CTSK encodes cathepsin K, a papain-family cysteine endopeptidase synthesized as a 329-residue secretory precursor and processed to a mature 215-residue enzyme. It acts in lysosomal compartments and after secretion, with a prominent role in osteoclast degradation of collagen-rich bone matrix. Its proteolysis extends to several extracellular matrix proteins, and glycosaminoglycans modulate its collagenolytic activity. Specialized thyroid pools also participate in thyroglobulin proteolysis and hormone liberation. Loss of CTSK function causes pycnodysostosis, characterized by impaired bone remodeling and brittle, dense bone.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000423 mitophagy | HMP PMID:24912190 Genome-wide RNAi screen identifies the Parkinson disease GWA... | KEEP AS NON CORE | Summary: CTSK is a validated human RNAi-screen hit retained as contextual mitophagy involvement. Reason: The original Results and Table 1 identify CTSK among 20 human hits in YFP-Parkin HeLa cells. Triplicate siRNA screening required scores more than three standard deviations from the negative control for both early Parkin translocation and later mitochondrial clearance after CCCP. This supports the existing HMP inference of contextual involvement. It does not establish a CTSK-specific mitochondrial substrate, direct mitochondrial proteolysis, selectivity for mitophagy, or a conserved core mechanism. The subsequent low-throughput rescue, lipogenesis and PINK1 experiments concern SREBF1 and other named factors, not CTSK. No independent contradiction of the CTSK screen result was found; a nonspecific lysosomal-flux explanation is not demonstrated by the inspected experiments. |
| GO:0001968 fibronectin binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibronectin engagement is retained as a substrate interaction. Reason: The current ARBA00091264 condition set matches CTSK. The independent human cathepsin K digestion of human plasma fibronectin in PMID:22952693 supports the positive substrate interaction. This does not establish a separate adhesive or matrix-assembly activity. |
| GO:0001968 fibronectin binding | IPI PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | KEEP AS NON CORE | Summary: The fibronectin interaction is supported at the proteolytic substrate level. Reason: The original compares purified cathepsins against human plasma fibronectin; the CTSK lane in supplementary Figure S2 shows degradation blocked by E-64. Its SPR and ELISA experiments principally concern nidogen binding to matrix partners, so they are not presented as a CTSK–fibronectin affinity measurement. Retain the curated positive interaction as contextual substrate engagement. |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited cysteine endopeptidase activity is supported. Reason: The actual PTHR12411 topology places CTSK below PTN000274640, where the positive GO:0004197 IBD is recorded; no relevant IRD or IKR lies on the target path. The target alignment matches the official 329-residue precursor, and its cysteine catalytic center and human enzyme assays establish retained activity. A contradictory NOT decoration in the tree leaf display is recorded as an unresolved metadata discrepancy, not treated as biological loss. Target self-evidence is legitimate. Supporting Evidence: GO_REF:0000033 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: Human CTSK performs cysteine-type endoproteolysis. Reason: The full original includes Pichia-produced human cathepsin K, active-site titration with E-64 and matrix-substrate cleavage. Supplementary Figure S2 directly separates CTSK from the other cathepsins and shows inhibitor-sensitive substrate degradation. The paper’s focus on cathepsin S does not exclude these positive CTSK experiments. Supporting Evidence: PMID:22952693 Comparative efficiencies of cathepsins B, S, K and L to degrade major BM constituents. file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic assertion identifies the correct catalytic class. Reason: The preserved source combines EC:3.4.22.38 with ARBA00028064. The official CTSK EC assignment and human active-site and substrate evidence establish cysteine endopeptidase activity. The current ARBA rule no longer matches the inspected target cross-references, a source-snapshot difference that is kept separate from the valid EC mapping and biological assertion. Supporting Evidence: GO_REF:0000120 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0004197 cysteine-type endopeptidase activity | TAS PMID:9143502 Structure and chromosomal assignment of the human cathepsin ... | ACCEPT | Summary: The established cysteine endopeptidase annotation is retained. Reason: The complete cached abstract identifies cathepsin K as a lysosomal cysteine proteinase, while the study itself maps the human gene and exon structure. This TAS is consistent with independently demonstrated human CTSK catalysis; it is not described as a new purified-enzyme experiment in this genomic paper. |
