COL4A1 encodes the alpha1 chain of type IV collagen, a network-forming constituent of basement membranes. The NC1-containing chain combines with COL4A2 in alpha1(IV)2alpha2(IV) protomers; associations through the C-terminal NC1 and N-terminal 7S regions connect protomers into a matrix network. Peroxidasin-dependent sulfilimine cross-links stabilize adjoining NC1 domains. This network supports tissue architecture and vascular, renal and other basement membranes, and pathogenic COL4A1 variants can disrupt their organization and integrity. Proteolysis can release the NC1-derived fragment arresten, which interacts with endothelial cell surfaces and suppresses angiogenic responses in experimental fragment preparations. Alternative splicing also produces a shortened chain lacking the NC1 region. The collagen IV gene family extends beyond animals to the filasterean Ministeria vibrans, whereas organized basement membranes have a distinct and variable distribution among animal lineages.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
COL4A1_ARRESTENPRO_0000390482 (residues 1445-1669) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001569 branching involved in blood vessel morphogenesis | IMP PMID:20818663 Novel COL4A1 mutations associated with HANAC syndrome: a rol... | UNDECIDED | Summary: Human HANAC vascular abnormalities implicate the collagen IV matrix, but the accessible source does not resolve coordinated vessel branching. Reason: The authentic complete PMID:20818663 abstract describes three human HANAC families, retinal arterial tortuosity and CB3[IV] glycine substitutions. That supports vascular matrix involvement, but the specific coordinated growth/sprouting assertion cannot be verified from this access scope. Publisher full-text access failed; retain the original experimental assertion pending the relevant full assay, without alleging an incorrect curator attribution. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | IEA GO_REF:0000002 | MODIFY | Summary: The NC1-containing alpha1(IV) chain supplies structural material to the mechanically stabilizing basement-membrane network. Reason: The broad structural classification is sound, but extracellular matrix structural constituent conferring tensile strength is the more informative established collagen activity. Its current GO comment explicitly permits extracellular matrix collagens. Human NC1 architecture and clinical basement-membrane disruption support the material contribution of the network-forming alpha1(IV) chain; this is not an assertion of fibrillar architecture or an isolated mechanical-force assay, and the NC1-lacking short product is not assumed equivalent. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005201 extracellular matrix structural constituent | IMP PMID:20818663 Novel COL4A1 mutations associated with HANAC syndrome: a rol... | MODIFY | Summary: Human CB3[IV] mutations support the matrix role; independent NC1 architecture supports the established collagen structural class. Reason: The source explicitly studies human COL4A1 mutations in the triple-helical CB3[IV] region. Its clinical and genetic evidence supports the established matrix role; independent human NC1 structure demonstrates the material contribution. Refine the broad activity to the existing collagen tensile-strength classification under the current GO collagen convention, judged holistically. The available abstract is not presented as an isolated mechanical-strength assay, and no equivalent activity is inferred for the NC1-lacking short product. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005515 protein binding | IPI PMID:12011424 The 1.9-A crystal structure of the noncollagenous (NC1) doma... | MODIFY | Summary: Human placental NC1 structure resolves contacts between alpha1(IV) and the collagen alpha2(IV) partner. Reason: Preserve the positive human COL4A1βCOL4A2 assertion. The two literal IntAct records report crystallography and molecular sieving; the human placental NC1 structure resolves alpha1/alpha2 contacts within the trimeric caps and opposing-cap interface. Binding to this collagen partner supports collagen binding. Assembly context is not a reason to discard the association; this refinement does not assert every splice product was tested. Current GO:0005518 defines collagen binding without excluding collagen-chain binders; its typed closure is distinct from GO:0005178. The measured NC1 association and type-IV-trimer membership describe different properties. The modified row does not provide effective integrin-binding coverage. Proposed replacements: collagen binding Supporting Evidence: PMID:12011424 In each trimer, the two Ξ±1 and one Ξ±2 triangular chain monomers are radially packed together |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | ACCEPT | Summary: The secreted collagen IV chain is extracellular; the cited plasma inventory does not resolve intact protomers or individual splice products. Reason: Extracellular localization is consistent with the secreted collagen IV network. The cited complete abstract describes the combined human plasma-proteome inventory; its exact COL4A1 table entry was not inspected. Retain this NAS location on independent structural evidence without claiming intact protomers, every isoform, or a specific plasma concentration from that inventory. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1454757 | ACCEPT | Summary: Extracellular collagen-derived gelatin is a substrate for the proteases represented in this event. Reason: Gelatin degradation places collagen-derived material extracellularly; the collagen is the protease substrate, not the enzyme. