{"gene":"STAM2","run_date":"2026-06-10T07:46:42","timeline":{"discoveries":[{"year":2000,"finding":"STAM2 is tyrosine-phosphorylated downstream of growth factor receptors (EGF, PDGF) and cytokines (IL-3, IL-2); it is phosphorylated by Jak1 and Jak2 (but not the unrelated Tec kinase Etk), requiring the ITAM domain for JAK-mediated phosphorylation; overexpression of wild-type STAM2 potentiates IL-2-mediated c-Myc promoter activation.","method":"Anti-phosphotyrosine affinity purification + mass spectrometry identification; co-expression with kinase constructs; deletion mutant analysis; reporter assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple deletion mutants and kinase co-expression with reporter assay in single lab, two orthogonal functional methods","pmids":["10993906"],"is_preprint":false},{"year":2000,"finding":"STAM2 physically associates with Jak2 and Jak3 and is involved in DNA synthesis and c-myc induction signaling downstream of IL-2 and GM-CSF; SH3 domain deletion mutants of STAM1 and STAM2 additively suppress DNA synthesis, indicating compensatory roles.","method":"Co-immunoprecipitation; SH3 deletion mutants; DNA synthesis assay; c-myc reporter assay","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and functional deletion mutants in single lab","pmids":["10899310"],"is_preprint":false},{"year":2002,"finding":"T-cell-specific double knockout of STAM1 and STAM2 causes significant reduction in thymocytes and peripheral T cells with defective TCR-stimulated proliferation; double-mutant thymocytes show prolonged p38 MAPK and JNK activation and increased apoptosis, but proximal IL-2/IL-7 signaling (STAT5, ERK, PKB/Akt) is normal, placing STAMs in a pro-survival pathway downstream of TCR that suppresses apoptosis.","method":"Conditional double knockout (Cre/loxP); flow cytometry; proliferation assays; western blot for signaling intermediates; cell viability assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (proliferation, signaling, apoptosis) establishing pathway position","pmids":["12446783"],"is_preprint":false},{"year":2010,"finding":"PTP1B directly dephosphorylates STAM2 at defined phosphotyrosine sites; knockdown of PTP1B augments STAM2 phosphorylation; phosphorylated STAM2 suppresses Akt activation, and a phosphorylation-deficient STAM2 mutant shows prolonged endosomal localization after EGF stimulation.","method":"Co-immunoprecipitation; PTP1B knockdown; phosphorylation-deficient mutant; subcellular localization by imaging; Akt activation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct substrate identification by co-IP plus phospho-mutant functional analysis in single lab","pmids":["20504764"],"is_preprint":false},{"year":2010,"finding":"NMR solution structure of the STAM2 VHS domain in complex with monoubiquitin; VHS binds K48-linked diubiquitin in a distinct mode (entering the hydrophobic pocket with differential affinity for each subunit) compared with monoubiquitin or K63-linked diubiquitin (similar binding mode to monoubiquitin), explaining VHS preference for K63 chains.","method":"Solution NMR; chemical shift perturbations; spin relaxation; paramagnetic relaxation enhancements","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structure with mechanistic validation of binding modes, single lab but multiple orthogonal NMR methods","pmids":["21121635"],"is_preprint":false},{"year":2012,"finding":"STAM2 VHS-UIM cooperatively binds K63-linked diubiquitin with avidity not seen for monoubiquitin or K48-linked diubiquitin; the distal ubiquitin of K63 chains stabilizes UIM helical structure and the complex adopts a specific structural organization, explaining better sorting efficiency for K63-polyubiquitinated cargo.","method":"NMR; ITC; binding affinity measurements with VHS-UIM construct and diubiquitin variants","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR plus thermodynamic measurements with defined constructs, single lab, multiple orthogonal methods","pmids":["22493438"],"is_preprint":false},{"year":2012,"finding":"The SH3 domain of STAM2 constitutes a third ubiquitin-binding domain; UBPY-derived peptide and ubiquitin compete for binding to the STAM2 SH3 domain, suggesting the SH3 domain plays dual roles in ubiquitin-mediated receptor sorting and DUB recruitment.","method":"NMR chemical shift perturbation; competitive binding assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — NMR demonstration of SH3–ubiquitin interaction and competition, single lab, single method","pmids":["22841719"],"is_preprint":false},{"year":2015,"finding":"STAM2 localizes to early endosomes in neurons; uniquely, STAM2 also localizes to the nucleus in neurons, distinct from other ESCRT-0 members (Hrs) which co-localize with STAM2 only in the cytoplasm.","method":"Subcellular fractionation; co-immunofluorescence confocal microscopy; lacZ reporter gene trap mouse line","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by fractionation and immunofluorescence with multiple markers in single lab","pmids":["26101075"],"is_preprint":false},{"year":2016,"finding":"Crystal