| GO:0004252 serine-type endopeptidase activity | TAS Reactome:R-HSA-1592362 | REMOVE | Summary: The serine mechanism is incompatible with CTSK catalysis. Reason: The actual R-HSA-1592362 path assigns the shared catalyst activity 1604695 to a heterogeneous MMP3/CTSK/CTSV set. Its GO:0004252 serine-nucleophile label does not describe human CTSK, a papain-family cysteine endopeptidase. Official sequence features and the exact human mature-chain structure 1MEM identify the catalytic cysteine; the deposited inhibitor is covalently linked to its sulfur. Remove this mechanistically wrong MF transfer while retaining independently supported extracellular matrix roles and locations. Supporting Evidence: Reactome:R-HSA-1592362 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0004252 serine-type endopeptidase activity | TAS Reactome:R-HSA-1604752 | REMOVE | Summary: The serine mechanism is incompatible with CTSK catalysis. Reason: The actual R-HSA-1604752 path assigns the shared catalyst activity 1604695 to a heterogeneous MMP3/CTSK/CTSV set. Its GO:0004252 serine-nucleophile label does not describe human CTSK, a papain-family cysteine endopeptidase. Official sequence features and the exact human mature-chain structure 1MEM identify the catalytic cysteine; the deposited inhibitor is covalently linked to its sulfur. Remove this mechanistically wrong MF transfer while retaining independently supported extracellular matrix roles and locations. Supporting Evidence: Reactome:R-HSA-1604752 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0004252 serine-type endopeptidase activity | TAS Reactome:R-HSA-2514772 | REMOVE | Summary: The serine mechanism is incompatible with CTSK catalysis. Reason: The actual R-HSA-2514772 path assigns the shared catalyst activity 1604695 to a heterogeneous MMP3/CTSK/CTSV set. Its GO:0004252 serine-nucleophile label does not describe human CTSK, a papain-family cysteine endopeptidase. Official sequence features and the exact human mature-chain structure 1MEM identify the catalytic cysteine; the deposited inhibitor is covalently linked to its sulfur. Remove this mechanistically wrong MF transfer while retaining independently supported extracellular matrix roles and locations. Supporting Evidence: Reactome:R-HSA-2514772 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0005515 protein binding | IPI PMID:12504904 Inhibition of the cysteine proteinases cathepsins K and L by... | KEEP AS NON CORE | Summary: SERPINB13 binding is retained as an inhibitory interaction. Reason: The complete original abstract reports recombinant headpin inhibition of cathepsin K, SDS-stable complexes and reactive-loop cleavage. The full article remained inaccessible, so no additional construct or kinetic detail is asserted. SERPINB13 is the inhibitor and CTSK is its enzyme target; the interaction does not make CTSK a peptidase inhibitor. The supported generic interaction is retained under the project’s positive-binding policy. Supporting Evidence: PMID:12504904 Headpin formed SDS-stable complexes with cathepsins K and L |
| GO:0005515 protein binding | IPI PMID:15752368 Inhibitory properties of cystatin F and its localization in ... | KEEP AS NON CORE | Summary: Cystatin F binding is retained at its demonstrated inhibition-assay scope. Reason: The original indexed Methods and Results describe human cathepsin K expressed in E. coli and its inhibition by activated recombinant cystatin F. The experiment supports the positive interaction, without establishing constitutive cellular colocalization: the U937 microscopy did not show CTSK–cystatin F colocalization. The generic binding annotation is retained as contextual inhibition rather than a separate core activity. Supporting Evidence: PMID:15752368 Cystatin F tightly inhibited cathepsins F, K and V file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0005518 collagen binding | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | KEEP AS NON CORE | Summary: Collagen binding is retained as substrate engagement within CTSK proteolysis. Reason: Purified human cathepsin K digests human placental type IV collagen in supplementary Figure S2, with E-64 controls. Retain the curated collagen interaction in this enzyme-substrate context, consistently with the fibronectin and perlecan substrate-binding annotations. The experiment does not establish a separate adhesive collagen-receptor role or equilibrium affinity. The core function remains cysteine endopeptidase activity with collagen catabolism and extracellular-matrix disassembly; a second binding core would duplicate that demonstrated catalytic role. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited extracellular localization is supported. Reason: The positive extracellular IBD at PTN000274640 lies on the actual CTSK path and agrees with human keratinocyte secretion and extracellular proteolysis. The current IBD adds two zebrafish identifiers relative to the preserved GOA donor list; their identity and experimental-source aliases are documented without rewriting the original source object. The current leaf metadata issue concerns catalytic/proteolytic terms, not this positive location. |