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-1454757 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1564142 | ACCEPT | Summary: The extracellular collagen IV network is degraded by metalloproteinases in this event. Reason: Type IV collagen degradation places the collagen network extracellularly; metalloproteinases perform the cleavage. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-1564142 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213207 | ACCEPT | Summary: NC1 and 7S interactions assemble type IV protomers into an extracellular network. Reason: The network-formation event represents extracellular association of type IV protomers through NC1 and 7S regions. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2213207 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327695 | ACCEPT | Summary: The integrin event places COL4A1-containing collagen ligand material extracellularly. Reason: The integrin-binding event represents extracellular collagen ligand material, with a verified current entity path to COL4A1; it does not establish all receptor interfaces on each isolated chain. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2327695 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327733 | ACCEPT | Summary: The fibronectin event includes extracellular collagen IV-containing material. Reason: The fibronectin-binding event places collagen IV-containing material outside cells; broad collagen-family binding context is distinct from an isolated COL4A1 affinity measurement. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2327733 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327738 | ACCEPT | Summary: The DDR1 event includes extracellular collagen IV without assigning receptor kinase activity to collagen. Reason: The DDR1 event includes nonfibrillar collagen IV as well as fibrillar collagens. Preserve its extracellular location without importing DDR kinase catalysis into collagen. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2327738 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396234 | ACCEPT | Summary: Collagen VII associates with the extracellular collagen IV basement-membrane network. Reason: The collagen VII association event concerns extracellular anchoring of the basement-membrane network; COL4A1 is a structural component of the collagen IV participant. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2396234 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2426450 | ACCEPT | Summary: Laminin and nidogen connect extracellular matrix networks containing collagen IV. Reason: The laminin/nidogen event links extracellular matrix networks. The target chain is represented within collagen IV, not as an enzyme catalyzing assembly. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2426450 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2559639 | ACCEPT | Summary: COL4A1 provides extracellular cross-linked residues; peroxidasin supplies the oxidant-generating activity. Reason: The cross-link event is extracellular. COL4A1 supplies the network residues, whereas peroxidasin generates the oxidant used for sulfilimine formation. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-2559639 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-375151 | ACCEPT | Summary: The NCAM1 association event includes extracellular collagen IV-containing material. Reason: The NCAM1 association event places collagen IV-containing ligand material in the extracellular region. It is not evidence that COL4A1 performs neural signaling chemistry. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-375151 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-382054 | ACCEPT | Summary: Matrix collagen participates in extracellular growth-factor retention by binding PDGF. Reason: The PDGF association event describes extracellular growth-factor retention by matrix molecules, consistent with the independent collagen-binding abstract. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-382054 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4084912 | ACCEPT | Summary: NC1-derived arresten is an extracellular ligand in the integrin-binding event. Reason: The arresten event places the processed COL4A1 NC1 ligand outside cells. Its current summary cites the nonretracted 2000 and 2008 studies; retain this location separately from the retracted 2005 detailed signaling claims. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-4084912 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9638628 | ACCEPT | Summary: Collagen IV is the extracellular host-matrix partner of the bacterial adhesin DraE. Reason: The DraE event concerns binding of a bacterial adhesin to extracellular collagen IV. COL4A1 is the host matrix participant, not a bacterial adhesin. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-HSA-9638628 |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-4084497 | ACCEPT | Summary: The preserved R-NUL collagen VII event reaches human COL4A1 through collagen IV-containing material. Reason: The R-NUL collagen VII association record remains an original source assertion. Current entity traversal reaches human COL4A1 through collagen IV-containing material; the nonhuman/unspecified event identifier itself is preserved without relabeling it as a new human experiment. The current target-material path corroborates this location. Supporting Evidence: Reactome:R-NUL-4084497 |
