FBN1 encodes profibrillin-1, a secreted, calcium-binding glycoprotein that is processed into functionally distinct extracellular products. Mature fibrillin-1 assembles into microfibrils that provide structural support in elastic and elastin-free connective tissues, organize elastic-fiber assembly, and connect the matrix to cell-surface integrins. Fibrillin microfibrils also control local TGF-beta and BMP availability by anchoring growth-factor complexes in the matrix. The released C-terminal product, asprosin, is a circulating hormone with glucogenic and appetite-stimulating activities, distinct from the structural functions of the mature matrix chain.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
FBN1_MATURE_FIBRILLIN1PRO_0000007581 (residues 45-2731) FBN1_ASPROSINPRO_0000436882 (residues 2732-2871) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001501 skeletal system development | IMP PMID:8188302 A novel mutation of the fibrillin gene causing ectopia lenti... | KEEP AS NON CORE | Summary: Fibrillin-1 contributes to skeletal development by controlling matrix-bound growth-factor availability during bone formation. Reason: The original operative evidence in the human family study PMID:8188302 remains inaccessible; its skeletal observation is not independently verified here. The gene-level developmental contribution can nevertheless be adjudicated from accessible mechanistic evidence. In PMID:20855508, Fbn1-null mouse osteoblast matrices retain less BMP and LTBP-associated material, media contain more available BMP/TGF-beta activity, and osteoblast maturation changes without corresponding increases in the ligand transcripts. Pathway-separation experiments support matrix sequestration as the contribution to bone formation. This is more than a Marfan phenotype or necessity inference. The study also excludes microfibrils as an obligatory mineralization substrate; that role is not asserted. Human fibrillin-1 fragments and human bone material in PMID:24039232 add product-relevant support for regulation of bone-cell differentiation, while its functional assays are in mouse systems. Retain skeletal development as non-core with this cross-species and original-source limit explicit. |
| GO:0001525 angiogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The transferred angiogenesis claim is based on a mutant vascular phenotype. Reason: Mouse Q61554 donor evidence PMID:17496220 measures impaired vascular responses and endothelial outgrowth in Tsk tissue, with improvement by the apoA-I mimetic D-4F. These are downstream disease and treatment outcomes; the study does not establish normal FBN1 as the entity performing angiogenic signaling or vessel formation. Retain the structural vascular context in the biological synthesis rather than transferring this process as an established FBN1 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED Mouse Q61554 donor evidence PMID:17496220 measures impaired vascular responses and endothelial outgrowth in Tsk tissue, with improvement by the apoA-I mimetic D-4F. These are downstream disease and treatment outcomes; the study does not establish normal FBN1 as the entity performing angiogenic signaling or vessel formation. Retain the structural vascular context in the biological synthesis rather than transferring this process as an established FBN1 function. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED Mouse Q61554 donor evidence PMID:17496220 measures impaired vascular responses and endothelial outgrowth in Tsk tissue, with improvement by the apoA-I mimetic D-4F. These are downstream disease and treatment outcomes; the study does not establish normal FBN1 as the entity performing angiogenic signaling or vessel formation. Retain the structural vascular context in the biological synthesis rather than transferring this process as an established FBN1 function. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:10424889 Ultrastructural distribution of 36-kD microfibril-associated... | ACCEPT | Summary: Original human-skin Methods and Figure 3 double immunogold labeling identify FBN1 on microfibrils. Reason: Original human-skin Methods and Figure 3 double immunogold labeling identify FBN1 on microfibrils. The separately sampled bovine tissues and MAGP36-specific elastin-interface pattern are not substituted for the human FBN1 result. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | ACCEPT | Summary: The original study localizes FBN1 with microfibril-associated LTBP1 and assays human FBN1βLTBP interactions. Reason: The original study localizes FBN1 with microfibril-associated LTBP1 and assays human FBN1βLTBP interactions. This supports the structural microfibril location independently of whether all interacting molecules coexist in one complex. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:1860873 Purification and partial characterization of fibrillin, a cy... | ACCEPT | Summary: The original purification study identifies secreted human fibrillin and uses two distinct antibodies to label tissue microfibrils periodically (Results and Figure 7). Reason: The original purification study identifies secreted human fibrillin and uses two distinct antibodies to label tissue microfibrils periodically (Results and Figure 7). The biochemical and ultrastructural observations directly support microfibril localization. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:22355679 Essential role of microfibrillar-associated protein 4 in hum... | ACCEPT | Summary: The original human skin/fibroblast experiments map FBN1 microfibril networks in the MFAP4 study. Reason: The original human skin/fibroblast experiments map FBN1 microfibril networks in the MFAP4 study. Title emphasis on the associated protein does not diminish the directly observed FBN1 localization. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:3536967 Fibrillin, a new 350-kD glycoprotein, is a component of extr... | ACCEPT | Summary: Human tissue immunoelectron microscopy identifies fibrillin in approximately 10-nm extracellular microfibrils, both associated with elastin cores and in separate bundles. Reason: Human tissue immunoelectron microscopy identifies fibrillin in approximately 10-nm extracellular microfibrils, both associated with elastin cores and in separate bundles. This is the defining structural localization in the original study. Supporting Evidence: |
| GO:0001527 microfibril | IDA PMID:7534784 The association of human fibulin-1 with elastic fibers: an i... | ACCEPT | Summary: Mature fibrillin-1 is a constituent of extracellular microfibrils. Reason: The PMID:7534784 abstract explicitly reports fibrillin antibody counterstaining in human tissues; its fibulin-focused title does not indicate misattribution. The operative experiment and figures from that paper remain inaccessible. The same human mature-matrix localization claim is directly established by the independently read immunogold localization in PMID:3536967 and the FBN1-specific tissue work in PMID:8120105. Accept the microfibril claim with deference to the original curator, without claiming that the unread assay was reproduced or that every tissue/figure in PMID:7534784 has been verified. |
| GO:0001527 microfibril | IDA PMID:8120105 Structure and expression of fibrillin-2, a novel microfibril... | ACCEPT | Summary: The original study assays both fibrillins: human fetal tissue immunohistochemistry and separately bovine-ligament immunoelectron microscopy support FBN1 microfibril localization. Reason: The original study assays both fibrillins: human fetal tissue immunohistochemistry and separately bovine-ligament immunoelectron microscopy support FBN1 microfibril localization. Figure 5 labels peripheral microfibrils rather than amorphous elastin; the FBN2-focused title is not a citation error. Supporting Evidence: |
| GO:0001527 microfibril | IEA GO_REF:0000120 | ACCEPT | Summary: Fibrillin-1 is a constituent of extracellular microfibrils. Reason: The combined ARBA00028288/mouse Q61554 source agrees with the actual human FBN1 microfibrillar localization and the target-specific Reactome polymer entities. The rule provides an inference, while human primary observations independently support this structural location; the term denotes a cellular anatomical structure, not a GO protein-containing complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028288 SUPPORTS TRANSFER The combined ARBA00028288/mouse Q61554 source agrees with the actual human FBN1 microfibrillar localization and the target-specific Reactome polymer entities. The rule provides an inference, while human primary observations independently support this structural location; the term denotes a cellular anatomical structure, not a GO protein-containing complex. UniProtKB:Q61554 SUPPORTS TRANSFER The combined ARBA00028288/mouse Q61554 source agrees with the actual human FBN1 microfibrillar localization and the target-specific Reactome polymer entities. The rule provides an inference, while human primary observations independently support this structural location; the term denotes a cellular anatomical structure, not a GO protein-containing complex. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER The combined ARBA00028288/mouse Q61554 source agrees with the actual human FBN1 microfibrillar localization and the target-specific Reactome polymer entities. The rule provides an inference, while human primary observations independently support this structural location; the term denotes a cellular anatomical structure, not a GO protein-containing complex. |
| GO:0001656 metanephros development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fibrillin-1 contributes extracellular structural support during metanephric development. Reason: The rat G3V9M6 donor traces to PMID:9815129. Its original abstract and Figure captions show mesenchymal/vascular/glomerular Fbn1 distribution and impaired metanephric organization after antisense perturbation. This supports a contextual matrix contribution to organ development, without making FBN1 a developmental signaling enzyme. The saved original capture ends before the full Results; no additional mechanistic claim is made. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:G3V9M6 SUPPORTS TRANSFER The rat G3V9M6 donor traces to PMID:9815129. Its original abstract and Figure captions show mesenchymal/vascular/glomerular Fbn1 distribution and impaired metanephric organization after antisense perturbation. This supports a contextual matrix contribution to organ development, without making FBN1 a developmental signaling enzyme. The saved original capture ends before the full Results; no additional mechanistic claim is made. ensembl:ENSRNOP00000052876 SUPPORTS TRANSFER The rat G3V9M6 donor traces to PMID:9815129. Its original abstract and Figure captions show mesenchymal/vascular/glomerular Fbn1 distribution and impaired metanephric organization after antisense perturbation. This supports a contextual matrix contribution to organ development, without making FBN1 a developmental signaling enzyme. The saved original capture ends before the full Results; no additional mechanistic claim is made. Supporting Evidence: |
| GO:0001822 kidney development | IEA GO_REF:0000107 | TOO GENERAL | Summary: Kidney development is already covered by the more specific retained metanephric context. Reason: GO:0001656 metanephros development is a direct is_a child of GO:0001822 kidney development. The retained metanephros-development context (GO:0001656; PMID:9815129) supplies that scope. The same rat source gives no independent broader renal developmental role in the evidence read; this redundancy judgment does not reject the source perturbation phenotype. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:G3V9M6 SUPPORTS TRANSFER GO:0001656 metanephros development is a direct is_a child of GO:0001822 kidney development. The retained metanephros-development context (GO:0001656; PMID:9815129) supplies that scope. The same rat source gives no independent broader renal developmental role in the evidence read; this redundancy judgment does not reject the source perturbation phenotype. ensembl:ENSRNOP00000052876 SUPPORTS TRANSFER GO:0001656 metanephros development is a direct is_a child of GO:0001822 kidney development. The retained metanephros-development context (GO:0001656; PMID:9815129) supplies that scope. The same rat source gives no independent broader renal developmental role in the evidence read; this redundancy judgment does not reject the source perturbation phenotype. Supporting Evidence: |
| GO:0005178 integrin binding | IPI PMID:12807887 Cell adhesion to fibrillin-1 molecules and microfibrils is m... | ACCEPT | Summary: Human recombinant FBN1 RGD-containing fragments support cell adhesion with alphavbeta3-dependent antibody inhibition. Reason: Human recombinant FBN1 RGD-containing fragments support cell adhesion with alphavbeta3-dependent antibody inhibition. Fragment and cell assays support the specified integrin interaction; the separate native-microfibril preparation is bovine. Supporting Evidence: |
| GO:0005178 integrin binding | IPI PMID:12807887 Cell adhesion to fibrillin-1 molecules and microfibrils is m... | ACCEPT | Summary: Human recombinant FBN1 fragments support alpha5beta1-dependent adhesion in the original cell/antibody experiments. Reason: Human recombinant FBN1 fragments support alpha5beta1-dependent adhesion in the original cell/antibody experiments. Fibronectin-blocking and early-time controls distinguish the FBN1 interaction from an obligatory fibronectin bridge; affinity and cell context need not match alphavbeta3. Supporting Evidence: |
| GO:0005178 integrin binding | IPI PMID:15062093 Structure of the integrin binding fragment from fibrillin-1 ... | ACCEPT | Summary: Human FBN1 integrin-binding fragments interact with purified human placental alphavbeta3 by surface plasmon resonance and support adhesion. Reason: Human FBN1 integrin-binding fragments interact with purified human placental alphavbeta3 by surface plasmon resonance and support adhesion. The alpha5beta1 negative in this fragment assay is not a universal absence of FBN1βalpha5beta1 interaction. Supporting Evidence: |
| GO:0005178 integrin binding | IPI PMID:17158881 alphaVbeta6 is a novel receptor for human fibrillin-1. Compa... | ACCEPT | Summary: Human fibrillin-1 supports alpha5beta1-integrin binding and adhesion. Reason: PMID:17158881 positively identifies alpha5beta1 in its abstract, but its operative Methods, construct controls and Results remain inaccessible. The same alpha5beta1 partner pair (P05556/P08648) is independently supported by the original human recombinant FBN1-fragment experiments in PMID:12807887: integrin-blocking antibodies, RGD-mutant controls and fibronectin-blocking/early-time controls establish the interaction and adhesion contribution. Accept this gene-and-partner claim; this does not verify the particular affinity estimate or keratinocyte distribution in the unread paper. The distinct alphaVbeta6 interaction from that paper is not established by the alpha5beta1 evidence. |
| GO:0005178 integrin binding | IPI PMID:17158881 alphaVbeta6 is a novel receptor for human fibrillin-1. Compa... | UNDECIDED | Summary: The original abstract positively reports human FBN1 integrin interactions and human keratinocyte/fibroblast adhesion comparisons. Reason: The original abstract positively reports human FBN1 integrin interactions and human keratinocyte/fibroblast adhesion comparisons. Operative Methods, construct controls and Results could not be recovered; independent integrin evidence does not verify this source-specific context. Supporting Evidence: |
