COL5A1 encodes the alpha1 chain of type V collagen, a secreted fibrillar matrix component that helps initiate collagen fibrils and regulate their diameter and organization. Alpha1(V) commonly assembles with alpha2(V) into type V heterotrimers that coassemble with type I collagen; tissue-specific V/XI hybrid assemblies also occur. Its retained N-terminal region interacts with matrix proteins and contributes to fibril organization and cellβmatrix behavior, whereas the C-propeptide participates in precursor assembly before processing. Reduced or altered alpha1(V) disrupts connective-tissue architecture and causes classical EhlersβDanlos syndrome, with skin, joint and ocular manifestations. Alternative splicing changes a segment of the C-terminal propeptide.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005178 integrin binding | NAS PMID:14970208 Human fibroblasts with mutations in COL5A1 and COL3A1 genes ... | KEEP AS NON CORE | Reason: Recovered original human fibroblast Methods/Results show abnormal collagen/fibronectin and integrin organization in COL5A1-deficient EDS cells, with responses to purified human type V collagen and integrin perturbations. This supports the existing contextual integrin-ligand assignment. It is not a purified binary affinity measurement of an isolated alpha1(V) chain, nor proof that all integrin effects are direct contacts. Keep the positive ligand context outside the principal structural core. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | IEA GO_REF:0000120 | MODIFY | Reason: The ortholog/domain assignment correctly identifies an extracellular matrix structural protein. Refine the broad structural term to the established collagen-specific structural activity. Human matrix-deposition/fibril observations and mouse loss-of-function fibril-initiation evidence support performed structural work; processing of the precursor by other proteins does not make COL5A1 a processing enzyme. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | KEEP AS NON CORE | Reason: The original N-propeptide study identifies human TIMP1 in the yeast two-hybrid screen and includes domain-based co-immunoprecipitation retesting with controls. Preserve this positive interaction as non-core. The official counterpart is a metalloproteinase inhibitor, but no verified more-specific binding term is established here; an inhibitor is not thereby an enzyme. No native inhibitory mechanism is assigned to COL5A1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | MODIFY | Reason: The original human N-propeptide screen and domain co-immunoprecipitation retests identify fibronectin, with the table mapping the FN fragment to residues 1100β1292. The preserved source specifies P02751-1; the tested fragment and engineered pN constructs do not establish every natural product combination. The direct positive partner class supports fibronectin binding without requiring a native contact-site or cell-signaling claim. Proposed replacements: fibronectin binding Supporting Evidence: PMID:20979576 Eleven interactions were confirmed |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | MODIFY | Reason: The original binary screen identifies MMP2 and the controlled domain retest supports the interaction; its Table 1 fragment is residues 346β660. MMP2 is an established protease, and GO:0002020 specifies binding to that partner class. This does not demonstrate contact with the active site, activation of MMP2, or a catalytic function of COL5A1; the tested fragment is kept distinct from the complete processed enzyme. The interaction evidence, rather than MMP2-mediated collagen degradation, grounds this refinement. Proposed replacements: protease binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | KEEP AS NON CORE | Reason: Retain the positive BMP1 association while distinguishing its assay from the N-propeptide screen hits. Actual source Methods/Results use BMP1 in procollagen processing reactions and examine PCPE1 enhancement; BMP1 is not listed among the Table 1 two-hybrid hits inspected here. Thus the source supports processing-associated contact, but does not establish an independently retested binary binding activity beyond substrate recognition. COL5A1 is processed by BMP1, not a BMP1-like enzyme. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | MODIFY | Reason: The actual human N-propeptide screen and domain retest identify tenascin C; Table 1 specifies the 1483β1622 fragment. The official TNC record establishes an extracellular-matrix component, matching GO:0050840. Refine the positive pair at this partner-class scope without claiming native matrix colocalization or a particular domain interface was independently resolved in every product. Proposed replacements: extracellular matrix binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | KEEP AS NON CORE | Reason: The original study tests PCPE1 by interaction screening and SPR and measures its enhancement of BMP1-mediated procollagen processing. Retain the positive PCOLCE association as a contextual activity. PCPE1 is a processing enhancer rather than the protease itself; no verified specific binding child is supplied here, and the experiment does not make COL5A1 an enzyme activator or scaffold. