COL1A1 encodes the pro-alpha-1 chain of type I collagen, a major fibrillar component of extracellular matrices in bone, skin, tendon and many other connective tissues. Its C-terminal propeptide helps select and assemble collagen chains in the endoplasmic reticulum. Two alpha-1(I) chains usually associate with one alpha-2(I) chain, although alpha-1(I) homotrimers also form. Following secretion and propeptide removal by other proteins, mature collagen molecules assemble into fibrils that provide tensile support and organize the matrix. Native triple-helical collagen-I fibrils also act as insoluble extracellular matrix receptor ligands that directly bind and activate the discoidin domain receptor tyrosine kinases DDR1 and DDR2, and interact with integrins and matricellular proteins to regulate cellular adhesion, migration and signaling. Pathogenic COL1A1 variants disrupt matrix quantity or architecture and cause osteogenesis imperfecta and other connective-tissue disorders.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001501 skeletal system development | IMP PMID:14976317 Gene targeting in stem cells from individuals with osteogene... | KEEP AS NON CORE | Summary: Retain the skeletal-development context of human COL1A1 disease. Reason: The complete original abstract reports targeting dominant-negative COL1A1 alleles in mesenchymal stem cells from people with osteogenesis imperfecta. Together with the established structural role, this supports the original developmental assertion. The abstract does not expose all differentiation or skeletal assays, and no separate developmental signaling activity is inferred. |
| GO:0001501 skeletal system development | IMP PMID:1874719 Substitutions for glycine alpha 1-637 and glycine alpha 2-69... | KEEP AS NON CORE | Summary: Human collagen-I mutations connect defective molecular structure to skeletal disease. Reason: The original abstract explicitly compares alpha-1(I) G637V and alpha-2(I) G694R procollagen from skin fibroblasts of probands with lethal osteogenesis imperfecta. Folding and unfolding defects support the structural basis of the skeletal phenotype, rather than a distinct developmental regulator activity. Supporting Evidence: |
| GO:0001501 skeletal system development | IMP PMID:8097422 Homology-mediated recombination between type I collagen gene... | KEEP AS NON CORE | Summary: Retain the human skeletal-development phenotype. Reason: The complete abstract identifies a COL1A1 tandem exon duplication in an infant with lethal osteogenesis imperfecta, preserving the Gly-X-Y repeat but extending the triple-helical region. This is target-specific genetic and structural evidence; no purified developmental mechanism is claimed from the unavailable full paper. Supporting Evidence: |
| GO:0001503 ossification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain ossification as a contextual orthology-derived role. Reason: The current rat Col1a1 exact-term source is an IEP annotation: shock-wave-treated bone shows collagen expression during osteogenesis. The collagen matrix contributes structural material to bone, but that experiment does not establish a separate COL1A1 signaling or enzymatic ossification activity. The original Ensembl source and evidence code are preserved. Supporting Evidence: |
| GO:0001568 blood vessel development | IMP PMID:17211858 Three arginine to cysteine substitutions in the pro-alpha (I... | KEEP AS NON CORE | Summary: Vascular phenotypes are consistent with collagen-I structural integrity. Reason: The original human COL1A1 arginine-to-cysteine study reports arterial dissections, abnormal collagen dimers and altered fibrils. Retain the existing blood-vessel-development annotation as a matrix-related phenotype, without converting arterial rupture into a separately demonstrated angiogenic signaling mechanism. Full experimental access remains limited to the complete abstract. Supporting Evidence: |
| GO:0001649 osteoblast differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: The source-specific differentiation inference remains unresolved beyond its positive marker readout. Reason: The current mouse Col1a1 donor points to PMID:16311053. Its actual Methods and Results measure increased Col1 expression during bone-marrow stromal-cell osteoblast differentiation as one of several differentiation markers; they do not test collagen intervention or establish a performed differentiation step. Structural matrix work could contribute to differentiation, but the inspected source does not resolve that exact role. Preserve the positive expression evidence and original transfer as source-scoped UNDECIDED, without a loss-of-function or historical-transfer-error claim. Supporting Evidence: |
| GO:0002020 protease binding | IPI PMID:19932771 MMP-12 catalytic domain recognizes and cleaves at multiple s... | KEEP AS NON CORE | Summary: MMP-12 binding is a supported substrate-associated interaction. Reason: The complete abstract explicitly reports recognition and cleavage of human skin collagen I and III and their constituent chains by the MMP-12 catalytic domain. Retain protease binding at this substrate/association scope. The peptidase activity belongs to MMP-12, not to COL1A1. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | IEA GO_REF:0000120 | MODIFY | Summary: Refine the general structural activity to the collagen tensile-strength class. Reason: The broad combined electronic annotation is sound. Official GO:0030020 explicitly accommodates extracellular-matrix collagens, and COL1A1 is a type-I fibrillar collagen chain with direct matrix detection and structural assembly evidence. This specificity does not mean a proteomics experiment measured the tensile modulus of an isolated alpha-1 chain. Proposed replacements: extracellular matrix structural constituent conferring tensile strength |
| GO:0005515 protein binding | IPI PMID:14749390 TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump... | KEEP AS NON CORE | Summary: Retain the translation-dependent TRAM2 association. Reason: Actual human-fibroblast experiments show COL1A1-associated TRAM2 by immunoprecipitation, with control proteins and reduced association after puromycin. The experiment supports a nascent-procollagen association rather than an autonomous COL1A1 adaptor or calcium-pump activity. Rat stellate-cell perturbations elsewhere in the paper are kept distinct. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18375391 Defective C-propeptides of the proalpha2(I) chain of type I ... | MODIFY | Summary: Refine the alpha-1(I)/alpha-2(I) association to collagen binding. Reason: The original human patient-fibroblast Methods and Results measure chain association during procollagen assembly, altered chain composition and secreted alpha-1 homotrimers after COL1A2 mutations. Control cells assemble alpha-1 and alpha-2 chains into heterotrimers. COL1A1 is the observed assembly partner, and COL1A2 is a collagen chain, supporting GO:0005518. A purified binary-affinity measurement is not required to recognize this established interchain association. The experiment does not test a COL1A1 mutation or an independent assembly-factor activity. Proposed replacements: collagen binding |
| GO:0005515 protein binding | IPI PMID:20015075 Aegyptin displays high-affinity for the von Willebrand facto... | KEEP AS NON CORE | Summary: Retain the positive aegyptin interaction at its assay scope. Reason: Five literal MINT records and the original binding experiments support aegyptin association with collagen preparations and mapped peptide regions. Methods specify horse fibrillar collagen and other commercial collagen preparations whose species is not fully stated. Preserve the human-mapped source assertion without claiming that a full-length sequence-verified human COL1A1 monomer was tested, or assigning an aegyptin activity to collagen. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20541508 Zinc induces structural reorganization of gelatin binding do... | MODIFY | Summary: Refine the recorded fibronectin association to fibronectin binding. Reason: The original abstract describes human fibronectin gelatin-binding-domain interaction with high-affinity collagen peptides and zinc-dependent inhibition. The full original peptide/construct details were not recovered. Independent direct COL1A1-peptide binding in PMID:25290767 supports the specific partner class without claiming a full-text read of PMID:20541508. Proposed replacements: fibronectin binding |