| GO:0005179 hormone activity | IBA GO_REF:0000033 | ACCEPT | Summary: The FBN1 precursor yields the secreted hormone asprosin. Reason: The PTN002778720 hormone assertion is biologically supported by the separately read human asprosin ligand studies, including glucogenic signaling and appetite regulation. This activity belongs to the C-terminal processed chain, not mature structural fibrillin-1. Glucogenic reproducibility remains disputed across preparations and laboratories, as recorded in the asprosin reference review. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002778720 SUPPORTS TRANSFER The PTN002778720 hormone assertion is biologically supported by the separately read human asprosin ligand studies, including glucogenic signaling and appetite regulation. This activity belongs to the C-terminal processed chain, not mature structural fibrillin-1. Glucogenic reproducibility remains disputed across preparations and laboratories, as recorded in the asprosin reference review. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. |
| GO:0005179 hormone activity | IDA PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | ACCEPT | Summary: Asprosin is a circulating glucogenic hormone derived from the C terminus of human profibrillin-1. Reason: The raw annotation is specifically P35555-PRO_0000436882. PMID:27087445 Methods identify human residues 2732β2871 with an N-terminal His tag; this reagent increased glucose output and cAMP/PKA signaling in primary mouse hepatocytes, with in vivo mouse and human-plasma evidence. The activity belongs to the released asprosin chain, not mature matrix fibrillin-1. Negative replication with other preparations in PMID:30879984 and later positive studies require assay/preparation limits, rather than denial of the product-specific hormone activity. |
| GO:0005179 hormone activity | IDA PMID:31230984 OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosi... | UNDECIDED | Summary: The cited receptor study supports asprosin hormone biology, but direct assay provenance for the human chain is unresolved. Reason: PMID:31230984 explicitly describes mouse-liver-derived Asprosin and mouse GST-Asprosin production. Human OR4M1 expression and human host cells do not establish that the ligand assayed was human. The source-specific human-chain IDA claim therefore remains unresolved; no source field is changed and no claim is made that the entire paper concerns the wrong gene. Human asprosin hormone activity is independently supported by PMID:27087445, so this judgment does not negate that activity. |
| GO:0005179 hormone activity | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse-derived hormone inference is supported for the asprosin product. Reason: Mouse Q61554 carries hormone evidence from PMID:31230984. That paper used mouse recombinant ligand, so it does not independently prove the exact human-ligand assay. Human C-terminal ligand evidence in PMID:27087445 and PMID:29106398 independently supports the hormone function of human FBN1-derived asprosin. This does not assign hormone activity to the mature matrix chain. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER Mouse Q61554 carries hormone evidence from PMID:31230984. That paper used mouse recombinant ligand, so it does not independently prove the exact human-ligand assay. Human C-terminal ligand evidence in PMID:27087445 and PMID:29106398 independently supports the hormone function of human FBN1-derived asprosin. This does not assign hormone activity to the mature matrix chain. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER Mouse Q61554 carries hormone evidence from PMID:31230984. That paper used mouse recombinant ligand, so it does not independently prove the exact human-ligand assay. Human C-terminal ligand evidence in PMID:27087445 and PMID:29106398 independently supports the hormone function of human FBN1-derived asprosin. This does not assign hormone activity to the mature matrix chain. |
| GO:0005201 extracellular matrix structural constituent | IBA GO_REF:0000033 | ACCEPT | Summary: Fibrillin-1 contributes structural integrity to extracellular matrices. Reason: The PTN000620536 inference agrees with human FBN1 microfibrils and their elastic and elastin-free matrix distributions. The broader structural function remains useful for anchorage and matrix scaffolding beyond elastic recoil, so the presence of GO:0030023 does not make it uninformative. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000620536 SUPPORTS TRANSFER The PTN000620536 inference agrees with human FBN1 microfibrils and their elastic and elastin-free matrix distributions. The broader structural function remains useful for anchorage and matrix scaffolding beyond elastic recoil, so the presence of GO:0030023 does not make it uninformative. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. |
| GO:0005201 extracellular matrix structural constituent | IDA PMID:3536967 Fibrillin, a new 350-kD glycoprotein, is a component of extr... | ACCEPT | Summary: The original human biochemical and immunoelectron experiments establish fibrillin as a major microfibrillar structural constituent. Reason: The original human biochemical and immunoelectron experiments establish fibrillin as a major microfibrillar structural constituent. The general structural role remains useful in elastic and nonelastic matrices; it is broader than the retained matrix-elasticity inference. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Human ascending-aorta ECM proteomics explicitly identifies FBN1_HUMAN in main Tables I/II, with unique-peptide and coverage columns. Reason: Human ascending-aorta ECM proteomics explicitly identifies FBN1_HUMAN in main Tables I/II, with unique-peptide and coverage columns. The RCA structural assignment is compatible with its established scaffold role, but the study itself is an identification/classification experiment rather than a mechanical assay. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | UNDECIDED | Summary: The original human endothelial ECM-proteomics Methods were read, but the FBN1 record in the relevant supplementary matrix tables could not be recovered. Reason: The original human endothelial ECM-proteomics Methods were read, but the FBN1 record in the relevant supplementary matrix tables could not be recovered. The source-specific target join remains unverified; this does not imply that FBN1 was absent or that its established ECM role is incorrect. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Additional File 2 identifies FBN1/P35555 as a core-matrisome ECM glycoprotein across human colon/liver samples. Reason: Additional File 2 identifies FBN1/P35555 as a core-matrisome ECM glycoprotein across human colon/liver samples. This supports the RCA structural classification together with the known scaffold function; the broader accession group includes other fibrillins, so every quantified peptide is not claimed to discriminate FBN1. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: The actual human atrial Table 1 names Fibrillin-1 in guanidine input and glycoprotein-enriched fractions. Reason: The actual human atrial Table 1 names Fibrillin-1 in guanidine input and glycoprotein-enriched fractions. The RCA structural classification is biologically coherent, although no FBN1-specific mechanical assay, accession-level peptide detail or positive glycopeptide-analysis result is supplied by this main table. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | UNDECIDED | Summary: The human cell-derived ECM proteomics study was read, but its main Table I interchanges fibrillin/fibulin names beside FBN1/2 and FBLN1/2 symbols. Reason: The human cell-derived ECM proteomics study was read, but its main Table I interchanges fibrillin/fibulin names beside FBN1/2 and FBLN1/2 symbols. An exact supplemental accession join could not be recovered, so this source-specific record remains unresolved without declaring wrong-gene annotation or negative localization. Supporting Evidence: |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: The original ACS supplementary workbook explicitly identifies sole human FBN1/P35555 records as ECM glycoprotein, including breast sheet B row 4 with 17 unique peptides. Reason: The original ACS supplementary workbook explicitly identifies sole human FBN1/P35555 records as ECM glycoprotein, including breast sheet B row 4 with 17 unique peptides. The RCA structural role is inferred from matrix identity and established scaffold biology; mixed fibrillin groups are distinguished and no direct mechanics assay is claimed. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:15062093 Structure of the integrin binding fragment from fibrillin-1 ... | ACCEPT | Summary: The original human FBN1 fragment structural study resolves calcium-associated cbEGF-domain architecture. Reason: The original human FBN1 fragment structural study resolves calcium-associated cbEGF-domain architecture. Calcium binding is a physical property of the extracellular scaffold, without implying a calcium-regulatory enzyme or cellular calcium-signaling activity. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:7691719 Fibrillin binds calcium and is coded by cDNAs that reveal a ... | ACCEPT | Summary: Fibrillin-1 binds calcium through its calcium-binding EGF domains. Reason: The authentic PMID:7691719 abstract explicitly reports calcium binding, but its operative assay remains inaccessible. Accessible original structures in PMID:15062093 directly resolve calcium coordinated by human FBN1 cbEGF22 and cbEGF23, independently establishing the same molecular activity. Accept calcium binding without claiming that the historical experiment, every repeat's affinity, or a calcium-signaling function has been verified. The crystal study finds little local structural change after calcium removal; an intrinsic mechanical spring or enzyme activity is not inferred from calcium coordination. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Calcium binding supports the structure of fibrillin-1 calcium-binding EGF domains. Reason: The actual IPR001881 domain and IPR018097 conserved-site records both map to GO:0005509, and the target UniProt record contains calcium-binding EGF domains. This is a coherent domain-to-function inference for the matrix protein. No site-specific mutational claim or verification of an inaccessible historical calcium assay is implied. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001881 SUPPORTS TRANSFER The actual IPR001881 domain and IPR018097 conserved-site records both map to GO:0005509, and the target UniProt record contains calcium-binding EGF domains. This is a coherent domain-to-function inference for the matrix protein. No site-specific mutational claim or verification of an inaccessible historical calcium assay is implied. InterPro:IPR018097 SUPPORTS TRANSFER The actual IPR001881 domain and IPR018097 conserved-site records both map to GO:0005509, and the target UniProt record contains calcium-binding EGF domains. This is a coherent domain-to-function inference for the matrix protein. No site-specific mutational claim or verification of an inaccessible historical calcium assay is implied. |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: Original human FBN1 assays support association with LTBP1 constructs. Reason: Original human FBN1 assays support association with LTBP1 constructs. The recorded partner accessions are preserved without inferring different natural isoform functions; generic binding is retained as non-core because the experiments do not establish a more specific molecular activity for FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: Original human FBN1 assays support association with LTBP1 constructs. Reason: Original human FBN1 assays support association with LTBP1 constructs. The recorded partner accessions are preserved without inferring different natural isoform functions; generic binding is retained as non-core because the experiments do not establish a more specific molecular activity for FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: Original human FBN1 assays support association with LTBP1 constructs. Reason: Original human FBN1 assays support association with LTBP1 constructs. The recorded partner accessions are preserved without inferring different natural isoform functions; generic binding is retained as non-core because the experiments do not establish a more specific molecular activity for FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: The original binding study includes human LTBP4 as a FBN1 interaction partner. Reason: The original binding study includes human LTBP4 as a FBN1 interaction partner. This is a matrix-targeting interaction, not direct binding to mature TGF-beta or a catalytic activity; retain the positive generic binding record as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15131124 MAGP-2 has multiple binding regions on fibrillins and has co... | KEEP AS NON CORE | Summary: The original paper tests human FBN1 with bovine MAGP1/P27424 as well as MAGP2. Reason: The original paper tests human FBN1 with bovine MAGP1/P27424 as well as MAGP2. The positive interaction is retained as non-core with its actual partner species; the MAGP2-focused title is not a reason to discard MAGP1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15131124 MAGP-2 has multiple binding regions on fibrillins and has co... | KEEP AS NON CORE | Summary: The original assays support human FBN1 interaction with bovine MAGP2/Q28022. Reason: The original assays support human FBN1 interaction with bovine MAGP2/Q28022. Retain this positive generic binding as non-core, distinguishing the tested partner species and recombinant binding from an inferred downstream molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15165854 Molecular structure and interaction of recombinant human typ... | UNDECIDED | Summary: The genuine abstract explicitly reports recombinant human collagenXVI interaction with FBN1. Reason: The genuine abstract explicitly reports recombinant human collagenXVI interaction with FBN1. The original operative binding experiment and its controls were inaccessible, so this specific interaction remains undecided; the collagen-focused title and an unread listed erratum do not establish misattribution. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15790312 Fibulin-5 interacts with fibrillin-1 molecules and microfibr... | KEEP AS NON CORE | Summary: Original solid-phase/inhibition assays directly test human tropoelastin with human FBN1 fragments. Reason: Original solid-phase/inhibition assays directly test human tropoelastin with human FBN1 fragments. Retain the positive generic interaction as non-core; binding to elastin does not make FBN1 an elastin-modifying enzyme. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15790312 Fibulin-5 interacts with fibrillin-1 molecules and microfibr... | KEEP AS NON CORE | Summary: Human fibulin5 binds FBN1 fragments in the original solid-phase assays. Reason: Human fibulin5 binds FBN1 fragments in the original solid-phase assays. A negative SPR orientation is explicitly discussed as assay dependent; the positive interaction is retained as non-core without inventing a catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17293099 LTBP-2 specifically interacts with the amino-terminal region... | KEEP AS NON CORE | Summary: Purified human LTBP2 binds human FBN1 in overlay/radioligand assays, and human LTBP1 is directly compared (Figure 5). Reason: Purified human LTBP2 binds human FBN1 in overlay/radioligand assays, and human LTBP1 is directly compared (Figure 5). Retain both recorded partners as non-core binding; competition is not itself a measured TGF-beta signaling response. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Human FBN1 N-terminal fragment rF23 binds the BMP10 prodomain. Reason: PMID:18339631, Results on fibrillinβpropeptide interactions, Figure 6 and Table 3, directly tests rF23 binding to the BMP10 prodomain. BMP binding describes the measured partner-specific interaction. The tested prodomain is not unrestricted free mature ligand, and this result alone does not assign receptor activation or a signaling direction. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Human FBN1 N-terminal fragment rF23 binds the BMP2 prodomain. Reason: PMID:18339631, Results on fibrillinβpropeptide interactions, Figure 6 and Table 3, directly tests rF23 binding to the BMP2 prodomain. BMP binding describes the measured partner-specific interaction. The tested prodomain is not unrestricted free mature ligand, and this result alone does not assign receptor activation or a signaling direction. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Human FBN1 N-terminal fragment rF23 binds the BMP4 prodomain. Reason: PMID:18339631, Results on fibrillinβpropeptide interactions, Figure 6 and Table 3, directly tests rF23 binding to the BMP4 prodomain. BMP binding describes the measured partner-specific interaction. The tested prodomain is not unrestricted free mature ligand, and this result alone does not assign receptor activation or a signaling direction. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Human FBN1 N-terminal fragment rF23 binds the BMP7 prodomain. Reason: PMID:18339631, Results on fibrillinβpropeptide interactions, Figure 6 and Table 3, directly tests rF23 binding to the BMP7 prodomain. BMP binding describes the measured partner-specific interaction. The tested prodomain is not unrestricted free mature ligand, and this result alone does not assign receptor activation or a signaling direction. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Human FBN1 N-terminal fragment rF23 binds the GDF5 prodomain. Reason: PMID:18339631, Results on fibrillinβpropeptide interactions, Figure 6 and Table 3, directly tests rF23 binding to the GDF5 prodomain. GDF5 is also named BMP14. BMP binding describes the measured partner-specific interaction. The tested prodomain is not unrestricted free mature ligand, and this result alone does not assign receptor activation or a signaling direction. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19349279 Latent transforming growth factor beta-binding proteins and ... | KEEP AS NON CORE | Summary: The original recombinant human binding assays support FBN1βfibulin4 interaction. Reason: The original recombinant human binding assays support FBN1βfibulin4 interaction. Retain positive generic binding as non-core; competition between matrix partners does not establish that all partners occupy FBN1 simultaneously. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19349279 Latent transforming growth factor beta-binding proteins and ... | KEEP AS NON CORE | Summary: Original human FBN1 assays separately test fibulin2, fibulin5, LTBP1 and LTBP4, matching the recorded partner set. Reason: Original human FBN1 assays separately test fibulin2, fibulin5, LTBP1 and LTBP4, matching the recorded partner set. Retain generic binding as non-core while preserving distinct affinities/competition and avoiding an obligatory simultaneous multi-protein complex. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19570982 Differential regulation of elastic fiber formation by fibuli... | KEEP AS NON CORE | Summary: The original human purified-protein assays support FBN1βfibulin4 binding by surface plasmon resonance and solid-phase measurements. Reason: The original human purified-protein assays support FBN1βfibulin4 binding by surface plasmon resonance and solid-phase measurements. Retain this matrix assembly interaction as non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19570982 Differential regulation of elastic fiber formation by fibuli... | KEEP AS NON CORE | Summary: Human unprocessed LOX binds FBN1 in a solid-phase assay; the SPR orientation was negative. Reason: Human unprocessed LOX binds FBN1 in a solid-phase assay; the SPR orientation was negative. The positive assay supports non-core binding, not lysyl-oxidase activity of FBN1 or an orientation-independent affinity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19570982 Differential regulation of elastic fiber formation by fibuli... | KEEP AS NON CORE | Summary: The original human fibulin5 solid-phase binding experiment is positive for FBN1. Reason: The original human fibulin5 solid-phase binding experiment is positive for FBN1. The source distinguishes assay-dependent binding and matrix assembly effects; retain the interaction as non-core rather than assigning fibulin or enzyme functions to FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21402694 ADAMTS10 protein interacts with fibrillin-1 and promotes its... | KEEP AS NON CORE | Summary: Purified human ADAMTS10 binds human FBN1 regions by overlay and reciprocal surface plasmon resonance. Reason: Purified human ADAMTS10 binds human FBN1 regions by overlay and reciprocal surface plasmon resonance. Retain the generic interaction as non-core; protease-related properties of ADAMTS10 do not establish protease activity of FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22355679 Essential role of microfibrillar-associated protein 4 in hum... | KEEP AS NON CORE | Summary: The human MFAP4 study reports association with FBN1 by co-immunoprecipitation and matrix-network experiments. Reason: The human MFAP4 study reports association with FBN1 by co-immunoprecipitation and matrix-network experiments. Retain positive generic binding as non-core while distinguishing co-association from purified binary binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24039232 Fibrillin-1 directly regulates osteoclast formation and func... | KEEP AS NON CORE | Summary: Soluble human FBN1 N-terminal half binds mouse RANKL/O35235 in calcium-dependent solid-phase assays. Reason: Soluble human FBN1 N-terminal half binds mouse RANKL/O35235 in calcium-dependent solid-phase assays. Shorter rF23 does not show that binding and has a different cellular effect; retain this exact partner context as non-core without assigning it to every fibrillin fragment or mature matrix. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25034023 Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self... | MODIFY | Summary: Human FBN1 fragments bind human plasma fibronectin. Reason: PMID:25034023 Methods 2.2 identifies human plasma fibronectin, and Results 3.3/Figure 3B describes binding of recombinant human FBN1 N- and C-terminal fragments to immobilized fibronectin. GO:0001968 fibronectin binding is the supported partner-specific molecular function. The heparin effect on fibrillin self-association is distinct from this positive interaction. The fragment assay does not establish a natural-splice-product-specific function or demonstrate a signaling consequence. Proposed replacements: fibronectin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25034023 Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self... | KEEP AS NON CORE | Summary: The original fragment assays test heterotypic human FBN1βFBN2 binding, separately from homotypic fibrillin interactions. Reason: The original fragment assays test heterotypic human FBN1βFBN2 binding, separately from homotypic fibrillin interactions. Retain the generic partner interaction as non-core without equating the paralogs or inferring isoform-specific functions. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26601954 Characterization of Microfibrillar-associated Protein 4 (MFA... | KEEP AS NON CORE | Summary: Purified human MFAP4 binds human FBN1 rF11/rF87 by surface plasmon resonance in the original study. Reason: Purified human MFAP4 binds human FBN1 rF11/rF87 by surface plasmon resonance in the original study. The interaction is calcium independent in that assay; separate mouse localization experiments do not change the human binary-binding identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The original HuRI PSI table contains explicit human FBN1βHGS/O14964 yeast-two-hybrid records. Reason: The original HuRI PSI table contains explicit human FBN1βHGS/O14964 yeast-two-hybrid records. Retain the verified screen interaction as non-core; yeast host, ORFeome constructs and partner accessions do not establish physiological colocalization, natural isoform specificity or the partner's molecular function in FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The original HuRI PSI table contains explicit human FBN1βGET4/Q7L5D6 yeast-two-hybrid records. Reason: The original HuRI PSI table contains explicit human FBN1βGET4/Q7L5D6 yeast-two-hybrid records. Retain the verified screen interaction as non-core; yeast host, ORFeome constructs and partner accessions do not establish physiological colocalization, natural isoform specificity or the partner's molecular function in FBN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The original HuRI PSI table contains explicit human FBN1βSGTB/Q96EQ0 yeast-two-hybrid records. Reason: The original HuRI PSI table contains explicit human FBN1βSGTB/Q96EQ0 yeast-two-hybrid records. Retain the verified screen interaction as non-core; yeast host, ORFeome constructs and partner accessions do not establish physiological colocalization, natural isoform specificity or the partner's molecular function in FBN1. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:24982166 C-terminal propeptide is required for fibrillin-1 secretion ... | ACCEPT | Summary: Original human-cell secretion/assembly assays detect extracellular FBN1 and distinguish secreted cleavage-site mutant from incorporation-competent protein. Reason: Original human-cell secretion/assembly assays detect extracellular FBN1 and distinguish secreted cleavage-site mutant from incorporation-competent protein. This supports an extracellular pool, without assigning endocrine activity or natural product identity to every recombinant construct. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | ACCEPT | Summary: The source paper demonstrates extracellular asprosin, while this imported annotation names the parent FBN1 gene product. Reason: This EXP annotation has raw product P35555, unlike the chain-specific IDA context at index 66. PMID:27087445 Figure 2 detects the released C-terminal product in human plasma and shows secretion in mammalian cell systems. This supports an extracellular location for an FBN1-derived product; it does not show an intact 2871-residue precursor circulating as the hormone or assign hormone activity to mature matrix fibrillin-1. The parent source identity remains exact. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Human aortic fractionation and the exact FBN1_HUMAN main-table records support extracellular detection. Reason: Human aortic fractionation and the exact FBN1_HUMAN main-table records support extracellular detection. The broader extracellular pool remains compatible with soluble and matrix-associated material; the separate ECM annotation uses colocalizes_with and is not an ultrastructural compartment assay. Supporting Evidence: |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | UNDECIDED | Summary: The human venous ECM-proteomics main paper was read, but no exact FBN1 supplementary record was recovered. Reason: The human venous ECM-proteomics main paper was read, but no exact FBN1 supplementary record was recovered. The accessible supplement archive contained main figures only; retain uncertainty about this particular source without inferring FBN1 absence. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:11461921 Interactions of fibrillin-1 with heparin/heparan sulfate, im... | ACCEPT | Summary: The original study directly detects FBN1 secreted into conditioned medium of normal human skin fibroblasts and tests that native material in binding assays. Reason: The original study directly detects FBN1 secreted into conditioned medium of normal human skin fibroblasts and tests that native material in binding assays. This establishes an extracellular pool separately from assembled microfibrils. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | ACCEPT | Summary: Asprosin is present in the extracellular compartment and human plasma. Reason: The raw P35555-PRO_0000436882 chain identity is explicit in the source-product join. PMID:27087445 Figure 2 and plasma immunoblot/ELISA Methods support the extracellular localization of this released product. Neither the mature fibrillin-1 matrix chain nor an unprocessed precursor is substituted for asprosin. Extracellular region is an appropriate current term; no obsolete extracellular-space replacement is proposed. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:34411563 POGLUT2 and POGLUT3 O-glucosylate multiple EGF repeats in fi... | ACCEPT | Summary: Endogenous FBN1 is immunoprecipitated from conditioned medium of primary human dermal fibroblasts in the original glycosylation study. Reason: Endogenous FBN1 is immunoprecipitated from conditioned medium of primary human dermal fibroblasts in the original glycosylation study. This directly supports extracellular secretion; FBN1 is the glycosylation substrate, not the glycosyltransferase. Supporting Evidence: |
