COL9A3 encodes the alpha3 chain of collagen IX, a fibril-associated collagen with interrupted triple helices. It assembles with alpha1(IX) and alpha2(IX) in cartilage and vitreous extracellular matrix. Its collagenous and noncollagenous regions contribute to chain assembly, and alpha3(IX) forms covalent connections within the type II/type IX collagen network. These structural interactions help organize and stabilize the matrix. Pathogenic variants cause multiple epiphyseal dysplasia and recessive Stickler syndrome with skeletal, auditory and ocular manifestations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2089971 | ACCEPT | Reason: The secretion event contains ER-luminal input and extracellular collagen output. This source assertion describes the destination of secreted type IX material, before specifying its eventual matrix associations. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213210 | MODIFY | Reason: This event specifically places collagen IX in covalent connections on type II fibrils, rather than only somewhere outside cells. Refine this source-scoped location to extracellular matrix, supported by the actual participant path to Q14050 and the human cartilage cross-link study. Other extracellular secretion or ligand-event assertions are retained at their own scope. No catalyst role is inferred from being cross-linked. Proposed replacements: extracellular matrix |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327695 | ACCEPT | Reason: The integrin alpha1beta1/alpha2beta1 event includes extracellular collagen IX within a multi-collagen ligand set. Its complex-level membership supports the location, without establishing isolated alpha3 affinity for each receptor. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-2327695 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-375151 | ACCEPT | Reason: The NCAM1 event contains extracellular collagen IX material. The location is supported; the event does not assign neural adhesion machinery activity to COL9A3. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-375151 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-382054 | ACCEPT | Reason: The PDGF event places collagen-containing extracellular material among growth-factor retention partners. It supports location without making alpha3 a PDGF receptor or providing a chain-specific affinity measurement. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-382054 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4084903 | ACCEPT | Reason: The integrin alpha10beta1 event includes collagen IX as extracellular ligand material, with alpha3 represented through its heterotrimer. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-4084903 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4086223 | ACCEPT | Reason: The integrin alpha11beta1 event likewise explicitly contains extracellular collagen IX. This is complex-level ligand context, not a new isolated alpha3 receptor-binding claim. The actual event summary, compartment and participant path to Q14050 were inspected; not all underlying primary event citations were independently recovered. Supporting Evidence: Reactome:R-HSA-4086223 |
| GO:0005594 collagen type IX trimer | IBA GO_REF:0000033 | ACCEPT | Reason: The exact current type IX trimer definition includes alpha1(IX), alpha2(IX) and alpha3(IX). Target-derived human chain identification and structural assembly evidence support this membership. COL9A3 appearing in its own PAINT descendant evidence is expected and is not circular. Current exact-term target records were checked; the historical IBD/node/tree was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008601345 UNRESOLVED The current PANTHER19 tree places the sequence-verified COL9A3 leaf below the recorded source node PTN008601345. The specific historical IBD record and curator rationale were not independently recovered; current topology and positive target composition evidence remain distinct. |
| GO:0005594 collagen type IX trimer | IDA PMID:8660302 Collagen type IX from human cartilage: a structural profile ... | ACCEPT | Reason: The original human fetal cartilage experiment resolves type IX collagen fragments and identifies the alpha3 chain by sequence. Its chain-specific cross-links establish incorporation into the native type II/IX network, consistent with alpha3 membership in the defined type IX heterotrimer. Distinguish this native material from isolated engineered domain complexes. Supporting Evidence: |
| GO:0005594 collagen type IX trimer | IPI PMID:27897211 Structural insight for chain selection and stagger control i... | ACCEPT | Reason: The actual structures contain all three distinct type IX NC2 chains, including alpha3, attached to engineered type I hostβguest triple-helical sequences. They establish a chain-selection/stagger interface consistent with type IX membership, not an atomic structure of intact collagen IX. The article calls this assembly region NC2; its label is preserved separately from current UniProt region nomenclature. Supporting Evidence: PMID:27897211 Three unique chains form a parallel Ξ±-helical right-handed bundle. |
| GO:0005594 collagen type IX trimer | TAS PMID:8586434 Molecular cloning of the alpha 3 chain of human type IX coll... | ACCEPT | Reason: The complete authentic abstract explicitly describes alpha1/alpha2/alpha3 composition, human alpha3 peptide sequencing and overlapping human cDNA/genomic clones. Retain the TAS membership with independent native and recombinant assembly evidence. Full original recovery remained unsuccessful after bounded publisher/API attempts; the abstract is not described as a newly read purified trimerization experiment. Supporting Evidence: PMID:8586434 encode for the entire alpha 3 chain of human type IX collagen. |