| GO:0005515 protein binding | IPI PMID:25290767 Structural and functional analysis of the fibronectin-bindin... | MODIFY | Summary: The tested collagen-I segment binds the fibronectin gelatin-binding domain. Reason: The authentic full publisher Results and fluorescence-depolarization Methods of PMID:25290767 directly test the collagen-alpha-1(I) 778β798 peptide against fibronectin fragments, including competition by FNE. The literal MINT feature agrees with this segment. This supports fibronectin binding without attributing the bacterial protein structure or a whole-fibril affinity measurement to COL1A1. Proposed replacements: fibronectin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26848503 Mapping and Exploring the Collagen-I Proteostasis Network. | MODIFY | Summary: Refine the recorded FN1 association to fibronectin binding. Reason: The preserved source identifies FN1 as the collagen partner in a DSP-crosslinked SILAC immunoprecipitation study of engineered human HT-1080 cells. Current GO:0001968 names binding to fibronectin; the positive curated pair and separately demonstrated COL1A1-peptide/FN binding support that partner-class refinement. The exact FN1 target table was not independently recovered, and the inspected individual retests do not include FN1. This source remains a co-complex association, not a newly verified binary assay; PMID:25290767 supplies distinct direct corroboration rather than replacing its provenance. Proposed replacements: fibronectin binding |
| GO:0005515 protein binding | IPI PMID:26848503 Mapping and Exploring the Collagen-I Proteostasis Network. | MODIFY | Summary: Refine the verified alpha-1/alpha-2 association to collagen binding. Reason: The original Results, Figure 2A and Methods describe HA-tagged human collagen-alpha-1(I) and FLAG-tagged human collagen-alpha-2(I) expressed in HT-1080 cells. Reciprocal immunoprecipitation demonstrates their association; protease resistance and secretion support assembled triple-helical procollagen. This is binding to the collagen partner COL1A2 and supports GO:0005518 at the tested tagged-chain scope. No autonomous assembly-factor or enzyme activity is assigned to COL1A1. Proposed replacements: collagen binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain the positive KEAP1 binary-screen interaction. Reason: Three literal positive array, prey-pooling and validated Y2H records map human COL1A1 and KEAP1, with no mapped fragment boundary and false negation. Canonical sequence identity is checked. HuRI establishes an assay interaction, not native extracellular KEAP1 colocalization or a collagen ubiquitin-ligase-complex role; neither genericity nor compartment expectations invalidate the positive source. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the SLC25A40 association detected by affinity proteomics. Reason: Two literal positive affinity-purification records identify tagged SLC25A40 bait and COL1A1 prey in human HEK293T and HCT116 cells. They support association, not necessarily direct contact or mature-matrix colocalization. An evidence-backed more specific binding activity has not been established for this pair in the present assessment, so retain the supported generic interaction under the campaign policy. Neither a mitochondrial transport activity of COL1A1 nor a requirement for native colocalization is inferred. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Human aortic proteomics supports extracellular collagen-I localization. Reason: The original Tables I and II explicitly identify CO1A1_HUMAN in NaCl and guanidine extracts from human aorta. Methods separate cellular material from ECM-enriched fractions. This supports extracellular localization, not a distinct tensile-force assay. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: Retain extracellular localization from human venous proteomics. Reason: Actual human normal and varicose saphenous-vein Methods and Results identify CO1A1 in ECM extracts and confirm its abundance change by targeted MRM. The original target workbook was not recovered, but the target is explicit in the Results and figure legends. No original figure-pixel reanalysis is claimed. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic extracellular localization matches collagen-I biology. Reason: Rat/mouse orthology and combined mappings are consistent with direct human secretion and extracellular ECM detection. This spatial assertion is not evidence that collagen performs every reaction in which it appears as a substrate. |
| GO:0005576 extracellular region | IMP PMID:20603131 Nonmuscle myosin-dependent synthesis of type I collagen. | ACCEPT | Summary: Human fibroblasts secrete collagen alpha-1(I) into the medium. Reason: The complete selected Methods/Results measure collagen chains in cells and serum-free medium from human lung and scleroderma fibroblasts. Myosin perturbation changes secretion and assembly; serum-free collection controls extracellular collagen from serum. The location applies to the secreted product, not a myosin motor activity of COL1A1. Supporting Evidence: |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-114577 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-114577 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Binding of GPVI:Fc Epsilon R1 gamma receptor complex with collagen, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-114577 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-114600 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-114600 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Fyn/Lyn-mediated phosphorylation of FcR1 gamma, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-114600 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-114670 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-114670 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GPIb-IX-V binds to vWF:Collagen complex, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-114670 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-114671 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-114671 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, vWF binds to collagen, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-114671 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-139842 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-139842 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Binding of Syk tyrosine kinase, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-139842 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1454757 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-1454757 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-1454757 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1454822 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-1454822 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Collagen type I degradation by MMP1,2,8,13, PRSS2, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-1454822 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1474266 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-1474266 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of collagen fibrils, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-1474266 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2002428 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2002428 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Removal of fibrillar collagen N-propeptides, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2002428 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2002440 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2002440 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Removal of fibrillar collagen C-propeptides, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2002440 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2002466 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2002466 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of allysine by LOX, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2002466 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2089971 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The secretion event includes both ER-luminal input procollagen and extracellular collagen output, each resolving to P02452. Retain the extracellular output location while keeping the separate original ER-lumen assertion. Cargo membership is not an autonomous secretion activity. Supporting Evidence: Reactome:R-HSA-2089971 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-216045 