| GO:0005576 extracellular region | IDA PMID:3536967 Fibrillin, a new 350-kD glycoprotein, is a component of extr... | ACCEPT | Summary: The original study immunoisolates fibrillin from human cell-conditioned medium and maps its deposited microfibrils. Reason: The original study immunoisolates fibrillin from human cell-conditioned medium and maps its deposited microfibrils. The secreted pool supplies information beyond the narrower assembled-matrix location. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: FBN1-derived proteins are secreted to the extracellular region. Reason: The combined subcellular-location and rat G3V9M6 evidence is consistent with target secretion and extracellular matrix incorporation. The indexed original PMID:17200203 Results detect fibrillin-1 in rat renal fibroblast supernatants; human secretion and processed soluble products independently support the broader extracellular location. It is not restricted to already assembled microfibrils. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:G3V9M6 SUPPORTS TRANSFER The combined subcellular-location and rat G3V9M6 evidence is consistent with target secretion and extracellular matrix incorporation. The indexed original PMID:17200203 Results detect fibrillin-1 in rat renal fibroblast supernatants; human secretion and processed soluble products independently support the broader extracellular location. It is not restricted to already assembled microfibrils. ensembl:ENSRNOP00000052876 SUPPORTS TRANSFER The combined subcellular-location and rat G3V9M6 evidence is consistent with target secretion and extracellular matrix incorporation. The indexed original PMID:17200203 Results detect fibrillin-1 in rat renal fibroblast supernatants; human secretion and processed soluble products independently support the broader extracellular location. It is not restricted to already assembled microfibrils. UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER The combined subcellular-location and rat G3V9M6 evidence is consistent with target secretion and extracellular matrix incorporation. The indexed original PMID:17200203 Results detect fibrillin-1 in rat renal fibroblast supernatants; human secretion and processed soluble products independently support the broader extracellular location. It is not restricted to already assembled microfibrils. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1592387 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Fibulin binds elastic fibres' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2161360 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-1592387 SUPPORTS TRANSFER The actual Reactome event 'Fibulin binds elastic fibres' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2161360 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129353 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Tropoelastin associates with microfibrils' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2129353 SUPPORTS TRANSFER The actual Reactome event 'Tropoelastin associates with microfibrils' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129357 | ACCEPT | Summary: The target-specific source supports extracellular localization. Reason: The actual Reactome event 'Fibrillin C-terminal processing' includes target-specific extracellular FBN1 entities (route 2159860 β 265402; 2159821 β 2159853; 2159858 β 2159838). This processing context includes both mature fibrillin-1 and the released C-terminal chain; retain extracellular region rather than assigning every state to microfibrils. The precursor coordinate 28 in this source is not adopted as a natural cleavage boundary. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129357 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin C-terminal processing' includes target-specific extracellular FBN1 entities (route 2159860 β 265402; 2159821 β 2159853; 2159858 β 2159838). This processing context includes both mature fibrillin-1 and the released C-terminal chain; retain extracellular region rather than assigning every state to microfibrils. The precursor coordinate 28 in this source is not adopted as a natural cleavage boundary. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129362 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Fibrillin microfibril assembly' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159821 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2129362 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin microfibril assembly' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159821 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129375 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Elastin cross-linking by lysyl oxidase' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2161254 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2129375 SUPPORTS TRANSFER The actual Reactome event 'Elastin cross-linking by lysyl oxidase' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2161254 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129385 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'MFAP2, MFAP5 bind microfibrils' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2129385 SUPPORTS TRANSFER The actual Reactome event 'MFAP2, MFAP5 bind microfibrils' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2161282 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Elastic fibres bind associated proteins' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2396077 β 2395337 β 2161360 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2161282 SUPPORTS TRANSFER The actual Reactome event 'Elastic fibres bind associated proteins' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2396077 β 2395337 β 2161360 β 2396329 β 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2328033 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Fibrillin-1 binds latent TGF-beta' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2328033 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin-1 binds latent TGF-beta' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2328037 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Fibrillin-1 binds integrins' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2328037 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin-1 binds integrins' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396399 | MODIFY | Summary: The source places mature fibrillin-1 in extracellular microfibrils. Reason: The actual Reactome event 'Fibrillins bind BMPs' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Reactome:R-HSA-2396399 SUPPORTS TRANSFER The actual Reactome event 'Fibrillins bind BMPs' contains target FBN1 entity 2159853, linked to UniProt P35555, in the microfibrillar assembly context (entity route 2159839 β 2159874 β 2159853). This supports the existing more specific microfibril location rather than only extracellular region. Event names do not assign FBN1 catalytic activity; in particular lysyl oxidase performs cross-linking, and LTBP-mediated latent TGFΞ² attachment is not direct binding to mature TGFΞ². Proposed replacements: microfibril |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2485148 | ACCEPT | Summary: The target-specific source supports extracellular localization. Reason: The actual Reactome event 'Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13' includes target-specific extracellular FBN1 entities (route 2159839 β 2159874 β 2159853; 2514788 β 2514812 β 2514785; 2514788 β 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2485148 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13' includes target-specific extracellular FBN1 entities (route 2159839 β 2159874 β 2159853; 2514788 β 2514812 β 2514785; 2514788 β 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2514772 | ACCEPT | Summary: The target-specific source supports extracellular localization. Reason: The actual Reactome event 'Fibrillin-1 degradation by MMP3, CTSK, CTSL2' includes target-specific extracellular FBN1 entities (route 2159874 β 2159853; 2514812 β 2514785; 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2514772 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin-1 degradation by MMP3, CTSK, CTSL2' includes target-specific extracellular FBN1 entities (route 2159874 β 2159853; 2514812 β 2514785; 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2514831 | ACCEPT | Summary: The target-specific source supports extracellular localization. Reason: The actual Reactome event 'Fibrillin-1 degradation by MMP14' includes target-specific extracellular FBN1 entities (route 2159874 β 2159853; 2514812 β 2514785; 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2514831 SUPPORTS TRANSFER The actual Reactome event 'Fibrillin-1 degradation by MMP14' includes target-specific extracellular FBN1 entities (route 2159874 β 2159853; 2514812 β 2514785; 2514812 β 2514817). The event includes intact substrate and cleaved states. Extracellular region covers these states without claiming that every released fragment remains part of matrix. FBN1 is the protease substrate, not the degrading enzyme; incomplete or inconsistent fragment coordinates are not new product definitions. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-265423 | ACCEPT | Summary: The target-specific source supports extracellular localization. Reason: The actual Reactome event 'Interaction of integrin alphaVbeta3 with Fibrillin' includes target-specific extracellular FBN1 entities (route 265402). The older receptor interaction entry contains a distinct FBN1 entity with legacy coordinates; its compartment supports extracellular localization, but those coordinates are not adopted as a natural product boundary. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-265423 SUPPORTS TRANSFER The actual Reactome event 'Interaction of integrin alphaVbeta3 with Fibrillin' includes target-specific extracellular FBN1 entities (route 265402). The older receptor interaction entry contains a distinct FBN1 entity with legacy coordinates; its compartment supports extracellular localization, but those coordinates are not adopted as a natural product boundary. |
| GO:0005604 basement membrane | IDA PMID:3536967 Fibrillin, a new 350-kD glycoprotein, is a component of extr... | KEEP AS NON CORE | Summary: Original human skin electron microscopy shows labeled FBN1 microfibrils approaching and inserting into the basal-lamina interface, while most lamina densa is unlabeled in that preparation. Reason: Original human skin electron microscopy shows labeled FBN1 microfibrils approaching and inserting into the basal-lamina interface, while most lamina densa is unlabeled in that preparation. Retain this basement-membrane-zone association as non-core; GO basement membrane includes the basal-lamina/reticular interface and the finding is not uniform lamina-densa residence. Supporting Evidence: |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Fibrillin-1 passes through the endoplasmic reticulum lumen during biosynthesis. Reason: Reactome R-HSA-8952289 contains FBN1 entity 8956726 through FAM20C substrate-set membership, with ER-lumen compartment and reference entity P35555. This is a transient secretory biosynthesis location rather than the site of mature matrix or hormone action. It assigns no kinase function to FBN1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: Reactome:R-HSA-8952289 SUPPORTS TRANSFER Reactome R-HSA-8952289 contains FBN1 entity 8956726 through FAM20C substrate-set membership, with ER-lumen compartment and reference entity P35555. This is a transient secretory biosynthesis location rather than the site of mature matrix or hormone action. It assigns no kinase function to FBN1. |
| GO:0006006 glucose metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Asprosin promotes glucose production through hormone signaling. Reason: GO:0006006 describes glucose metabolic reactions, whereas FBN1-derived asprosin is an extracellular regulator of those reactions. The target evidence used at PTN002778720 supports positive regulation of glucose metabolic process (GO:0010907), matching the direct PMID:27087445 refinement to positive regulation of glucose metabolic process. No glucose-metabolizing enzyme activity is assigned, and unresolved glucogenic replication limits remain explicit. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002778720 SUPPORTS TRANSFER GO:0006006 describes glucose metabolic reactions, whereas FBN1-derived asprosin is an extracellular regulator of those reactions. The target evidence used at PTN002778720 supports positive regulation of glucose metabolic process (GO:0010907), matching the direct PMID:27087445 refinement to positive regulation of glucose metabolic process. No glucose-metabolizing enzyme activity is assigned, and unresolved glucogenic replication limits remain explicit. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Proposed replacements: positive regulation of glucose metabolic process |
| GO:0006006 glucose metabolic process | IDA PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | MODIFY | Summary: Asprosin positively regulates glucose metabolism through endocrine signaling rather than executing glucose-metabolic chemical reactions. Reason: GO:0006006 denotes chemical reactions and pathways involving glucose. PMID:27087445 tests human asprosin as an extracellular signal that increases hepatic glucose output, including in isolated primary mouse hepatocytes; the hepatocyte metabolic machinery performs the chemical conversions. Replace this with GO:0010907, positive regulation of glucose metabolic process. This is a correction of the product role, not an is_a/part_of refinement and not a new annotation. The original study does not resolve all glucose flux into a single pathway such as gluconeogenesis, so that narrower replacement is not asserted. Exact target and typed ancestor/descendant comparisons against all 154 imported terms found no existing regulatory context. Proposed replacements: positive regulation of glucose metabolic process Supporting Evidence: |
| GO:0006954 inflammatory response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Tsk-associated inflammation does not establish a normal inflammatory effector role for FBN1. Reason: The Q61554 source PMID:17496220 reports inflammatory HDL, angiostatin and autoantibody changes in a mutant background and their reduction by D-4F. It does not show fibrillin-1 carrying out the immune or inflammatory machinery. This is a disease-context role conflation, not a wrong-gene claim. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED The Q61554 source PMID:17496220 reports inflammatory HDL, angiostatin and autoantibody changes in a mutant background and their reduction by D-4F. It does not show fibrillin-1 carrying out the immune or inflammatory machinery. This is a disease-context role conflation, not a wrong-gene claim. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED The Q61554 source PMID:17496220 reports inflammatory HDL, angiostatin and autoantibody changes in a mutant background and their reduction by D-4F. It does not show fibrillin-1 carrying out the immune or inflammatory machinery. This is a disease-context role conflation, not a wrong-gene claim. Supporting Evidence: |
| GO:0006955 immune response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The immune-response transfer describes consequences of the Tsk mutant background. Reason: PMID:17581616 actually studies BAFF/BAFF-receptor activity, B-cell changes and autoantibody production in Tsk mice. The measured immune actors are BAFF signaling and B cells; the Fbn1 mutation supplies a disease background. These Results do not establish normal human fibrillin-1 as immune-response machinery. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED PMID:17581616 actually studies BAFF/BAFF-receptor activity, B-cell changes and autoantibody production in Tsk mice. The measured immune actors are BAFF signaling and B cells; the Fbn1 mutation supplies a disease background. These Results do not establish normal human fibrillin-1 as immune-response machinery. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED PMID:17581616 actually studies BAFF/BAFF-receptor activity, B-cell changes and autoantibody production in Tsk mice. The measured immune actors are BAFF signaling and B cells; the Fbn1 mutation supplies a disease background. These Results do not establish normal human fibrillin-1 as immune-response machinery. Supporting Evidence: |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Oxidative-stress phenotypes in Tsk mice are not a demonstrated FBN1 stress-response function. Reason: The donor study PMID:17496220 measures oxidative/inflammatory vascular abnormalities and improvement by D-4F. An altered matrix can influence this physiology, but the operative evidence does not identify FBN1 as the actor responding to oxidative stress. The transfer promotes a downstream mutant phenotype to a normal molecular role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED The donor study PMID:17496220 measures oxidative/inflammatory vascular abnormalities and improvement by D-4F. An altered matrix can influence this physiology, but the operative evidence does not identify FBN1 as the actor responding to oxidative stress. The transfer promotes a downstream mutant phenotype to a normal molecular role. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED The donor study PMID:17496220 measures oxidative/inflammatory vascular abnormalities and improvement by D-4F. An altered matrix can influence this physiology, but the operative evidence does not identify FBN1 as the actor responding to oxidative stress. The transfer promotes a downstream mutant phenotype to a normal molecular role. Supporting Evidence: |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | TOO GENERAL | Summary: Generic signal transduction adds no scope beyond the specific retained asprosin signaling context. Reason: This logical inference is derived from hormone activity. The retained adenylate-cyclase-activating GPCR signaling context GO:0007189 reaches GO:0007165 through GO:0007188 and GO:0007186 by three is_a edges. The broad process is therefore true but adds no additional functional scope. Evidence for another receptor does not exclude the GPCR context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO:0005179 SUPPORTS TRANSFER This logical inference is derived from hormone activity. The retained adenylate-cyclase-activating GPCR signaling context GO:0007189 reaches GO:0007165 through GO:0007188 and GO:0007186 by three is_a edges. The broad process is therefore true but adds no additional functional scope. Evidence for another receptor does not exclude the GPCR context. |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IDA PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | ACCEPT | Summary: Human recombinant asprosin activates a cAMP/PKA signaling response with pharmacological support for a G-protein-coupled pathway. Reason: PMID:27087445 Figure 6 and Methods show cAMP/PKA responses to the human 2732β2871 reagent in mice and primary mouse hepatocytes, with inhibition of signaling/glucose output by suramin and of output by a PKA antagonist. These experiments support the annotated pathway but do not identify a receptor or prove exclusivity. PMID:31230984 provides mouse-ligand OLFR734/human-OR4M1 context, and PMID:41671088 adds PTPRF-dependent signaling without experimentally excluding the earlier GPCR route. The 2019 negative-replication report and the 2026 BLI reagent-label ambiguity are retained as source limitations; neither warrants silently replacing or removing this observed source-specific pathway. |
