COL4A3 encodes the alpha-3 chain of type-IV collagen, a secreted basement-membrane protein. It assembles with alpha-4 and alpha-5 chains into triple-helical protomers that associate through terminal domains to form a matrix network, particularly important in the glomerular basement membrane. Disruption of this architecture causes Alport-spectrum kidney disease and can affect hearing. Proteolytic release of its C-terminal NC1 region produces tumstatin, a fragment that binds integrins and inhibits endothelial proliferation and pathological angiogenesis in experimental systems. Alternative transcripts change or remove portions of the C-terminal region, so their assembly and fragment activities need not be equivalent.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005178 integrin binding | IDA PMID:12682293 Human tumstatin and human endostatin exhibit distinct antian... | ACCEPT | Summary: Retain integrin binding by the tumstatin fragment. Reason: The selected original abstract reports human tumstatin interaction with alphaVbeta3. The original PNAS source has figure-specific integrity concerns documented in PMID:31749508 and a later correction, PMID:42467515. Its 2026 repeat measures differential Akt phosphorylation, not integrin blockade or angiogenesis. Separate PMID:10837460 and actual human-recombinant/mouse functional experiments in PMID:12842087 support the retained biological activity; no whole-paper invalidation or complete revalidation is inferred. This activity belongs to the released NC1-derived fragment, not automatically to intact matrix collagen or every alternative product. |
| GO:0005178 integrin binding | TAS PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | ACCEPT | Summary: Retain the fragment-specific integrin-binding assertion. Reason: The original fragment study and independent PMID:10837460 binding-site evidence support the integrin-binding assertion. PMID:12842087 supplies beta3-dependent functional support. Newly recovered original Methods specify recombinant human NC1; these fragment experiments do not establish equivalent activity of all splice products. |
| GO:0005198 structural molecule activity | NAS PMID:3025878 Human collagen genes encoding basement membrane alpha 1 (IV)... | MODIFY | Summary: Specify the collagen matrix tensile-strength class. Reason: The original NAS source abstract maps alpha1/alpha2 collagen-IV genes and does not expose a target-specific alpha3 assay; its full text was not recovered. Independent alpha3/alpha4/alpha5 assembly evidence and the official human target record establish COL4A3 structural matrix participation. GO:0030020 explicitly permits extracellular-matrix collagen proteins under its current comment. This refinement applies that convention and actual assembly evidence; it does not assert a direct force measurement on isolated human alpha3 or every alternative product. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005201 extracellular matrix structural constituent | IEA GO_REF:0000002 | MODIFY | Summary: Specify the collagen matrix tensile-strength class. Reason: The InterPro collagen-domain mapping agrees with the alpha3 chain's participation in type-IV matrix networks. GO:0030020 explicitly permits extracellular-matrix collagen proteins under its current comment. This refinement applies that convention and actual assembly evidence; it does not assert a direct force measurement on isolated human alpha3 or every alternative product. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001442 SUPPORTS TRANSFER Official target domain identity and collagen assembly support the structural/complex class; the source mapping itself is preserved. InterPro:IPR036954 SUPPORTS TRANSFER Official target domain identity and collagen assembly support the structural/complex class; the source mapping itself is preserved. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005515 protein binding | IPI PMID:10212244 Characterization of a novel type of serine/threonine kinase ... | KEEP AS NON CORE | Summary: Retain the positive interaction with the mapped GPBP/CERT1 protein. Reason: The complete original abstract reports a recombinant 624-residue GPBP product interacting with the N-terminal region of the human Goodpasture antigen. The official Q9Y5P4 record identifies the current CERT1 lipid-transfer protein and cautions about its original kinase attribution. Positive binding is preserved without inferring kinase binding from that historical claim or transmembrane-transporter binding from intermembrane lipid transfer. No exact target/paper pair was returned by the selected IntAct/MINT exports; that absence does not negate the primary interaction. The original full Methods were not recovered. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12682293 Human tumstatin and human endostatin exhibit distinct antian... | MODIFY | Summary: Specify the positive integrin interaction. Reason: The original IPI partner is ITGB3/P05106, the beta3 component of the integrin receptor, so integrin binding is more informative than generic protein binding. The original PNAS source has figure-specific integrity concerns documented in PMID:31749508 and a later correction, PMID:42467515. Its 2026 repeat measures differential Akt phosphorylation, not integrin blockade or angiogenesis. Separate PMID:10837460 and actual human-recombinant/mouse functional experiments in PMID:12842087 support the retained biological activity; no whole-paper invalidation or complete revalidation is inferred. This is an assay-scoped fragment interaction, not an assignment of integrin receptor activity to collagen. Proposed replacements: integrin binding |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1454757 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-1454757 (Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-1454757 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1564142 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-1564142 (Collagen type IV degradation by MMP2,3,4,9,10,12) has 36 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-1564142 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213207 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2213207 (Formation of collagen networks) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2213207 