CSTB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0002020 protease binding	IDA PMID:11514663 Role of the single cysteine residue, Cys 3, of human and bov...	ACCEPT	Summary: Direct evidence supports the preserved protease interaction or inhibitory activity. Reason: Direct human CSTB WT/C3S binding and inhibition kinetics support protease binding as a central interaction. The original selected Results/Methods distinguish sheep cathepsin L, pig cathepsin H and human cathepsin B. These are mixed-species target-enzyme assays. Inhibitor activity is separately captured by GO:0004869. Supporting Evidence: PMID:11514663 binding tightly to papain and cathepsin L
GO:0002020 protease binding	IEA GO_REF:0000117	ACCEPT	Summary: The matched ARBA rule supports protease binding. Reason: The actual ARBA00087861 branch 6 matches the target stefin family and taxonomic predicates. Direct human CSTB binding in PMID:11514663 corroborates the rule. Protease binding is informative here and its retrieved caspase/ubiquitin-specific-protease children do not describe the demonstrated targets. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087861 SUPPORTS TRANSFER All eight current condition sets were evaluated; branch 6 matches. Its explicit GO:0002020 output agrees with measured CSTB–protease interactions.
GO:0002020 protease binding	IPI PMID:6203523 The place of human gamma-trace (cystatin C) amongst the cyst...	ACCEPT	Summary: Direct evidence supports the preserved protease interaction or inhibitory activity. Reason: The full indexed original explicitly includes human cystatin B and human cathepsin H. Its comparative Table 1 reproduces earlier CSTB inhibition constants; preserve the positive protease-binding assertion and P09668 source entity, without describing a new CSTB kinetic experiment in this paper. The 2001 paper independently corroborates binding using pig cathepsin H, not the exact human partner assay.
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	MODIFY	Summary: UV-crosslink capture identifies CSTB as an mRNA-binding protein. Reason: PMID:22658674 uses UV crosslinking in living human HeLa cells, stringent oligo(dT) purification and mass spectrometry. Actual Table S1 row 603 identifies CSTB/NP_000091 in the mRNA-interactome, detected in crosslinked samples and not identified in the control. This supports the more specific mRNA-binding term. It does not establish a target transcript, regulatory consequence or a second physiological core; the separately tested GFP-tagged validation panel is not assigned to CSTB. Proposed replacements: mRNA binding Supporting Evidence: file:human/CSTB/CSTB-primary-excerpts.md CSTB \| mRNA-interactome \| identified \| not identified \| NP_000091
GO:0004866 endopeptidase inhibitor activity	IDA PMID:3053245 Cloning a synthetic gene for human stefin B and its expressi...	MODIFY	Summary: The positive assertion can be stated at the demonstrated biochemical specificity. Reason: The actual abstract reports papain inhibition by native recombinant human stefin B and CNBr-cleaved fusion protein, supporting cysteine-type specificity. Full 1988 text remains unrecovered; precise historical substitutions are not reconstructed from the abstract. This refines a positive inhibitor assertion, not a negative judgment from incomplete access. Proposed replacements: cysteine-type endopeptidase inhibitor activity Supporting Evidence: PMID:3053245 native recombinant stefin B were inhibitory to papain
GO:0004866 endopeptidase inhibitor activity	IEA GO_REF:0000002	ACCEPT	Summary: The stefin-family mapping correctly predicts inhibitor activity. Reason: The current IPR001713 stefin-family entry explicitly maps GO:0004866, and the official CSTB record carries that family. Its broad electronic activity is biologically sound and independently supported by recombinant human inhibition. Retain this valid broad mapping alongside separately refined experimental rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001713 SUPPORTS TRANSFER Current entry is the stefin family, despite historical stefin-A-centered descriptions. Target membership and the actual GO:0004866 output are verified; this is not a CSTB/CSTA confusion.
GO:0004866 endopeptidase inhibitor activity	TAS PMID:3053245 Cloning a synthetic gene for human stefin B and its expressi...	MODIFY	Summary: The positive assertion can be stated at the demonstrated biochemical specificity. Reason: Preserve this separate TAS assertion. The actual abstract reports inhibition of papain by recombinant human stefin B; GO:0004869 identifies the demonstrated cysteine-type activity more precisely than GO:0004866. Full 1988 methods remain unavailable. Proposed replacements: cysteine-type endopeptidase inhibitor activity Supporting Evidence: PMID:3053245 native recombinant stefin B were inhibitory to papain
GO:0004869 cysteine-type endopeptidase inhibitor activity	IBA GO_REF:0000033	ACCEPT	Summary: Cysteine-protease inhibition is inherited from an experimentally grounded ancestral node. Reason: The actual GO:0004869 IBD at PTN000151700 lies on the current human CSTB path, with an exact 98-residue target MSA sequence. Same-term experimental descendants include human CSTB, cystatin A and two Dictyostelium cystatins. PMID:15255188 directly reports recombinant papain/cathepsin B inhibition in its abstract; human target experiments independently establish the activity. No target-path loss is present and the target serving as descendant evidence is expected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000151700 SUPPORTS TRANSFER Literal IBD is on the 171-node family tree target path. Actual donor IDs and current same-term records are preserved in the public index; self-target descendant evidence is valid.