structure of the HD-PTP Bro1 domain in complex with the STAM2 core region shows STAM2 binds the hydrophobic concave pocket of HD-PTP Bro1 in the opposite orientation to CHMP4B; Thr145 of HD-PTP is the key determinant distinguishing HD-PTP from Alix/Brox, as Alix- or Brox-mimicking mutations of this residue abolish STAM2 binding.","method":"X-ray crystal structure; mutagenesis; binding assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus mutagenesis validation of key residue in single rigorous study","pmids":["26866605"],"is_preprint":false},{"year":2016,"finding":"The AMSH SH3 binding motif (AMSH-SBM) outcompetes Lys63-linked diubiquitin for binding to the STAM2 SH3 domain; NMR structure of AMSH-SBM/SH3 complex reveals structural organization where AMSH-SBM correctly positions AMSH for polyubiquitin chain cleavage, explaining how STAM2 stimulates AMSH deubiquitinase activity.","method":"NMR; solution NMR structure; competitive binding assays with kinetic analysis","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structure with competition binding and kinetic analysis in single rigorous study","pmids":["27725184"],"is_preprint":false},{"year":2019,"finding":"Linker length and flexibility between the UIM and SH3 domains of STAM2 modulates recognition of Lys63-linked diubiquitin; shortening or lengthening the linker reduces affinity for Lys63-Ub2 up to ~8-fold, indicating interdomain dynamics tune binding.","method":"SAXS; NMR; engineered linker variants with affinity measurements","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — SAXS and NMR with engineered constructs, single lab, multiple orthogonal biophysical methods","pmids":["31601934"],"is_preprint":false},{"year":2021,"finding":"STAM2 knockdown in gastric cancer cells inhibits proliferation, cell cycle progression, migration, and invasion, and decreases phosphorylation of JAK2 and STAT3 as well as expression of MMP2 and MMP9, placing STAM2 upstream of the JAK2/STAT3 signaling axis.","method":"siRNA knockdown; CCK-8, EdU, flow cytometry, wound-healing, Boyden chamber assays; western blot; rescue assays","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with multiple functional assays and rescue in single lab","pmids":["33778841"],"is_preprint":false},{"year":2025,"finding":"STAM2 (not STAM1) directly binds cell-surface PD-L1 via its VHS domain and binds HRS via its ITAM domain, acting as a molecular bridge to initiate biogenesis of PD-L1+ small extracellular vesicles in oral squamous cell carcinoma.","method":"Co-immunoprecipitation; domain deletion/mutant analysis; sEV isolation and characterization","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP with domain-mapping mutants in single lab establishing direct binding partners","pmids":["40541896"],"is_preprint":false},{"year":2025,"finding":"O-GlcNAcylation of STAM2 at serine 375 (driven by GFAT1 upregulation) stabilizes STAM2 protein by inhibiting proteasomal degradation and ubiquitination; O-GlcNAcylated STAM2 promotes JAK2 and STAT3 phosphorylation to activate epithelial-mesenchymal transition in bladder cancer.","method":"GFAT1 inhibition; OGT inhibitor; mass spectrometry identification of modification site; proteasome assay; western blot for STAT3/JAK2 phosphorylation; metastasis assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — site-specific PTM identified by MS plus functional inhibition experiments in single lab","pmids":["40075080"],"is_preprint":false}],"current_model":"STAM2 is an ESCRT-0 adaptor protein that functions as a molecular scaffold linking ubiquitinated cargo recognition (via cooperative VHS-UIM and SH3 ubiquitin-binding domains with selectivity for K63-linked polyubiquitin), recruitment of deubiquitinases (AMSH, UBPY via SH3), and initiation of endosomal sorting for lysosomal degradation; it is tyrosine-phosphorylated by JAK1/JAK2 through its ITAM domain and dephosphorylated by PTP1B, with phosphorylation state controlling endosomal dwell time and Akt signaling output; its VHS domain directly bridges cargo (e.g., PD-L1) to HRS; and it can be O-GlcNAcylated at S375 to stabilize the protein and activate JAK2/STAT3 signaling, while T-cell-specific loss reveals a pro-survival anti-apoptotic function required for thymocyte development."},"narrative":{"mechanistic_narrative":"STAM2 is an ESCRT-0 adaptor that recognizes ubiquitinated cargo on early endosomes and couples it to deubiquitination and lysosomal sorting machinery [PMID:21121635, PMID:27725184]. Cargo recognition is achieved through cooperative use of three ubiquitin-binding modules: the VHS and UIM domains together bind K63-linked polyubiquitin with avidity not seen for monoubiquitin or K48 chains, with the distal ubiquitin stabilizing UIM helix formation, and the SH3 domain providing a third ubiquitin-binding site, explaining the selectivity for K63-polyubiquitinated cargo destined for degradation [PMID:21121635, PMID:22493438, PMID:22841719]. Interdomain linker length and flexibility between UIM and SH3 tune this K63-diubiquitin recognition [PMID:31601934]. The