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-216045 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Collagen type I binds integrin alpha11beta1, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-216045 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213201 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2213201 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of collagen fibres, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2213201 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2213205 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2213205 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Type XII and XIV collagens associate with type I and type II fibrils, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2213205 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2243926 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2243926 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of histidino-hydroxylysinonorleucine cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2243926 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2243931 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2243931 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of dehydro-lysinonorleucine cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2243931 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2250301 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2250301 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of lysyl-pyrrole cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2250301 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327733 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2327733 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, FN1 binds Collagen types I-V, VII, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2327733 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327738 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2327738 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, DDR1 binds collagen type I, II, III, IV, V, XI fibrils, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2327738 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327909 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2327909 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, DCN binds collagen I, II, III, VI fibrils, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2327909 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395223 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395223 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of hydroxylysyl-pyridinoline cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395223 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395257 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395257 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of dehydro-hydroxylysino-norleucine cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395257 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395302 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395302 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of hydroxylysino-5-ketonorleucine cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395302 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395314 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395314 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of lysino-5-ketonorleucine cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395314 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395322 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395322 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of lysyl-pyridinoline cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395322 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395324 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395324 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of hydroxylysyl-pyrrole cross-links, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395324 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395340 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2395340 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Formation of hydroxyallysine by LOX, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2395340 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396234 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2396234 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Collagen type VII binds laminin-322 and collagen IV, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2396234 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2424243 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2424243 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, SPARC binds Collagen type I fibril, hydroxylapatite and Ca2+, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2424243 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2424252 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2424252 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, COMP binds collagen, fibronectin, aggrecan and matrilins, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2424252 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2465890 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2465890 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, DDR2 binds collagen type I, II, III, V, X fibrils, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2465890 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2466106 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2466106 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, BGN binds Collagen types I, VI, (IX), supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2466106 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2473596 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-2473596 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Collagen type I degradation by MMP15, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-2473596 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-429529 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-429529 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Thrombin binding to GP1b:IX:V, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-429529 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-430073 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-430073 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GPIb-IX-V binding to 14-3-3 zeta is reduced by shear stress, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-430073 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-430076 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-430076 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GP1b-IX-V binds 14-3-3-zeta, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-430076 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-430096 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-430096 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GP1b-IX-V binds filamin, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-430096 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-437118 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-437118 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GPVI stimulates PI3K beta, gamma, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-437118 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-443402 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-443402 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GP1b-IX-V:13-3-3-zeta complexes with p85 PI3K, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-443402 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-443418 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-443418 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GP1b signaling involves c-Src, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-443418 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-453183 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-453183 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, p-Y348-SYK dissociates, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-453183 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-453200 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-453200 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, SYK autophosphorylates, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-453200 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5696356 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-5696356 