GO:0004869 cysteine-type endopeptidase inhibitor activity	IDA PMID:3488317 Isolation of six cysteine proteinase inhibitors from human u...	ACCEPT	Summary: Direct evidence supports the preserved protease interaction or inhibitory activity. Reason: The original 1986 Results identify urinary CSTB independently and report its inhibition of papain and isolated human cathepsin B, with continuous fluorimetric assays. This is CSTB-specific evidence within the six-inhibitor study; the stronger extracellular role proposed for cystatin C is not transferred to CSTB. Supporting Evidence: PMID:3488317 one as cystatin B
GO:0004869 cysteine-type endopeptidase inhibitor activity	IDA PMID:6203523 The place of human gamma-trace (cystatin C) amongst the cyst...	ACCEPT	Summary: Direct evidence supports the preserved protease interaction or inhibitory activity. Reason: The comparative original Table 1 and Discussion explicitly support CSTB inhibition of cysteine proteases. CSTB constants are identified as previously published values rather than new measurements in the 1984 paper. Preserve the positive assertion; independent 1986 and 2001 experiments corroborate the activity.
GO:0004869 cysteine-type endopeptidase inhibitor activity	IEA GO_REF:0000002	ACCEPT	Summary: The cystatin-domain mapping agrees with directly established CSTB activity. Reason: IPR000010 explicitly outputs GO:0004869 and is present on human CSTB. The domain family is broader than uniformly active inhibitors, so target-specific experiments, rather than domain presence alone, establish transfer in this case. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000010 SUPPORTS TRANSFER Actual cystatin-domain GO:0004869 mapping and official target match are verified; direct human inhibition supplies the target-specific corroboration.
GO:0005576 extracellular region	HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter...	UNDECIDED	Summary: The tear-proteomics attribution could not be verified at the CSTB row. Reason: The complete PMID:23580065 abstract describes human tear shotgun proteomics but does not identify the CSTB result. Publisher and repository routes did not yield accessible full Methods or the relevant table. Its emphasis on cystatin S is not evidence of misattribution. Extracellular CSTB is independently established in urine, but the specific tear-screen source remains unresolved.
GO:0005576 extracellular region	IDA PMID:3488317 Isolation of six cysteine proteinase inhibitors from human u...	KEEP AS NON CORE	Summary: CSTB occurs in human urine and other extracellular fluids. Reason: CSTB was isolated and immunochemically identified from proteinuric human urine, and CSTB-specific fluid measurements are reported. This supports extracellular occurrence. It does not establish constitutive secretion or make extracellular inhibition the compact core; the paper itself distinguishes presence from predicted physiological efficacy. Supporting Evidence: PMID:3488317 isolated from human urine
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798745	KEEP AS NON CORE	Summary: Reactome places CSTB in the extracellular output of granule release. Reason: The actual R-HSA-6798745 output set contains the human P04080 CSTB entity, residues 1–98, in the extracellular region; its input set places CSTB in the tertiary granule lumen. This preserves the curated cargo localization. It does not assign CSTB the machinery of exocytosis or infer constitutive secretion from an intracellular inhibitor.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Reactome places CSTB in the extracellular output of granule release. Reason: The actual R-HSA-6798748 output set contains the human P04080 CSTB entity, residues 1–98, in the extracellular region; its input set places CSTB in the secretory granule lumen. This preserves the curated cargo localization. It does not assign CSTB the machinery of exocytosis or infer constitutive secretion from an intracellular inhibitor.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Reactome places CSTB in the extracellular output of granule release. Reason: The actual R-HSA-6800434 output set contains the human P04080 CSTB entity, residues 1–98, in the extracellular region; its input set places CSTB in the ficolin-1-rich granule lumen. This preserves the curated cargo localization. It does not assign CSTB the machinery of exocytosis or infer constitutive secretion from an intracellular inhibitor.