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327695 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2327695 (Collagen types III, IV, V, VI, VIII, IX, XVI bind integrins alpha1beta1 and alpha2beta1) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2327695 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327733 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2327733 (FN1 binds Collagen types I-V, VII) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2327733 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327738 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2327738 (DDR1 binds collagen type I, II, III, IV, V, XI fibrils) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2327738 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396234 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2396234 (Collagen type VII binds laminin-322 and collagen IV) has 12 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2396234 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2426450 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2426450 (Laminins:Nidogens binds collagen type IV networks) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2426450 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2559639 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-2559639 (Collagen type IV sulfilimine cross-linking by peroxidasin) has 39 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2559639 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-375151 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-375151 (Interaction of NCAM1 with collagens) has 2 enumerated routes to Q01955. A representative input route resolves COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-375151 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-382054 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-382054 (PDGF binds to extracellular matrix proteins) has 2 enumerated routes to Q01955. A representative input route resolves COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-382054 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4085083 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-4085083 (Tumstatin binds integrin alphaVbeta 3, alpha3beta1) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(1426-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. The tumstatin entity is the cleaved 1426–1670 fragment, distinct from the intact chain. Supporting Evidence: Reactome:R-HSA-4085083 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9638628 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-HSA-9638628 (DraE binds Collagen IV) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-9638628 |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-4084497 | ACCEPT | Summary: Retain the modeled extracellular region location. Reason: Authenticated event R-NUL-4084497 (Collagen VII binds collagen IV) has 12 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [extracellular region]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. This is an explicitly chimeric human collagen-IV/mouse collagen-VII event, not a new all-human binding assay. Supporting Evidence: Reactome:R-NUL-4084497 |
| GO:0005581 collagen trimer | IEA GO_REF:0000002 | MODIFY | Summary: Specify the type-IV collagen trimer. Reason: The InterPro-derived generic collagen-trimer class is correct but can be refined using the independently established alpha3/alpha4/alpha5 heterotrimer. GO:0005587 explicitly describes the network-forming type-IV class; the alpha1/alpha2 composition in its definition is an example rather than an exclusion of the alpha3-containing protomer. Preserve the original source fields and avoid an additional redundant complex annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001442 SUPPORTS TRANSFER Official target domain identity and collagen assembly support the structural/complex class; the source mapping itself is preserved. InterPro:IPR036954 SUPPORTS TRANSFER Official target domain identity and collagen assembly support the structural/complex class; the source mapping itself is preserved. Proposed replacements: collagen type IV trimer Supporting Evidence: |
| GO:0005587 collagen type IV trimer | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the PAINT type-IV trimer assignment. Reason: The target has an experimental type-IV-trimer record and therefore legitimately appears among the descendants supporting its inherited annotation. The exact current records and alpha3/alpha4/alpha5 assembly evidence are concordant. The historical PTN node, alignment and IBD placement were not reconstructed, so current target grounding is not presented as a new phylogenetic read. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN009074928 UNRESOLVED Original ancestral node preserved; historical tree, MSA and IBD placement were not reconstructed. Current descendant/target experimental evidence is documented separately, without a donor-count criterion or self-evidence circularity claim. UniProtKB:Q01955 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. |
| GO:0005587 collagen type IV trimer | IDA PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | ACCEPT | Summary: Retain the type-IV complex identity. Reason: The original fragment study identifies human alpha3(IV) NC1; independent PMID:12193605 protomer evidence supports type-IV membership. Recovery of the original fragment Methods does not turn them into an intact-heterotrimer assembly experiment or establish equivalent assembly of all splice products. |
| GO:0005587 collagen type IV trimer | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the conserved type-IV trimer assignment. Reason: The exact mouse Q9QZS0 and Ensembl source identities resolve to Col4a3, with current experimental and transfer records for this complex. The available PMID:12101409 abstract does not expose the target-specific complex assay, so that donor experiment is not claimed as newly verified. Independent alpha3/alpha4/alpha5 assembly and the official human record support the target class. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ensembl:ENSMUSP00000109084 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. Supporting Evidence: |
