FBN1 produces a secreted precursor whose mature fibrillin-1 chain assembles into extracellular microfibrils. Human biochemical isolation and tissue immunoelectron microscopy place fibrillin in microfibrils associated with elastic fibers and in bundles without an elastin core (PMID:3536967(https://pubmed.ncbi.nlm.nih.gov/3536967/)). The matrix framework therefore supports both elastic and elastin-free connective tissues. An extracellular matrix constituent can contribute to matrix recoil without being elastin or independently demonstrating recoil as an isolated molecule; the microfibril-based elasticity annotation is an inference about that matrix role (PMID:8120105(https://pubmed.ncbi.nlm.nih.gov/8120105/)).
Fibrillin-1 self-association contributes to microfibril assembly. Human C-terminal multimers bind N-terminal regions, and later fragment experiments resolve a more specific N-terminal/C-terminal interaction without establishing the complete native microfibril structure (PMID:18448684(https://pubmed.ncbi.nlm.nih.gov/18448684/), PMID:24035709(https://pubmed.ncbi.nlm.nih.gov/24035709/)). Calcium and heparin/heparan-sulfate interactions support this extracellular architecture; they do not imply catalytic activity.
Human RGD-containing fibrillin-1 fragments support integrin-dependent adhesion. Blocking antibodies, RGD controls and direct binding measurements distinguish this activity from a nonspecific association with matrix proteins. Receptor usage varies with the fragment and assay: failure of one fragment to bind alpha5beta1 does not overturn positive results with other constructs (PMID:12807887(https://pubmed.ncbi.nlm.nih.gov/12807887/), PMID:15062093(https://pubmed.ncbi.nlm.nih.gov/15062093/)).
Microfibrils organize growth-factor availability through LTBP-associated latent TGF-beta complexes and through BMP prodomains (PMID:12429738(https://pubmed.ncbi.nlm.nih.gov/12429738/), PMID:18339631(https://pubmed.ncbi.nlm.nih.gov/18339631/)). Fbn1-deficient mouse osteoblast experiments connect impaired matrix sequestration to increased TGF-beta and BMP activity. The direction of the effect depends on tissue and developmental context; it is not a universal rule that every fibrillin perturbation increases both pathways (PMID:20855508(https://pubmed.ncbi.nlm.nih.gov/20855508/)).
The two recorded cleavage products are mature fibrillin-1, residues 45–2731, and asprosin, residues 2732–2871. They are processed products of the precursor, rather than demonstrated alternative splice isoforms. N-terminal sequencing supports the mature-chain boundary, and C-terminal processing experiments distinguish secretion from matrix incorporation (PMID:10636927(https://pubmed.ncbi.nlm.nih.gov/10636927/), PMID:24982166(https://pubmed.ncbi.nlm.nih.gov/24982166/)). Experimental fragments, tagged proteins and processing mutants are kept distinct from those natural products.
Asprosin has reported glucogenic and appetite-stimulating hormonal activities. Human recombinant ligand was tested in rodent hepatocyte and neuronal systems; observations in people and the endogenous circulating product provide separate evidence (PMID:27087445(https://pubmed.ncbi.nlm.nih.gov/27087445/), PMID:29106398(https://pubmed.ncbi.nlm.nih.gov/29106398/)). This activity regulates glucose metabolism rather than catalyzing glucose-metabolic reactions.
Assay reproducibility remains a substantive limit. The negative replication study tested several expression and administration approaches, including mammalian preparations, so its findings cannot be explained simply as an inactive bacterial tag (PMID:30879984(https://pubmed.ncbi.nlm.nih.gov/30879984/)). Later human asprosin/PTPRF work supplies additional positive evidence but does not resolve every earlier discrepancy or establish one exclusive receptor mechanism (PMID:41671088(https://pubmed.ncbi.nlm.nih.gov/41671088/)). The source guide distinguishes ligand species, constructs, receptor identity and the unresolved reagent-catalog description.
Human tissue localization, purified human fragments, mouse phenotypes and cross-species binding assays answer different questions. Downstream expression or inflammatory changes after a matrix perturbation do not by themselves establish that fibrillin performs the steps of gene expression or immunity. Conversely, a paper centered on a fibrillin partner or paralog can still directly assay FBN1; title emphasis is not a reason to reject an annotation.
Supported generic protein-binding observations are retained as non-core under this project's policy. Source-specific observations remain undecided when the operative experiments or exact supplementary protein identifiers could not be verified. Those decisions do not assert that the published observation is false or that fibrillin lacks its independently established matrix function. The accompanying source guides and decision tables preserve the distinction between positive evidence, bounded inference and inaccessible evidence.
The source guide records primary-source locators, exact proteomics target joins and access limits. The binding evidence table and direct decision table retain full machine-source keys and methods.
Matrix fibrillin supports structural microfibrils, integrin-mediated adhesion, self-association and interactions with growth-factor prodomains or latent-complex targeting proteins. Binding to LOX, ADAMTS10 or glycosylation enzymes does not assign their catalytic functions to FBN1. Recombinant fragments, human targets tested with bovine or mouse partners, and human ORFeome constructs tested in yeast retain their actual scope.
The matrix-elasticity IC inference concerns tissue-level recoil and structural contribution. General structural-constituent coverage remains useful for elastin-free matrix support and scaffold functions. Integrin binding supplies the ligand in adhesion; the same experiment does not need a redundant protein-complex-binding parent. Soluble fragment inhibition of mouse osteoclast formation remains conditional and non-core, with the more specific development term retaining the positive differentiation evidence.