| GO:0005604 basement membrane | IBA GO_REF:0000033 | UNDECIDED | Reason: The current definition names a specific collagen-containing layer at tissue interfaces, not extracellular matrix generally. Recorded mouse Col15a1 and Col7a1 have genuine same-term experimental annotations. The actual current PANTHER tree now confirms that COL9A3 descends from the annotated node, but neither that topology nor cartilage/vitreous matrix identity resolves the target-specific basement-membrane premise or the historical location rationale. Preserve the assertion as uncertain without claiming a wrong clade, donor-count weakness, circularity or biological absence. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN002770818 UNRESOLVED The current PANTHER19 tree places the sequence-verified COL9A3 leaf below the recorded source node PTN002770818. This resolves current topology, but not the location-specific historical rationale or target basement-membrane premise; those remain unresolved. Supporting Evidence: GO_REF:0000033 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | KEEP AS NON CORE | Reason: The triple-helix event places alpha3-containing precursors in the ER lumen during assembly; other proteins provide hydroxylation, isomerization and chaperone activities. Retain this precursor compartment outside the principal mature-matrix core; no enzymatic role is inferred. Supporting Evidence: Reactome:R-HSA-2022073 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | KEEP AS NON CORE | Reason: The secretion event explicitly has ER-luminal precursor input, distinct from the extracellular output reviewed separately. Retain this precursor compartment outside the principal mature-matrix core; no enzymatic role is inferred. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944229 | KEEP AS NON CORE | Reason: The type IX association event directly includes alpha3 precursor material in the ER lumen. Its generic C-terminal-propeptide narrative does not replace the target-specific evidence for NC2 and other domain contributions to IX assembly. Retain this precursor compartment outside the principal mature-matrix core; no enzymatic role is inferred. Supporting Evidence: Reactome:R-HSA-8944229 |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IBA GO_REF:0000033 | ACCEPT | Reason: The actual PANTHER19 tree places PTN001166351 at the Metazoa-Choanoflagellida node, above sequence-verified COL9A3 and several collagen branches, not specifically collagen IV. Its dated IBD record lists COL4A1/P02462 and WBGene00002280 (let-2/P17140); donor identities alone do not define the node scope. The current GO:0030020 comment explicitly permits extracellular-matrix collagen proteins. Native alpha3 matrix cross-links and its heterotrimer interfaces provide the target structural premise, so the existing annotation and structural core are retained. This does not claim an isolated-chain tensile experiment or independent formation of the major fibrillar scaffold. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001166351 SUPPORTS TRANSFER The dated IBD record at PTN001166351 and the actual PANTHER19 PTHR24023 topology place the sequence-verified COL9A3 leaf below this source node. This verifies current inheritance context, not a replay of the historical curator session or an isolated-chain assay. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IC PMID:8660302 Collagen type IX from human cartilage: a structural profile ... | ACCEPT | Reason: The IC assertion uses established type IX membership to infer structural matrix contribution. Original human cartilage sequencing identifies alpha3βtype II and alpha3βalpha3/alpha1 IX cross-links, providing an explicit network-integration premise. It is not a direct isolated-chain tensile assay or a claim that COL9A3 catalyzes cross-link formation. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: The original human ECM-enrichment proteomics study detects COL9A3/Q14050 in supplementary workbook row 128 in both complete-data and matrisome sheets. Its RCA structural assignment is consistent with independent type IX chain and matrix evidence. Keep the distinction between protein detection/classification and a direct mechanical-strength experiment. |
| GO:0030198 extracellular matrix organization | IBA GO_REF:0000033 | ACCEPT | Reason: Alpha3 contributes physical assembly interfaces and covalent links that arrange the extracellular type II/IX network, fitting the existing matrix-organization process. This is a structural participation premise, not only disease association or being a substrate of another enzyme. The dated IBD and actual PANTHER19 topology now confirm the target below PTN002770636; the historical curator session is not replayed. Current descendant records, donor number and absent present-day rows are not used to diagnose a placement error. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002770636 SUPPORTS TRANSFER The dated IBD record at PTN002770636 and the actual PANTHER19 PTHR24023 topology place the sequence-verified COL9A3 leaf below this source node. This verifies current inheritance context, not a replay of the historical curator session or an isolated-chain assay. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: Actual human tissue extraction/MS Methods and the original supplementary workbook identify Q14050/COL9A3 in ECM-enriched material. Retain the extracellular matrix location. The study does not by itself establish a tumor-driving function, molecular interface or tensile-force phenotype. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IPI PMID:8660302 Collagen type IX from human cartilage: a structural profile ... | KEEP AS NON CORE | Reason: Original human cartilage sequencing specifically identifies an alpha3(IX) COL2-to-alpha3(IX) NC1 intermolecular connection among native IXβIX cross-links. This is positive same-chain association in the matrix, not an isolated native two-chain complex. Separately, PMID:17880280 reports recombinant full-length alpha3 expressed alone mainly as monomeric/dimeric material in insect cells. Retain the positive homodimerization annotation with these source limits, outside the principal heterotrimeric structural core; no native alpha3 homotrimer is inferred. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: What target-specific localization or ancestral placement supports the inherited COL9A3 basement-membrane annotation, and does it concern the vitreoretinal interface rather than vitreous fibrils themselves?
Q: How do alpha3βalpha3 and alpha3βtype II cross-links contribute separately to the mechanics and stability of the native cartilage and vitreous network?
Q: What is the physiological fate of alpha3-only dimers seen after recombinant expression, and how does coexpression of alpha1/alpha2 control their incorporation into collagen IX?
Q: How should current sequence-feature NC2/NC3 labels be reconciled with the experimentally named NC2 assembly domain spanning the alpha3 517β553 structural construct?
Experiment: Map sequence-verified alpha3 chains and site-specific native cross-links in cartilage and vitreous, combining cross-link mass spectrometry with matrix mechanics after selective site substitution.
Hypothesis: Different alpha3 cross-links make distinguishable contributions to native matrix connectivity.
Experiment: Use alpha3-specific immunogold localization at the vitreoretinal interface with fibril and basement-membrane markers and chain-deficient controls.
Hypothesis: Target-specific localization can distinguish vitreous-fibril residence from a basement-membrane-associated pool.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)