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Reason: The 2017 BioPlex record identifies an association of human COL5A1 with canonical MMP2 in HEK293T affinity-purification mass spectrometry. MMP2 is a protease, supporting refinement of the accepted partner class to protease binding. This spoke-expanded co-complex observation does not establish direct contact, a native extracellular encounter, MMP2 regulation or catalytic activity of COL5A1. It is distinct from the N-propeptide binary/domain retest in PMID:20979576 and is not inferred from collagen degradation. Proposed replacements: protease binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Reason: The 2017 BioPlex record identifies physical association of human COL5A1 with canonical PTPN2 in HEK293T affinity-purification mass spectrometry. PTPN2 is a protein tyrosine phosphatase, supporting the more specific protein-phosphatase partner class. The co-complex assay does not resolve direct contact, a native encounter or phosphatase regulation by COL5A1; no catalytic activity is assigned to the collagen chain. Proposed replacements: protein phosphatase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Reason: The 2021 BioPlex record identifies an association of human COL5A1 with canonical MMP2 in HEK293T affinity-purification mass spectrometry. MMP2 is a protease, supporting refinement of the accepted partner class to protease binding. This spoke-expanded co-complex observation does not establish direct contact, a native extracellular encounter, MMP2 regulation or catalytic activity of COL5A1. It is distinct from the N-propeptide binary/domain retest in PMID:20979576 and is not inferred from collagen degradation. Proposed replacements: protease binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Reason: The 2021 BioPlex record identifies physical association of human COL5A1 with canonical PTPN2 in HEK293T affinity-purification mass spectrometry. PTPN2 is a protein tyrosine phosphatase, supporting the more specific protein-phosphatase partner class. The co-complex assay does not resolve direct contact, a native encounter or phosphatase regulation by COL5A1; no catalytic activity is assigned to the collagen chain. Proposed replacements: protein phosphatase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Reason: Preserve the source-curated MMP2 association from the U2OS AP-MS interaction study. Actual source Methods establish tagged-bait purification and network scoring, but the exact target table row was not recovered and no matching current pair was returned in the bounded interaction query. That absence is not a negative experiment. Retain the positive association without claiming direct binary contact, a specific protease-binding interface or an independently verified target-table entry. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Reason: The original study analyzes extracellular-matrix-enriched human vein samples using fractionation and mass spectrometry. Actual extraction/MS Methods and Figure3 legend explicitly identify CO5A1 in GuHCl extracts from six normal and six varicose saphenous veins, with plotting intensity scaled tenfold. The supplemental target row remains uninspected; no figure-pixel value or target-specific significance is claimed. Retain this positive extracellular detection without presenting it as a direct vascular regulatory mechanism. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1474266 | ACCEPT | Reason: Formation of collagen fibrils contains type V collagen in extracellular fibrils; the chain contributes structure to assembly. Supporting Evidence: Reactome:R-HSA-1474266 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1564164 | ACCEPT | Reason: The type V collagen degradation event contains extracellular COL5A1 as a substrate of MMP2, MMP9 and MMP10. The metalloproteinases perform the degradation; the collagen is not itself a protease. Supporting Evidence: Reactome:R-HSA-1564164 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2002428 | ACCEPT | Reason: N-terminal propeptide processing places collagen V precursor-derived material extracellularly. Type V processing is partial, and the summary describes BMP1 cleavage of alpha1(V); the collagen chain does not catalyze proteolysis. Supporting Evidence: Reactome:R-HSA-2002428 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2002440 | ACCEPT | Reason: C-terminal propeptide cleavage occurs in procollagen-containing material. The summary distinguishes chain-dependent type V processing by furin-like convertases and/or BMP1; COL5A1 is their substrate. Retain the source extracellular location without claiming that every processing event occurs exclusively outside cells. Supporting Evidence: Reactome:R-HSA-2002440 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2089971 | ACCEPT | Reason: The association/secretion event includes both luminal precursors and exported collagen material. This source assertion concerns its extracellular destination; its separate ER annotation is retained independently. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213201 | ACCEPT | Reason: Formation of collagen fibers places fibrils in extracellular supramolecular structures. The summary discusses tissue-specific organization and surface-associated GAG/proteoglycan interactions; this is not an isolated alpha1(V) crosslink-enzyme assay. Supporting Evidence: Reactome:R-HSA-2213201 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327695 | ACCEPT | Reason: The integrin-ligand event contains extracellular collagen V within a collagen set. A target membership path supports location, not isolated alpha1(V) binding to every listed integrin. Supporting Evidence: Reactome:R-HSA-2327695 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327733 | ACCEPT | Reason: The FN1 association event contains extracellular type V collagen; its exact participant path agrees with the independently tested N-propeptide/fibronectin interaction. Supporting Evidence: Reactome:R-HSA-2327733 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327738 | ACCEPT | Reason: The DDR1 association event includes type V collagen as extracellular ligand material. Retain location without assigning receptor kinase activity to COL5A1 or claiming a target-chain-specific affinity measurement from a family-set path. Supporting Evidence: Reactome:R-HSA-2327738 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396370 | ACCEPT | Reason: The vitronectin association event includes collagen types II, III and V extracellularly. Retain the COL5A1 location while distinguishing the collagen participant from its VTN counterpart and from an isolated alpha1(V)-specific interface assay. Supporting Evidence: Reactome:R-HSA-2396370 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2465890 | ACCEPT | Reason: The DDR2 association event includes extracellular type V collagen. The collagen is the ligand material rather than the receptor kinase; participant-set membership does not independently resolve every alpha-chain contact. Supporting Evidence: Reactome:R-HSA-2465890 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-375151 | ACCEPT | Reason: NCAM1 association uses a broad extracellular collagen set whose membership path reaches COL5A1. Its summary lists other collagen types; this target location is not a new alpha1(V)-specific NCAM1 binding assay. Supporting Evidence: Reactome:R-HSA-375151 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-382054 | ACCEPT | Reason: PDGF association places collagen-containing material extracellularly. Broad participant membership is distinguished from a direct alpha1(V)-specific affinity measurement; the independent original PDGF source is assessed separately. Supporting Evidence: Reactome:R-HSA-382054 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9638561 | ACCEPT | Reason: The bacterial collagen-associated event places human collagen extracellularly; a host matrix substrate or ligand is not itself a bacterial virulence activity. Supporting Evidence: Reactome:R-HSA-9638561 |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-2731094 | ACCEPT | Reason: The distinct R-NUL syndecan-1 association source currently reports Homo sapiens and resolves to COL5A1 through extracellular collagen-containing entities. Preserve this identifier and assertion separately from any R-HSA event; the prefix is not evidence of a nonhuman experiment. Family-set participation does not establish an isolated alpha1(V)-specific syndecan interface. Supporting Evidence: Reactome:R-NUL-2731094 |
| GO:0005581 collagen trimer | IEA GO_REF:0000107 | MODIFY | Reason: The generic trimer transfer from mouse Col5a1 can be refined to the established type V collagen trimer. Actual human studies and the source-specific mouse evidence agree with alpha1(V) assembly; this does not assign identical precursor assembly efficiencies to the two human splice products. Proposed replacements: collagen type V trimer |
| GO:0005588 collagen type V trimer | IBA GO_REF:0000033 | ACCEPT | Reason: Type V trimer membership agrees with human chain-composition and assembly observations. The target in the PAINT WITH/FROM list is legitimate descendant grounding, not circular evidence. Current same-term records corroborate the placement; the historical IBD node/tree was not reconstructed and no placement error is alleged. |
| GO:0005588 collagen type V trimer | IMP PMID:9683580 A point mutation in an intronic branch site results in aberr... | ACCEPT | Reason: The complete human-family abstract reports COL5A1 splice disruption and the established alpha1(V)2alpha2(V) heterotrimer. Its proposed dominant-negative incorporation mechanism is qualified rather than newly demonstrated here. Retain the correct complex membership through this positive clinical/sequence context and independent human chain-composition evidence. |
| GO:0005588 collagen type V trimer | IPI PMID:29853175 Collagen Fibril Assembly and Function. | ACCEPT | Reason: Known type V collagen-trimer membership is independently well supported. The original review abstract is authentic but full target passages were not recovered, so this source is not presented as a newly read binary or stoichiometric experiment. Retain correct membership with curator deference and independent target evidence. |
| GO:0005588 collagen type V trimer | NAS PMID:37158802 The Chemistry and Biology of Collagen Hybridization. | ACCEPT | Reason: The authenticated review discusses collagen triple helices and hybridization broadly. The full selected review is available and its actual triple-helix/peptide-assembly and remodeling passages were inspected, but a target-specific membership passage remains unverified. Retain independently established type V complex membership rather than attributing a new alpha1(V) assembly experiment to this review. |