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, OSCAR binds collagen and SP-D, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-5696356 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5696357 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-5696357 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, LAIR2 binds collagen, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-5696357 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822532 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9822532 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, ADAMTS13 cleaves VWF multimer, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9822532 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822539 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9822539 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, VWF multimer binds to collagen type I, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9822539 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9822734 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9822734 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, Caplacizumab binds VWF, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9822734 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9823065 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9823065 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GPIb:IX:V binds to VWF multimer:collagen, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9823065 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9823593 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9823593 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, VWF variant does not bind to collagen type I, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9823593 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9823706 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9823706 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, VWF variant does not bind GPIb:IX:V, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9823706 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9824402 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9824402 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, ADAMTS13 variant does not cleave VWF multimer, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9824402 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9844241 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9844241 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, ADAMTS13 cleaves VWF variant multimer, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9844241 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9844251 | ACCEPT | Summary: Retain the original extracellular location in this Reactome event. Reason: The current Reactome:R-HSA-9844251 physical-entity hierarchy reaches the exact P02452 collagen chain in extracellular collagen or its processed fragments. The event, GP1BA variant binds to VWF multimer:collagen, supplies curated compartment context; its other receptor, protease or kinase participants perform their own activities. Preserve this original extracellular-region assertion without manufacturing a new signaling, degradation or processing annotation. Supporting Evidence: Reactome:R-HSA-9844251 |
| GO:0005581 collagen trimer | IEA GO_REF:0000107 | MODIFY | Summary: Specify the established type-I collagen trimer. Reason: The mouse orthology-derived general collagen-trimer assertion is correct. Human alpha-1(I) chains assemble into type-I heterotrimers and homotrimers, which are explicitly included in the current type-I term definition. The source object is preserved while the reviewed term becomes more informative. Proposed replacements: collagen type I trimer |
| GO:0005583 fibrillar collagen trimer | IEA GO_REF:0000117 | MODIFY | Summary: Specify collagen type I within fibrillar collagen trimers. Reason: ARBA captures the fibrillar-collagen class. Human chain-composition and assembly experiments establish type I, rather than an unspecified fibrillar trimer. No additional trimer annotation is proposed and no mature mechanics are inferred from the C-propeptide crystal alone. Proposed replacements: collagen type I trimer |
| GO:0005584 collagen type I trimer | IDA PMID:19932771 MMP-12 catalytic domain recognizes and cleaves at multiple s... | ACCEPT | Summary: The source uses human collagen-I material and constituent chains. Reason: The complete original abstract identifies human skin type-I collagen in MMP-12 binding and cleavage experiments. This supports the original complex identity; type-I composition is independently established by human chain-assembly studies. MMP-12 supplies proteolysis. |
| GO:0005584 collagen type I trimer | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined electronic type-I-trimer assertion. Reason: Exact rat/mouse identities and current same-term source rows are preserved. Independent human chain-assembly evidence supports this type-I complex, including both common heterotrimers and alpha-1 homotrimers. No ancestral PAINT reconstruction is asserted for this IEA. |
| GO:0005584 collagen type I trimer | IMP PMID:14976317 Gene targeting in stem cells from individuals with osteogene... | ACCEPT | Summary: The type-I-trimer assignment is independently well established. Reason: The original human COL1A1 gene-targeting abstract supports target identity but does not expose every trimer assay behind the original IMP. Retain this correct complex assignment with curator deference and independent human assembly evidence rather than rejecting it from abstract incompleteness. |
| GO:0005584 collagen type I trimer | IMP PMID:17576241 RNAi-mediated inhibition of COL1A1 and COL3A1 in human skin ... | ACCEPT | Summary: Retain collagen-I complex membership in the human RNAi context. Reason: The original complete abstract describes selective COL1A1 knockdown in human skin fibroblasts. It is not a purified trimer measurement; independent chain-assembly experiments establish the complex membership. Preserve the source evidence and do not manufacture assay detail absent from the abstract. |
| GO:0005584 collagen type I trimer | IPI PMID:26848503 Mapping and Exploring the Collagen-I Proteostasis Network. | ACCEPT | Summary: Human alpha-1 and alpha-2 chains form correctly folded collagen-I assemblies. Reason: The genuine fresh full source demonstrates reciprocal tagged-chain association and protease-resistant triple-helical material in human HT-1080 cells. Those assays support type-I complex membership at the engineered construct scope. Supporting Evidence: |
| GO:0005584 collagen type I trimer | IPI PMID:28281531 Structural basis of homo- and heterotrimerization of collage... | ACCEPT | Summary: Human C-propeptides support type-I chain selection and trimer assembly. Reason: The original study resolves an alpha-1 C-propeptide homotrimer crystal and measures heterotrimer composition and SAXS. Heterotrimer interfaces are modeled because heterotrimer crystals were not obtained. This is direct assembly evidence for the type-I complex, not a mature-fibril tensile experiment. Supporting Evidence: PMID:28281531 corresponding to the disulfide-bonded trimer |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the broad intracellular precursor context with donor-source caution. Reason: GO:0005737 includes organellar contents and is not synonymous with cytosol. The mouse donor has a dental-follicle collagen expression/localization source and an additional RPRM-paper link whose COL1A1-specific attribution was not established from the inspected body. Direct human ER-localized procollagen independently supports the broad intracellular context; do not infer a soluble cytosolic collagen function or silently discard either source record. |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Procollagen occupies the ER lumen during assembly. Reason: The ARBA location is supported by direct human collagen-chain immunostaining with calnexin and by the modeled precursor-assembly pathway. It is a valid transient biosynthetic compartment, while mature structural collagen acts principally in the extracellular matrix. Supporting Evidence: |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-1650808 | KEEP AS NON CORE | Summary: Retain the ER-luminal location of procollagen assembly intermediates. Reason: The current Reactome:R-HSA-1650808 hierarchy resolves P02452 precursor chains in the ER lumen during prolyl 4-hydroxylase converts collagen prolines to 4-hydroxyprolines. This is a genuine biosynthetic intermediate location, distinct from the principal extracellular mature-matrix role. Hydroxylation, disulfide isomerization and transport performed by other proteins are not assigned to COL1A1. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2002460 | KEEP AS NON CORE | Summary: Retain the ER-luminal location of procollagen assembly intermediates. Reason: The current Reactome:R-HSA-2002460 hierarchy resolves P02452 precursor chains in the ER lumen during p4hb binds collagen chains. This is a genuine biosynthetic intermediate location, distinct from the principal extracellular mature-matrix role. Hydroxylation, disulfide isomerization and transport performed by other proteins are not assigned to COL1A1. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | KEEP AS NON CORE | Summary: Retain the ER-luminal location of procollagen assembly intermediates. Reason: The current Reactome:R-HSA-2022073 hierarchy resolves P02452 precursor chains in the ER lumen during procollagen triple helix formation. This is a genuine biosynthetic intermediate location, distinct from the principal extracellular mature-matrix role. Hydroxylation, disulfide isomerization and transport performed by other proteins are not assigned to COL1A1. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2089971 | KEEP AS NON CORE | Summary: Retain the ER-luminal location of procollagen assembly intermediates. Reason: The current Reactome:R-HSA-2089971 hierarchy resolves P02452 precursor chains in the ER lumen during secretion of collagens. This is a genuine biosynthetic intermediate location, distinct from the principal extracellular mature-matrix role. Hydroxylation, disulfide isomerization and transport performed by other proteins are not assigned to COL1A1. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8944214 | KEEP AS NON CORE | Summary: Retain the ER-luminal location of procollagen assembly intermediates. Reason: The current Reactome:R-HSA-8944214 hierarchy resolves P02452 precursor chains in the ER lumen during association of procollagen type i. This is a genuine biosynthetic intermediate location, distinct from the principal extracellular mature-matrix role. Hydroxylation, disulfide isomerization and transport performed by other proteins are not assigned to COL1A1. |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the donor nutrient-response context. Reason: The current rat source measures developmental gene-expression changes under vitamin-A deficiency. This supports a context-dependent collagen expression response, not a separate COL1A1 nutrient-sensing molecular activity. Human transfer remains the original Ensembl inference. Supporting Evidence: |
| GO:0007601 visual perception | IMP PMID:17557158 The COL1A1 gene and high myopia susceptibility in Japanese. | UNDECIDED | Summary: The positive high-myopia association does not resolve the exact visual-process assertion. Reason: The recovered original human study genotypes COL1A1 polymorphisms in high-myopia cases and controls. The authors report association but state that the associated SNPs do not appear causal, and leave the functional mechanism unresolved. A structural ocular-matrix contribution can support vision without phototransduction; however, general matrix biology does not establish this exact source assertion. Retain the positive genetic observations and original IMP object as source-scoped UNDECIDED, without declaring the variants definitively noncausal or denying a possible structural contribution to vision. Supporting Evidence: |
| GO:0007605 sensory perception of sound | IMP PMID:17489845 Single-nucleotide polymorphisms in the COL1A1 regulatory reg... | KEEP AS NON CORE | Summary: Retain hearing-related collagen-I structural context. Reason: The complete original abstract links human COL1A1 regulatory polymorphisms to otosclerosis and includes promoter effects, with separate mouse Col1a2 hearing context. This supports a matrix-related auditory phenotype rather than an ion-channel or sensory-transduction activity. Full original experimental detail was not recovered. Supporting Evidence: |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the drug-responsive collagen expression context. Reason: The rat doxazosin study reports time-dependent collagen-I expression and prostate matrix changes. This supports the current donor response annotation at a tissue-response level, not xenobiotic metabolism or direct drug binding by human collagen. Supporting Evidence: |
| GO:0009612 response to mechanical stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mechanically responsive collagen expression as non-core. Reason: Rat cardiac-fibroblast stretch and unloading/reloading studies connect mechanical conditions to collagen transcription or tissue deposition. The original orthology assertion is preserved; those readouts do not independently make COL1A1 a force sensor. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IDA PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t... | KEEP AS NON CORE | Summary: Collagen-I substrate promotes EMT in the tested human-cell contexts. Reason: Actual Methods/Results compare collagen-coated cultures with controls, including ILK knockdown and downstream transcription-factor perturbation. Human pancreatic, colon and renal epithelial contexts show EMT-related changes. The commercial collagen coating is an assembled preparation whose species is not fully specified, not an isolated human COL1A1-chain activity or universal developmental core. Supporting Evidence: |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: Original human bone-marrow ECM workbooks explicitly contain COL1A1 target rows; the protected main text is abstract-only. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment. The exact original workbook rows were read separately from the protected abstract cache; full original Methods access remains limited. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: Original human aortic Tables I and II explicitly detect the alpha-1(I) chain in extracellular extracts. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment. The exact original Tables I and II and the relevant extraction Methods were read in the authentic article XML. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: Original human colorectal/normal-tissue workbook rows identify COL1A1 in ECM-enriched proteomes. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment. The exact original workbook rows and the relevant ECM-enrichment Methods were read. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: The selected text contains the complete abstract and limited body material; the exact cardiac target table was not recovered. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment; incomplete table access is recorded in the reference assessment. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: The available body discusses type-I collagen in human cell-derived matrisomes, but the exact COL1A1 target table remains uninspected. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment; incomplete table access is recorded in the reference assessment. |
| GO:0030020 extracellular matrix structural constituent conferring tensile strength | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Retain collagen-I tensile structural function with source-specific assay limits. Reason: The normal body and methods context establish ECM proteomics, but linked target workbooks were not recovered as readable spreadsheets. These proteomic/classification sources support identity and matrix context rather than directly measuring tensile force. The current GO collagen convention and independently established fibrillar structural biology support the molecular-function judgment; incomplete table access is recorded in the reference assessment. |
| GO:0030141 secretory granule | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the source-scoped secretory-granule localization. Reason: The complete rat odontoblast abstract describes immunogold detection of the alpha-1(I) telopeptide in ER/Golgi/secretory-granule compartments. Retain the original orthology-derived precursor trafficking location; it is not the principal extracellular mature-protein compartment or an autonomous granule-secretion activity. Supporting Evidence: |