| GO:0007507 heart development | IMP PMID:15781745 Treatment of aortic disease in patients with Marfan syndrome... | UNDECIDED | Summary: The cited publication is a clinical aortic-disease review whose full operative text was inaccessible. Reason: The cited publication is a clinical aortic-disease review whose full operative text was inaccessible. The source-specific evidence for heart-development IMP cannot be assessed from citation metadata and management excerpts; no wrong-reference claim is inferred from the title. Supporting Evidence: |
| GO:0008104 intracellular protein localization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The donor phenotype concerns extracellular matrix deposition, not intracellular protein localization. Reason: In PMID:15610515, Tsk Fbn1 changes accompany altered extracellular fibulin-2/fibulin-5 matrices and elastic-fiber distribution. The operative Discussion places these proteins in hypodermal matrix and fibroblast extracellular deposits. That is not evidence that FBN1 transports or maintains proteins at intracellular destinations as required by GO:0008104. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED In PMID:15610515, Tsk Fbn1 changes accompany altered extracellular fibulin-2/fibulin-5 matrices and elastic-fiber distribution. The operative Discussion places these proteins in hypodermal matrix and fibroblast extracellular deposits. That is not evidence that FBN1 transports or maintains proteins at intracellular destinations as required by GO:0008104. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED In PMID:15610515, Tsk Fbn1 changes accompany altered extracellular fibulin-2/fibulin-5 matrices and elastic-fiber distribution. The operative Discussion places these proteins in hypodermal matrix and fibroblast extracellular deposits. That is not evidence that FBN1 transports or maintains proteins at intracellular destinations as required by GO:0008104. Supporting Evidence: |
| GO:0008201 heparin binding | IDA PMID:11461921 Interactions of fibrillin-1 with heparin/heparan sulfate, im... | KEEP AS NON CORE | Summary: Native human fibroblast-secreted FBN1 and recombinant human fragments bind heparin in controlled solid-phase and affinity-column assays. Reason: Native human fibroblast-secreted FBN1 and recombinant human fragments bind heparin in controlled solid-phase and affinity-column assays. Heparin models a sulfated glycosaminoglycan interaction; competition by selected heparan sulfate does not imply equal affinity for every physiological HS structure. Retain this positive molecular interaction as non-core. The original study deliberately uses heparin as an experimental glycosaminoglycan analog, and competition depends on the sulfation and presentation of the heparan-sulfate preparation. This is a supported ligand-specific affinity/modulation property, rather than an additional principal activity in the synthesis; it is not rejected or converted into a universal physiological heparan-sulfate interaction. Supporting Evidence: |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for the xenobiotic-response context remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the xenobiotic-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the xenobiotic-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the xenobiotic-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:0009612 response to mechanical stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Altered tissue mechanics do not establish fibrillin-1 as an active mechanical-response component. Reason: The saved operative PMID:16439805 Discussion concerns weak alveolar networks, altered collagen/microfibrillar architecture and mechanical forces that accelerate tissue failure in Tsk mice. This supports a structural load-bearing role and disease susceptibility; it does not establish a FBN1-mediated response mechanism to mechanical stimulation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED The saved operative PMID:16439805 Discussion concerns weak alveolar networks, altered collagen/microfibrillar architecture and mechanical forces that accelerate tissue failure in Tsk mice. This supports a structural load-bearing role and disease susceptibility; it does not establish a FBN1-mediated response mechanism to mechanical stimulation. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED The saved operative PMID:16439805 Discussion concerns weak alveolar networks, altered collagen/microfibrillar architecture and mechanical forces that accelerate tissue failure in Tsk mice. This supports a structural load-bearing role and disease susceptibility; it does not establish a FBN1-mediated response mechanism to mechanical stimulation. Supporting Evidence: |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Changes in other genes in Tsk disease models do not make FBN1 gene-expression machinery. Reason: The traced donor studies report altered transcripts or protein abundance downstream of mutant matrix, BAFF signaling, or CDH11 inhibition (PMID:16439805, PMID:17496220, PMID:17581616 and PMID:29112946). GO:0010467 concerns production of a gene product from its sequence. The actual Results do not show fibrillin-1 performing that machinery; extracellular signaling effects should be represented at their supported regulatory roles. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED The traced donor studies report altered transcripts or protein abundance downstream of mutant matrix, BAFF signaling, or CDH11 inhibition (PMID:16439805, PMID:17496220, PMID:17581616 and PMID:29112946). GO:0010467 concerns production of a gene product from its sequence. The actual Results do not show fibrillin-1 performing that machinery; extracellular signaling effects should be represented at their supported regulatory roles. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED The traced donor studies report altered transcripts or protein abundance downstream of mutant matrix, BAFF signaling, or CDH11 inhibition (PMID:16439805, PMID:17496220, PMID:17581616 and PMID:29112946). GO:0010467 concerns production of a gene product from its sequence. The actual Results do not show fibrillin-1 performing that machinery; extracellular signaling effects should be represented at their supported regulatory roles. |
| GO:0010467 gene expression | ISO PMID:20182440 Antagonistic effect of the matricellular signaling protein C... | MARK AS OVER ANNOTATED | Summary: The original study measures CCN3 expression changes after mutant FBN1/matrix perturbation and examines CCN3-dependent fibrillin deposition. Reason: The original study measures CCN3 expression changes after mutant FBN1/matrix perturbation and examines CCN3-dependent fibrillin deposition. These are downstream responses; they do not establish FBN1 as performing gene-to-RNA/protein expression steps. The broad process claim overextends the demonstrated extracellular scaffold/signaling relationship. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P35555 Β· FBN1 SOURCE WEAK OR INFERRED The exact recorded self source is preserved. Original PMID20182440 experiments were read; matrix perturbation and fibrillin deposition do not demonstrate the assigned gene-expression or collagen-organization role. This is a process-role assessment, not a claim of circularity, wrong orthology or target-specific evolutionary loss. Supporting Evidence: |
| GO:0030023 extracellular matrix constituent conferring elasticity | IC PMID:8120105 Structure and expression of fibrillin-2, a novel microfibril... | KEEP AS NON CORE | Summary: Retain the IC inference from microfibril structure: the original study supports FBN1 as a component of the tissue microfibrillar scaffold contributing to biomechanical properties. Reason: Retain the IC inference from microfibril structure: the original study supports FBN1 as a component of the tissue microfibrillar scaffold contributing to biomechanical properties. GO:0030023 concerns the matrix's ability to recoil after stretching, not an isolated-fibril recoil assay. This is a structural contribution to elastic matrices, distinct from claiming that FBN1 itself is elastin. Retain this true, context-dependent mechanical contribution as non-core while the structural core captures the broader scaffold function in both elastic and elastin-free matrices. A separate elasticity core would repeat that scaffold contribution rather than identify a separately resolved mechanism. This prioritization does not require an isolated-fibril force assay for an IC annotation, deny tissue recoil, or make the broader structural activity uninformative. Supporting Evidence: |
| GO:0030023 extracellular matrix constituent conferring elasticity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-1 contributes to the elastic properties of extracellular matrix. Reason: ARBA00086221 assigns GO:0030023 from a primate/FunFam condition set. Its biological conclusion agrees with the established microfibrillar scaffold contribution to tissue recoil discussed in PMID:8120105 and the elastin-free mesangial matrix in PMID:11012893. The term concerns matrix recoil, not proof that an isolated fibrillin molecule has elastin-like recoil. The exact rule conjunction was not independently rematched to the target. Retain the positive tissue-mechanical contribution as non-core consistently with the IC elasticity context. The broad structural core remains informative for elastin-free matrix support and growth-factor storage as well as elastic matrices. No redundant parent/child core pair is added, and the choice does not negate the rule's biological conclusion or demand that fibrillin itself have elastin-like single-molecule recoil. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00086221 SUPPORTS TRANSFER ARBA00086221 assigns GO:0030023 from a primate/FunFam condition set. Its biological conclusion agrees with the established microfibrillar scaffold contribution to tissue recoil discussed in PMID:8120105 and the elastin-free mesangial matrix in PMID:11012893. The term concerns matrix recoil, not proof that an isolated fibrillin molecule has elastin-like recoil. The exact rule conjunction was not independently rematched to the target. Retain the positive tissue-mechanical contribution as non-core consistently with the IC elasticity context. The broad structural core remains informative for elastin-free matrix support and growth-factor storage as well as elastic matrices. No redundant parent/child core pair is added, and the choice does not negate the rule's biological conclusion or demand that fibrillin itself have elastin-like single-molecule recoil. |
| GO:0030199 collagen fibril organization | ISO PMID:20182440 Antagonistic effect of the matricellular signaling protein C... | MARK AS OVER ANNOTATED | Summary: The original source measures fibrillin-network assembly and matrix-dependent CCN3 responses, not an FBN1-directed collagen-fibril organization mechanism. Reason: The original source measures fibrillin-network assembly and matrix-dependent CCN3 responses, not an FBN1-directed collagen-fibril organization mechanism. Fibrillin microfibrils and collagen fibrils are different assemblies; the ISO process assignment overextends these observations without negating a broader connective-tissue role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P35555 Β· FBN1 SOURCE WEAK OR INFERRED The exact recorded self source is preserved. Original PMID20182440 experiments were read; matrix perturbation and fibrillin deposition do not demonstrate the assigned gene-expression or collagen-organization role. This is a process-role assessment, not a claim of circularity, wrong orthology or target-specific evolutionary loss. Supporting Evidence: |
| GO:0030324 lung development | IEA GO_REF:0000107 | TOO GENERAL | Summary: The retained alveolar developmental context already covers lung development. Reason: GO:0048286 lung alveolus development is a direct part_of child of GO:0030324 lung development. The retained lung-alveolus-development context (GO:0048286; PMID:16439805) captures the mouse-supported structural contribution; no separate broader lung developmental activity is established by this same source. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER GO:0048286 lung alveolus development is a direct part_of child of GO:0030324 lung development. The retained lung-alveolus-development context (GO:0048286; PMID:16439805) captures the mouse-supported structural contribution; no separate broader lung developmental activity is established by this same source. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER GO:0048286 lung alveolus development is a direct part_of child of GO:0030324 lung development. The retained lung-alveolus-development context (GO:0048286; PMID:16439805) captures the mouse-supported structural contribution; no separate broader lung developmental activity is established by this same source. Supporting Evidence: |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Fibrillin-1 matrix restricts local availability of latent TGFΞ². Reason: The mouse Q61554 source PMID:20855508 directly compares Fbn1-null osteoblasts: less matrix LTBP1, increased activated TGFΞ² and signaling despite normal total TGFΞ² and transcript levels. This supports extracellular sequestration as a negative regulatory role, consistent with human FBN1βLTBP attachment evidence. It is context dependent and does not assert direct binding to free mature TGFΞ². Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER The mouse Q61554 source PMID:20855508 directly compares Fbn1-null osteoblasts: less matrix LTBP1, increased activated TGFΞ² and signaling despite normal total TGFΞ² and transcript levels. This supports extracellular sequestration as a negative regulatory role, consistent with human FBN1βLTBP attachment evidence. It is context dependent and does not assert direct binding to free mature TGFΞ². ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER The mouse Q61554 source PMID:20855508 directly compares Fbn1-null osteoblasts: less matrix LTBP1, increased activated TGFΞ² and signaling despite normal total TGFΞ² and transcript levels. This supports extracellular sequestration as a negative regulatory role, consistent with human FBN1βLTBP attachment evidence. It is context dependent and does not assert direct binding to free mature TGFΞ². |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Fibrillin-1 matrix restricts local availability of latent TGFΞ². Reason: The mouse Q61554 source PMID:20855508 directly compares Fbn1-null osteoblasts: less matrix LTBP1, increased activated TGFΞ² and signaling despite normal total TGFΞ² and transcript levels. This supports extracellular sequestration as a negative regulatory role, consistent with human FBN1βLTBP attachment evidence. It is context dependent and does not assert direct binding to free mature TGFΞ². Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER The mouse Q61554 source PMID:20855508 directly compares Fbn1-null osteoblasts: less matrix LTBP1, increased activated TGFΞ² and signaling despite normal total TGFΞ² and transcript levels. This supports extracellular sequestration as a negative regulatory role, consistent with human FBN1βLTBP attachment evidence. It is context dependent and does not assert direct binding to free mature TGFΞ². |