SH3 domain doubles as a deubiquitinase-recruitment surface: an AMSH-derived motif outcompetes K63-diubiquitin for SH3 binding and positions AMSH for chain cleavage, while a UBPY-derived peptide likewise competes for the same site [PMID:22841719, PMID:27725184]. STAM2 engages downstream sorting machinery through a defined interface with the HD-PTP Bro1 domain, where Thr145 of HD-PTP discriminates it from Alix/Brox [PMID:26866605]. STAM2 is tyrosine-phosphorylated by JAK1/JAK2 in a manner requiring its ITAM domain and is dephosphorylated by PTP1B; phosphorylation state controls endosomal dwell time and Akt output, with phosphorylation-deficient STAM2 showing prolonged endosomal localization and suppressed Akt activation [PMID:10993906, PMID:20504764]. In T cells, combined loss of STAM1/STAM2 reduces thymocyte and peripheral T-cell numbers and increases apoptosis, defining a pro-survival role downstream of TCR signaling [PMID:12446783]. In cancer contexts STAM2 bridges cell-surface PD-L1 to HRS to drive PD-L1+ extracellular vesicle biogenesis, and O-GlcNAcylation at Ser375 stabilizes STAM2 to promote JAK2/STAT3-driven phenotypes [PMID:40541896, PMID:40075080].","teleology":[{"year":2000,"claim":"Established STAM2 as a substrate and partner of JAK kinases, linking it to cytokine and growth factor receptor signaling rather than only endosomal trafficking.","evidence":"Anti-phosphotyrosine purification/MS, kinase co-expression, ITAM deletion mutants and c-Myc reporter assays; reciprocal co-IP with Jak2/Jak3 and SH3 deletion mutants in DNA synthesis assays","pmids":["10993906","10899310"],"confidence":"Medium","gaps":["Phosphorylation sites not mapped at this stage","Functional consequence of JAK association on trafficking not addressed","Relative contribution of STAM1 vs STAM2 unresolved"]},{"year":2002,"claim":"Defined an in vivo physiological role for STAMs as pro-survival factors required for T-cell development, distinct from proximal cytokine signaling.","evidence":"Conditional STAM1/STAM2 double knockout with flow cytometry, proliferation, signaling western blots and viability assays","pmids":["12446783"],"confidence":"High","gaps":["STAM2-specific (vs STAM1) contribution not isolated","Molecular link between ESCRT function and apoptosis suppression unknown","How prolonged p38/JNK activation arises mechanistically not resolved"]},{"year":2010,"claim":"Identified PTP1B as the phosphatase regulating STAM2 and linked its phosphorylation state to endosomal dwell time and Akt signaling output.","evidence":"Co-IP, PTP1B knockdown, phospho-deficient mutant imaging and Akt activation assays","pmids":["20504764"],"confidence":"Medium","gaps":["Specific tyrosine sites controlling localization not fully defined","Mechanism connecting phospho-state to dwell time unclear","Single-lab finding without reciprocal validation"]},{"year":2012,"claim":"Provided structural basis for STAM2's selectivity toward K63-linked polyubiquitin, explaining preferential sorting of K63-modified cargo.","evidence":"NMR solution structures with monoubiquitin and diubiquitin variants, ITC affinity measurements with VHS and VHS-UIM constructs","pmids":["21121635","22493438"],"confidence":"High","gaps":["In vivo cargo specificity not directly tested","Length of physiological polyubiquitin chains engaged unknown","Contribution of full-length protein context not assessed"]},{"year":2016,"claim":"Resolved how STAM2 SH3 doubles as a ubiquitin-binding and DUB-recruitment surface and how it docks onto downstream sorting machinery.","evidence":"NMR structure of AMSH-SBM/SH3 complex with competitive binding and kinetics; crystal structure of HD-PTP Bro1 domain with STAM2 core and Thr145 mutagenesis","pmids":["27725184","26866605","22841719"],"confidence":"High","gaps":["Ordering/handoff between ubiquitin binding and DUB recruitment in cells not established","Functional consequence of HD-PTP interaction on sorting not measured","Competition dynamics in native complexes unquantified"]},{"year":2019,"claim":"Showed that interdomain dynamics, not just individual domain affinities, tune K63-diubiquitin recognition.","evidence":"SAXS, NMR and engineered UIM-SH3 linker variants with affinity measurements","pmids":["31601934"],"confidence":"Medium","gaps":["Physiological regulation of linker conformation unknown","Whether linker dynamics are modulated in cells unaddressed"]},{"year":2025,"claim":"Extended STAM2 function to cargo-specific extracellular vesicle biogenesis and PTM-dependent oncogenic signaling.","evidence":"Co-IP/domain mapping for PD-L1-VHS and HRS-ITAM bridging with sEV isolation; MS site mapping of Ser375 O-GlcNAcylation with proteasome and JAK2/STAT3 phosphorylation assays; gastric cancer knockdown with functional and rescue assays","pmids":["40541896","40075080","33778841"],"confidence":"Medium","gaps":["Generality of PD-L1 bridging beyond OSCC not tested","Link between O-GlcNAcylation and ESCRT sorting function unclear","Direct vs indirect role in JAK2/STAT3 activation not dissected"]},{"year":null,"claim":"How STAM2 