| GO:0005587 collagen type IV trimer | NAS PMID:29853175 Collagen Fibril Assembly and Function. | ACCEPT | Summary: Retain the type-IV trimer class independently of the review-title emphasis. Reason: The cited review is available only as an abstract about collagen fibrils; this does not expose its exact alpha3 passage. The target nevertheless belongs to the experimentally established alpha3/alpha4/alpha5 type-IV protomer. Preserve the positive complex annotation while marking the source-specific citation link unverified rather than claiming a wrong-gene paper. Supporting Evidence: |
| GO:0005604 basement membrane | IDA PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | ACCEPT | Summary: Retain basement-membrane localization. Reason: The original fragment study identifies basement-membrane-derived alpha3(IV), and actual human Alport material independently links COL4A3 to glomerular basement membrane. Original clinical immunostaining and human matrix proteomics support the structural location; released tumstatin is a distinct soluble fragment. Supporting Evidence: PMID:7987396 Homozygous mutations were found in alpha 3(IV) in two families |
| GO:0005604 basement membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the composite basement-membrane assignment. Reason: The composite electronic source combines ARBA00027708, the mouse ortholog and the official basement-membrane location. Current mouse records include experimental localization, while direct human clinical and matrix evidence independently support the target. The retrieved ARBA rule has multiple alternatives; its Glires collagen branch is not a human taxon match, and target-specific FunFam activation was not reconstructed. Acceptance does not rely on claiming that branch applies to human. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027708 UNRESOLVED Rule read in full. Its collagen-domain Glires condition is not a human match; target-specific activation of alternative FunFam branches was not reconstructed. Other composite-source and direct target evidence support basement membrane. UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ensembl:ENSMUSP00000109084 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB-SubCell:SL-0025 SUPPORTS TRANSFER Official basement-membrane location agrees with direct target structural/localization context. |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the ER-lumen precursor location. Reason: The current ARBA00028691 response includes a Hominidae/IPR050938 condition concordant with the official human target lineage/domain. Independently, collagen-IV chain association and the authenticated Reactome precursor routes place the chain in the ER lumen before secretion. This is a biosynthetic compartment, not the final matrix location or evidence of COL4A3 catalysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028691 SUPPORTS TRANSFER Actual current ARBA rule Hominidae/IPR050938 condition matches the official human target lineage/domain. Independent precursor assembly/Reactome location supports the same compartment. Supporting Evidence: Reactome:R-HSA-8944265 Reactome:R-HSA-2022073 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | ACCEPT | Summary: Retain the modeled endoplasmic reticulum lumen location. Reason: Authenticated event R-HSA-2022073 (Procollagen triple helix formation) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [endoplasmic reticulum lumen]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2022073 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | ACCEPT | Summary: Retain the modeled endoplasmic reticulum lumen location. Reason: Authenticated event R-HSA-2089971 (Secretion of collagens) has 12 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [endoplasmic reticulum lumen]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944265 | ACCEPT | Summary: Retain the modeled endoplasmic reticulum lumen location. Reason: Authenticated event R-HSA-8944265 (Association of procollagen type IV) has 24 enumerated routes to Q01955. A representative input route resolves 3x4Hyp-3Hyp-GalHyl-COL4A3(29-1670) [endoplasmic reticulum lumen]. This supports the source compartment; ER-lumen precursor inputs and extracellular entities are distinguished. The chain may supply structure or be a bound/processed substrate, but this CC annotation does not assign the enzyme, trafficking or receptor activity to collagen. Supporting Evidence: Reactome:R-HSA-8944265 |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain receptor-signaling participation by the released fragment. Reason: The resolved mouse exact-term donor has IDA evidence from PMID:12842087. Actual beta3-null versus wild-type endothelial and Matrigel experiments show receptor-dependent response to tumstatin, and human recombinant fragment rescues pathological angiogenesis in mouse hosts. The fragment performs a receptor-engagement step; no intracellular kinase activity, human physiological equivalence or all-product scope is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ensembl:ENSMUSP00000109084 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. Supporting Evidence: |
| GO:0007166 cell surface receptor signaling pathway | NAS PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | KEEP AS NON CORE | Summary: Retain the fragment-mediated receptor-signaling context. Reason: Independent fragment binding and functional sources support the integrin-mediated signaling context. Retain this broad NAS process as secondary to the specific binding activity; the original fragment assays and the disputed PNAS blots do not by themselves define a complete signaling cascade. |
| GO:0007605 sensory perception of sound | TAS PMID:7987396 Identification of mutations in the alpha 3(IV) and alpha 4(I... | KEEP AS NON CORE | Summary: Retain the source-scoped structural hearing context. Reason: Human COL4A3 families VB and DU in PMID:7987396 have sensorineural hearing loss, alongside mutation and basement-membrane findings. The alpha3-containing cochlear basement membrane supplies structural context for hearing, so this TAS process is retained as non-core. The clinical source supports that contextual contribution without identifying the exact cochlear mechanical defect. Supporting Evidence: PMID:7987396 progressive renal failure and deafness |