| GO:0005588 collagen type V trimer | TAS PMID:9042913 Mutations in the COL5A1 gene are causal in the Ehlers-Danlos... | ACCEPT | Reason: The complete human EDS abstract explicitly describes a C-propeptide cysteine substitution that prevents mutant proalpha1(V) incorporation into type V trimers and reduces collagen V. Retain target complex membership, preserving the disease-variant experiment separately from the normal alternative splice products. Supporting Evidence: |
| GO:0005592 collagen type XI trimer | IEA GO_REF:0000117 | MODIFY | Reason: The collagen V/XI family shares fibrillar assembly biology, but GO:0005592 currently specifies the alpha1(XI)/alpha2(XI)/alpha1(II) composition. The review PMID:20705069 groups V and XI as tissue-specific isoforms of one collagen type, including alpha1(V)-containing type V trimers. Independently, PMID:19103590 identifies alpha1(V) in bovine V/XI polymers and partially resolves alpha1(XI)/alpha1(V)/alpha3(XI) hybrids. GO:0005583 retains the supported fibrillar-trimer assertion without assigning the canonical XI chain composition. This corrects an existing electronic source assertion; it adds no NEW coverage beyond the separate type V trimer annotations. The exact hybrid composition remains explicit here and in the ontology question. Proposed replacements: fibrillar collagen trimer |
| GO:0005592 collagen type XI trimer | TAS PMID:20705069 Focus on molecules: collagens V and XI. | MODIFY | Reason: PMID:20705069 explicitly treats collagens V and XI as one collagen type with tissue-specific isoforms, listing alpha1(V)-containing type V trimers alongside canonical XI and a V/XI hybrid example. That positive family framing is broader than the current GO:0005592 definition, which enumerates alpha1(XI)/alpha2(XI)/alpha1(II). Refine this source assertion to the supported fibrillar collagen trimer class, GO:0005583. The separate bovine primary PMID:19103590 provides alpha1(V)-containing hybrid evidence; it is not attributed to the review as a new experiment. The replacement preserves a supported source assertion rather than proposing redundant NEW coverage; an ontology question retains the more specific hybrid issue. Proposed replacements: fibrillar collagen trimer |
| GO:0005604 basement membrane | IEA GO_REF:0000107 | UNDECIDED | Reason: The exact mouse Col5a1 identity and a current same-term IDA record are verified, but its original PMID:14676276 cache is abstract-only and focuses on usherin/type IV collagen. Bounded original full-text recovery failed. That title/abstract is insufficient to reject the curator or infer a paralog error; the specific type V basement-membrane localization supporting this electronic transfer remains unresolved. Preserve the source and distinguish basement membrane from the independently established interstitial matrix role. |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The secreted procollagen precursor enters the ER lumen for modification and chain assembly before secretion. Retain this biosynthetic location outside the principal mature-matrix core. The ARBA source is preserved; luminal residence does not imply a chaperone, export-machine or processing-enzyme activity. Supporting Evidence: Reactome:R-HSA-2022073 Reactome:R-HSA-2089971 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | KEEP AS NON CORE | Reason: The current triple-helix formation event resolves the COL5A1 precursor in the ER lumen. Retain this location while distinguishing COL5A1 structural assembly from the enzymes and transport machinery acting on it. Its separate extracellular source assertions concern later material and remain intact. Supporting Evidence: Reactome:R-HSA-2022073 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | KEEP AS NON CORE | Reason: The current procollagen association and secretion event resolves the COL5A1 precursor in the ER lumen. Retain this location while distinguishing COL5A1 structural assembly from the enzymes and transport machinery acting on it. Its separate extracellular source assertions concern later material and remain intact. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944223 | KEEP AS NON CORE | Reason: The current procollagen modification/assembly event resolves the COL5A1 precursor in the ER lumen. Retain this location while distinguishing COL5A1 structural assembly from the enzymes and transport machinery acting on it. Its separate extracellular source assertions concern later material and remain intact. Supporting Evidence: Reactome:R-HSA-8944223 |
| GO:0007155 cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The PAINT adhesion placement is compatible with matrix-mediated cell adhesion and actual human collagen V rescue/ligand experiments. Current target evidence is legitimate grounding; the historical IBD node was not reconstructed. This contextual cellβmatrix role is retained outside the principal fibril-structural core without turning the collagen chain into an autonomous signaling receptor. |
| GO:0007155 cell adhesion | IMP PMID:18305566 Rescue of migratory defects of Ehlers-Danlos syndrome fibrob... | KEEP AS NON CORE | Reason: Actual human dermal-fibroblast experiments compare COL5A1-haploinsufficient EDS cultures and controls, and add purified human type V collagen, improving scratch-edge attachment stability and migration. Retain this performed matrix-ligand context as non-core; it is not a separate quantitative adhesion assay, a demonstration that COL5A1 catalyzes adhesion or a test of every splice product. Supporting Evidence: |