| GO:0005576 extracellular region | IDA PMID:11082042 Cathepsin K in thyroid epithelial cells: sequence, localizat... | ACCEPT | Summary: The secreted CTSK pool is retained with the original assay-access limit. Reason: The complete original abstract reports secreted cathepsin K in the follicular lumen and at the apical surface. Its porcine cloning result does not establish the species of every localization assay; the full human tissue and reagent details remain unverified. Retain the positive curated human extracellular annotation with this limit, supported independently by human keratinocyte secretion. |
| GO:0005576 extracellular region | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: Human keratinocytes secrete CTSK. Reason: The original Methods and Results separately detect cathepsin K in human keratinocyte supernatants, alongside other cysteine cathepsins. The positive extracellular localization is directly relevant to its matrix proteolysis; it is not inferred merely from the paper’s cathepsin S title. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: The conserved extracellular pool is supported by genuine donor experiments. Reason: The literal mouse Ctsk and Ensembl source identities match the official ortholog. The current mouse donor has independent experimental extracellular annotations, in addition to human-derived transfers, and the UniProt secreted-location mapping is compatible. Mouse thyroid work distinguishes follicular-lumen secretion from membrane-associated staining; human secretion is independently observed in keratinocytes. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1592362 | ACCEPT | Summary: The extracellular compartment assignment is retained. Reason: The actual R-HSA-1592362 event contains CTSK entity 2470897 in the extracellular region through its catalyst set. Human secretion and extracellular substrate assays independently support this location. The mixed-set serine catalyst label is a separate MF error and does not invalidate the compartment; membership is not used to assert that CTSK alone performs every listed MMP reaction. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1604752 | ACCEPT | Summary: The extracellular compartment assignment is retained. Reason: The actual R-HSA-1604752 event contains CTSK entity 2470897 in the extracellular region through its catalyst set. Human secretion and extracellular substrate assays independently support this location. The mixed-set serine catalyst label is a separate MF error and does not invalidate the compartment; membership is not used to assert that CTSK alone performs every listed MMP reaction. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2168923 | ACCEPT | Summary: The extracellular compartment assignment is retained. Reason: The actual R-HSA-2168923 event contains CTSK entity 2470897 in the extracellular region through its catalyst set. Human secretion and extracellular substrate assays independently support this location. The mixed-set serine catalyst label is a separate MF error and does not invalidate the compartment; membership is not used to assert that CTSK alone performs every listed MMP reaction. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2471621 | ACCEPT | Summary: The extracellular compartment assignment is retained. Reason: The actual R-HSA-2471621 event contains CTSK entity 2470897 in the extracellular region through its catalyst set. Human secretion and extracellular substrate assays independently support this location. The mixed-set serine catalyst label is a separate MF error and does not invalidate the compartment; membership is not used to assert that CTSK alone performs every listed MMP reaction. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2514772 | ACCEPT | Summary: The extracellular compartment assignment is retained. Reason: The actual R-HSA-2514772 event contains CTSK entity 2470897 in the extracellular region through its catalyst set. Human secretion and extracellular substrate assays independently support this location. The mixed-set serine catalyst label is a separate MF error and does not invalidate the compartment; membership is not used to assert that CTSK alone performs every listed MMP reaction. |