Matrix-dependent CCN3 expression and fibrillin deposition do not establish that FBN1 performs gene-expression machinery or organizes collagen fibrils. These two inferred process contexts overextend the experiments, while their real extracellular signaling observations are retained.
No new quotations, source-annotation changes or natural splice-product assignments are made. Precursor processing and released asprosin are assessed separately from matrix interactions; recombinant truncations and grouped proteomics accessions are not natural-product definitions. The genuine provider attempts failed with authentication/quota errors; this authored guide is not a provider output.
Independent evidence resolves several gene-level claims without verifying an inaccessible experiment. Fbn1-null mouse osteoblast matrices retain less BMP and LTBP-associated material, with altered growth-factor availability and maturation despite unchanged ligand transcripts. This is a matrix-sequestration contribution to bone formation; the same study excludes microfibrils as an obligatory mineralization substrate (PMID:20855508(https://pubmed.ncbi.nlm.nih.gov/20855508/), Fbn1-null osteoblast Results and pathway-separation experiments). Skeletal development is retained as non-core, preserving the original human family paper's access limit and the mouse functional scope. Human FBN1 fragments and human bone material are separately documented in PMID:24039232(https://pubmed.ncbi.nlm.nih.gov/24039232/), Figures 1–4 and Methods; its functional osteoclast assays are in mouse systems.
Human dermal fibrillin is collagenase-resistant and occurs in immunogold-labeled microfibrils among unlabeled collagen, including elastin-free bundles (PMID:3536967(https://pubmed.ncbi.nlm.nih.gov/3536967/), tissue-localization Results and Figures 4–9). This supports noncollagenous interstitial matrix independently of the unverified MatrisomeDB target record. It does not imply uniform residence in basement-membrane lamina densa.
The same-claim reassessment accepts microfibril localization, alpha5beta1 binding, integrin-mediated adhesion and calcium binding using accessible independent human evidence. AlphaVbeta6, collagen XVI, human processed ligand versus mouse ligand, and unresolved proteomics target joins remain distinct claims. They are not resolved by another source with only the same broad GO label. The feedback decisions preserve exact source keys and the retained uncertainty.
Five molecular contributions organize the synthesis: broad matrix scaffolding, FBN1 self-association, calcium coordination, integrin-mediated adhesion and released-asprosin hormone activity. Self-association supplies intermolecular assembly contacts (PMID:18448684(https://pubmed.ncbi.nlm.nih.gov/18448684/), multimer/competition Results; PMID:24035709(https://pubmed.ncbi.nlm.nih.gov/24035709/), human fragment pull-down controls). Calcium is directly coordinated in human cbEGF22/23 structures (PMID:15062093(https://pubmed.ncbi.nlm.nih.gov/15062093/), crystal structures and calcium-removal comparison). Neither implies an assembly enzyme or an experimentally established molecular spring. Heparin affinity and the matrix-elasticity IC inference remain positive non-core properties. Heparin is an experimental glycosaminoglycan analog with sulfation/presentation dependence (PMID:11461921(https://pubmed.ncbi.nlm.nih.gov/11461921/), native human FBN1 binding and competition experiments); the broad structural core also covers nonelastic anchorage and growth-factor storage.
Asprosin's hormonal core includes the reported cAMP/PKA-associated signaling and glucose-homeostasis roles, without asserting glucose-metabolic catalysis or exclusive receptor usage. Human ligand tested in rodent systems is not the same evidence as mouse ligand tested with a human receptor. The new scoped gaps and experiments address preparation-dependent replication and matched receptor contributions. Negative mammalian and hydrodynamic-expression results are retained, as is the unresolved catalog identity in the 2026 BLI Methods (PMID:30879984(https://pubmed.ncbi.nlm.nih.gov/30879984/), Case 2; PMID:41671088(https://pubmed.ncbi.nlm.nih.gov/41671088/), receptor Results and BLI Methods). Existing DISPUTED reference assessments and both cleavage-product objects are unchanged.
Five source contexts (indices 42–46) now refine generic binding to GO:0036122 BMP binding. The original human FBN1 rF23 experiments directly measure BMP2, BMP4, BMP7, BMP10 and GDF5/BMP14 prodomain binding (PMID:18339631(https://doi.org/10.1074/jbc.M707820200), Results, Figure 6 and Table 3). The prodomain scope remains explicit; mature-ligand binding and receptor signaling are not inferred. This applies the same evidence-specific rule as the FBN2 review. All other annotation decisions, reference assessments, quotations and product objects remain unchanged.
The imported human fibronectin context (index 55, PMID:25034023, partner P02751) now uses MODIFY with GO:0001968 fibronectin binding. Original Methods 2.2 and Results 3.3/Figure 3B distinguish the positive recombinant human FBN1-fragment interaction from heparin effects on fibrillin self-association. The five previous BMP-prodomain refinements remain exact. The direct source guide now also records the actual PMID:18339631 Figure 6A–B caption and Table 3 locators from the recovered original.
MODIFY specifies a better term; it does not automatically classify the supported interaction as outside the core. The current structural core already describes fibrillin’s matrix-scaffold contribution to storage and availability of BMP complexes, supported separately by the prodomain binding and osteoblast matrix-sequestration evidence. A separate BMP-binding core would repeat that contribution here, so the existing core synthesis is retained. Prodomain binding alone is not assigned receptor activation or an unrestricted mature-ligand signaling effect.
All other 153 review objects, all imported source objects, complete references, products and quotations remain unchanged. No new source, annotation, core term or quotation is added. Existing journal/history records are preserved; ROOT owns the follow-up history and PR linkage.