| GO:0005581 collagen trimer | IEA GO_REF:0000002 | MODIFY | Summary: The demonstrated assembly is the alpha1(IV)2alpha2(IV) collagen type IV trimer. Reason: The broad collagen-trimer classification is correct, but collagen type IV trimer identifies the demonstrated complex. Human placental NC1 structure resolves caps containing two alpha1(IV) chains and one alpha2(IV) chain, supporting the alpha1(IV)2alpha2(IV) protomer. Retain the original InterPro source object while refining the reviewed term; the 519-residue alternative product lacks NC1 and was not shown equivalent. Proposed replacements: collagen type IV trimer Supporting Evidence: |
| GO:0005587 collagen type IV trimer | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited type IV trimer assignment agrees with direct human NC1 chain stoichiometry. Reason: The PAINT assertion agrees with direct human trimer structure and current target experimental annotations. The human target in WITH/FROM is legitimate descendant evidence for an ancestral placement, not circularity. The historical IBD tree/node was not independently reconstructed, so donor count or current donor gaps are not used to overturn the placement. Supporting Evidence: |
| GO:0005587 collagen type IV trimer | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse-ortholog transfer agrees with independently demonstrated human type IV trimer architecture. Reason: The combined mouse-ortholog and Ensembl transfer is consistent with human alpha1(IV)2alpha2(IV) architecture. Current mouse same-term records and official identities corroborate the transfer; this does not claim a reconstruction of every historical mapping or experimental equivalence of both human products. Supporting Evidence: |
| GO:0005587 collagen type IV trimer | IMP PMID:16107487 Novel mutations in three families confirm a major role of CO... | ACCEPT | Summary: Human mutation evidence concerns collagen IV assembly, and independent human structure establishes trimer membership. Reason: The human porencephaly paper examines COL4A1 mutations and interprets disruption of collagen IV assembly; it is not an isolated trimer structure assay. The type IV trimer assignment is nevertheless directly established independently by human placental NC1 structure and is retained with that source distinction. Supporting Evidence: PMID:16107487 There were two missense mutations of glycine residues predicted to result in abnormal collagen IV assembly |
| GO:0005587 collagen type IV trimer | IPI PMID:12011424 The 1.9-A crystal structure of the noncollagenous (NC1) doma... | ACCEPT | Summary: Each human placental NC1 cap contains two alpha1(IV) chains and one alpha2(IV) chain. Reason: Human placental NC1 hexamers contain two caps, each with two alpha1 and one alpha2 chain. The actual crystallographic chain assignments directly substantiate collagen type IV trimer membership; the NC1 structure is not a test of the 519-residue alternative product. Supporting Evidence: |
| GO:0005604 basement membrane | IC PMID:23065703 Novel COL4A1 mutations cause cerebral small vessel disease b... | ACCEPT | Summary: Patient skin and fibroblast evidence connects the alpha1(IV) chain to basement-membrane structure. Reason: Human fibroblast expression studies and patient skin electron microscopy connect COL4A1 haploinsufficiency to altered capillary basement membrane. The IC location agrees with the structural chain role; it is not a lipid-membrane assignment. Supporting Evidence: |
| GO:0005604 basement membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic basement-membrane assignments agree with independent human network and tissue evidence. Reason: The combined electronic basement-membrane sources agree with human NC1 structure and patient tissue evidence. Current mouse identity/same-term records support the ortholog context; the retained source identifiers are not silently converted into new direct human experiments. |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The collagen precursor folds and assembles in the endoplasmic-reticulum lumen. Reason: The secreted precursor folds and assembles in the ER lumen before entering the extracellular network. Retain the ARBA location as a biosynthetic compartment, distinct from the mature chainβs principal site of structural action. Supporting Evidence: |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | KEEP AS NON CORE | Summary: The triple-helix event supports a biosynthetic ER location, with unresolved current target-path provenance. Reason: The preserved Reactome triple-helix formation assertion is consistent with precursor assembly in the ER lumen. The current scoped graph traversal did not resolve a literal P02462 path for this event; that is recorded as unresolved current provenance, not proof that the historical curator mapping or the ER location was wrong. Retain the biosynthetic location; collagen is not assigned chaperone, prolyl-isomerase or export-machine activity. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | KEEP AS NON CORE | Summary: The secretion event supports precursor ER localization, with unresolved current target-path provenance. Reason: The preserved Reactome collagen secretion assertion is consistent with precursor assembly in the ER lumen. The current scoped graph traversal did not resolve a literal P02462 path for this event; that is recorded as unresolved current provenance, not proof that the historical curator mapping or the ER location was wrong. Retain the biosynthetic location; collagen is not assigned chaperone, prolyl-isomerase or export-machine activity. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944265 | KEEP AS NON CORE | Summary: The procollagen IV association event supports precursor ER localization, with unresolved current target-path provenance. Reason: The preserved Reactome procollagen IV association assertion is consistent with precursor assembly in the ER lumen. The current scoped graph traversal did not resolve a literal P02462 path for this event; that is recorded as unresolved current provenance, not proof that the historical curator mapping or the ER location was wrong. Retain the biosynthetic location; collagen is not assigned chaperone, prolyl-isomerase or export-machine activity. |