| GO:0008201 heparin binding | IDA PMID:2203476 Primary structure of the heparin-binding site of type V coll... | KEEP AS NON CORE | Reason: The complete original abstract reports heparin binding by collagen V and an alpha1(V)-derived 30-kDa fragment; loss of basic-region sequence abolishes the tested binding. This positive molecular interaction is retained. Full original Methods and exact preparation species were not recovered, so no human-product-specific affinity or in-vivo heparin-regulatory role is asserted. Supporting Evidence: |
| GO:0016477 cell migration | IMP PMID:18305566 Rescue of migratory defects of Ehlers-Danlos syndrome fibrob... | KEEP AS NON CORE | Reason: Purified human type V collagen rescues scratch-wound closure/migration behavior of COL5A1-haploinsufficient human dermal fibroblasts in the actual source. Retain this matrix-dependent movement as contextual. The IGFBP1 Transwell experiment is separate and is not described as a collagen-V Transwell assay or proof that COL5A1 is itself a motility motor. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Reason: The authentic source abstract and original human ECM-proteomics workbooks identify COL5A1 as a collagen-class core-matrisome component. Exact S2 and S3 target rows were inspected. The collagen structural term is independently supported by fibril architecture/assembly evidence; a protein-identification experiment is not represented as a direct force assay. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IBA GO_REF:0000033 | ACCEPT | Reason: The inherited collagen structural function agrees with target human fibril architecture and mouse initiation evidence. Resolved current descendant records span collagen proteins with diverse tissue/network contexts; the GO comment explicitly permits ECM collagens. Donor number, target self-evidence or fibrillar-versus-network differences alone do not invalidate the historical PAINT placement, which was not reconstructed. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Reason: Actual human aortic extraction Methods/Results and exact Table II target row were inspected. Retain the independently established collagen structural role. The source is used at its actual identification/classification scope, not as a direct tensile measurement, and missing table access is not treated as contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: Actual human colon/liver ECM-enrichment Methods/Results and exact target rows in both original workbook sheets were inspected. Retain the independently established collagen structural role. The source is used at its actual identification/classification scope, not as a direct tensile measurement, and missing table access is not treated as contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Reason: The selected normal cache remains partial, but genuine original full HTML was recovered separately. Actual human atrial extraction/MS Methods and Table1 identify collagen alpha-1(V) in GuHCl input, with no enrichment/glycopeptide detection marked. Retain the independently established collagen structural role. The source is used at its actual identification/classification scope, not as a direct tensile measurement, and missing table access is not treated as contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Reason: The selected normal cache remains partial; authentic external full HTML supplies actual cell-culture/quantification Methods and Table1 grouped COL5A1/2 collagen V classification. This group listing is not an individually quantified alpha1(V) peptide result. Retain the independently established collagen structural role. The source is used at its actual identification/classification scope, not as a direct tensile measurement, and missing table access is not treated as contrary evidence. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Reason: Available selected Results/Discussion describe ECM-proteomics optimization; the attempted supplementary workbook is HTML rather than a valid workbook, and the exact target row remains uninspected. Retain the independently established collagen structural role. The source is used at its actual identification/classification scope, not as a direct tensile measurement, and missing table access is not treated as contrary evidence. |
| GO:0030199 collagen fibril organization | IBA GO_REF:0000033 | ACCEPT | Reason: The PAINT fibril-organization placement agrees with human target-dependent fibril morphology and mouse fibril-initiation evidence. Current exact donor identities and same-term records were resolved separately; some records are inferred and are not relabeled as experiments. The historical tree/node was not reconstructed, and the target appearing as a descendant source is expected. |
| GO:0030199 collagen fibril organization | IMP PMID:11278977 COL5A1 exon 14 splice acceptor mutation causes a functional ... | ACCEPT | Reason: The complete human-family abstract reports reduced secreted collagen V and abnormal dermal fibril diameters, including both larger and smaller fibrils. This supports a structural contribution to fibril organization, not merely a disease association. Full original Methods were not recovered; exact additional assays are not invented. Supporting Evidence: PMID:11278977 greater heterogeneity |