| GO:0030199 collagen fibril organization | IEA GO_REF:0000120 | ACCEPT | Summary: Collagen-I chains contribute structure to fibril organization. Reason: Combined electronic mappings agree with direct collagen-chain assembly, type-I identity and human mutation-associated changes in fibril diameter and interfibrillar spacing. This is performed structural participation, distinguished from enzymes that process propeptides. |
| GO:0030199 collagen fibril organization | IMP PMID:14976317 Gene targeting in stem cells from individuals with osteogene... | ACCEPT | Summary: Retain the established fibril-organization role despite incomplete original assay access. Reason: The human COL1A1 gene-targeting abstract does not show all fibril assays behind the IMP. Independent target structural and ultrastructural evidence supports the role, so the original is retained with curator deference rather than rejected from an abstract-only cache. |
| GO:0030199 collagen fibril organization | IMP PMID:15095409 Reduced type I collagen utilization: a pathogenic mechanism ... | ACCEPT | Summary: The original source includes a genuine COL1A1-deficient comparator. Reason: The complete abstract compares COL5A1-deficient EDS cultures with COL1A1-haploinsufficient osteogenesis-imperfecta cultures and reports altered collagen deposition and fibril diameter. It is not a wrong-gene paper. Full text was not recovered; the fibril role is independently supported by other human evidence. |
| GO:0030199 collagen fibril organization | IMP PMID:17211858 Three arginine to cysteine substitutions in the pro-alpha (I... | ACCEPT | Summary: Human COL1A1 variants alter collagen fibril architecture. Reason: The complete original abstract explicitly reports variable fibril diameter and irregular interfibrillar spacing in the human arginine-to-cysteine study. That is target-specific structural evidence for fibril organization. Mutant disulfide dimers are not presented as a wild-type binding assay. Supporting Evidence: PMID:17211858 variable diameter and irregular interfibrillar spaces |
| GO:0030199 collagen fibril organization | IMP PMID:18375391 Defective C-propeptides of the proalpha2(I) chain of type I ... | ACCEPT | Summary: Retain fibril organization with the intracellular-assembly boundary explicit. Reason: Actual human patient-fibroblast experiments measure alpha-chain association and secreted collagen molecular composition after COL1A2 defects. They do not directly image extracellular fibril size or arrangement. COL1A1 performs the structural assembly step, and independent human fibril evidence supports the downstream organization judgment; no extracellular-morphology assay is attributed to this paper. |
| GO:0030199 collagen fibril organization | NAS PMID:1916105 Collagen family of proteins. | ACCEPT | Summary: Retain the established fibrillar-collagen organization role. Reason: The complete family-review abstract describes type-I-containing connective-tissue fibrils and supramolecular collagen assemblies. This is contextual review support, not a new primary assay; target-specific human structural evidence independently substantiates the role. |
| GO:0030199 collagen fibril organization | NAS PMID:28281531 Structural basis of homo- and heterotrimerization of collage... | ACCEPT | Summary: C-propeptide chain selection supports the structural assembly contribution. Reason: The original human recombinant C-propeptide experiments establish chain association and type-I trimer composition. They do not directly measure extracellular fibril diameter or tensile mechanics. Retain the NAS fibril-organization role in combination with independent target ultrastructure, without assigning processing-enzyme activity to the precursor. |
| GO:0030335 positive regulation of cell migration | IDA PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t... | KEEP AS NON CORE | Summary: Collagen-I coating enhances migration in the tested cell assay. Reason: Actual human-cell transwell experiments and ILK/NF-kappaB/LEF-1 perturbations support context-dependent migration on collagen-I. Retain this extracellular-matrix signaling consequence separately from a universal motility program or COL1A1 motor activity. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: The exact CO1A1_HUMAN rows in original aortic NaCl/guanidine tables and the extraction Methods were inspected. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Original Table I identifies COL1A1 in human feeder and HUES1 cell-derived ECM; human and mouse columns are distinguished. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Original complete and matrisome workbook rows identify COL1A1 in the human colorectal/normal-tissue ECM workflow. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: The exact cardiac target table was not recovered; limited authentic body material and the complete abstract were read. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Available human cell-derived ECM text describes fibrillar collagen-I, but the exact target table was not inspected. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: Original S2/S3 human bone-marrow ECM workbooks contain exact COL1A1 rows across the indicated sample categories. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Retain extracellular-matrix localization. Reason: The authentic ECM-proteomics body is available, while the exact target workbook remained inaccessible. The annotation is independently consistent with secreted fibrillar collagen-I; proteomic detection is not an isolated-chain mechanics assay. |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the orthology-derived extracellular-matrix location. Reason: The mouse target identity and current source records are concordant with independently observed human COL1A1 in ECM-enriched samples. No unsupported isoform-specific location is inferred. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nutrient status modulates collagen expression in the donor tissue. Reason: The complete rat high-fat-diet abstract reports reduced skin collagen-I RNA and protein. Retain the original response context without turning it into an independent nutrient-sensing function of human COL1A1. Supporting Evidence: |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact alpha-1 donor support for estradiol response remains unresolved. Reason: The current rat Col1a1 source points to PMID:2456904, whose complete abstract explicitly identifies alpha-2(I), alpha-1(III) and alpha-2(V) collagen transcripts. Full experimental text was not recovered, so alpha-1(I) support cannot be verified from the abstract. Preserve the original inference as undecided, not as a disproven response or a confident wrong-gene claim. Supporting Evidence: |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain insulin-responsive collagen expression as contextual. Reason: The rat diabetic-bone study reports reduced collagen expression and reversal by insulin treatment. This supports the original expression-response inference, not insulin binding or an autonomous signaling activity of COL1A1. Supporting Evidence: |
| GO:0032964 collagen biosynthetic process | IMP PMID:15095409 Reduced type I collagen utilization: a pathogenic mechanism ... | UNDECIDED | Summary: The precise biosynthetic-process attribution remains unresolved. Reason: PMID:15095409 explicitly includes human COL1A1-haploinsufficient cultures and reduced collagen synthesis/deposition, but full experimental text was not recovered after bounded publisher and repository-location attempts. Reduced product abundance alone does not identify the step COL1A1 performs in biosynthesis. Its separately demonstrated structural self-assembly is retained; no synthase or propeptide-cleaving activity is inferred. |
| GO:0034504 protein localization to nucleus | IDA PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t... | MODIFY | Summary: Type-I collagen positively regulates NF-kappaB nuclear localization in the tested cells. Reason: The original Results and Figure 2A show increased nuclear NF-kappaB after cells are grown on type-I collagen rather than laminin. GO:0034504 concerns a protein transporting or maintaining another protein in the nucleus; the assay supports upstream regulation of that outcome rather than collagen acting as localization machinery. Refine to GO:1900182, which does not require distinguishing import from nuclear retention. PANC-1, DLD1 and HK-2 recipient cells are human, but the commercial collagen reagent species and isolated alpha-1-chain contribution are not specified. Keep this contextual effect outside the structural core. Proposed replacements: positive regulation of protein localization to nucleus Supporting Evidence: PMID:20018240 those grown on type I collagen had strong nuclear localization of NF-ΞΊB |