| GO:0007420 brain development | IMP PMID:16107487 Novel mutations in three families confirm a major role of CO... | KEEP AS NON CORE | Summary: Vascular basement-membrane defects can contribute structurally to brain development and integrity. Reason: Human familial porencephaly and the paperβs vascular-basement-membrane interpretation support a contextual contribution to brain development and integrity. A vascular structural role can contribute to this broad brain-development process. Retain non-core rather than rejecting the annotation solely because the lesions arise through vascular injury; the human genetics and cited mouse mechanisms remain distinct. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Bone-marrow proteomics detects the COL4A1 protein group; independent architecture supports its collagen structural class. Reason: The original human bone-marrow ECM workbooks contain a COL4A1/P02462 protein group, with the donor summary and underlying cohort observations having different reporting thresholds. Proteomics establishes detection/classification, not an isolated tensile assay. Accept the collagen structural activity using the direct network architecture; no exact splice-product equivalence is inferred from shared peptides. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetically inferred structural activity agrees with direct collagen IV network evidence. Reason: The PAINT structural assertion matches direct target network architecture and GOβs explicit allowance for extracellular-matrix collagens in this term. Target experimental evidence in WITH/FROM is legitimate ancestral grounding. No historical node-placement error is inferred from the available donor list. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | IMP PMID:16107487 Novel mutations in three families confirm a major role of CO... | ACCEPT | Summary: Human COL4A1 mutation effects support disruption of a structural collagen IV network. Reason: The human mutation study supports disruption of the structural collagen IV network, and human NC1 architecture independently establishes the chainβs matrix contribution. Accept the structural term without describing the clinical study as a direct force-extension experiment. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: Human endothelial proteomics is consistent with collagen structural classification, but the exact target table remains uninspected. Reason: The selected cache contains the abstract and discussion for human endothelial morphogenesis, not the complete Methods or exact COL4A1 supplementary row. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, without overruling the curator from incomplete target-table access. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Human colorectal and liver workbooks detect the COL4A1-containing protein group in matrix preparations. Reason: Original complete-MS and matrisome workbook rows identify the COL4A1/P02462 group in human colorectal/liver samples; the group contains additional collagen/isoform identifiers. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, with protein-group and shared-peptide limits retained. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: Human vein proteomics provides tissue context, while the exact COL4A1 supplementary entry remains unverified. Reason: The original Methods describe sequential extraction and LC-MS of human normal/varicose veins. The main-table COL4A2 row is not treated as COL4A1; the exact COL4A1 supplementary entry was not recovered. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, without overruling the curator from incomplete target-table access. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Human atrial glycoproteomics provides matrix context without a verified COL4A1 target-table read. Reason: The selected cache exposes abstract and partial results/discussion from the human atrial glycoproteomics study; its exact COL4A1 target table and complete Methods were not inspected. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, without overruling the curator from incomplete target-table access. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: Human stromal-cell ECM text reports network-forming collagen IV, without resolving the COL4A1 target table. Reason: The inspected human stromal-cell ECM study describes proteomic characterization and network-forming collagen IV, but its chain-specific COL4A1 target table was not inspected. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, without overruling the curator from incomplete target-table access. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Human tissue ECM proteomics supports matrix context; the attempted COL4A1 workbooks were inaccessible. Reason: The inspected original text describes human tissue ECM enrichment and proteomics. The attempted target workbooks returned HTML challenge pages, not usable spreadsheets; no exact COL4A1 workbook read is claimed. The RCA term is a matrisome functional classification rather than a direct tensile measurement. Preserve the valid structural activity, independently supported by human collagen IV architecture, without overruling the curator from incomplete target-table access. |