| GO:0005764 lysosome | IDA PMID:11082042 Cathepsin K in thyroid epithelial cells: sequence, localizat... | ACCEPT | Summary: Lysosomal CTSK is a well-established component of the proteolytic compartment. Reason: The original abstract explicitly reports lysosomal localization alongside secreted and apical pools. Full human assay particulars remain inaccessible, so the curated positive location is retained with curator deference and the official localization record. This does not narrow vesicle staining to a finer luminal subcompartment. Supporting Evidence: file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0005764 lysosome | IDA PMID:22365146 Regulation of cathepsins S and L by cystatin F during matura... | ACCEPT | Summary: Established lysosomal localization is retained with a source-access limit. Reason: The cached abstract describes cystatin F and other cathepsins, and the original target-specific CTSK localization panel could not be inspected. Lysosomal CTSK is established by the official localization record and the broader thyroid evidence, so this positive curated location is retained with curator deference. No wrong-gene inference is drawn from the title or abstract. |
| GO:0005764 lysosome | IEA GO_REF:0000120 | ACCEPT | Summary: The lysosomal mapping and independent mouse donor support the location. Reason: The preserved combined source joins mouse Ctsk and the official lysosome vocabulary term. The donor has genuine experimental lysosome records, rather than only a return transfer from human CTSK. Retain the established organelle location without assigning assay details or exact luminal positioning not demonstrated by the retrieved staining. Supporting Evidence: GO_REF:0000120 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0005773 vacuole | IBA GO_REF:0000033 | MODIFY | Summary: The broad inherited vacuolar location can be refined to lysosome. Reason: The actual positive vacuole IBD at PTN000274640 is ancestral to CTSK and is biologically sound. For the human protein, the established localization and official record identify lysosomes, an actual descendant of vacuole. The refinement overlaps existing lysosome assertions but preserves this distinct phylogenetic source rather than alleging faulty ancestry. Proposed replacements: lysosome Supporting Evidence: GO_REF:0000033 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: Proteolysis is a performed function of CTSK. Reason: The target carries the papain-family InterPro domain used by the source mapping. Human recombinant CTSK directly cleaves protein substrates, independently confirming the broad proteolysis assertion rather than merely inferring it from family membership. |
| GO:0006508 proteolysis | TAS PMID:7818555 Molecular cloning of human cDNA for cathepsin K: novel cyste... | ACCEPT | Summary: The broad proteolysis TAS is biologically supported. Reason: The original cached abstract describes cloning of the human osteoclast-associated cysteine proteinase. Its expression and sequence results are distinguished from the direct human enzyme digestions reported elsewhere. Those experiments establish that CTSK itself performs proteolysis, so the positive TAS is retained with its original citation. |
| GO:0006590 thyroid hormone generation | IDA PMID:11082042 Cathepsin K in thyroid epithelial cells: sequence, localizat... | KEEP AS NON CORE | Summary: Thyroid hormone liberation is retained as a tissue-specific proteolytic role. Reason: The complete original abstract reports recombinant cathepsin K release of thyroxine from thyroglobulin at neutral pH. The enzyme performs the cleavage step, so this is participation rather than substrate necessity. The species of that recombinant reagent and of all tissue assays could not be established from the recovered first page; the existing human IDA is retained with curator deference at this specialized thyroid scope. Supporting Evidence: PMID:11082042 recombinant cathepsin K liberated thyroxine from thyroglobulin file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0006590 thyroid hormone generation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The inherited thyroid role has independent experimental donor grounding. Reason: The mouse Ctsk source carries experimental thyroid-hormone evidence. In the inspected mouse primary, combined Ctsk/Ctsl deficiency reduces serum thyroxine, whereas Ctsk deficiency alone is compensated. The study separates thyroglobulin solubilization from hormone liberation. Retain this contextual conserved role without claiming an uncompensated CTSK-only requirement or inventing human assay provenance. Supporting Evidence: GO_REF:0000107 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | MODIFY | Summary: The transferred peptidase activity has a more informative catalytic class. Reason: The literal mouse Ctsk donor is correctly identified and carries an experimental peptidase assertion. Human CTSK biochemical and structural evidence specifies hydrolysis of internal peptide bonds by a catalytic cysteine. Refine the broad activity to cysteine-type endopeptidase without replacing the mouse source provenance or claiming that the source experiment used human protein. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: GO_REF:0000107 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0008234 cysteine-type peptidase activity | IDA PMID:15752368 Inhibitory properties of cystatin F and its localization in ... | MODIFY | Summary: The assayed activity is cysteine-type endopeptidase activity. Reason: The actual original uses recombinant human CTSK and the Z-Phe-Arg-AMC substrate in the cystatin F inhibition assay. Together with the established internal protein cleavage mechanism, this supports the more informative endopeptidase term; the broader positive cysteine-peptidase assertion remains the source being refined. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0008234 cysteine-type peptidase activity | IDA PMID:19834056 Glycosaminoglycan-mediated loss of cathepsin K collagenolyti... | MODIFY | Summary: Direct human collagen cleavage supports the cysteine endopeptidase refinement. Reason: The original distinguishes mouse tissue and osteoclast experiments from digestions with recombinant human CTSK. Type II collagen cleavage and bone collagen solubilization directly support endoproteolysis, with glycosaminoglycans modulating collagenolysis. This is performed catalysis, not only a mutant phenotype. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: The mapped papain-family activity can be specified as endopeptidase activity. Reason: Both literal InterPro signatures occur in the official human CTSK record. They support the cysteine-peptidase family, while human protein-substrate cleavage and the catalytic center identify the more specific cysteine endopeptidase activity. The original electronic signatures are retained. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0008234 cysteine-type peptidase activity | TAS PMID:7818555 Molecular cloning of human cDNA for cathepsin K: novel cyste... | MODIFY | Summary: The established cysteine proteinase can be assigned its endopeptidase class. Reason: The cached original abstract reports the human cDNA and osteoclast-associated expression. Direct human enzyme studies independently show internal collagen and matrix-substrate cleavage. Refine the broad TAS activity without presenting the cloning paper as a purified-human-enzyme assay. Proposed replacements: cysteine-type endopeptidase activity |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A specialized apical-surface pool is supported by two thyroid sources with distinct access and genotype limits. Reason: The literal mouse Ctsk donor has independent experimental external-plasma-membrane evidence. PMID:12782676 specifically shows apical cathepsin K staining in Ctsb-deficient mouse thyrocytes, alongside vesicular and follicular-lumen pools. Independently, the complete PMID:11082042 abstract reports association with the apical plasma membrane and proteolytic activity of cell-surface-associated cathepsin K. Its porcine cloning experiment does not resolve every localization assay species or genotype without the full Methods. Retain this specialized external-surface localization without restricting all thyroid observations to the mouse knockout or treating it as the universal CTSK distribution. Supporting Evidence: GO_REF:0000107 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0016324 apical plasma membrane | EXP PMID:11082042 Cathepsin K in thyroid epithelial cells: sequence, localizat... | KEEP AS NON CORE | Summary: The curated apical thyroid pool is retained with explicit source limits. Reason: The original abstract reports cathepsin K associated with the apical plasma membrane and proteolytically active at the cell surface. Its recovered first page does not resolve all human tissue and reagent particulars. Retain the positive curated specialized location with curator deference, without extending it to all CTSK-expressing cells. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The official apical-location mapping describes a specialized CTSK pool. Reason: The official UniProt apical plasma membrane annotation is grounded in the thyroid study and maps to the existing GO compartment. The established secreted and lysosomal pools coexist with this specialized surface association; the electronic assertion does not make CTSK an integral membrane protein or imply universal apical localization. |