phosphorylation, O-GlcNAcylation, and its ESCRT-0 sorting activity are integrated into a single regulatory logic governing cargo fate and signaling output remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model connecting PTM state to cargo selectivity","STAM2-specific in vivo functions separate from STAM1 not defined","Structural picture of full ESCRT-0 cargo-loaded complex absent"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[8,9,12]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[3,7]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[7]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[8,12]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2]}],"complexes":["ESCRT-0"],"partners":["JAK2","PTP1B","HD-PTP","AMSH","UBPY","HRS","PD-L1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75886","full_name":"Signal transducing adapter molecule 2","aliases":["Hrs-binding protein"],"length_aa":525,"mass_kda":58.2,"function":"Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity)","subcellular_location":"Cytoplasm; Early endosome membrane","url":"https://www.uniprot.org/uniprotkb/O75886/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STAM2","classification":"Not Classified","n_dependent_lines":20,"n_total_lines":1208,"dependency_fraction":0.016556291390728478},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000115145","cell_line_id":"CID000786","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"HGS","stoichiometry":10.0},{"gene":"STAM","stoichiometry":4.0},{"gene":"COPA","stoichiometry":0.2},{"gene":"COPB2","stoichiometry":0.2},{"gene":"HSPH1","stoichiometry":0.2},{"gene":"IST1","stoichiometry":0.2},{"gene":"MVB12A","stoichiometry":0.2},{"gene":"PARP1","stoichiometry":0.2},{"gene":"TSG101","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000786","total_profiled":1310},"omim":[{"mim_id":"606247","title":"STAM-BINDING PROTEIN; STAMBP","url":"https://www.omim.org/entry/606247"},{"mim_id":"606244","title":"SIGNAL-TRANSDUCING ADAPTOR MOLECULE 2; STAM2","url":"https://www.omim.org/entry/606244"},{"mim_id":"603158","title":"UBIQUITIN-SPECIFIC PROTEASE 8; USP8","url":"https://www.omim.org/entry/603158"},{"mim_id":"601899","title":"SIGNAL-TRANSDUCING ADAPTOR MOLECULE 1; STAM","url":"https://www.omim.org/entry/601899"},{"mim_id":"131550","title":"EPIDERMAL GROWTH FACTOR RECEPTOR; EGFR","url":"https://www.omim.org/entry/131550"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/STAM2"},"hgnc":{"alias_symbol":["Hbp"],"prev_symbol":[]},"alphafold":{"accession":"O75886","domains":[{"cath_id":"1.25.40.90","chopping":"10-140","consensus_level":"high","plddt":94.651,"start":10,"end":140},{"cath_id":"2.30.30.40","chopping":"207-258","consensus_level":"high","plddt":91.3081,"start":207,"end":258},{"cath_id":"-","chopping":"295-303_317-362","consensus_level":"medium","plddt":91.6022,"start":295,"end":362}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75886","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75886-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75886-F1-predicted_aligned_error_v6.png","plddt_mean":68.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STAM2","jax_strain_url":"https://www.jax.org/strain/search?query=STAM2"},"sequence":{"accession":"O75886","fasta_url":"https://rest.uniprot.org/uniprotkb/O75886.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75886/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75886"}},"corpus_meta":[{"pmid":"10993906","id":"PMC_10993906","title":"Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10993906","citation_count":97,"is_preprint":false},{"pmid":"10899310","id":"PMC_10899310","title":"STAM2, a new member of the STAM family, binding to the Janus kinases.","date":"2000","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/10899310","citation_count":65,"is_preprint":false},{"pmid":"12446783","id":"PMC_12446783","title":"Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-cell development and survival.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12446783","citation_count":51,"is_preprint":false},{"pmid":"20504764","id":"PMC_20504764","title":"PTP1B targets the endosomal sorting machinery: dephosphorylation of regulatory sites on the endosomal sorting complex required for transport component STAM2.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20504764","citation_count":41,"is_preprint":false},{"pmid":"22493438","id":"PMC_22493438","title":"Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to Lys63-linked diubiquitin.