| GO:0034505 tooth mineralization | IMP PMID:17118335 Abnormal dentin structure in two novel gene mutations [COL1A... | KEEP AS NON CORE | Summary: Retain dentin-related structural/mineralization context. Reason: The complete original abstract explicitly includes a human COL1A1 Arg-to-Cys case, distinct from an ADAMTS2 case, with dentin histology, immunostaining and abnormal collagen-fiber organization. The annotation reflects matrix-related tooth formation, not a COL1A1 mineralizing enzyme or direct calcium-nucleation assay. Supporting Evidence: |
| GO:0042542 response to hydrogen peroxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the hydrogen-peroxide-responsive donor expression context. Reason: The rat stellate-cell source links hydrogen peroxide/TGF-beta conditions to COL1A1 promoter and expression changes. This preserves the curated response without assigning peroxide catalysis, sensing or a separate oxidative-stress core to collagen. Supporting Evidence: |
| GO:0042802 identical protein binding | IDA PMID:17211858 Three arginine to cysteine substitutions in the pro-alpha (I... | ACCEPT | Summary: Retain self-association as part of collagen-I structural assembly. Reason: The original abstract reports disulfide-linked alpha-1 dimers from human Arg-to-Cys variants, not a generic wild-type dimer assay. Independent wild-type human C-propeptide homotrimer experiments establish self-association, supporting the broader identical-protein-binding assertion as an enabling part of the integrated structural core. Do not narrow it to homodimerization. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Self-association is compatible with alpha-1(I) homotrimer assembly. Reason: The mouse orthology assertion is independently corroborated by direct human alpha-1 C-propeptide homotrimer structure and chain assembly. It does not require a separate generic binding core or claim that all collagen I in vivo is homotrimeric. |
| GO:0043434 response to peptide hormone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain peptide-hormone-responsive collagen expression. Reason: The donor study uses a rat Col1a1 promoter in transgenic mouse calvarial cultures and reports PTH/cAMP regulation of promoter activity and collagen synthesis. Preserve the experimental construct/species boundary and original transfer; no direct hormone binding by collagen is inferred. Supporting Evidence: |
| GO:0043589 skin morphogenesis | IMP PMID:17211858 Three arginine to cysteine substitutions in the pro-alpha (I... | KEEP AS NON CORE | Summary: Retain skin morphology as a matrix-related phenotype. Reason: The human Arg-to-Cys source reports Ehlers-Danlos features and abnormal dermal fibril ultrastructure. This is consistent with collagen-I contribution to skin architecture, rather than a separate skin-patterning activity. Supporting Evidence: |
| GO:0044344 cellular response to fibroblast growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain FGF-responsive expression at its donor-cell scope. Reason: The rat calvarial-cell abstract reports long-term FGF2-associated changes in COL1 expression during osteoblast culture. It supports the preserved response context, not FGF receptor activity of COL1A1. Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t... | KEEP AS NON CORE | Summary: Collagen-I substrate can increase transcription in the tested cells. Reason: GO:0045893 describes increasing transcription, not DNA-binding transcription-factor activity. Actual NF-kappaB and LEF-1 reporters increase on type-I collagen versus laminin; ILK siRNA inhibits the NF-kappaB response, and ILK or NF-kappaB siRNA inhibits the LEF-1 response. Reporter normalization, empty-vector and scrambled-siRNA controls are described. These perturbations support a context-dependent extracellular matrix signal regulating transcription. The human recipient cells do not establish that the commercial collagen reagent is human or that isolated COL1A1 alone was tested. Retain non-core without assigning DNA binding or adding a new process. 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 | Summary: Platelet-derived growth factor binding is supported as a secondary capability. Reason: The complete original abstract reports radiolabeled PDGF isoforms binding collagens IβVI and constituent chains, with biological availability experiments. Preserve the direct binding annotation, but do not infer that COL1A1 is PDGF itself or a PDGF receptor. Full original construct details remain unavailable. Supporting Evidence: |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad organ-development context as secondary to matrix structure. Reason: The ARBA process is biologically consistent with matrix-dependent tissue architecture and human skeletal, dermal and dental phenotypes. Its breadth adds no distinct molecular core; no specific new organ mechanism is inferred from the electronic rule. |
| GO:0048545 response to steroid hormone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain steroid-responsive collagen expression in the donor context. Reason: The rat anabolic-steroid/tendon study reports collagen expression changes under the tested treatment and training conditions. This is a response-associated matrix readout rather than steroid binding or signaling catalysis by human COL1A1. Supporting Evidence: |
| GO:0048706 embryonic skeletal system development | IMP PMID:18553566 Prenatal cortical hyperostosis with COL1A1 gene mutation. | KEEP AS NON CORE | Summary: Human prenatal COL1A1 disease supports embryonic skeletal context. Reason: The complete original case-report abstract describes a human fetal COL1A1 mutation with radiographic and histologic cortical hyperostosis. Retain the structural skeletal-development phenotype without presenting the case report as an autonomous embryonic patterning assay. Supporting Evidence: |
| GO:0051591 response to cAMP | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain cAMP-sensitive collagen expression in the tested promoter system. Reason: The donor experiment couples PTH/cAMP treatment to rat Col1a1 promoter activity in transgenic mouse calvariae and to collagen synthesis. It does not show cAMP binding by the collagen protein. The original electronic annotation is preserved at this response scope. Supporting Evidence: |
| GO:0055093 response to hyperoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the hyperoxic healing-response context. Reason: The rat ligament study connects hyperbaric oxygen treatment to collagen expression and healing-associated matrix deposition. Retain the existing response annotation without assigning oxygen-sensing or catalytic activity to human collagen. Supporting Evidence: |
| GO:0071260 cellular response to mechanical stimulus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain mechanically responsive matrix expression. Reason: Current rat and mouse sources include loaded tendon-cell cultures and tenogenic/osteogenic expression readouts. COL1A1 is measured as an expression/matrix marker; this is not a direct demonstration of a collagen mechanosensor. Combined electronic identities are preserved. |
| GO:0071300 cellular response to retinoic acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain retinoic-acid-responsive collagen production in donor cells. Reason: Rat fetal-lung and hepatic-stellate-cell abstracts report altered collagen synthesis, chain ratios or COL1 expression after retinoid treatment. Preserve those response contexts and their original orthology inference without claiming direct retinoid binding by COL1A1. |
| GO:0071306 cellular response to vitamin E | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The vitamin-E-associated Col1a1 change is a phenotype readout with insufficient response-participation support. Reason: The complete rat-chondrocyte abstract reports reduced Col1a1 expression during vitamin-E protection, alongside increased Agc1/Col2a1 expression and proteoglycan, viability and differentiation readouts. It establishes a transcriptional response, but does not establish alpha1(I) collagen as a component performing that protective response. Mark the participation inference as over-annotated at this source scope. Preserve the positive IEP donor result and the abstract-only access limit; no universal absence of collagen involvement is asserted. Supporting Evidence: |