| GO:0008191 metalloendopeptidase inhibitor activity | NAS PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | MARK AS OVER ANNOTATED | Summary: The cited paper proposes, rather than demonstrates, metalloproteinase inhibition. Reason: GO:0008191 requires binding to and reducing metalloendopeptidase activity. The recovered PMID:10766752 Discussion proposes MMP inhibition by analogy with PEX, whereas its Methods test cellular and angiogenic responses, not MMP binding or inhibition. The NAS activity exceeds that speculative mechanism. This source-specific assessment does not deny possible inhibitor activity or confuse MMP-mediated fragment generation with inhibition. Supporting Evidence: |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:10837460 Two RGD-independent alpha vbeta 3 integrin binding sites on ... | KEEP AS NON CORE | Summary: Retain the measured antiproliferative fragment activity. Reason: The complete original abstract maps two RGD-independent binding regions with distinct endothelial versus melanoma-cell effects. The antitumor C-terminal segment is exposed by truncation, so this broad cell-population effect cannot be assigned uniformly to intact collagen or all splice products. The positive treatment response is retained as a secondary function of the tested fragments. Supporting Evidence: |
| GO:0016525 negative regulation of angiogenesis | IDA PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | ACCEPT | Summary: Retain inhibition of angiogenesis by tumstatin. Reason: The recovered original human NC1/deletion-fragment Methods and Results support antiangiogenic effects. Independent human recombinant tumstatin rescue and beta3-dependent mouse assays in PMID:12842087 support receptor-dependent work. The latter study distinguishes pathological angiogenesis from the tested repair responses; neither source establishes equivalent activity of all products. |
| GO:0016525 negative regulation of angiogenesis | IDA PMID:12682293 Human tumstatin and human endostatin exhibit distinct antian... | ACCEPT | Summary: Retain the independently supported antiangiogenic fragment function. Reason: The original source reports inhibition of endothelial proliferation and angiogenesis. The original PNAS source has figure-specific integrity concerns documented in PMID:31749508 and a later correction, PMID:42467515. Its 2026 repeat measures differential Akt phosphorylation, not integrin blockade or angiogenesis. Separate PMID:10837460 and actual human-recombinant/mouse functional experiments in PMID:12842087 support the retained biological activity; no whole-paper invalidation or complete revalidation is inferred. Retention concerns the supported integrin-dependent fragment effect, not endorsement of every original signaling blot. |
| GO:0016525 negative regulation of angiogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the conserved antiangiogenic fragment activity with construct limits. Reason: The current mouse donor has IDA evidence from tumor-directed expression of an engineered RGD-containing NC1 construct. Its accessible abstract supports endothelial/tube and tumor effects but does not establish an unmodified native human product assay. Independent human recombinant tumstatin in mouse receptor-dependent assays corroborates the target function. Do not transfer engineered targeting behavior to every COL4A3 product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ensembl:ENSMUSP00000109084 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Retain the collagen tensile-strength structural class. Reason: Original bone-marrow ECM S2 and five S3 COL4A3 rows are verified; the protein group contains the canonical accession and four alternatives. S2 threshold classifications do not negate positive individual MGUS detections in S3. Proteomic detection is not a tensile assay. The current GO:0030020 comment explicitly permits ECM collagens, and independent alpha3-containing network architecture supports that convention without an isolated-chain force measurement. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited collagen structural class. Reason: The exact current P02462 and worm let-2 source identities and term-level records were inspected; experimental grounding is distinct from the historical PAINT node, which was not reconstructed. The official collagen-term convention and COL4A3 network assembly support the target without treating donor number as evidence strength or copying a fibrillar-collagen architecture onto type IV. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001166351 UNRESOLVED Original ancestral node preserved; historical tree, MSA and IBD placement were not reconstructed. Current descendant/target experimental evidence is documented separately, without a donor-count criterion or self-evidence circularity claim. UniProtKB:P02462 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. WB:WBGene00002280 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Retain the collagen tensile-strength structural class. Reason: Both original human colon/liver ECM workbook rows identify the COL4A3 protein group with 40 total unique peptides. The grouped accessions do not uniquely resolve a splice product. Proteomic detection is not a tensile assay. The current GO:0030020 comment explicitly permits ECM collagens, and independent alpha3-containing network architecture supports that convention without an isolated-chain force measurement. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Retain the collagen tensile-strength structural class. Reason: Actual selected human tissue ECM protocol text is available, but the exact COL4A3 supplementary target row remains uninspected. The source-specific relationship is marked unverified while independent target assembly/proteomics support the class. Proteomic detection is not a tensile assay. The current GO:0030020 comment explicitly permits ECM collagens, and independent alpha3-containing network architecture supports that convention without an isolated-chain force measurement. Supporting Evidence: |