| GO:0022617 extracellular matrix disassembly | IEA GO_REF:0000117 | ACCEPT | Summary: CTSK directly contributes to extracellular matrix breakdown. Reason: The current ARBA00091895 rule matches the inspected CTSK cross-references. Independent human enzyme assays digest collagen, fibronectin and perlecan and the mixed basement-membrane preparation. CTSK supplies the proteolytic work, so this is a performed matrix-disassembly process. Supporting Evidence: GO_REF:0000117 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0022617 extracellular matrix disassembly | TAS Reactome:R-HSA-1474228 | ACCEPT | Summary: The matrix-disassembly assertion is supported by direct CTSK proteolysis. Reason: The Reactome pathway includes a positive CTSK membership path but is primarily described through MMP reactions. Human CTSK collagen and basement-membrane digestions independently establish the broad process. Retain the original pathway citation without transferring every MMP-specific activation mechanism or the incorrect shared serine catalyst label to CTSK. Supporting Evidence: Reactome:R-HSA-1474228 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0022617 extracellular matrix disassembly | TAS Reactome:R-HSA-1592389 | ACCEPT | Summary: The matrix-disassembly assertion is supported by direct CTSK proteolysis. Reason: The Reactome pathway includes a positive CTSK membership path but is primarily described through MMP reactions. Human CTSK collagen and basement-membrane digestions independently establish the broad process. Retain the original pathway citation without transferring every MMP-specific activation mechanism or the incorrect shared serine catalyst label to CTSK. Supporting Evidence: Reactome:R-HSA-1592389 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0030163 protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited protein-catabolic role is supported. Reason: The actual protein-catabolism IBD at PTN000274640 lies on the CTSK path, with genuine experimental donor grounding and no on-path loss record in the captured GAF. Human protein-substrate cleavage establishes the target’s performed catabolic role. The contradictory negative leaf decoration is retained as a source-display question, not interpreted as loss of catalysis. Supporting Evidence: GO_REF:0000033 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0030163 protein catabolic process | IDA PMID:11082042 Cathepsin K in thyroid epithelial cells: sequence, localizat... | ACCEPT | Summary: Thyroglobulin proteolysis supports the broad protein-catabolic assertion. Reason: The original abstract reports limited recombinant cathepsin K proteolysis of thyroglobulin with thyroxine liberation. The full assay-species details are unresolved, so the original human IDA remains under curator deference; independent human matrix-protein digestions support the broad performed catabolic role. Hormone liberation is not equated with every step of thyroglobulin solubilization. |
| GO:0030163 protein catabolic process | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: CTSK performs protein breakdown in the original matrix assays. Reason: Supplementary Figure S2 compares purified human CTSK against human collagen IV, human fibronectin, mouse perlecan and a mouse basement-membrane extract. Its inhibitor-sensitive cleavage demonstrates protein catabolism by CTSK itself, distinct from the nidogen-binding experiments centered on cathepsin S. |
| GO:0030163 protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: The transferred protein-catabolism assertion has experimental donor support. Reason: The current mouse Ctsk source includes independent experimental protein-catabolism evidence from thyroid work, as well as propagated annotations. The enzyme performs proteolysis, and human CTSK substrate digestions independently substantiate the broad catabolic role. Preserve the mouse source and its conditional thyroid context. Supporting Evidence: GO_REF:0000107 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0030574 collagen catabolic process | IDA PMID:19834056 Glycosaminoglycan-mediated loss of cathepsin K collagenolyti... | ACCEPT | Summary: Human CTSK directly catalyzes collagen degradation. Reason: The original directly tests recombinant human CTSK against collagen and murine bone material, in addition to mouse tissue and osteoclast perturbations. Chondroitin sulfate supports collagenolysis, whereas dermatan and heparan sulfate suppress it under the tested conditions. This direct enzymatic work supports collagen catabolism; the tissue species are not relabeled as human. Supporting Evidence: PMID:19834056 cathepsin K is able to effectively degrade type II collagen |
| GO:0030574 collagen catabolic process | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: CTSK cleaves type IV collagen in the matrix-substrate panel. Reason: The human CTSK lane in supplementary Figure S2 demonstrates cleavage of human placental type IV collagen at acidic pH, with E-64 inhibition. The measured substrate breakdown supports collagen catabolism directly, rather than through a generalized protease-family assignment. |
