy; colocalization with EEA1 marker\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live-imaging and colocalization with organelle markers in two orthogonal microscopy approaches, single lab\",\n      \"pmids\": [\"12095985\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"STEAP2 protein localizes mainly to the plasma membrane, as demonstrated by GFP fusion construct.\",\n      \"method\": \"GFP fusion construct and fluorescence microscopy\",\n      \"journal\": \"Laboratory investigation; a journal of technical methods and pathology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (GFP localization only), no functional consequence linked\",\n      \"pmids\": [\"12429817\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"STEAP2 (STAMP1) promotes prostate cancer cell proliferation and survival: ectopic expression increased proliferation and activated ERK signaling, while siRNA knockdown inhibited growth, induced cell cycle arrest, and increased apoptosis (including TRAIL-induced apoptosis). Knockdown cells showed dramatically reduced xenograft growth in nude mice.\",\n      \"method\": \"Ectopic overexpression in DU145/COS-7 cells; siRNA knockdown in LNCaP cells; cell cycle analysis; apoptosis assays; ERK activation by Western blot; nude mouse xenograft\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (overexpression, siRNA KD, in vitro proliferation/apoptosis assays, in vivo xenograft, ERK pathway readout), single lab with comprehensive coverage\",\n      \"pmids\": [\"20587517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"STEAP2 overexpression in normal prostate epithelial PNT2 cells conferred the ability to migrate and invade, establishing a direct functional role for STEAP2 in driving invasive behavior.\",\n      \"method\": \"STEAP2 overexpression in PNT2 cells; migration and invasion assays (transwell)\",\n      \"journal\": \"Clinical & experimental metastasis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function in normal cells with defined invasive phenotype readout, single lab\",\n      \"pmids\": [\"25248617\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STEAP2 knockdown in PC3 and LNCaP prostate cancer cells significantly decreased invasion; downstream targets identified include MMP3, MMP10, MMP13, FGFR4, IL1β, KiSS1, SERPINE1 (PC3), MMP7 (LNCaP), and CD82 (both lines), indicating STEAP2 regulates invasion-related gene expression programs.\",\n      \"method\": \"siRNA knockdown; proliferation, migration, and invasion assays; gene expression analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined phenotypic readout and transcriptional pathway mapping, single lab\",\n      \"pmids\": [\"29674723\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STEAP2 undergoes rapid internalization from the cell surface and traffics to the Golgi region and endosome-like puncta; acute inhibition of endocytosis increases detectable STEAP2 at the plasma membrane. Membrane cholesterol content modulates a conformation-sensitive epitope in the second extracellular loop of STEAP2, suggesting cholesterol-dependent conformational regulation during trafficking. STEAP2's metalloreductase activity was not detectable at the plasma membrane (negative finding).\",\n      \"method\": \"Monoclonal antibody recognizing conformation-sensitive epitope; antibody internalization assay; cholesterol manipulation; endocytosis inhibition; cell-based metalloreductase activity assay using STEAP4 as positive control\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal approaches (antibody epitope mapping, internalization tracking, pharmacological inhibition, functional metalloreductase assay), single lab\",\n      \"pmids\": [\"29940176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"STEAP2 upregulation in breast cancer cells inhibited EMT and suppressed PI3K/AKT/mTOR signaling pathway activity, reducing proliferation and invasion; conversely, STEAP2 downregulation promoted EMT and activated PI3K/AKT/mTOR signaling.\",\n      \"method\": \"Lentiviral overexpression and shRNA knockdown; Western blot for PI3K/AKT/mTOR phosphorylation; EMT marker profiling; in vitro invasion assays; in vivo xenograft\",\n      \"journal\": \"Cancer biology & therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — bidirectional (gain and loss of function) with pathway readout, single lab\",\n      \"pmids\": [\"31696760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"METTL3-mediated m6A modification of STEAP2 mRNA stabilizes STEAP2 mRNA and promotes its translation in an m6A-dependent manner via the reader protein YTHDF1; this METTL3-STEAP2 axis suppresses EMT and Hedgehog signaling in papillary thyroid cancer cells.\",\n      \"method\": \"m6A modification assays; METTL3 overexpression/silencing; YTHDF1 reader identification; rescue experiments; cell proliferation, migration and invasion assays; in vivo xenograft\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple experimental approaches linking writer (METTL3), reader (YTHDF1), and target (STEAP2 mRNA stability/translation) with rescue validation, single lab\",\n      \"pmids\": [\"35436987\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"STEAP2 promotes osteosarcoma cell EMT, invasion, and migration via the PI3K/AKT/mTOR signaling axis; EFEMP2 overexpression reduces invasiveness and EMT partly by targeting STEAP2, and EFEMP2-induced PI3K/AKT/mTOR activation and EMT are abrogated when STEAP2 or Akt is knocked down, placing STEAP2 downstream of EFEMP2 in this pathway.