| GO:0030198 extracellular matrix organization | IBA GO_REF:0000033 | ACCEPT | Summary: COL4A1 supplies the chain and NC1 interfaces that physically organize the collagen IV matrix. Reason: COL4A1 contributes the physical chain and NC1 interfaces used to assemble the extracellular collagen IV network. This is performed structural work, not merely substrate necessity. The IBA is consistent with target architecture; current donor term gaps and failed ancestral-node endpoint requests do not establish a PAINT placement error. |
| GO:0030199 collagen fibril organization | NAS PMID:29853175 Collagen Fibril Assembly and Function. | UNDECIDED | Summary: The NAS fibril-organization claim remains unresolved because the target-specific full source was not recovered. Reason: GO:0030199 covers processes determining collagen-fibril size or arrangement. A network-forming collagen could influence that organization; network membership alone does not contradict the term. The complete PMID:29853175 abstract discusses fibril assembly generally, but the relevant full target discussion remains unrecovered after the recorded author-repository failure. Retain source-specific uncertainty for this NAS assertion rather than infer a wrong target or a disproved matrix contribution from the abstract. Supporting Evidence: |
| GO:0030855 epithelial cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: Rat Col4a1 expression changes accompany epithelial differentiation, but the exact transferred process contribution is unresolved. Reason: The current rat F1MA59 donor is Col4a1, with IEP support from PMID:8635488. Its complete abstract reports reduced alpha1(IV) collagen expression during differentiation of rat tracheal epithelial cells on type I collagen gel; the gel is not a COL4A1 substrate perturbation. GO:0030855 concerns acquisition of epithelial features, and this expression endpoint alone does not establish the collagen productβs contribution to that process. The donor full text remains unrecovered. Preserve the positive expression observation and literal IEA transfer as UNDECIDED without claiming either established participation or biological absence. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: The original human stem-cell-supporting ECM table identifies COL4A1 in extracellular preparations. Reason: The official original Table 1 lists COL4A1 in human fibroblast/stem-cell-supporting ECM preparations; the inspected LC-MS identification method requires validated peptide evidence. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: Human endothelial ECM proteomics is consistent with the established matrix location, with unresolved target-table scope. Reason: The selected cache contains the abstract and discussion for human endothelial morphogenesis, not the complete Methods or exact COL4A1 supplementary row. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Original human colorectal and liver workbook rows identify a COL4A1-containing matrix protein group. Reason: Original complete-MS and matrisome workbook rows identify the COL4A1/P02462 group in human colorectal/liver samples; the group contains additional collagen/isoform identifiers. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: The established ECM location is retained while the human vein studyβs COL4A1 supplementary entry remains unverified. Reason: The original Methods describe sequential extraction and LC-MS of human normal/varicose veins. The main-table COL4A2 row is not treated as COL4A1; the exact COL4A1 supplementary entry was not recovered. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: The established ECM location is retained with the human atrial studyβs limited target-table access. Reason: The selected cache exposes abstract and partial results/discussion from the human atrial glycoproteomics study; its exact COL4A1 target table and complete Methods were not inspected. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: The human stromal ECM study reports collagen IV, while chain-specific target-table access remains limited. Reason: The inspected human stromal-cell ECM study describes proteomic characterization and network-forming collagen IV, but its chain-specific COL4A1 target table was not inspected. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Original human bone-marrow workbooks identify a COL4A1 group in extracellular matrix preparations. Reason: Original Tables S2/S3 identify the COL4A1 group in human bone-marrow extracellular-matrix preparations, with cohort thresholds and shared-peptide product limits retained. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: The established ECM location is retained despite inaccessible target workbooks from the tissue proteomics protocol. Reason: The inspected original text describes human tissue ECM enrichment and proteomics. The attempted target workbooks returned HTML challenge pages, not usable spreadsheets; no exact COL4A1 workbook read is claimed. Extracellular-matrix membership is independently established by the collagen IV network. Retain the HDA location with its actual access scope; this is neither a plasma-membrane claim nor proof that every natural isoform was detected. |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetically inherited ECM location agrees with direct collagen IV network evidence. Reason: The inherited ECM location agrees with the experimentally established collagen IV network. Current same-term donor identities/records are corroborating context, while the original PAINT IBD placement is retained without claiming that all historical nodes were reanalyzed. Supporting Evidence: |