| GO:0030514 negative regulation of BMP signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Fibrillin-1 matrix can restrict BMP bioavailability and signaling. Reason: PMID:20855508 measures elevated BMP reporter activity and nuclear pSmad1/5/8 in Fbn1-null osteoblasts, with less matrix-bound BMP and more released BMP despite unchanged Bmp transcripts. Independent interference separates this from the TGFΞ² increase. This supports context-dependent BMP sequestration by FBN1 matrix, corroborated by human fibrillin binding to BMP prodomains; it does not generalize to every tissue or free mature BMP. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER PMID:20855508 measures elevated BMP reporter activity and nuclear pSmad1/5/8 in Fbn1-null osteoblasts, with less matrix-bound BMP and more released BMP despite unchanged Bmp transcripts. Independent interference separates this from the TGFΞ² increase. This supports context-dependent BMP sequestration by FBN1 matrix, corroborated by human fibrillin binding to BMP prodomains; it does not generalize to every tissue or free mature BMP. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER PMID:20855508 measures elevated BMP reporter activity and nuclear pSmad1/5/8 in Fbn1-null osteoblasts, with less matrix-bound BMP and more released BMP despite unchanged Bmp transcripts. Independent interference separates this from the TGFΞ² increase. This supports context-dependent BMP sequestration by FBN1 matrix, corroborated by human fibrillin binding to BMP prodomains; it does not generalize to every tissue or free mature BMP. |
| GO:0030514 negative regulation of BMP signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Fibrillin-1 matrix can restrict BMP bioavailability and signaling. Reason: PMID:20855508 measures elevated BMP reporter activity and nuclear pSmad1/5/8 in Fbn1-null osteoblasts, with less matrix-bound BMP and more released BMP despite unchanged Bmp transcripts. Independent interference separates this from the TGFΞ² increase. This supports context-dependent BMP sequestration by FBN1 matrix, corroborated by human fibrillin binding to BMP prodomains; it does not generalize to every tissue or free mature BMP. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER PMID:20855508 measures elevated BMP reporter activity and nuclear pSmad1/5/8 in Fbn1-null osteoblasts, with less matrix-bound BMP and more released BMP despite unchanged Bmp transcripts. Independent interference separates this from the TGFΞ² increase. This supports context-dependent BMP sequestration by FBN1 matrix, corroborated by human fibrillin binding to BMP prodomains; it does not generalize to every tissue or free mature BMP. |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Main Tables I/II directly identify FBN1_HUMAN in human aortic ECM-enriched fractions. Reason: Main Tables I/II directly identify FBN1_HUMAN in human aortic ECM-enriched fractions. Retain the source qualifier colocalizes_with and the biochemical-fraction scope rather than implying ultrastructural localization from mass spectrometry. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: The exact original Table 1 contains human FBN1 in ihPSF and HUES1 matrix preparations, with hPSF not detected and mouse feeder samples distinguished. Reason: The exact original Table 1 contains human FBN1 in ihPSF and HUES1 matrix preparations, with hPSF not detected and mouse feeder samples distinguished. This supports ECM association in the measured human cultures; it is not a claim of detection in every culture or a uniform fibrillar network. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | UNDECIDED | Summary: The original human endothelial ECM-proteomics Methods were read, but the FBN1 record in the relevant supplementary matrix tables could not be recovered. Reason: The original human endothelial ECM-proteomics Methods were read, but the FBN1 record in the relevant supplementary matrix tables could not be recovered. The source-specific target join remains unverified; this does not imply that FBN1 was absent or that its established ECM role is incorrect. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Additional File 2 row 5 explicitly identifies FBN1/P35555 in human colon/liver ECM-enriched preparations. Reason: Additional File 2 row 5 explicitly identifies FBN1/P35555 in human colon/liver ECM-enriched preparations. Preserve the principal-accession assignment and sample context while acknowledging the broader grouped-accession list; no every-peptide specificity or tumor-specific function is inferred. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: The original human atrial Table 1 explicitly lists Fibrillin-1 in guanidine input and glycoprotein enrichment. Reason: The original human atrial Table 1 explicitly lists Fibrillin-1 in guanidine input and glycoprotein enrichment. This supports ECM-proteomics detection with no accession/peptide detail claimed from that table; the blank glycopeptide column is not converted to a positive result. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | UNDECIDED | Summary: The human cell-derived ECM proteomics study was read, but its main Table I interchanges fibrillin/fibulin names beside FBN1/2 and FBLN1/2 symbols. Reason: The human cell-derived ECM proteomics study was read, but its main Table I interchanges fibrillin/fibulin names beside FBN1/2 and FBLN1/2 symbols. An exact supplemental accession join could not be recovered, so this source-specific record remains unresolved without declaring wrong-gene annotation or negative localization. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: The original supplementary workbook includes unambiguous human FBN1/P35555 ECM records as well as mixed fibrillin groups. Reason: The original supplementary workbook includes unambiguous human FBN1/P35555 ECM records as well as mixed fibrillin groups. The sole-FBN1 records support this localization in human breast/omental preparations; the grouped records and asterisked hydroxylation lists are not natural isoforms. Supporting Evidence: |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Fibrillin-1 is a structural extracellular matrix protein. Reason: The PTN000620536 source agrees with target human matrix localization and fibrillin microfibrils. Extracellular matrix remains useful beyond a single assembly state, including nonelastic scaffolds and growth-factor-associated matrix. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000620536 SUPPORTS TRANSFER The PTN000620536 source agrees with target human matrix localization and fibrillin microfibrils. Extracellular matrix remains useful beyond a single assembly state, including nonelastic scaffolds and growth-factor-associated matrix. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. |
| GO:0031012 extracellular matrix | IDA PMID:3536967 Fibrillin, a new 350-kD glycoprotein, is a component of extr... | ACCEPT | Summary: The original human biochemical and tissue experiments directly place fibrillin in extracellular matrix. Reason: The original human biochemical and tissue experiments directly place fibrillin in extracellular matrix. This general location accommodates its distribution across matrix structures and remains useful alongside microfibril localization. Supporting Evidence: |
| GO:0031012 extracellular matrix | IEA GO_REF:0000120 | ACCEPT | Summary: Combined ortholog evidence supports extracellular matrix localization. Reason: Mouse Q61554 and rat G3V9M6 source annotations agree with target human extracellular fibrillin matrices. Independently read PMID:11012893 shows fibrillin-1 in human, rat and mouse mesangial ECM, while PMID:24039232 identifies human bone matrix fibrillin. The rat donor record is traced in private provenance, but its operative original was not read; independent target evidence supports the location without declaring universal basement-membrane membership. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:G3V9M6 SUPPORTS TRANSFER Mouse Q61554 and rat G3V9M6 source annotations agree with target human extracellular fibrillin matrices. Independently read PMID:11012893 shows fibrillin-1 in human, rat and mouse mesangial ECM, while PMID:24039232 identifies human bone matrix fibrillin. The rat donor record is traced in private provenance, but its operative original was not read; independent target evidence supports the location without declaring universal basement-membrane membership. ensembl:ENSRNOP00000052876 SUPPORTS TRANSFER Mouse Q61554 and rat G3V9M6 source annotations agree with target human extracellular fibrillin matrices. Independently read PMID:11012893 shows fibrillin-1 in human, rat and mouse mesangial ECM, while PMID:24039232 identifies human bone matrix fibrillin. The rat donor record is traced in private provenance, but its operative original was not read; independent target evidence supports the location without declaring universal basement-membrane membership. UniProtKB:Q61554 SUPPORTS TRANSFER Mouse Q61554 and rat G3V9M6 source annotations agree with target human extracellular fibrillin matrices. Independently read PMID:11012893 shows fibrillin-1 in human, rat and mouse mesangial ECM, while PMID:24039232 identifies human bone matrix fibrillin. The rat donor record is traced in private provenance, but its operative original was not read; independent target evidence supports the location without declaring universal basement-membrane membership. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER Mouse Q61554 and rat G3V9M6 source annotations agree with target human extracellular fibrillin matrices. Independently read PMID:11012893 shows fibrillin-1 in human, rat and mouse mesangial ECM, while PMID:24039232 identifies human bone matrix fibrillin. The rat donor record is traced in private provenance, but its operative original was not read; independent target evidence supports the location without declaring universal basement-membrane membership. |
| GO:0032100 positive regulation of appetite | ISS GO_REF:0000024 | ACCEPT | Summary: The processed asprosin chain promotes appetite in the studied rodent setting. Reason: The original source explicitly names mouse Q61554-PRO_0000436884, and the raw human annotation identifies P35555-PRO_0000436882; the seeder omitted that product field, so the exact sidecar join is retained. PMID:29106398 tests recombinant human FBN1 residues 2732β2871 in mouse feeding and neuronal assays, including rescue and AgRP-neuron activation. This supports the endocrine contribution rather than a role for mature matrix fibrillin-1. The current exact processed-chain QuickGO query returned no rows; historical product provenance is retained, not silently replaced. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554-PRO_0000436884 SUPPORTS TRANSFER The original source explicitly names mouse Q61554-PRO_0000436884, and the raw human annotation identifies P35555-PRO_0000436882; the seeder omitted that product field, so the exact sidecar join is retained. PMID:29106398 tests recombinant human FBN1 residues 2732β2871 in mouse feeding and neuronal assays, including rescue and AgRP-neuron activation. This supports the endocrine contribution rather than a role for mature matrix fibrillin-1. The current exact processed-chain QuickGO query returned no rows; historical product provenance is retained, not silently replaced. Supporting Evidence: |
| GO:0033198 response to ATP | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for the ATP-response context remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the ATP-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the ATP-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the ATP-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:0033627 cell adhesion mediated by integrin | IDA PMID:12807887 Cell adhesion to fibrillin-1 molecules and microfibrils is m... | ACCEPT | Summary: Human FBN1 RGD-containing fragments support cell attachment/spreading with integrin-blocking and RGD-mutant controls. Reason: Human FBN1 RGD-containing fragments support cell attachment/spreading with integrin-blocking and RGD-mutant controls. FBN1 supplies the extracellular adhesive ligand, so it contributes directly to integrin-mediated adhesion rather than merely causing an indirect phenotype. Supporting Evidence: |
| GO:0033627 cell adhesion mediated by integrin | IDA PMID:17158881 alphaVbeta6 is a novel receptor for human fibrillin-1. Compa... | ACCEPT | Summary: Mature fibrillin-1 supports integrin-mediated cell adhesion. Reason: PMID:17158881 reports positive human FBN1 adhesion in its abstract, but its operative construct and cell-assay details remain inaccessible. The gene-level adhesion contribution is independently demonstrated by human FBN1-fragment/antibody experiments in PMID:12807887 and structural, purified-integrin and cell-adhesion experiments in PMID:15062093. Fibrillin-1 supplies the extracellular adhesive ligand; the cells execute the downstream attachment and signaling responses. Accept that contribution without transferring a specific unread alphaVbeta6 mechanism or claiming identical responses in every cell type. |
| GO:0042311 vasodilation | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for vasodilation remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish vasodilation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish vasodilation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish vasodilation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:0042593 glucose homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: Asprosin contributes to glucose homeostasis through endocrine signaling. Reason: The PTN002778720 inference is consistent with human asprosin ligand experiments affecting glucose output and blood glucose. This is an endocrine homeostatic role, not enzymatic glucose metabolism. Unresolved replication of glucogenic activity across laboratories and preparations remains explicit in the whole-paper assessment. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002778720 SUPPORTS TRANSFER The PTN002778720 inference is consistent with human asprosin ligand experiments affecting glucose output and blood glucose. This is an endocrine homeostatic role, not enzymatic glucose metabolism. Unresolved replication of glucogenic activity across laboratories and preparations remains explicit in the whole-paper assessment. The saved PAINT material establishes the family and literal node/term joins, but topology/MSA retrieval failed; target descent was not independently reconstructed. Human self-donor evidence is legitimate, not circular. |