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22493438","citation_count":20,"is_preprint":false},{"pmid":"26866605","id":"PMC_26866605","title":"Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26866605","citation_count":18,"is_preprint":false},{"pmid":"33778841","id":"PMC_33778841","title":"STAM2 knockdown inhibits proliferation, migration, and invasion by affecting the JAK2/STAT3 signaling pathway in gastric cancer.","date":"2021","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/33778841","citation_count":16,"is_preprint":false},{"pmid":"22841719","id":"PMC_22841719","title":"Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR.","date":"2012","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/22841719","citation_count":12,"is_preprint":false},{"pmid":"21121635","id":"PMC_21121635","title":"NMR reveals a different mode of binding of the Stam2 VHS domain to ubiquitin and diubiquitin.","date":"2010","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21121635","citation_count":12,"is_preprint":false},{"pmid":"26101075","id":"PMC_26101075","title":"STAM2, a member of the endosome-associated complex ESCRT-0 is highly expressed in neurons.","date":"2015","source":"Molecular and cellular 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2007)","url":"https://pubmed.ncbi.nlm.nih.gov/22140097","citation_count":5,"is_preprint":false},{"pmid":"18405059","id":"PMC_18405059","title":"Expression pattern and functional analysis of mouse Stam2 in the olfactory system.","date":"2008","source":"Collegium antropologicum","url":"https://pubmed.ncbi.nlm.nih.gov/18405059","citation_count":4,"is_preprint":false},{"pmid":"31601934","id":"PMC_31601934","title":"Molecular recognition of ubiquitin and Lys63-linked diubiquitin by STAM2 UIM-SH3 dual domain: the effect of its linker length and flexibility.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31601934","citation_count":4,"is_preprint":false},{"pmid":"22143071","id":"PMC_22143071","title":"Stam2 expression pattern during embryo development.","date":"2011","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/22143071","citation_count":3,"is_preprint":false},{"pmid":"24085429","id":"PMC_24085429","title":"Molecular cloning, polymorphisms, and association analysis of the promoter region of the STAM2 gene in Wuchuan Black cattle.","date":"2013","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/24085429","citation_count":3,"is_preprint":false},{"pmid":"39060946","id":"PMC_39060946","title":"GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis.","date":"2024","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39060946","citation_count":2,"is_preprint":false},{"pmid":"40541896","id":"PMC_40541896","title":"STAM2-mediated fine-tuning of PD-L1 secretion via small extracellular vesicles in oral squamous cell carcinoma.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40541896","citation_count":2,"is_preprint":false},{"pmid":"38593891","id":"PMC_38593891","title":"STAM2 negatively regulates the MyD88-mediated NF-κB signaling pathway in miiuy croaker, Miichthys miiuy.","date":"2024","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38593891","citation_count":2,"is_preprint":false},{"pmid":"24778033","id":"PMC_24778033","title":"Immunohistochemical expression of STAM2 in gastrointestinal stromal tumors.","date":"2014","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/24778033","citation_count":2,"is_preprint":false},{"pmid":"40075080","id":"PMC_40075080","title":"Starvation-induced HBP metabolic reprogramming and STAM2 O-GlcNAcylation facilitate bladder cancer metastasis.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40075080","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12118,"output_tokens":3448,"usd":0.044037,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10928,"output_tokens":3136,"usd":0.06652,"stage2_stop_reason":"end_turn"},"total_usd":0.110557,"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\": 2000,\n      \"finding\": \"STAM2 is tyrosine-phosphorylated downstream of growth factor receptors (EGF, PDGF) and cytokines (IL-3, IL-2); it is phosphorylated by Jak1 and Jak2 (but not the unrelated Tec kinase Etk), requiring the ITAM domain for JAK-mediated phosphorylation; overexpression of wild-type STAM2 potentiates IL-2-mediated c-Myc promoter activation.\",\n      \"method\": \"Anti-phosphotyrosine affinity purification + mass spectrometry identification; co-expression with kinase constructs; deletion mutant analysis; reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple deletion mutants and kinase co-expression with reporter assay in single lab, two orthogonal functional methods\",\n      \"pmids\": [\"10993906\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"STAM2 physically associates with Jak2 and Jak3 and is involved in DNA synthesis and c-myc induction signaling downstream of IL-2 and GM-CSF; SH3 domain deletion mutants of STAM1 and STAM2 additively suppress DNA synthesis, indicating compensatory roles.\",\n      \"method\": \"Co-immunoprecipitation; SH3 deletion mutants; DNA synthesis assay; c-myc reporter assay\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and functional deletion mutants in single lab\",\n      \"pmids\": [\"10899310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"T-cell-specific double knockout of STAM1 and STAM2 causes significant reduction in thymocytes and peripheral T cells with defective TCR-stimulated proliferation; double-mutant thymocytes show prolonged p38 MAPK and JNK activation and increased apoptosis, but proximal IL-2/IL-7 signaling (STAT5, ERK, PKB/Akt) is normal, placing STAMs in a pro-survival pathway downstream of TCR that suppresses apoptosis.