| GO:0031012 extracellular matrix | ISS PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeli... | ACCEPT | Summary: Porcine cardiac proteomics supports ortholog context for the independently established human ECM location. Reason: The original paperβs complete abstract explicitly describes porcine cardiac ECM extraction and proteomics, and the current F1KQQ4 donor is pig Col4a1 with same-term records. The exact porcine target table remains uninspected. The ISS location is nevertheless consistent with direct human ECM evidence, so retain it without turning pig tissue proteomics into a human isoform-specific assay. |
| 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 | Summary: Collagen IV and constituent chains bind PDGF in the cited experiments, without resolving every alpha-chain construct. Reason: The complete original abstract explicitly reports radiolabeled PDGF isoforms interacting with collagen IV and constituent collagen chains, with competition and retained growth-factor activity. Preserve this positive matrix-associated binding capability as non-core; the abstract alone does not resolve every type IV chain/construct or justify an isolated COL4A1 affinity value. Supporting Evidence: |
| GO:0048514 blood vessel morphogenesis | IMP PMID:20818663 Novel COL4A1 mutations associated with HANAC syndrome: a rol... | KEEP AS NON CORE | Summary: Human HANAC vascular abnormalities support a contextual matrix contribution to vessel morphogenesis. Reason: The human HANAC clinical/genetic study reports vascular abnormalities and COL4A1 CB3[IV] substitutions. Retain the broad contextual vessel-architecture role of the matrix chain, without claiming the abstract contains a directly observed branching or integrin-signaling assay. Supporting Evidence: |
| GO:0061304 retinal blood vessel morphogenesis | IMP PMID:20818663 Novel COL4A1 mutations associated with HANAC syndrome: a rol... | KEEP AS NON CORE | Summary: Human retinal arterial tortuosity supports a contextual matrix contribution to retinal vessel architecture. Reason: Retinal arterial tortuosity is an explicit human finding in the source abstract and fits a contextual vascular-matrix contribution. Preserve this existing retinal-vessel morphogenesis assertion non-core with curator deference; no full developmental time course or branching assay was inspected. Supporting Evidence: |
| GO:0061333 renal tubule morphogenesis | IMP PMID:18160688 COL4A1 mutations and hereditary angiopathy, nephropathy, ane... | KEEP AS NON CORE | Summary: Human renal abnormalities and tubular basement-membrane defects support a structural contribution to tubule morphology. Reason: The recovered original HANAC Methods/Results document human renal abnormalities and altered tubular basement membranes. These support a contextual structural contribution to tubular architecture. Cysts and matrix defects are not a direct assay of each fate-specification or morphogenetic substep, so retain this existing broad process as non-core rather than create additional developmental assertions. Supporting Evidence: PMID:18160688 include hematuria and bilateral, large cysts |
| GO:0071711 basement membrane organization | IMP PMID:18160688 COL4A1 mutations and hereditary angiopathy, nephropathy, ane... | ACCEPT | Summary: Human HANAC tissues show altered basement-membrane thickness, continuity and organization. Reason: Original human HANAC histology and immunolabeling demonstrate thickened, split or interrupted renal/skin basement membranes. This directly supports organization of the matrix to which COL4A1 contributes structural material. The report does not show universal loss of collagen staining or assign an enzymatic assembly activity to the chain. Supporting Evidence: PMID:18160688 Histologic analysis revealed complex basement-membrane defects in kidney and skin. |
| GO:0071711 basement membrane organization | IMP PMID:19949034 Cerebrovascular disease related to COL4A1 mutations in HANAC... | ACCEPT | Summary: Human HANAC skin ultrastructure shows replicated lamina densa and disorganized vascular basement membrane. Reason: Actual skin ultrastructure in affected human HANAC subjects shows replicated lamina densa and abnormal vessel basement-membrane organization. The target is a physical network constituent, so this is a structural contribution to the process; the clinical phenotypes are not substituted for all mechanistic steps. Supporting Evidence: PMID:19949034 Replication of the lamina densa was observed at the dermoepidermal junction |
| GO:0071711 basement membrane organization | IMP PMID:23065703 Novel COL4A1 mutations cause cerebral small vessel disease b... | ACCEPT | Summary: Human COL4A1 haploinsufficiency reduces chain abundance and alters capillary basement-membrane organization. Reason: Human patient skin microscopy and fibroblast transcript/protein studies establish reduced COL4A1 and abnormal capillary basement-membrane thickness in haploinsufficient families. This supports basement-membrane organization by the structural chain, with the human dosage-loss mechanism distinguished from earlier dominant-negative mouse models. Supporting Evidence: |