\",\n      \"method\": \"STEAP2 and EFEMP2 overexpression/knockdown; Western blot for PI3K/AKT/mTOR; EMT markers; invasion/migration assays; epistasis via double KD; in vivo assays\",\n      \"journal\": \"Cancer biology & therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis (double KD placing STEAP2 downstream of EFEMP2) with multiple functional readouts, single lab\",\n      \"pmids\": [\"36316642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"STEAP2 functions as a metalloreductase that drives HCC cell migration and invasion by increasing intracellular copper levels and activating stress-activated MAP kinases p38 and JNK; copper supplementation rescued migration defects caused by STEAP2 knockdown, and p38 or JNK inhibitors blocked copper-mediated migration rescue.\",\n      \"method\": \"Stable STEAP2 KD and overexpression in HCC cell lines; intracellular copper measurement; Western blot for p38 and JNK activation; copper rescue experiment; p38/JNK pharmacological inhibition; in vitro migration/invasion; in vivo tumor growth\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mechanistic pathway established by bidirectional manipulation, copper measurement, chemical rescue and pharmacological epistasis in multiple orthogonal experiments, single lab with comprehensive validation\",\n      \"pmids\": [\"38830975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"High-resolution crystal structures of the STEAP2 N-terminal cytosolic oxidoreductase domain (OxRD) bound to NADPH were solved; single-crystal spectroscopy directly validated the redox state of bound NADPH. Comparison with cryo-EM structure revealed conformational differences in the FAD-binding region, suggesting domain reorientation between OxRD and the transmembrane domain facilitates FADH2 loading and FAD release as part of the electron transfer pathway (NADPH→FAD→heme→extracellular metal ions).\",\n      \"method\": \"High-resolution X-ray crystallography; single-crystal UV-visible spectroscopy for redox-state validation; comparison with cryo-EM structure\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with direct spectroscopic validation of cofactor redox state; orthogonal structural methods (X-ray + cryo-EM comparison) establishing mechanistic electron transfer model\",\n      \"pmids\": [\"41101505\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ETV1 transcriptionally activates miR-3175 through direct promoter binding; miR-3175 directly suppresses STEAP2 expression via conserved 3'UTR binding sites; STEAP2 functions as a tumor suppressor in glioma such that its overexpression inhibits malignant phenotypes. This ETV1/miR-3175/STEAP2 axis was confirmed by rescue experiments.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP); luciferase reporter assays; biotin-streptavidin pulldown; RNA immunoprecipitation; gain/loss-of-function studies; rescue experiments; in vivo xenograft\",\n      \"journal\": \"BioFactors (Oxford, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal molecular methods (ChIP, luciferase, RIP, pulldown) establishing regulatory axis with rescue validation, single lab\",\n      \"pmids\": [\"41856673\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STEAP2 is a six-transmembrane metalloreductase that transfers electrons from cytosolic NADPH through FAD and heme to extracellular ferric and cupric ions (structurally validated by crystal structure with spectroscopic redox confirmation); it localizes to the trans-Golgi network, plasma membrane, and endosomes via cholesterol-modulated conformational changes during dynamic trafficking, with metalloreductase activity suppressed at the plasma membrane; functionally, STEAP2 promotes cell proliferation, migration, and invasion in multiple cancer contexts by activating ERK and PI3K/AKT/mTOR signaling and, in hepatocellular carcinoma, by elevating intracellular copper levels to activate p38 and JNK MAP kinases; its expression is post-transcriptionally regulated by METTL3-mediated m6A modification read by YTHDF1, and transcriptionally repressed by the ETV1/miR-3175 axis in glioma.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STEAP2 is a six-transmembrane metalloreductase that transfers electrons from cytosolic NADPH through FAD and heme cofactors to reduce extracellular metal ions, a mechanism resolved by crystal structures of its NADPH-bound N-terminal oxidoreductase domain with spectroscopic validation of the cofactor redox state [#10]. The protein traffics dynamically among the trans-Golgi network, plasma membrane, and endosomes, undergoing rapid surface internalization, and its second extracellular loop adopts a cholesterol-modulated conformation; notably, its metalloreductase activity is not detectable at the plasma membrane [#0, #5]. Functionally, STEAP2 acts as a metal-handling driver of cancer cell behavior, but with context-dependent and opposing outcomes across tissues: in prostate cancer it promotes proliferation, survival, migration, and invasion through ERK activation and regulation of invasion-associated gene programs [#2, #4], whereas in hepatocellular carcinoma it elevates intracellular copper to activate the stress kinases p38 and JNK and thereby drive migration and invasion [#9]. In breast cancer, thyroid cancer, and glioma, by contrast, STEAP2 suppresses malignant phenotypes—inhibiting EMT and PI3K/AKT/mTOR signaling [#6] and acting as a tumor suppressor [#11]. STEAP2 expression is post-transcriptionally controlled by METTL3-deposited m6A marks read by YTHDF1, which stabilize and promote translation of STEAP2 mRNA [#7], and transcriptionally repressed through an ETV1-driven miR-3175 axis [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the subcellular distribution of STEAP2, framing it as a protein of the secretory and endocytic system rather than a static surface marker.