\",\n      \"method\": \"Conditional double knockout (Cre/loxP); flow cytometry; proliferation assays; western blot for signaling intermediates; cell viability assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean conditional KO with multiple orthogonal readouts (proliferation, signaling, apoptosis) establishing pathway position\",\n      \"pmids\": [\"12446783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PTP1B directly dephosphorylates STAM2 at defined phosphotyrosine sites; knockdown of PTP1B augments STAM2 phosphorylation; phosphorylated STAM2 suppresses Akt activation, and a phosphorylation-deficient STAM2 mutant shows prolonged endosomal localization after EGF stimulation.\",\n      \"method\": \"Co-immunoprecipitation; PTP1B knockdown; phosphorylation-deficient mutant; subcellular localization by imaging; Akt activation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct substrate identification by co-IP plus phospho-mutant functional analysis in single lab\",\n      \"pmids\": [\"20504764\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"NMR solution structure of the STAM2 VHS domain in complex with monoubiquitin; VHS binds K48-linked diubiquitin in a distinct mode (entering the hydrophobic pocket with differential affinity for each subunit) compared with monoubiquitin or K63-linked diubiquitin (similar binding mode to monoubiquitin), explaining VHS preference for K63 chains.\",\n      \"method\": \"Solution NMR; chemical shift perturbations; spin relaxation; paramagnetic relaxation enhancements\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structure with mechanistic validation of binding modes, single lab but multiple orthogonal NMR methods\",\n      \"pmids\": [\"21121635\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"STAM2 VHS-UIM cooperatively binds K63-linked diubiquitin with avidity not seen for monoubiquitin or K48-linked diubiquitin; the distal ubiquitin of K63 chains stabilizes UIM helical structure and the complex adopts a specific structural organization, explaining better sorting efficiency for K63-polyubiquitinated cargo.\",\n      \"method\": \"NMR; ITC; binding affinity measurements with VHS-UIM construct and diubiquitin variants\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR plus thermodynamic measurements with defined constructs, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"22493438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The SH3 domain of STAM2 constitutes a third ubiquitin-binding domain; UBPY-derived peptide and ubiquitin compete for binding to the STAM2 SH3 domain, suggesting the SH3 domain plays dual roles in ubiquitin-mediated receptor sorting and DUB recruitment.\",\n      \"method\": \"NMR chemical shift perturbation; competitive binding assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — NMR demonstration of SH3–ubiquitin interaction and competition, single lab, single method\",\n      \"pmids\": [\"22841719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"STAM2 localizes to early endosomes in neurons; uniquely, STAM2 also localizes to the nucleus in neurons, distinct from other ESCRT-0 members (Hrs) which co-localize with STAM2 only in the cytoplasm.\",\n      \"method\": \"Subcellular fractionation; co-immunofluorescence confocal microscopy; lacZ reporter gene trap mouse line\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by fractionation and immunofluorescence with multiple markers in single lab\",\n      \"pmids\": [\"26101075\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of the HD-PTP Bro1 domain in complex with the STAM2 core region shows STAM2 binds the hydrophobic concave pocket of HD-PTP Bro1 in the opposite orientation to CHMP4B; Thr145 of HD-PTP is the key determinant distinguishing HD-PTP from Alix/Brox, as Alix- or Brox-mimicking mutations of this residue abolish STAM2 binding.\",\n      \"method\": \"X-ray crystal structure; mutagenesis; binding assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus mutagenesis validation of key residue in single rigorous study\",\n      \"pmids\": [\"26866605\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The AMSH SH3 binding motif (AMSH-SBM) outcompetes Lys63-linked diubiquitin for binding to the STAM2 SH3 domain; NMR structure of AMSH-SBM/SH3 complex reveals structural organization where AMSH-SBM correctly positions AMSH for polyubiquitin chain cleavage, explaining how STAM2 stimulates AMSH deubiquitinase activity.\",\n      \"method\": \"NMR; solution NMR structure; competitive binding assays with kinetic analysis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structure with competition binding and kinetic analysis in single rigorous study\",\n      \"pmids\": [\"27725184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Linker length and flexibility between the UIM and SH3 domains of STAM2 modulates recognition of Lys63-linked diubiquitin; shortening or lengthening the linker reduces affinity for Lys63-Ub2 up to ~8-fold, indicating interdomain dynamics tune binding.