GO:0005634 nucleus	IDA PMID:11139332 Nuclear localization of cystatin B, the cathepsin inhibitor ...	ACCEPT	Summary: CSTB localizes to nuclei in human cells. Reason: The original PMID:11139332 Methods and Results include antibody controls, confocal microscopy and immunogold localization in human SH-SY5Y and Saos-2 cells, with separate monkey/rat preparations. Nuclear enrichment is prominent in proliferating cells and distribution changes with differentiation. PMID:20075068 independently supplies nuclear protease-regulation evidence; no fixed exclusion from the cytosol is inferred. Supporting Evidence: PMID:11139332 B is found mainly in the nucleus of proliferating cells
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt nucleus mapping agrees with direct localization. Reason: The official CSTB subcellular-location record and SL-0191 map to GO:0005634. Human imaging in PMID:11139332 independently supports the location, and PMID:20075068 supports nuclear protease regulation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER Actual SL-0191→GO:0005634 mapping and target nuclear location are present; primary human localization corroborates them.
GO:0005730 nucleolus	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA records nucleolar localization in defined human cell lines. Reason: Current HPA antibody HPA017380 records nucleoli plus cytosol in U-251MG and nucleoli in KOLF2.1J iPSCs, with supported reliability. These are actual antibody-specific records; image pixels were not reinterpreted. The localization does not establish a nucleolar biochemical role or ribosome-biogenesis activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: HPA:HPA017380 SUPPORTS TRANSFER Actual current antibody blocks support the same nucleolar term. Localization is retained without assigning an untested nucleolar function.
GO:0005737 cytoplasm	IDA PMID:11139332 Nuclear localization of cystatin B, the cathepsin inhibitor ...	ACCEPT	Summary: The original imaging supports a broad cytoplasmic distribution alongside nuclear localization. Reason: PMID:11139332 observes nuclear and cytoplasmic CSTB in human SH-SY5Y cells. Its immunogold Results explicitly include mitochondrial labeling within the cytoplasmic pool, so replacing this source assertion by cytosol alone would narrow its observed scope. Independently supported cytosol annotations and the nucleus/cytosol core remain valid; no new mitochondrial assertion is inferred here.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: The broad electronic cytoplasm mapping is correct. Reason: SL-0086 explicitly maps cytoplasm and is recorded for CSTB. Cytosolic localization is independently supported, making the broader electronic term true; retain it without claiming that every cytoplasmic compartment was tested. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER Verified target location and actual SL-0086 mapping support transfer; the broad mapping remains sound alongside a more precise experimental refinement.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Cytosolic localization has a genuine inherited PAINT assertion. Reason: The actual current GO:0005829 IBD at PTN000151700 is on the CSTB target path. Its human and Dictyostelium descendant records are present; the human HPA evidence and PMID:20075068 independently corroborate target cytosol localization. The Dictyostelium full Methods were not recovered, so no new donor assay details are inferred from its abstract. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000151700 SUPPORTS TRANSFER Current same-term IBD, ancestral placement and exact target MSA match are verified. Human target evidence is a legitimate descendant source, not circular.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA supports the cytosolic CSTB pool. Reason: HPA017380 ICC/IF records cytosol in A-431 and U-251MG, with supported reliability and a separate nucleolar iPSC pattern. This agrees with the broader primary intracellular localization evidence. It does not establish identical distribution in all cell types. Propagation Review Root cause: NO FAILURE CORE Sources checked: HPA:HPA017380 SUPPORTS TRANSFER Actual antibody-specific A-431/U-251MG blocks contain GO:0005829; aggregate and cell-level records agree.
GO:0031012 extracellular matrix	HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ...	KEEP AS NON CORE	Summary: CSTB is detected in ECM-enriched human tissue fractions. Reason: PMID:25037231 sequentially extracts cytosolic, nuclear, membrane and cytoskeletal material before analyzing an ECM-enriched insoluble fraction from human colon/liver tissues and cancers. Actual supplementary workbook sheets A/B row 247 identify P04080/CSTB with multiple peptides in several preparations. Enrichment and matrisome classification support contextual association, not a structural scaffold function or exclusive extracellular residence. Supporting Evidence: file:human/CSTB/CSTB-primary-excerpts.md ECM Regulators \| Cystatin-B \| CSTB \| P04080
GO:0031012 extracellular matrix	HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D...	KEEP AS NON CORE	Summary: CSTB is detected in selected ECM-enriched omental preparations. Reason: PMID:28675934 supplementary Table S1 identifies P04080/CSTB in metastatic and normal omentum urea-soluble fractions (sheets C/D), with single-peptide observations in these rows. The main Results describe ECM enrichment and fractionation. Retain the source-scoped location; no CSTB-specific matrix-building activity, universal tissue detection or full Methods read is claimed.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Reactome explicitly records CSTB in the secretory granule lumen. Reason: The literal R-HSA-6798748 input set has a human P04080 CSTB member, residues 1–98, in the secretory granule lumen; its matched output is extracellular. This is positive curated cargo-location evidence. The original neutrophil proteomics table was not independently reanalyzed, and the location is not used to invent a degranulation process annotation.