| GO:0042593 glucose homeostasis | IDA PMID:27087445 Asprosin, a Fasting-Induced Glucogenic Protein Hormone. | ACCEPT | Summary: The asprosin cleavage product contributes to glucose homeostasis through its glucogenic hormone activity. Reason: The raw annotation identifies P35555-PRO_0000436882. PMID:27087445 combines human plasma/genetic observations with human recombinant asprosin administration and mouse-hepatocyte responses, linking the released chain to regulation of circulating glucose. This is a signaling contribution to glucose homeostasis, not direct glucose-metabolic catalysis by fibrillin-1. Reported negative replication with other protein preparations and later receptor studies limit universal claims about dose, preparation and receptor usage; they do not erase the convergent evidence for this product-level role. |
| GO:0042802 identical protein binding | IPI PMID:18448684 Biogenesis of extracellular microfibrils: Multimerization of... | ACCEPT | Summary: Human FBN1 C-terminal multimers bind N-terminal FBN1 fragments, with domain controls, biochemical measurements and assembly experiments. Reason: Human FBN1 C-terminal multimers bind N-terminal FBN1 fragments, with domain controls, biochemical measurements and assembly experiments. Specific self-association is part of the microfibril assembly mechanism rather than an uninformative generic partner interaction. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:24035709 Structure of the fibrillin-1 N-terminal domains suggests tha... | ACCEPT | Summary: Human N-terminal FUN-EGF3 binds C-terminal cbEGF41β43 in the original pull-down experiments with unrelated-domain controls. Reason: Human N-terminal FUN-EGF3 binds C-terminal cbEGF41β43 in the original pull-down experiments with unrelated-domain controls. This supports FBN1 self-association; fragment and NMR limitations do not justify claiming a resolved complete-fibril complex structure. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:25034023 Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self... | ACCEPT | Summary: The original solid-phase assays directly test homotypic human FBN1 interactions and their modulation by heparin, separately from FBN1βFBN2 and fibronectin binding. Reason: The original solid-phase assays directly test homotypic human FBN1 interactions and their modulation by heparin, separately from FBN1βFBN2 and fibronectin binding. Specific self-association contributes to the matrix assembly mechanism. Supporting Evidence: |
| GO:0043010 camera-type eye development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-1 contributes matrix structure during eye development. Reason: ARBA00084629 assigns this developmental term. Independent human PMID:25406291 uses specific antibodies to demonstrate stage- and structure-dependent FBN1 matrix in fetal and juvenile eyes, including the zonule. Retain a contextual structural contribution, not a unique eye-patterning activity; the study is localization/IEP evidence and does not establish FBN1-specific causal morphogenesis. The exact ARBA conjunction was not independently rematched. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084629 SUPPORTS TRANSFER ARBA00084629 assigns this developmental term. Independent human PMID:25406291 uses specific antibodies to demonstrate stage- and structure-dependent FBN1 matrix in fetal and juvenile eyes, including the zonule. Retain a contextual structural contribution, not a unique eye-patterning activity; the study is localization/IEP evidence and does not establish FBN1-specific causal morphogenesis. The exact ARBA conjunction was not independently rematched. Supporting Evidence: |
| GO:0043010 camera-type eye development | IEP PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Reason: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Retain the IEP developmental context as non-core; expression/localization is not a gene-specific perturbation establishing each morphogenetic step, and the paper's fibrillin isoforms are paralogs rather than demonstrated FBN1 splice products. Supporting Evidence: |
| GO:0043588 skin development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The donor study concerns pathological skin fibrosis rather than normal skin development. Reason: PMID:17581616 demonstrates BAFF-dependent B-cell/cytokine effects and reduced hypodermal fibrosis after BAFF blockade in Tsk mice. This does not establish a normal FBN1 skin-development program. The structural matrix role is real, but the specific donor transfers a disease-remodeling outcome to developmental participation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED PMID:17581616 demonstrates BAFF-dependent B-cell/cytokine effects and reduced hypodermal fibrosis after BAFF blockade in Tsk mice. This does not establish a normal FBN1 skin-development program. The structural matrix role is real, but the specific donor transfers a disease-remodeling outcome to developmental participation. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED PMID:17581616 demonstrates BAFF-dependent B-cell/cytokine effects and reduced hypodermal fibrosis after BAFF blockade in Tsk mice. This does not establish a normal FBN1 skin-development program. The structural matrix role is real, but the specific donor transfers a disease-remodeling outcome to developmental participation. Supporting Evidence: |
| GO:0044877 protein-containing complex binding | IPI PMID:15062093 Structure of the integrin binding fragment from fibrillin-1 ... | TOO GENERAL | Summary: The same original fragment/integrin experiment supports the retained integrin-binding annotation. Reason: The same original fragment/integrin experiment supports the retained integrin-binding annotation. GO:0005178 is an explicit is_a child of protein-containing complex binding, so this parent adds no interaction coverage in this source context; its positive biology is preserved by the more informative term. Supporting Evidence: |
| GO:0045446 endothelial cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for endothelial cell differentiation remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish endothelial cell differentiation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish endothelial cell differentiation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish endothelial cell differentiation from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:0045671 negative regulation of osteoclast differentiation | IDA PMID:24039232 Fibrillin-1 directly regulates osteoclast formation and func... | TOO GENERAL | Summary: The original soluble-human-FBN1 fragment experiments support the retained negative regulation of osteoclast development annotation. Reason: The original soluble-human-FBN1 fragment experiments support the retained negative regulation of osteoclast development annotation. GO:2001205 is an explicit is_a child of GO:0045671, so this broader differentiation parent adds no coverage; the positive fragment-specific mouse-cell evidence is preserved. Supporting Evidence: |
| GO:0045671 negative regulation of osteoclast differentiation | IEA GO_REF:0000107 | TOO GENERAL | Summary: The more specific retained osteoclast-development term covers this inhibition. Reason: GO:2001205 negative regulation of osteoclast development is a direct is_a child of GO:0045671. The retained negative-regulation-of-osteoclast-development context (GO:2001205) preserves the soluble-fragment evidence from PMID:24039232. The broader term adds no separate scope; the source does not imply that all assembled fibrillin matrix inhibits differentiation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER GO:2001205 negative regulation of osteoclast development is a direct is_a child of GO:0045671. The retained negative-regulation-of-osteoclast-development context (GO:2001205) preserves the soluble-fragment evidence from PMID:24039232. The broader term adds no separate scope; the source does not imply that all assembled fibrillin matrix inhibits differentiation. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER GO:2001205 negative regulation of osteoclast development is a direct is_a child of GO:0045671. The retained negative-regulation-of-osteoclast-development context (GO:2001205) preserves the soluble-fragment evidence from PMID:24039232. The broader term adds no separate scope; the source does not imply that all assembled fibrillin matrix inhibits differentiation. Supporting Evidence: |
| GO:0048048 embryonic eye morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Embryonic ocular fibrillin matrix provides a contextual developmental contribution. Reason: The live ARBA00090262 rule assigns embryonic eye morphogenesis. Human PMID:25406291 maps FBN1 in fetal ocular matrix and developing ciliary/lens-associated structures. Retain the contextual matrix contribution with the same observational boundary as the direct IEP annotation: this is not a demonstrated FBN1-specific patterning mechanism, and the exact rule conjunction was not independently rematched. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00090262 SUPPORTS TRANSFER The live ARBA00090262 rule assigns embryonic eye morphogenesis. Human PMID:25406291 maps FBN1 in fetal ocular matrix and developing ciliary/lens-associated structures. Retain the contextual matrix contribution with the same observational boundary as the direct IEP annotation: this is not a demonstrated FBN1-specific patterning mechanism, and the exact rule conjunction was not independently rematched. Supporting Evidence: |
| GO:0048048 embryonic eye morphogenesis | IEP PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Reason: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Retain the IEP developmental context as non-core; expression/localization is not a gene-specific perturbation establishing each morphogenetic step, and the paper's fibrillin isoforms are paralogs rather than demonstrated FBN1 splice products. Supporting Evidence: |
| GO:0048050 post-embryonic eye morphogenesis | IEP PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Reason: The original study maps stage- and structure-dependent FBN1 protein expression in human fetal and juvenile eyes, including the zonule. Retain the IEP developmental context as non-core; expression/localization is not a gene-specific perturbation establishing each morphogenetic step, and the paper's fibrillin isoforms are paralogs rather than demonstrated FBN1 splice products. Supporting Evidence: |
| GO:0048251 elastic fiber assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Fibrillin-1 microfibrils contribute the scaffold for elastic-fiber assembly. Reason: The mouse source PMID:15610515 associates the Tsk Fbn1 alteration with disorganized elastic-fiber and fibulin matrices. This agrees with actual human/bovine microfibril localization and target-specific elastic-fiber Reactome assemblies. FBN1 contributes structure required by assembly; lysyl oxidase and other proteins perform distinct enzymatic or organizing roles. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER The mouse source PMID:15610515 associates the Tsk Fbn1 alteration with disorganized elastic-fiber and fibulin matrices. This agrees with actual human/bovine microfibril localization and target-specific elastic-fiber Reactome assemblies. FBN1 contributes structure required by assembly; lysyl oxidase and other proteins perform distinct enzymatic or organizing roles. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER The mouse source PMID:15610515 associates the Tsk Fbn1 alteration with disorganized elastic-fiber and fibulin matrices. This agrees with actual human/bovine microfibril localization and target-specific elastic-fiber Reactome assemblies. FBN1 contributes structure required by assembly; lysyl oxidase and other proteins perform distinct enzymatic or organizing roles. |
| GO:0048286 lung alveolus development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fibrillin microfibrils contribute to normal alveolar structure during lung development. Reason: The mouse Q61554 source PMID:16439805 studies developmental emphysema, abnormal alveolar architecture and weakened matrix in Tsk mice. Retain a contextual structural contribution to alveolar development, rather than claiming FBN1 specifies alveolar cell fates. The saved original Discussion supports matrix failure and tissue architecture; it does not establish a separate morphogenetic signaling mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61554 SUPPORTS TRANSFER The mouse Q61554 source PMID:16439805 studies developmental emphysema, abnormal alveolar architecture and weakened matrix in Tsk mice. Retain a contextual structural contribution to alveolar development, rather than claiming FBN1 specifies alveolar cell fates. The saved original Discussion supports matrix failure and tissue architecture; it does not establish a separate morphogenetic signaling mechanism. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER The mouse Q61554 source PMID:16439805 studies developmental emphysema, abnormal alveolar architecture and weakened matrix in Tsk mice. Retain a contextual structural contribution to alveolar development, rather than claiming FBN1 specifies alveolar cell fates. The saved original Discussion supports matrix failure and tissue architecture; it does not establish a separate morphogenetic signaling mechanism. Supporting Evidence: |
| GO:0070328 triglyceride homeostasis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The Tsk lipid phenotype does not establish a specific FBN1 triglyceride-homeostasis function. Reason: PMID:17496220 reports systemic lipid/inflammatory profiles in a mutant vascular model and treatment effects. Those observations do not show a FBN1 product executing triglyceride homeostasis. The separately supported asprosin glucose/appetite functions do not automatically validate every lipid phenotype transferred from this disease context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED PMID:17496220 reports systemic lipid/inflammatory profiles in a mutant vascular model and treatment effects. Those observations do not show a FBN1 product executing triglyceride homeostasis. The separately supported asprosin glucose/appetite functions do not automatically validate every lipid phenotype transferred from this disease context. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED PMID:17496220 reports systemic lipid/inflammatory profiles in a mutant vascular model and treatment effects. Those observations do not show a FBN1 product executing triglyceride homeostasis. The separately supported asprosin glucose/appetite functions do not automatically validate every lipid phenotype transferred from this disease context. Supporting Evidence: |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: TGFΞ²-induced FBN1 expression is an output of a cellular response. Reason: PMID:11012893 directly measures increased Fbn1 mRNA after TGFΞ² in rat mesangial cells, with analogous human and mouse expression changes. That establishes regulated expression of a matrix component, not FBN1 executing the TGFΞ² response machinery. Its independently demonstrated extracellular negative regulation of TGFΞ² availability is retained at the appropriate term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:G3V9M6 SOURCE WEAK OR INFERRED PMID:11012893 directly measures increased Fbn1 mRNA after TGFΞ² in rat mesangial cells, with analogous human and mouse expression changes. That establishes regulated expression of a matrix component, not FBN1 executing the TGFΞ² response machinery. Its independently demonstrated extracellular negative regulation of TGFΞ² availability is retained at the appropriate term. ensembl:ENSRNOP00000052876 SOURCE WEAK OR INFERRED PMID:11012893 directly measures increased Fbn1 mRNA after TGFΞ² in rat mesangial cells, with analogous human and mouse expression changes. That establishes regulated expression of a matrix component, not FBN1 executing the TGFΞ² response machinery. Its independently demonstrated extracellular negative regulation of TGFΞ² availability is retained at the appropriate term. |