\",\n      \"method\": \"SAXS; NMR; engineered linker variants with affinity measurements\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — SAXS and NMR with engineered constructs, single lab, multiple orthogonal biophysical methods\",\n      \"pmids\": [\"31601934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"STAM2 knockdown in gastric cancer cells inhibits proliferation, cell cycle progression, migration, and invasion, and decreases phosphorylation of JAK2 and STAT3 as well as expression of MMP2 and MMP9, placing STAM2 upstream of the JAK2/STAT3 signaling axis.\",\n      \"method\": \"siRNA knockdown; CCK-8, EdU, flow cytometry, wound-healing, Boyden chamber assays; western blot; rescue assays\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with multiple functional assays and rescue in single lab\",\n      \"pmids\": [\"33778841\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"STAM2 (not STAM1) directly binds cell-surface PD-L1 via its VHS domain and binds HRS via its ITAM domain, acting as a molecular bridge to initiate biogenesis of PD-L1+ small extracellular vesicles in oral squamous cell carcinoma.\",\n      \"method\": \"Co-immunoprecipitation; domain deletion/mutant analysis; sEV isolation and characterization\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP with domain-mapping mutants in single lab establishing direct binding partners\",\n      \"pmids\": [\"40541896\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"O-GlcNAcylation of STAM2 at serine 375 (driven by GFAT1 upregulation) stabilizes STAM2 protein by inhibiting proteasomal degradation and ubiquitination; O-GlcNAcylated STAM2 promotes JAK2 and STAT3 phosphorylation to activate epithelial-mesenchymal transition in bladder cancer.\",\n      \"method\": \"GFAT1 inhibition; OGT inhibitor; mass spectrometry identification of modification site; proteasome assay; western blot for STAT3/JAK2 phosphorylation; metastasis assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — site-specific PTM identified by MS plus functional inhibition experiments in single lab\",\n      \"pmids\": [\"40075080\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STAM2 is an ESCRT-0 adaptor protein that functions as a molecular scaffold linking ubiquitinated cargo recognition (via cooperative VHS-UIM and SH3 ubiquitin-binding domains with selectivity for K63-linked polyubiquitin), recruitment of deubiquitinases (AMSH, UBPY via SH3), and initiation of endosomal sorting for lysosomal degradation; it is tyrosine-phosphorylated by JAK1/JAK2 through its ITAM domain and dephosphorylated by PTP1B, with phosphorylation state controlling endosomal dwell time and Akt signaling output; its VHS domain directly bridges cargo (e.g., PD-L1) to HRS; and it can be O-GlcNAcylated at S375 to stabilize the protein and activate JAK2/STAT3 signaling, while T-cell-specific loss reveals a pro-survival anti-apoptotic function required for thymocyte development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STAM2 is an ESCRT-0 adaptor that recognizes ubiquitinated cargo on early endosomes and couples it to deubiquitination and lysosomal sorting machinery [#4, #9]. Cargo recognition is achieved through cooperative use of three ubiquitin-binding modules: the VHS and UIM domains together bind K63-linked polyubiquitin with avidity not seen for monoubiquitin or K48 chains, with the distal ubiquitin stabilizing UIM helix formation, and the SH3 domain providing a third ubiquitin-binding site, explaining the selectivity for K63-polyubiquitinated cargo destined for degradation [#4, #5, #6]. Interdomain linker length and flexibility between UIM and SH3 tune this K63-diubiquitin recognition [#10]. The SH3 domain doubles as a deubiquitinase-recruitment surface: an AMSH-derived motif outcompetes K63-diubiquitin for SH3 binding and positions AMSH for chain cleavage, while a UBPY-derived peptide likewise competes for the same site [#6, #9]. STAM2 engages downstream sorting machinery through a defined interface with the HD-PTP Bro1 domain, where Thr145 of HD-PTP discriminates it from Alix/Brox [#8]. STAM2 is tyrosine-phosphorylated by JAK1/JAK2 in a manner requiring its ITAM domain and is dephosphorylated by PTP1B; phosphorylation state controls endosomal dwell time and Akt output, with phosphorylation-deficient STAM2 showing prolonged endosomal localization and suppressed Akt activation [#0, #3]. In T cells, combined loss of STAM1/STAM2 reduces thymocyte and peripheral T-cell numbers and increases apoptosis, defining a pro-survival role downstream of TCR signaling [#2]. In cancer contexts STAM2 bridges cell-surface PD-L1 to HRS to drive PD-L1+ extracellular vesicle biogenesis, and O-GlcNAcylation at Ser375 stabilizes STAM2 to promote JAK2/STAT3-driven phenotypes [#12, #13].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established STAM2 as a substrate and partner of JAK kinases, linking it to cytokine and growth factor receptor signaling rather than only endosomal trafficking.