| GO:0030198 extracellular matrix organization | IBA GO_REF:0000033 | ACCEPT | Summary: Retain extracellular-matrix organization through network assembly. Reason: The alpha3 chain contributes the structural interfaces of the alpha3/alpha4/alpha5 protomer and terminal-domain network. This is performed assembly work rather than mere necessity or being a processing substrate. Current family source records corroborate ECM context; historical PAINT node placement is uninspected. The broad organization process does not require a fibrillar type-I-like architecture. Propagation Review Root cause: NO FAILURE CORE Sources checked: FB:FBgn0000299 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. FB:FBgn0016075 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. FB:FBgn0260660 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:104687 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:104688 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:1095415 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:2152695 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:2672118 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88446 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:88447 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:88451 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88452 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:88453 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88457 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:88458 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. MGI:MGI:88468 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. PANTHER:PTN002770636 UNRESOLVED Original ancestral node preserved; historical tree, MSA and IBD placement were not reconstructed. Current descendant/target experimental evidence is documented separately, without a donor-count criterion or self-evidence circularity claim. RGD:61817 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. RGD:621351 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P02458 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P02461 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P02462 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P05997 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P08123 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P13942 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P20908 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P53420 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. WB:WBGene00001263 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ZFIN:ZDB-GENE-030131-9102 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. ZFIN:ZDB-GENE-101001-1 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. ZFIN:ZDB-GENE-101001-2 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. |
| GO:0030199 collagen fibril organization | NAS PMID:29853175 Collagen Fibril Assembly and Function. | UNDECIDED | Summary: The specific collagen-fibril-organization allocation remains unresolved. Reason: GO:0030199 specifies collagen fibril size and arrangement and is a descendant of extracellular matrix organization. Type-IV network assembly alone does not establish that narrower process. The PMID:29853175 abstract and bounded full-text attempts still do not resolve the alpha3-specific premise. Retain UNDECIDED: a network-forming protein could influence other fibrils, so neither its structural classification nor another gene review proves this NAS assertion false. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Actual original human tissue extraction Methods and both COL4A3 workbook rows support matrix detection. All five accession variants occur in one protein group, not five separately measured isoforms. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Original S2 and five S3 target rows support human bone-marrow ECM detection. S2 MGUS nd and S3 two MGUS observations use different summarization criteria; no universal disease-condition absence is inferred. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: The actual selected article describes ECM extraction/proteomics, but its exact COL4A3 supplemental row is uninspected. Preserve the curated location using independent direct human target matrix evidence, while the original reference-to-target table relationship remains unverified. Supporting Evidence: |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited extracellular-matrix location. Reason: Current exact-term source records include direct human target proteomics; target self-evidence is valid experimental grounding, not circularity. The chain is an established type-IV matrix component. Preserve the source qualifier and distinguish inspected current records from the uninspected historical PAINT alignment/node. Propagation Review Root cause: NO FAILURE CORE Sources checked: FB:FBgn0000299 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. FB:FBgn0016075 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:104687 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:104688 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:1858212 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:2152695 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:2672118 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:2685312 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88445 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88446 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88449 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88451 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88452 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88453 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88454 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88455 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88456 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88457 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88462 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88463 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88467 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. MGI:MGI:88468 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. PANTHER:PTN008390299 UNRESOLVED Original ancestral node preserved; historical tree, MSA and IBD placement were not reconstructed. Current descendant/target experimental evidence is documented separately, without a donor-count criterion or self-evidence circularity claim. RGD:2372 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. RGD:2374 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. RGD:61817 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. RGD:621351 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. RGD:70922 