GO:0045861 negative regulation of proteolysis	IDA PMID:3488317 Isolation of six cysteine proteinase inhibitors from human u...	MODIFY	Summary: The positive assertion can be stated at the demonstrated biochemical specificity. Reason: CSTB directly reduces substrate cleavage by papain and human cathepsin B in the original assay. Negative regulation of endopeptidase activity is a retrieved descendant of GO:0045861 that states this performed inhibitory step. No dominant in-vivo extracellular CTSB control is inferred from these kinetics or detection. Proposed replacements: negative regulation of endopeptidase activity Supporting Evidence: PMID:3488317 papain and human cathepsin B
GO:0045861 negative regulation of proteolysis	IDA PMID:6203523 The place of human gamma-trace (cystatin C) amongst the cyst...	MODIFY	Summary: The positive assertion can be stated at the demonstrated biochemical specificity. Reason: The original comparative table positively supports the endopeptidase-inhibition component of the CSTB spectrum, including papain and cathepsins B/L. Refine to negative regulation of endopeptidase activity while preserving the historical IDA source and acknowledging that its CSTB constants reproduce earlier work. Broader amino-/dipeptidase activity remains represented in integrated core prose/BP, not denied. The quoted PMID:3488317 supplies independent direct human CSTB assay corroboration; it is not presented as a new measurement made in PMID:6203523. Proposed replacements: negative regulation of endopeptidase activity Supporting Evidence: PMID:3488317 papain and human cathepsin B
GO:0045861 negative regulation of proteolysis	IEA GO_REF:0000117	ACCEPT	Summary: The matched rule captures direct suppression of proteolysis. Reason: All current ARBA00029031 branches were evaluated; branch 9 matches the official target conditions and outputs GO:0045861. Human inhibition assays establish the negative regulation itself. The broad electronic process is retained while experimental source rows are refined to the measured endopeptidase component. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029031 SUPPORTS TRANSFER All 12 condition sets were evaluated, with branch 9 matching and no unknown predicates. The explicit GO:0045861 output agrees with measured inhibition.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Human urinary vesicle preparations contain CSTB. Reason: The original PMID:19056867 Methods and Results define a low-density urinary membrane fraction chiefly containing exosomes and describe peptide-disambiguation controls. The authors’ linked NHLBI database explicitly lists CSTB/NP_000091 with two peptides under reference 2 (Gonzales 2009). This is detection in a vesicle preparation, not evidence that CSTB performs vesicle biogenesis or a quantified intravesicular topology assay.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	KEEP AS NON CORE	Summary: CSTB is identified in the human parotid exosome proteome. Reason: The authentic PMID:19199708 supplementary Table S2 row 353 identifies CSTB/IPI00021828.1, with seven peptides, 20 spectra and 55.1% coverage for a 98-residue product. The accessible main abstract and Discussion place the preparation in human parotid saliva; the selected cache lacks most original Methods/Results. Preserve this direct table-supported location without inventing a secretion mechanism or target-specific vesicle function. Supporting Evidence: file:human/CSTB/CSTB-primary-excerpts.md Cystatin B \| 7 \| 20
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	UNDECIDED	Summary: The EPS-urine exosome target attribution remains unverified. Reason: The accessible original PMID:23533145 main text reports ultracentrifugation of pooled human EPS-urines, replicate mass spectrometry and a nearly 900-protein supplementary table. That target table was not recovered, so CSTB cannot be independently verified within this particular study. Independent urinary/parotid detections make the location plausible, but do not replace the missing source-specific row. This is not evidence that the original annotation is false.
GO:1904724 tertiary granule lumen	TAS Reactome:R-HSA-6798745	KEEP AS NON CORE	Summary: Reactome explicitly records CSTB in the tertiary granule lumen. Reason: The literal R-HSA-6798745 input set has a human P04080 CSTB member, residues 1–98, in the tertiary granule lumen; its matched output is extracellular. This is positive curated cargo-location evidence. The original neutrophil proteomics table was not independently reanalyzed, and the location is not used to invent a degranulation process annotation.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Reactome explicitly records CSTB in the ficolin-1-rich granule lumen. Reason: The literal R-HSA-6800434 input set has a human P04080 CSTB member, residues 1–98, in the ficolin-1-rich granule lumen; its matched output is extracellular. This is positive curated cargo-location evidence. The original neutrophil proteomics table was not independently reanalyzed, and the location is not used to invent a degranulation process annotation.

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