| GO:0071333 cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the high-glucose-associated type-I collagen response at the recovered figure scope. Reason: The current rat donor assigns Col1a1 by IEP. In the original publisher Figure 4, high-glucose NRK-52E cells show increased collagen-I immunofluorescence and a collagen-I immunoblot band, reduced by Lefty-1 relative to the high-glucose and vector controls. This supports the type-I matrix-production response and the preserved contextual annotation. Full Methods and the antibody chain specificity were not recovered, so the exact alpha-1 assignment remains curator supplied; no human glucose-sensing activity or independent osmolarity control is claimed. Supporting Evidence: |
| GO:0071356 cellular response to tumor necrosis factor | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain TNF-dependent donor collagen expression. Reason: The rat stellate-cell abstract reports TNF-alpha/glutathione-linked suppression of COL1 expression. It supports the preserved cellular-response context without assigning TNF receptor or redox enzyme activity to COL1A1. Supporting Evidence: |
| GO:0071364 cellular response to epidermal growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain EGF-associated collagen synthesis changes. Reason: The rat fetal-lung study reports reduced collagen production and altered chain/trimer ratios after EGF exposure. Keep the original expression-response inference separate from EGF binding or receptor activity of the collagen protein. Supporting Evidence: |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain TGF-beta-responsive collagen expression. Reason: Actual rat cardiac-fibroblast Methods/Results in PMID:23560091 measure COL1A1 RNA, cell-associated collagen, secreted collagen and promoter methylation after TGF-beta treatment. The second donor reference foregrounds COL1A2 and remains unresolved for the alpha-1-specific link; the directly verified source independently supports the contextual response. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IDA PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t... | KEEP AS NON CORE | Summary: Retain context-dependent beta-catenin/LEF signaling enhancement. Reason: The actual human-cell source measures collagen-I-dependent LEF-1 and beta-catenin-associated reporter responses with ILK/NF-kappaB perturbations. This is pathway cross-talk elicited by collagen substrate, not evidence that COL1A1 is a Wnt ligand or that every collagen matrix activates canonical Wnt signaling. Supporting Evidence: |
| GO:1902617 response to fluoride | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The restricted fluoride-associated transcript change does not establish matrix participation in the measured response. Reason: The complete rat-skin abstract reports reduced Col1a1 RNA in males after six months of fluoride exposure, but no corresponding effect on the measured collagen-form concentrations or chain ratios. The positive expression result is preserved; inferring collagen-product participation from it exceeds the demonstrated response, so mark this source-specific inference as over-annotated. This is not a claim that COL1A1 cannot respond to fluoride. The separate osteoblast source with reduced type-I protein output remains distinct. Supporting Evidence: |
| GO:1902618 cellular response to fluoride | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain cellular fluoride-responsive expression. Reason: The rat osteoblast source specifically reports COL1A1 mRNA/protein reduction, distinct from COL1A2, under the tested fluoride condition. This supports the original response inference, not direct fluoride recognition by collagen. Supporting Evidence: |
| GO:1905641 cellular response to acetaldehyde | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain acetaldehyde-responsive expression in stellate cells. Reason: The rat hepatic-stellate-cell abstract reports collagen-I expression under acetaldehyde/leptin conditions; the negative leptin synergy result is not converted into an absence of the acetaldehyde response. Keep this contextual transcriptional response separate from acetaldehyde metabolism or sensing by COL1A1. Supporting Evidence: |
| GO:0048018 receptor ligand activity | IC Reactome:R-HSA-2327738 | NEW | Summary: Propose NEW receptor ligand activity for native triple-helical collagen type I fibrils activating DDR1 and DDR2 receptor tyrosine kinases. Reason: Beyond its primary structural role in the extracellular matrix (GO:0030020), native triple-helical type I collagen ([alpha-1(I)]2[alpha-2(I)], GO:0005584) presents conserved discoidin-domain binding motifs (such as GVMGFO) that directly bind and activate the cell-surface receptor tyrosine kinases DDR1 and DDR2 (GO:0038062; Reactome:R-HSA-2327738, Reactome:R-HSA-2465890), functioning as an insoluble extracellular matrix receptor ligand (Category C structural/ligand protein). Supporting Evidence: Reactome:R-HSA-2327738 Discoidin domain receptors (DDRs) are a subfamily of receptor tyrosine kinases, the only members known to respond to an ECM component. DDR1 binds several of the major fibrillar collagens (types I, II, III, and V) and the non-fibrillar collagen IV (Shrivastava et al. 1997, Vogel et al. 1997, Hou et al. 2001). DDR proteins bind collagen as dimers (Leitinger 2003, 2011). Reactome:R-HSA-2465890 Discoidin domain receptors (DDRs) are a subfamily of receptor tyrosine kinases, the only members known to respond to an ECM component. DDR2 binds the major fibrillar collagens types I, II, III, and V) and the non-fibrillar collagen X (Shrivastava et al. 1997, Vogel et al. 1997, Leitinger & Kwan 2006). |
| GO:0038063 collagen-activated tyrosine kinase receptor signaling pathway | IC Reactome:R-HSA-2327738 | NEW | Summary: Propose NEW annotation for collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063). Reason: Native triple-helical type I collagen fibrils containing COL1A1 directly bind the extracellular discoidin domains of DDR1 and DDR2 dimers to trigger sustained receptor tyrosine kinase autophosphorylation and downstream signaling (Reactome:R-HSA-2327738, Reactome:R-HSA-2465890). Current GOA and PAINT curation annotate GO:0038063 on the receptors (DDR1, DDR2) and on COL4A2/COL4A6, but omit the major fibrillar collagens (COL1A1, COL1A2, COL2A1, COL3A1). Supporting Evidence: Reactome:R-HSA-2327738 Discoidin domain receptors (DDRs) are a subfamily of receptor tyrosine kinases, the only members known to respond to an ECM component. DDR1 binds several of the major fibrillar collagens (types I, II, III, and V) and the non-fibrillar collagen IV (Shrivastava et al. 1997, Vogel et al. 1997, Hou et al. 2001). DDR proteins bind collagen as dimers (Leitinger 2003, 2011). Reactome:R-HSA-2465890 Discoidin domain receptors (DDRs) are a subfamily of receptor tyrosine kinases, the only members known to respond to an ECM component. DDR2 binds the major fibrillar collagens types I, II, III, and V) and the non-fibrillar collagen X (Shrivastava et al. 1997, Vogel et al. 1997, Leitinger & Kwan 2006). |
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Download this section (compressed HTML)Q: Which context-dependent expression-response annotations describe a conserved performed matrix contribution, and which primarily record COL1A1 as a stimulus-responsive marker?
Q: What assays behind the original collagen-biosynthesis annotation distinguish structural self-assembly from synthesis or processing performed by other proteins?
Q: How do precursor, mature heterotrimer and alpha-1 homotrimer states differ in fibronectin binding and context-specific signaling?
Experiment: Compare sequence-verified human wild-type and interface-mutant COL1A1 with controlled COL1A2 supply; separately quantify precursor assembly, secretion, propeptide processing, mature fibril dimensions and tensile behavior. Normalize matrix amount and retain folding and processing controls.
Hypothesis: Propeptide-dependent chain selection changes mature matrix architecture independently of overall collagen production.
Experiment: Test sequence-verified regulatory alleles in isogenic ocular matrix-producing cells, measuring allele-dependent expression, deposited matrix and optical/mechanical properties. Include neutral-variant and expression-rescue controls before assigning causality from association.
Hypothesis: Some disease-associated COL1A1 regulatory variants change ocular matrix organization.
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