\",\n      \"evidence\": \"GFP-fusion live imaging and immunofluorescence with EEA1 colocalization in cultured cells\",\n      \"pmids\": [\"12095985\", \"12429817\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization studies alone did not assign a molecular activity\", \"Relative steady-state distribution between Golgi and plasma membrane unresolved across the two reports\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Provided the first functional link between STEAP2 and cancer, showing it drives prostate cancer proliferation and survival via ERK.\",\n      \"evidence\": \"Ectopic overexpression and siRNA knockdown with cell cycle/apoptosis assays, ERK Western blot, and nude mouse xenograft\",\n      \"pmids\": [\"20587517\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not connect the proliferative phenotype to STEAP2's enzymatic metalloreductase activity\", \"Mechanism of ERK activation downstream of STEAP2 not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated that STEAP2 is sufficient to confer invasive/migratory capacity, extending its role beyond proliferation to metastatic behavior.\",\n      \"evidence\": \"Gain-of-function overexpression in normal PNT2 prostate epithelial cells with transwell migration/invasion assays\",\n      \"pmids\": [\"25248617\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular effectors of the invasive phenotype identified\", \"Gain-of-function in a single normal cell line\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapped invasion-related transcriptional targets of STEAP2 and clarified its trafficking and the spatial restriction of its enzymatic activity.\",\n      \"evidence\": \"siRNA knockdown with invasion assays and gene-expression analysis (MMPs, CD82 etc.); conformation-sensitive antibody internalization, cholesterol manipulation, and cell-based metalloreductase assay\",\n      \"pmids\": [\"29674723\", \"29940176\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the identified invasion genes are direct or indirect targets unresolved\", \"Why metalloreductase activity is undetectable at the plasma membrane mechanistically unexplained\", \"Functional role of cholesterol-dependent conformational change not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed that STEAP2 can act as a suppressor of EMT and PI3K/AKT/mTOR signaling, introducing tissue-dependent directionality to its function.\",\n      \"evidence\": \"Bidirectional lentiviral overexpression/shRNA in breast cancer cells with PI3K/AKT/mTOR Western blots, EMT profiling, invasion assays, and xenograft\",\n      \"pmids\": [\"31696760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not explain why STEAP2 is oncogenic in prostate but suppressive in breast\", \"Link between metalloreductase activity and PI3K/AKT/mTOR not made\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined upstream regulatory inputs to STEAP2 and placed it within signaling epistasis, identifying m6A control and an EFEMP2 axis.\",\n      \"evidence\": \"m6A assays with METTL3/YTHDF1 manipulation and rescue in thyroid cancer; STEAP2/EFEMP2 double-knockdown epistasis with PI3K/AKT/mTOR readouts in osteosarcoma\",\n      \"pmids\": [\"35436987\", \"36316642\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of YTHDF1 to STEAP2 transcript versus indirect effect not fully separated\", \"How EFEMP2 connects mechanistically to STEAP2 unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked STEAP2's enzymatic identity to a downstream signaling output by showing it raises intracellular copper to activate p38/JNK.\",\n      \"evidence\": \"Bidirectional knockdown/overexpression in HCC cells with copper measurement, p38/JNK Western blots, copper rescue, pharmacological kinase inhibition, and in vivo growth\",\n      \"pmids\": [\"38830975\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether copper elevation reflects direct cupric reductase activity of STEAP2 not structurally confirmed in this context\", \"Mechanism connecting copper to p38/JNK activation undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved the structural basis of the electron-transfer mechanism, validating NADPH→FAD→heme→metal flux through the oxidoreductase domain.\",\n      \"evidence\": \"High-resolution X-ray crystallography of the NADPH-bound OxRD with single-crystal UV-visible spectroscopy and cryo-EM comparison\",\n      \"pmids\": [\"41101505\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Dynamics of OxRD-transmembrane domain reorientation not directly observed in real time\", \"Structure does not address physiological metal-substrate selectivity in cells\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Established a transcriptional repression circuit and reinforced STEAP2's tumor-suppressive role in glioma.\",\n      \"evidence\": \"ChIP, luciferase reporters, biotin-streptavidin pulldown, RNA immunoprecipitation, gain/loss-of-function, and rescue with xenograft\",\n      \"pmids\": [\"41856673\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not reconcile tumor-suppressive role with oncogenic roles in other tissues\", \"Whether suppression depends on STEAP2 metalloreductase activity untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how STEAP2's metalloreductase electron-transfer activity is mechanistically coupled to its opposing oncogenic versus tumor-suppressive signaling outcomes across tissues.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model linking metal reduction to context-dependent ERK/AKT/p38/JNK outcomes\", \"Catalytically inactive mutants not used to test whether signaling roles require enzymatic activity\", \"Physiological (non-cancer) function not characterized in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016491\", \"supporting_discovery_ids\": [9, 10]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 5]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 6, 9]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":5,"faith_total":5,"faith_pct":100.0}}