| GO:0030199 collagen fibril organization | IMP PMID:15095409 Reduced type I collagen utilization: a pathogenic mechanism ... | ACCEPT | Reason: The complete original abstract reports COL5A1-haploinsufficient human fibroblasts depositing markedly fewer fibrils with altered diameters despite near-normal total collagen synthesis. It explicitly includes a COL1A1-haploinsufficient OI comparator. This is positive target fibril-organization evidence; the paper is not dismissed as a different-gene study. Supporting Evidence: |
| GO:0030199 collagen fibril organization | IMP PMID:9683580 A point mutation in an intronic branch site results in aberr... | ACCEPT | Reason: The human-family abstract establishes a COL5A1 splice defect and connective-tissue phenotype, while describing type V fibril coassembly as biological context. Mutant-chain dominant-negative incorporation remains the authorsβ qualified proposal. Retain the correct fibril role using independent target morphology/deposition evidence rather than claiming this abstract is a complete fibrillogenesis assay. |
| GO:0030199 collagen fibril organization | NAS PMID:16430677 The COL5A1 gene and Achilles tendon pathology. | ACCEPT | Reason: The source abstract directly reports an Achilles-tendon genotype association, not a biochemical fibril-organization experiment. Nevertheless, the NAS biological role is independently established by human fibril/deposition and mouse initiation evidence. Retain that role while making the association-only source scope explicit; no claim that the associated allele has a demonstrated causal assembly effect. |
| GO:0030199 collagen fibril organization | NAS PMID:29853175 Collagen Fibril Assembly and Function. | ACCEPT | Reason: The authentic review abstract describes collagen assembly broadly; the exact target passage is not available. Independent human COL5A1 fibril-morphology/deposition evidence supports the existing role. Retain it with explicit full-access limits instead of treating missing review text as negative. |
| GO:0030199 collagen fibril organization | NAS PMID:37158802 The Chemistry and Biology of Collagen Hybridization. | ACCEPT | Reason: The full selected review concerns collagen hybridization and triple-helix chemistry; actual peptide-assembly and remodeling passages were read, but the precise target-specific link remains unverified. Independently established COL5A1 fibril organization supports retention of the NAS role; the review is not presented as a new alpha1(V) intervention experiment. |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Reason: Actual human aortic extraction Methods/Results and exact Table II target row were inspected. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Reason: Actual human colon/liver ECM-enrichment Methods/Results and exact target rows in both original workbook sheets were inspected. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Reason: The selected normal cache remains partial, but genuine original full HTML was recovered separately. Actual human atrial extraction/MS Methods and Table1 identify collagen alpha-1(V) in GuHCl input, with no enrichment/glycopeptide detection marked. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Reason: The selected normal cache remains partial; authentic external full HTML supplies actual cell-culture/quantification Methods and Table1 grouped COL5A1/2 collagen V classification. This group listing is not an individually quantified alpha1(V) peptide result. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Reason: Original S2/S3 workbook target rows and the complete authentic source abstract were inspected. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Reason: Available selected Results/Discussion describe ECM-proteomics optimization; the attempted supplementary workbook is HTML rather than a valid workbook, and the exact target row remains uninspected. Extracellular matrix is the established location of mature type V collagen. Retain the source-curated detection without converting proteomic presence into tissue-specific signaling or a directly measured mechanical function. |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Reason: The PAINT extracellular-matrix placement agrees with secretion and matrix incorporation of collagen V. Resolved current same-term descendant records corroborate location across collagen family members, while the historical IBD tree/node remains uninspected. No donor-count or self-donor circularity argument is used. |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Reason: The official mouse Col5a1 ortholog and current same-term extracellular-matrix records agree with the established human matrix location. Preserve the original electronic-transfer identifier; this check corroborates the annotation without claiming to reconstruct its complete historical pipeline. |
| GO:0031012 extracellular matrix | IMP PMID:14970208 Human fibroblasts with mutations in COL5A1 and COL3A1 genes ... | ACCEPT | Reason: Recovered original human fibroblast Methods/Results directly examine collagen V/fibronectin matrix organization and restoration after purified human collagen supplementation. Retain extracellular matrix localization, separating COL5A1-deficient and COL3A1-deficient cell experiments and avoiding an inference of purified receptor affinity. Supporting Evidence: |