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. RGD:71029 SUPPORTS TRANSFER Exact current term-level source includes experimental IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P02458 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P02461 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P02462 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P02467 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. UniProtKB:P05997 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P08123 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P08572 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P12107 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P20849 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P20908 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA, IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P29400 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:P53420 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q01955 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q03692 SUPPORTS TRANSFER Exact current term-level source includes experimental EXP, HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q14031 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q14050 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q14055 SUPPORTS TRANSFER Exact current term-level source includes experimental HDA. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. UniProtKB:Q7SIB2 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. WB:WBGene00000527 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. WB:WBGene00001263 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. WB:WBGene00002280 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. |
| GO:0032836 glomerular basement membrane development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain glomerular-basement-membrane maturation as a structural context. Reason: The exact mouse Col4a3 donor and original PMID:12631063 abstract describe an initially normal downregulation of laminin-1 followed by its reexpression in maturing deficient GBM. The collagen network supplies matrix structure needed for this developmental transition and maintenance. Retain the IEA context without assigning laminin biosynthesis, a developmental signaling enzyme or a direct human isoform-specific assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. ensembl:ENSMUSP00000109084 UNRESOLVED Original source entity preserved with its exact current resolution. Direct grounding or activation of this particular source was not independently established; this is not evidence of biological absence. |
| GO:0032836 glomerular basement membrane development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain glomerular-basement-membrane maturation as a structural context. Reason: The exact mouse Col4a3 donor and original PMID:12631063 abstract describe an initially normal downregulation of laminin-1 followed by its reexpression in maturing deficient GBM. The collagen network supplies matrix structure needed for this developmental transition and maintenance. Retain the ISS context without assigning laminin biosynthesis, a developmental signaling enzyme or a direct human isoform-specific assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9QZS0 SUPPORTS TRANSFER Exact current term-level source includes experimental IMP. Original source qualifier/species remain in the literal index. This is current premise support, not a claim to have read every cited primary or reconstructed historical PAINT placement. |
| GO:0072577 endothelial cell apoptotic process | IDA PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | KEEP AS NON CORE | Summary: Retain the source-scoped endothelial apoptosis context. Reason: The recovered original reports annexin-V and caspase-3 responses in bovine endothelial cells and TUNEL/morphological apoptosis in mouse xenograft vessels treated with recombinant human tumstatin. Retain the fragment-scoped non-core process; neither intact-network activity nor all-product equivalence follows. Supporting Evidence: PMID:10766752 associated with in vivo endothelial cell-specific apoptosis. |
| GO:1905563 negative regulation of vascular endothelial cell proliferation | IDA PMID:10766752 Distinct antitumor properties of a type IV collagen domain d... | KEEP AS NON CORE | Summary: Retain inhibition of vascular endothelial proliferation by the tested fragment. Reason: The original NC1/deletion-fragment study reports inhibition of endothelial proliferation, and independent actual beta3-dependent mouse endothelial assays corroborate that response to tumstatin. The released fragment performs receptor-related work; the effect is not automatically the activity of the assembled collagen network or every alternative product. Preserve the original source qualifier without adding a new process. |
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Download this section (compressed HTML)Q: Which alternative COL4A3 products form secreted alpha3/alpha4/alpha5 protomers, and which retain biologically active tumstatin regions?
Q: Does a sequence-defined COL4A3 fragment directly bind and inhibit a particular metalloendopeptidase, separately from its integrin-mediated effects?
Q: Does COL4A3 perform a defined collagen-fibril-organization step in addition to its established type-IV network role?
Q: Which original signaling conclusions survive independent replication after distinguishing the 2019 affected panels from the limited 2026 Akt repeat?
Experiment: Compare sequence-authenticated human products in heterotrimer assembly, secretion and network-incorporation assays. Separately assay purified released fragments for integrin binding and receptor-dependent endothelial effects, with matching expression and processing controls.
Hypothesis: C-terminal splice changes alter collagen-IV assembly and released-fragment integrin activity.
Experiment: If the original proposed enzyme can be identified, measure binding and catalytic activity with purified metalloendopeptidase, substrate and sequence-defined COL4A3 fragments, using inhibitor and cleavage controls.
Hypothesis: The inherited enzyme-inhibitor assertion represents a direct fragment-enzyme interaction distinct from fragment generation.
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