| GO:0030574 collagen catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic collagen-catabolism assertion agrees with direct human catalysis. Reason: The current ARBA00086982 condition set matches CTSK. Recombinant human CTSK collagen digestion independently substantiates the performed process and supplies stronger biological grounding than the rule alone. Supporting Evidence: GO_REF:0000117 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0036021 endolysosome lumen | IEA GO_REF:0000117 | ACCEPT | Summary: The matching ARBA rule and curated protease compartment support endolysosomal lumen localization. Reason: The current ARBA00090216 branch 0 matches CTSK through FunFam 3.90.70.10:FF:000006 and Primates (9443), both present in the inspected official target record and taxonomy. The independent curated TLR-processing model also places CTSK in the endolysosomal lumen. This supports localization without assigning every modeled TLR cleavage specifically to CTSK. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-1678920 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0036021 endolysosome lumen | TAS Reactome:R-HSA-1678920 | ACCEPT | Summary: CTSK is assigned to the lumen of the endolysosomal protease compartment. Reason: The actual Reactome path reaches CTSK entity 1678985 within the endolysosomal lumen through the cathepsin set. The model explicitly notes disagreement among studies on individual protease contributions to TLR processing. Retain the location without adding a claim that CTSK uniquely or obligatorily performs each TLR cleavage. Supporting Evidence: Reactome:R-HSA-1678920 file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-8938121 | ACCEPT | Summary: The lysosomal lumen assignment is consistent with the CTSK–SERPINB13 model. Reason: The actual Reactome input entity 1181226 identifies CTSK in the lysosomal lumen. Independent official localization and human CTSK work support this compartment. The primary SERPINB13 abstract establishes enzyme inhibition and complex formation; it is not presented as direct microscopy of the modeled compartment. Supporting Evidence: Reactome:R-HSA-8938121 file:human/CTSK/CTSK-uniprot.txt file:human/CTSK/CTSK-source-evidence.yaml |
| GO:0043394 proteoglycan binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Proteoglycan interaction is retained at the demonstrated substrate-contact scope. Reason: The current ARBA00086247 branch 0 matches CTSK through FunFam 3.90.70.10:FF:000006 and Primates (9443). Independent human CTSK digestion of mouse perlecan supports the positive substrate interaction. This remains contextual proteoglycan engagement; it does not establish an adhesive or receptor activity or equate perlecan cleavage with every glycosaminoglycan effect. |
| GO:0043394 proteoglycan binding | IPI PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | KEEP AS NON CORE | Summary: The perlecan interaction is supported as enzyme–substrate engagement. Reason: The original uses human recombinant CTSK and mouse EHS-derived perlecan; the literal partner Q05793 is mouse Hspg2. Supplementary Figure S2 demonstrates inhibitor-sensitive substrate breakdown. Retain the positive curated interaction at this cross-species assay scope, without claiming that the nidogen SPR experiments measured a CTSK–perlecan binding constant. |
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Download this section (compressed HTML)Q: Why do the current PANTHER leaf GO-slim display fields mark CTSK catalytic and protein-catabolic terms NOT when the actual positive PTN000274640 IBDs have no relevant loss record on the CTSK path and human enzymology supports activity?
Q: Can the human tissue and recombinant-reagent identities in the complete original thyroid study be confirmed, while retaining its reported thyroglobulin-cleavage and localization observations?
Q: What CTSK-specific mechanism explains its human mitophagy-screen hit, and can it be distinguished from general lysosomal proteolysis without transferring the SREBF1 mechanism?
Q: Can the mixed Reactome catalyst sets be given chemistry compatible with their individual members, including CTSK’s cysteine mechanism, while preserving valid extracellular compartments and substrate contexts?
Q: Does CTSK-mediated degradation of bone matrix warrant a separate bone-resorption annotation beyond the existing collagen-catabolism and matrix-disassembly coverage, given that current human MMP9, MMP13 and MMP14 matrix-protease comparators also lack the bone-resorption term in the captured queries?
Experiment: Test CTSK depletion and rescue with wild-type and catalytically inactive CTSK in the original mitophagy assay, measuring lysosomal competence, mitochondrial clearance and Parkin recruitment separately.
Experiment: Measure collagen and other matrix-protein cleavage under matched extracellular pH and glycosaminoglycan conditions, distinguishing substrate engagement from stable noncatalytic binding.
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