| GO:0032964 collagen biosynthetic process | IMP PMID:11278977 COL5A1 exon 14 splice acceptor mutation causes a functional ... | UNDECIDED | Reason: The complete human-family abstract reports reduced COL5A1 transcript abundance and secreted type V collagen, plus altered fibril morphology; full original Methods remain unavailable. Reduced production establishes a consequence but does not by itself resolve the specific biosynthetic step performed by alpha1(V). Intrinsic structural assembly can count as performed work, so the annotation is unresolved rather than denied simply because the protein is a precursor. Independently, the PMID:9042913 human EDS abstract reports a C-propeptide cysteine substitution preventing mutant-chain incorporation into type V trimers, supporting intrinsic assembly work. That positive premise does not resolve the exact biosynthetic step attributed by this source whose full Methods remain unavailable. |
| GO:0032964 collagen biosynthetic process | IMP PMID:15095409 Reduced type I collagen utilization: a pathogenic mechanism ... | UNDECIDED | Reason: The original abstract distinguishes near-normal total collagen synthesis from strongly reduced matrix deposition/fibril number in COL5A1-haploinsufficient cultures. Full original Methods were not recovered. This clearly supports assembly/organization, but leaves the source-specific collagen-biosynthesis assignment unresolved. Do not equate deposition with chemical synthesis or conclude that a structural precursor can never contribute to formation. Independently, the PMID:9042913 human EDS abstract reports a C-propeptide cysteine substitution preventing mutant-chain incorporation into type V trimers, supporting intrinsic assembly work. That positive premise does not resolve the exact biosynthetic step attributed by this source whose full Methods remain unavailable. |
| GO:0035313 wound healing, spreading of epidermal cells | IMP PMID:18305566 Rescue of migratory defects of Ehlers-Danlos syndrome fibrob... | MODIFY | Reason: Human COL5A1-haploinsufficient dermal fibroblasts show impaired closure of a scraped monolayer, and purified human type V collagen restores migration across the gap. GO:0035313 requires epidermal cells, whereas its parent GO:0044319 covers cell migration through a wound gap that restores a continuous surface. The parent therefore preserves the demonstrated scratch-repair context without the unsupported epidermal identity. This matrix-dependent contribution is not a claim that COL5A1 propels cells or that the assay measures all stages of wound healing; the IGFBP1 Transwell assay is separate. Proposed replacements: wound healing, spreading of cells Supporting Evidence: |
| GO:0043394 proteoglycan binding | IPI PMID:9099729 The membrane-spanning proteoglycan NG2 binds to collagens V ... | KEEP AS NON CORE | Reason: Recovered original Methods use pepsinized human amniotic-membrane collagen V and rat NG2/CSPG4, with solid-phase assays and rotary shadowing supporting central-core-protein interaction. The source Q00657 is the rat partner and remains unchanged. Retain proteoglycan binding at this tested preparation scope, without treating it as a human-human pair or assuming intact N-propeptide/native isoform equivalence. Supporting Evidence: |
| GO:0043588 skin development | IMP PMID:9683580 A point mutation in an intronic branch site results in aberr... | KEEP AS NON CORE | Reason: The original human EDS-family abstract establishes splice disruption and a skin-fragility connective-tissue phenotype. A structural contribution to skin integrity/development is biologically coherent, but no complete developmental time course or independently measured mutant assembly mechanism was inspected. Retain this contextual process outside the principal fibril core. Supporting Evidence: |
| GO:0045112 integrin biosynthetic process | IMP PMID:18305566 Rescue of migratory defects of Ehlers-Danlos syndrome fibrob... | MARK AS OVER ANNOTATED | Reason: Actual source integrin assays primarily measure organization/localization by immunofluorescence and matrix-dependent cell behavior. GO:0045112 concerns the chemical reactions/pathways forming integrins; those observations do not establish such a COL5A1-performed synthesis step. Mark this source-level specificity as over-annotated while retaining the positive integrin reorganization, ligand context, adhesion and migration findings. This is not a claim that altered matrix could never influence integrin expression. Supporting Evidence: |
| GO:0048407 platelet-derived growth factor binding | IDA PMID:8900172 Type I, II, III, IV, V, and VI collagens serve as extracellu... | KEEP AS NON CORE | Reason: The complete original abstract directly reports PDGF association with several collagen types including type V and their constituent chains, with collagen-bound growth factor retaining activity in cell assays. Retain the binding context. The reported affinity range pools tested collagens; exact preparation species and a COL5A1-specific value are not established from the available abstract. Supporting Evidence: |
| GO:0048592 eye morphogenesis | IMP PMID:16431952 Structural abnormalities of the cornea and lid resulting fro... | KEEP AS NON CORE | Reason: Actual original human EDS examinations and separate mouse Col5a1-haploinsufficiency Methods/Results show altered corneal/lid architecture and increased fibril diameter with reduced stromal collagen, while cylindrical fibrils remain regularly packed in organized lamellae. Retain the structural contribution to eye morphology. Human COL5A1 and COL5A2 cases are distinguished, and this does not require COL5A1 to be a phototransduction protein or assign a direct activity to every clinical variant. Supporting Evidence: |