| GO:0071731 response to nitric oxide | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for the nitric-oxide response remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the nitric-oxide response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the nitric-oxide response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the nitric-oxide response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:0072359 circulatory system development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-1 supplies structural matrix in the developing circulation. Reason: The live ARBA00027039 rule assigns circulatory system development. Independently read human fetal aorta localization in PMID:8120105 and vascular/mesangial matrix in PMID:11012893 support a contextual structural contribution. This is not evidence that FBN1 is an endothelial differentiation factor or an angiogenic signaling enzyme. No exact target-specific ARBA condition match or causal developmental experiment is claimed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00027039 SUPPORTS TRANSFER The live ARBA00027039 rule assigns circulatory system development. Independently read human fetal aorta localization in PMID:8120105 and vascular/mesangial matrix in PMID:11012893 support a contextual structural contribution. This is not evidence that FBN1 is an endothelial differentiation factor or an angiogenic signaling enzyme. No exact target-specific ARBA condition match or causal developmental experiment is claimed. |
| GO:0097006 regulation of plasma lipoprotein particle levels | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Disease-associated plasma lipoprotein changes do not establish FBN1 as their regulator. Reason: The Q61554 evidence PMID:17496220 measures proinflammatory HDL and lipid profiles in Tsk mice, with effects of D-4F. The actual measured intervention is an apolipoprotein mimetic and the model has broad matrix disease; the evidence does not isolate normal FBN1 as a plasma-lipoprotein regulator. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q61554 SOURCE WEAK OR INFERRED The Q61554 evidence PMID:17496220 measures proinflammatory HDL and lipid profiles in Tsk mice, with effects of D-4F. The actual measured intervention is an apolipoprotein mimetic and the model has broad matrix disease; the evidence does not isolate normal FBN1 as a plasma-lipoprotein regulator. ensembl:ENSMUSP00000099524 SOURCE WEAK OR INFERRED The Q61554 evidence PMID:17496220 measures proinflammatory HDL and lipid profiles in Tsk mice, with effects of D-4F. The actual measured intervention is an apolipoprotein mimetic and the model has broad matrix disease; the evidence does not isolate normal FBN1 as a plasma-lipoprotein regulator. Supporting Evidence: |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:11886530 Assembly of epithelial cell fibrillins. | UNDECIDED | Summary: The genuine abstract positively reports FBN1 throughout epithelial lamina densa, but the original operative assay and figures could not be accessed. Reason: The genuine abstract positively reports FBN1 throughout epithelial lamina densa, but the original operative assay and figures could not be accessed. Preserve this source-specific uncertainty; different papers' lamina-sparing results do not establish universal absence from basement membrane. Supporting Evidence: |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:15657057 Microfibrils at basement membrane zones interact with perlec... | KEEP AS NON CORE | Summary: The original human basement-membrane-zone localization and perlecan-binding experiments support FBN1 in the noncollagenous interface microfibrils. Reason: The original human basement-membrane-zone localization and perlecan-binding experiments support FBN1 in the noncollagenous interface microfibrils. Retain the location as non-core without extending it to uniform occupancy of every basement-membrane stratum or tissue. Supporting Evidence: |
| GO:0140144 non-collagenous component of basement membrane | IEA GO_REF:0000117 | UNDECIDED | Summary: Basement-membrane localization is source- and tissue-dependent. Reason: ARBA00096893 assigns non-collagenous component of basement membrane. PMID:11012893 localizes glomerular FBN1 to adjacent mesangial matrix while sparing the glomerular basement membrane, but PMID:11886530 explicitly reports FBN1 in dermalβepidermal lamina densa. The latter original operative body was not accessible, so its exact ultrastructural/nonfibrillar context cannot be checked here. Do not infer global absence or reject this rule from the kidney study alone. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: ARBA:ARBA00096893 UNRESOLVED ARBA00096893 assigns non-collagenous component of basement membrane. PMID:11012893 localizes glomerular FBN1 to adjacent mesangial matrix while sparing the glomerular basement membrane, but PMID:11886530 explicitly reports FBN1 in dermalβepidermal lamina densa. The latter original operative body was not accessible, so its exact ultrastructural/nonfibrillar context cannot be checked here. Do not infer global absence or reject this rule from the kidney study alone. |
| GO:0140149 non-collagenous component of interstitial matrix | TAS PMID:36399478 MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge d... | KEEP AS NON CORE | Summary: Fibrillin-1 is a non-collagenous constituent of interstitial microfibrillar matrix. Reason: The original MatrisomeDB methodology in PMID:36399478 was read, but its exact FBN1 database record remains unverified. The compartment claim is independently supported by the actual human tissue experiments in PMID:3536967: collagenase-resistant fibrillin, dermal connective tissue fibers, and immunogold-labeled microfibrils among unlabeled collagen, including elastin-associated and elastin-free bundles. These observations establish a noncollagenous interstitial-matrix constituent, rather than only generic extracellular localization. Retain this anatomical context as non-core; do not claim that the inaccessible MatrisomeDB target join was recovered or that fibrillin uniformly occupies basement-membrane lamina densa. |
| GO:1901652 response to peptide | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for the peptide-response context remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the peptide-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the peptide-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the peptide-response context from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:1905144 response to acetylcholine | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact donor evidence for the acetylcholine response remains insufficiently accessible. Reason: The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the acetylcholine response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q61554 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the acetylcholine response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. ensembl:ENSMUSP00000099524 UNRESOLVED The mouse Q61554 term is traced to PMID:12485443. Its accessible original record describes vascular responses in Tsk aorta, but the complete operative body needed to distinguish the acetylcholine response from downstream mutant effects was not recovered. The annotation is not rejected from its abstract. Independent Tsk disease studies do not verify this exact source context. Supporting Evidence: |
| GO:1990314 cellular response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IGF-I-induced fibrillin synthesis is a response output, not a demonstrated response-executing role. Reason: The original PMID:17200203 Results quantify increased fibrillin-1 synthesis/secretion in rat renal fibroblasts after decorin or IGF-I, blocked through IGF-I receptor signaling. FBN1 is the regulated product; decorin, IGF-I receptor and downstream signaling components execute the response. This does not justify transferring GO:1990314 to human FBN1 as a functional process assignment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:G3V9M6 SOURCE WEAK OR INFERRED The original PMID:17200203 Results quantify increased fibrillin-1 synthesis/secretion in rat renal fibroblasts after decorin or IGF-I, blocked through IGF-I receptor signaling. FBN1 is the regulated product; decorin, IGF-I receptor and downstream signaling components execute the response. This does not justify transferring GO:1990314 to human FBN1 as a functional process assignment. ensembl:ENSRNOP00000052876 SOURCE WEAK OR INFERRED The original PMID:17200203 Results quantify increased fibrillin-1 synthesis/secretion in rat renal fibroblasts after decorin or IGF-I, blocked through IGF-I receptor signaling. FBN1 is the regulated product; decorin, IGF-I receptor and downstream signaling components execute the response. This does not justify transferring GO:1990314 to human FBN1 as a functional process assignment. Supporting Evidence: |
| GO:2001205 negative regulation of osteoclast development | IDA PMID:24039232 Fibrillin-1 directly regulates osteoclast formation and func... | KEEP AS NON CORE | Summary: Soluble human FBN1 N-terminal fragments inhibit mouse osteoclast formation in cell and animal assays. Reason: Soluble human FBN1 N-terminal fragments inhibit mouse osteoclast formation in cell and animal assays. The N-terminal half binds RANKL, whereas shorter rF23 uses a different calcium/NFAT-associated mechanism; mineral-immobilized N-terminal half lacks the inhibitory effect. Retain this conditional fragment-associated process as non-core without generalizing it to all mature matrix. Supporting Evidence: |
| GO:2001205 negative regulation of osteoclast development | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Soluble N-terminal FBN1 fragments can inhibit osteoclast development. Reason: The combined mouse Q61554/ARBA00088112 inference is supported by PMID:24039232 experiments with human recombinant FBN1 fragments on mouse osteoclast systems. The N-terminal half binds RANKL, while a shorter fragment affects calcium/NFATc1 by a different mechanism. Mineral-immobilized N-terminal material did not inhibit differentiation. Keep this contextual fragment function without defining an unestablished natural active cleavage product or generalizing to all fibrillin matrix. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00088112 SUPPORTS TRANSFER The combined mouse Q61554/ARBA00088112 inference is supported by PMID:24039232 experiments with human recombinant FBN1 fragments on mouse osteoclast systems. The N-terminal half binds RANKL, while a shorter fragment affects calcium/NFATc1 by a different mechanism. Mineral-immobilized N-terminal material did not inhibit differentiation. Keep this contextual fragment function without defining an unestablished natural active cleavage product or generalizing to all fibrillin matrix. UniProtKB:Q61554 SUPPORTS TRANSFER The combined mouse Q61554/ARBA00088112 inference is supported by PMID:24039232 experiments with human recombinant FBN1 fragments on mouse osteoclast systems. The N-terminal half binds RANKL, while a shorter fragment affects calcium/NFATc1 by a different mechanism. Mineral-immobilized N-terminal material did not inhibit differentiation. Keep this contextual fragment function without defining an unestablished natural active cleavage product or generalizing to all fibrillin matrix. ensembl:ENSMUSP00000099524 SUPPORTS TRANSFER The combined mouse Q61554/ARBA00088112 inference is supported by PMID:24039232 experiments with human recombinant FBN1 fragments on mouse osteoclast systems. The N-terminal half binds RANKL, while a shorter fragment affects calcium/NFATc1 by a different mechanism. Mineral-immobilized N-terminal material did not inhibit differentiation. Keep this contextual fragment function without defining an unestablished natural active cleavage product or generalizing to all fibrillin matrix. Supporting Evidence: |
Loading supporting contentβ¦
Download this section (compressed HTML)Experiment: Compare blinded human asprosin residues 2732β2871 preparations from bacterial and mammalian systems across laboratories. Verify sequence, tag, glycosylation, aggregation and endotoxin; measure hepatocyte cAMP, PKA and glucose output with matched vehicle and tag controls.
Hypothesis: A measurable preparation feature or assay condition accounts for at least part of the discrepant glucogenic responses.
Experiment: Using sequence-verified ligand and explicitly matched human or mouse receptors, compare OLFR734/OR4M1 and PTPRF single and combined perturbations with rescue, orthogonal binding assays and glucose-output measurements. Confirm the proteins used in the disputed BLI reagent record before comparing affinities.
Hypothesis: The reported receptor routes make distinguishable, potentially overlapping contributions that depend on ligand preparation, species or cellular context.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The inspected asprosin reports do not resolve why glucogenic activity differs among recombinant preparations and laboratories, including negative mammalian-expression and hydrodynamic-expression experiments.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Human asprosin increased hepatocyte cAMP/PKA and glucose output in the 2016 study. The 2019 replication report tested several expression and administration approaches, so failed replication cannot be reduced to one inactive bacterial His-tagged preparation.
Significance: Preparation-dependent activity limits quantitative physiological and receptor comparisons.
What would resolve it: Compare sequence-verified preparations across laboratories with matched aggregation, modification, tag and contaminant measurements and blinded hepatocyte assays.
Provenance (the field's own admissions):
Gap: The inspected studies do not resolve the relative contributions of the reported OLFR734/OR4M1 and PTPRF routes to glucogenic signaling by verified human asprosin under matched conditions.
OPEN BIOLOGYCURATION RESIDUAL_SUBGAP
What is known: The 2019 receptor study used mouse ligand; the 2026 study supplies matched human co-immunoprecipitation and a PTPRF mechanism, but unchanged Olfr734 expression does not exclude a GPCR contribution. Its BLI Methods attach a PTPRF catalog identifier to the ligand, leaving that human affinity measurement unresolved.
Significance: Species, reagent identity and receptor contribution must be separated before assigning a single universal pathway.
What would resolve it: Clarify the BLI reagent record and compare receptor perturbation/rescue with matched species and verified ligand preparations.
Provenance (the field's own admissions):
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)