| GO:0016525 negative regulation of angiogenesis | IDA PMID:18775695 Characterization of the anti-angiogenic properties of arrest... | NEW | Summary: Applied human NC1-derived arresten suppresses angiogenic responses with alpha1-integrin-dependent assay controls. Reason: Administered recombinant human NC1-derived arresten itself performs extracellular ligand work: controlled endothelial attachment/survival experiments and Matrigel/tumor assays show an alpha1-integrin-dependent reduction of angiogenic responses. This is not an inference from precursor cleavage or knockout necessity alone. The earlier nonretracted human-arresten study corroborates the effect. The scope is the tested released/engineered fragment preparations, not all precursor/alternative products; the 2005 retracted article is excluded. Typed is_a/part_of ancestor/descendant coverage against every original and replacement term is disjoint. Same-role processed canstatin and tumstatin carry direct IDA annotations to this term; the exact endostatin query was empty and is not treated as a negative finding. More specific branching/sprouting/adhesion-regulation descendants are not independently resolved, and the current GO-CAM index has no target match. The structured COL4A1_ARRESTEN cleavage-product class records this restriction; its official 1445-1669 mapping identifies the natural-chain feature, not identical endpoints for every engineered preparation. Supporting Evidence: PMID:18775695 the number of blood vessels decreased to 60% of control |
| GO:0005178 integrin binding | IDA PMID:18775695 Characterization of the anti-angiogenic properties of arrest... | NEW | Summary: Applied human arresten/NC1 engages endothelial alpha1beta1 integrin in controlled cell-attachment assays. Reason: This assertion is limited to the COL4A1_ARRESTEN cleavage-product class and the tested human NC1-derived preparations, not every intact chain or splice product. In the nonretracted 2008 study, an alpha1beta1-blocking antibody reduced wild-type mouse lung endothelial attachment to immobilized recombinant human arresten, whereas alpha1-null cells lacked that antibody-sensitive response; IgG and fibronectin controls distinguish the ligand/receptor interaction. The human HUVEC anti-alpha1/anti-beta1 attachment experiments in the separate 2000 paper corroborate it. These are cell-based binding assays, not purified-integrin affinity measurements; tagged/refolded constructs, collagenase-isolated placental material and endogenous cleavage products are not assumed equivalent. The retracted 2005 paper supplies no support. The effective annotations contain neither this term nor an ancestor/descendant: row 3 retains original GO:0005515 as provenance but replaces its output with GO:0005518. The child GO:0098640 can describe the coated-substrate attachment context. Broad GO:0005178 is used here for the shared receptor-engagement activity across attachment and soluble-fragment inhibition; a second, redundant child assertion is not added. Existing arresten mapping and core retain this product restriction. Supporting Evidence: PMID:18775695 the attachment of the wild type MLEC was reduced to half |
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Download this section (compressed HTML)Q: At endogenous concentrations, which released COL4A1 NC1 fragments occur in human tissues, and how do their receptor interactions differ from the tagged or refolded arresten preparations?
Q: Does the 519-residue alternative COL4A1 product enter any extracellular complex, and what processing, stability and tissue distribution distinguish it from the NC1-containing chain?
Q: Which specific COL4A1-performed step supports the existing branching, fibril-organization and epithelial-differentiation source assertions? Full source access and assay/product attribution could resolve their present uncertainty.
Q: What does Ministeria type IV collagen do during aggregation, and which ancestral PAINT node placements distinguish collagen presence from organized basement-membrane function? Current sequence presence/expression alone does not settle those roles.
Q: How do HANAC CB3[IV] variants affect integrin engagement relative to network assembly, and which effects explain tissue-specific matrix phenotypes?
Experiment: Compare defined native-like and tagged human arresten preparations in receptor-controlled endothelial assays, measuring direct receptor association and angiogenic endpoints at quantified physiological concentrations.
Hypothesis: The released NC1 ligand retains an integrin-dependent activity, but receptor affinity and response depend on processing and preparation.
Experiment: Track each authentic COL4A1 splice product through secretion, NC1-dependent association and extracellular matrix incorporation using product-specific sequence tags and controls.
Hypothesis: The short product lacking NC1 does not reproduce the canonical chainβs assembly and released-fragment functions.
Experiment: Compare wild-type and HANAC CB3[IV] network preparations for ultrastructure and cell-receptor engagement, distinguishing the matrix from separately applied NC1 fragments.
Hypothesis: Variant-specific effects on matrix assembly and cell interaction can differ without assigning collagen catalytic processing activity.
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