\",\n      \"evidence\": \"Anti-phosphotyrosine purification/MS, kinase co-expression, ITAM deletion mutants and c-Myc reporter assays; reciprocal co-IP with Jak2/Jak3 and SH3 deletion mutants in DNA synthesis assays\",\n      \"pmids\": [\"10993906\", \"10899310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphorylation sites not mapped at this stage\", \"Functional consequence of JAK association on trafficking not addressed\", \"Relative contribution of STAM1 vs STAM2 unresolved\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined an in vivo physiological role for STAMs as pro-survival factors required for T-cell development, distinct from proximal cytokine signaling.\",\n      \"evidence\": \"Conditional STAM1/STAM2 double knockout with flow cytometry, proliferation, signaling western blots and viability assays\",\n      \"pmids\": [\"12446783\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"STAM2-specific (vs STAM1) contribution not isolated\", \"Molecular link between ESCRT function and apoptosis suppression unknown\", \"How prolonged p38/JNK activation arises mechanistically not resolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified PTP1B as the phosphatase regulating STAM2 and linked its phosphorylation state to endosomal dwell time and Akt signaling output.\",\n      \"evidence\": \"Co-IP, PTP1B knockdown, phospho-deficient mutant imaging and Akt activation assays\",\n      \"pmids\": [\"20504764\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific tyrosine sites controlling localization not fully defined\", \"Mechanism connecting phospho-state to dwell time unclear\", \"Single-lab finding without reciprocal validation\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Provided structural basis for STAM2's selectivity toward K63-linked polyubiquitin, explaining preferential sorting of K63-modified cargo.\",\n      \"evidence\": \"NMR solution structures with monoubiquitin and diubiquitin variants, ITC affinity measurements with VHS and VHS-UIM constructs\",\n      \"pmids\": [\"21121635\", \"22493438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo cargo specificity not directly tested\", \"Length of physiological polyubiquitin chains engaged unknown\", \"Contribution of full-length protein context not assessed\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Resolved how STAM2 SH3 doubles as a ubiquitin-binding and DUB-recruitment surface and how it docks onto downstream sorting machinery.\",\n      \"evidence\": \"NMR structure of AMSH-SBM/SH3 complex with competitive binding and kinetics; crystal structure of HD-PTP Bro1 domain with STAM2 core and Thr145 mutagenesis\",\n      \"pmids\": [\"27725184\", \"26866605\", \"22841719\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ordering/handoff between ubiquitin binding and DUB recruitment in cells not established\", \"Functional consequence of HD-PTP interaction on sorting not measured\", \"Competition dynamics in native complexes unquantified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed that interdomain dynamics, not just individual domain affinities, tune K63-diubiquitin recognition.\",\n      \"evidence\": \"SAXS, NMR and engineered UIM-SH3 linker variants with affinity measurements\",\n      \"pmids\": [\"31601934\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological regulation of linker conformation unknown\", \"Whether linker dynamics are modulated in cells unaddressed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended STAM2 function to cargo-specific extracellular vesicle biogenesis and PTM-dependent oncogenic signaling.\",\n      \"evidence\": \"Co-IP/domain mapping for PD-L1-VHS and HRS-ITAM bridging with sEV isolation; MS site mapping of Ser375 O-GlcNAcylation with proteasome and JAK2/STAT3 phosphorylation assays; gastric cancer knockdown with functional and rescue assays\",\n      \"pmids\": [\"40541896\", \"40075080\", \"33778841\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generality of PD-L1 bridging beyond OSCC not tested\", \"Link between O-GlcNAcylation and ESCRT sorting function unclear\", \"Direct vs indirect role in JAK2/STAT3 activation not dissected\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How STAM2 phosphorylation, O-GlcNAcylation, and its ESCRT-0 sorting activity are integrated into a single regulatory logic governing cargo fate and signaling output remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model connecting PTM state to cargo selectivity\", \"STAM2-specific in vivo functions separate from STAM1 not defined\", \"Structural picture of full ESCRT-0 cargo-loaded complex absent\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [8, 9, 12]},\n      {\"term_id\": \"GO:0043130\", \"supporting_discovery_ids\": [4, 5, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [3, 7]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [8, 12]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"ESCRT-0\"],\n    \"partners\": [\"JAK2\", \"PTP1B\", \"HD-PTP\", \"AMSH\", \"UBPY\", \"HRS\", \"PD-L1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}