| GO:0048705 skeletal system morphogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The PAINT skeletal-morphogenesis placement is compatible with collagen-mediated tissue architecture and current resolved descendant evidence. Retain this contextual developmental role outside the core molecular function. The historical IBD node was not reconstructed; differing collagen family roles and a short donor list alone do not demonstrate a placement error. |
| GO:0097435 supramolecular fiber organization | IMP PMID:14970208 Human fibroblasts with mutations in COL5A1 and COL3A1 genes ... | ACCEPT | Reason: Recovered original human fibroblast experiments concern organization of collagen and fibronectin networks and their restoration by purified collagen treatment. The broader fiber-organization term therefore captures performed matrix work beyond a collagen-only fibril-size endpoint. Retain it without forcing a narrower replacement or making every integrin response a direct binding assay. Supporting Evidence: |
| GO:1903225 negative regulation of endodermal cell differentiation | IDA PMID:23154389 Regulation of endodermal differentiation of human embryonic ... | KEEP AS NON CORE | Reason: Actual human embryonic-stem-cell experiments expose cells to printed extracellular-matrix combinations under Wnt/Activin differentiation conditions. Factorial analysis associates inclusion of collagen V with reduced definitive-endoderm output measured by SOX17; this is a controlled extracellular cue experiment, not merely COL5A1 marker expression. Retain the contextual effect without proposing a universal endogenous developmental mechanism, a receptor or equal activity of all alpha1(V) products. Supporting Evidence: |
| GO:0005518 collagen binding | IDA PMID:20979576 Identification of binding partners interacting with the Ξ±1-N... | NEW | Reason: The human alpha1(V) N-propeptide binds pepsinized type I and VI collagens in SPR experiments, and selected collagen domains are retested by controlled co-immunoprecipitation. Separate solid-phase assays implicate this N-propeptide in the native collagen VβVI interaction. This directly supports collagen binding at the tested domain/preparation scope, without assigning equal affinity to both precursor splice products, a new matrix-bridging process or an autonomous adaptor mechanism. Current GO:0005518 has no ancestor/descendant overlap with the source or effective MF terms; its adhesion-specific and collagen-V-ligand children do not describe these assays. Supporting Evidence: PMID:20979576 interaction between native type V collagen and type VI collagen |
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Download this section (compressed HTML)Q: How do the two alpha1(V) C-propeptide splice variants differ in chain selection, secretion and processing when their mature-chain sequences are the same?
Q: Which human tissues contain alpha1(V)-bearing V/XI hybrid trimers, and should the ontology distinguish these from the strictly enumerated canonical type XI trimer?
Q: Which N-propeptide interactions govern fibril initiation or diameter in native human matrix, rather than only in isolated domain or engineered-construct assays?
Q: Does collagen V alter integrin production as well as organization, and which receptor-dependent events explain fibroblast migration and the endoderm response to applied collagen V?
Q: What exact performed formation step underlies the two existing collagen-biosynthesis annotations, beyond reduced collagen abundance or matrix deposition?
Q: What target-specific localization experiment supports the mouse type V basement-membrane record used for the electronic transfer, distinct from the available usherin/type IV abstract?
Experiment: Compare sequence-defined human alpha1(V) splice products in matched alpha2(V)-containing precursor assemblies, measuring secretion, cleavage, trimer composition and fibril architecture separately.
Hypothesis: C-propeptide differences can affect precursor selection or processing despite an identical mature-chain sequence.
Experiment: Use native human cartilage/tendon crosslink proteomics with chain-specific peptides to distinguish canonical type V, canonical type XI and alpha1(V)-containing hybrids.
Hypothesis: Hybrid chain composition varies by tissue and age and is not captured by a single canonical complex definition.
Experiment: Perturb verified N-propeptide partner interfaces in reconstituted collagen I/V matrices and measure fibril initiation, diameter and cell responses, with matrix abundance and processing controlled.
Hypothesis: Selected contacts contribute structural organization independently of general collagen abundance.
Experiment: In the fibroblast-rescue and ESC matrix-cue settings, separate integrin transcription/translation from receptor redistribution and quantify migration or endoderm differentiation after receptor loss/rescue.
Hypothesis: Matrix organization and receptor redistribution can account for some responses without requiring increased integrin biosynthesis.
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