Fibrillin-2 is a secreted glycoprotein that forms extracellular microfibrils in connective tissues and contributes to the scaffold for early elastic-fiber assembly. Its matrix chain contains repeated calcium-binding EGF-like domains and provides structural organization in both elastic and nonelastic matrices, including binding sites for latent growth-factor complexes. In mouse osteoblasts, fibrillin-2-dependent matrix sequestration limits TGF-Ξ² bioavailability and supports maturation. Pathogenic FBN2 variants cause congenital contractural arachnodactyly, and rare variants have also been associated with early-onset macular degeneration. The long precursor is the source of placensin, a secreted C-terminal product detected in human placenta, trophoblast cultures and circulation. Recombinant human placensin stimulates glucose production in mouse hepatocytes and invasion by human trophoblast cells. The shorter splice product lacks the C-terminal placensin sequence.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
FBN2_MATURE_FIBRILLIN2PRO_0000007584 (residues 78-2779) FBN2_PLACENSINPRO_0000436888 (residues 2780-2912) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001527 microfibril | IDA PMID:8120105 Structure and expression of fibrillin-2, a novel microfibril... | ACCEPT | Summary: FBN2 is a component of extracellular microfibrils. Reason: Target-specific human fetal immunostaining and bovine immunogold microscopy establish the matrix context in the source. Later human fetal-skin immunogold independently confirms FBN2-containing microfibrils; the species of the original ultrastructural panel remains explicit. |
| GO:0001527 microfibril | IEA GO_REF:0000120 | ACCEPT | Summary: Fibrillin-2 is a constituent of extracellular microfibrils. Reason: The combined electronic record joins ARBA and mouse/Ensembl sources. Actual human fetal matrix localization and bovine microfibril immunogold in PMID:8120105, together with mouse Fbn2 matrix evidence in PMID:20855508, support the microfibrillar location. Mouse Q61555 has independent experimental microfibril records; the reciprocal electronic human/mouse annotations are not the only grounding. This concerns matrix fibrillin-2, not a claim that soluble placensin belongs to microfibrils. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028288 Β· ARBA00028288 SUPPORTS TRANSFER Actual rule conditions and GO:0001527 consequence were inspected; target InterPro cross-references support the fibrillin-related domain context, but all alternative FunFam rule matches were not independently replayed. UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Current QuickGO includes microfibril IDA records as well as the PMID:20855508 matrix statement; human-to-mouse electronic rows are separately identifiable. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. |
| GO:0001527 microfibril | TAS PMID:20855508 Fibrillin-1 and -2 differentially modulate endogenous TGF-Ξ² ... | ACCEPT | Summary: FBN2-containing microfibrils provide a matrix platform for latent growth-factor complexes. Reason: The paper assays FBN2 in osteoblast matrix and recombinant FBN2βLTBP binding, consistent with the established microfibril compartment. Mouse loss-of-function signaling results are not substituted for direct human localization. |
| GO:0005179 hormone activity | IBA GO_REF:0000033 | ACCEPT | Summary: The C-terminal FBN2 product placensin has hormone activity. Reason: The PAINT hormone assertion is supported independently on the target: PMID:32329225 reports endogenous human trophoblast secretion and serum immunoreactivity/IP-MS, and a recombinant human C-terminal placensin construct activates recipient-cell cAMP/PKA and glucose output. The glucose assays used mouse hepatocytes/liver/mice; human trophoblast responses were also tested. The exact endogenous cleavage boundary and furin necessity were not demonstrated in the inspected experiments. This activity is assigned to the C-terminal product of the displayed precursor, not to mature matrix fibrillin-2 or the truncated 1,473-residue splice isoform 2. Target self-WITH is legitimate descendant grounding. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002778720 Β· PTN002778720 SUPPORTS TRANSFER The actual PANTHER v19 tree places human FBN2 leaf PTN002513885 below this node; its ungapped 2,912-residue alignment exactly matches official P35556. Current InterPro/PANTHER source files use PTHR47333, whereas the live v19 geneinfo/tree use PTHR24039; these releases are kept distinct. The selected positive IBD row is hormone activity; target P35556 is a legitimate experimental seed. Current GOA adds MGI:95490 relative to the selected IBD seed list; the source difference is retained. |
| GO:0005201 extracellular matrix structural constituent | IBA GO_REF:0000033 | ACCEPT | Summary: Mature fibrillin-2 contributes to the extracellular matrix structure. Reason: The target lies within the actual structural IBD clade and the source assertion agrees with microfibril localization and matrix assembly evidence. PMID:8120105 distinguishes fibrillar matrix from the amorphous elastin core, and PMID:20855508 supports a matrix role in local growth-factor storage. The broad structural MF remains informative for nonelastic matrices and organization beyond the contextual elasticity inference. No single-molecule recoil or enzyme activity is implied. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000620536 Β· PTN000620536 SUPPORTS TRANSFER The actual PANTHER v19 tree places human FBN2 leaf PTN002513885 below this node; its ungapped 2,912-residue alignment exactly matches official P35556. Current InterPro/PANTHER source files use PTHR47333, whereas the live v19 geneinfo/tree use PTHR24039; these releases are kept distinct. The selected positive GO:0005201 IBD and current GOA both cite P35555 and WB:WBGene00001403. Node placement and target matrix evidence support transfer; donor count is not used as a confidence measure. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: The generic extracellular structural role is supported independently of the unresolved screen join. Reason: RCA denotes matrisome classification. The original table has inverted fibrillin/fibulin labels and its FBN2 accession-level supplement was not recovered. Exact human FBN2 microfibril/coassembly evidence independently supports this generic structural claim; it does not verify the separate HDA detection. The role includes nonelastic matrix and is broader than elasticity alone. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: FBN2 is an extracellular structural glycoprotein identified in the original matrix proteomics. Reason: Four sole-FBN2/P35556 workbook records corroborate matrisome classification, separately from mixed fibrillin groups. RCA is not a direct mechanics assay; human microfibril coassembly provides independent structural evidence. Nonelastic matrix functions justify retaining the broader molecular function. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Fibrillin-2 contains calcium-binding EGF-like domains. Reason: Actual target-specific InterPro responses map P35556 to IPR001881 and IPR018097 and associate both entries with GO:0005509. The response reports 44 domain intervals and 17 conserved-site intervals on the displayed sequence. This supports calcium binding in the extracellular domain architecture; it does not assign calcium signaling or quantify affinity at every repeat. The scope is the domain-bearing precursor/matrix product, without implying that isolated placensin contains these mapped domains. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001881 Β· EGF-like calcium-binding domain SUPPORTS TRANSFER The actual P35556 response includes the GO:0005509 mapping and 44 located domain hits. InterPro:IPR018097 Β· EGF-like calcium-binding, conserved site SUPPORTS TRANSFER The actual P35556 response includes the GO:0005509 mapping and 17 located conserved-site hits. |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: FBN2 fragments bind LTBP1; the source partner is B7ZLY3 (an unreviewed human LTBP1 entry). Reason: Blot-overlay and solid-phase assays support the LTBP1 interaction. The exact B7ZLY3 transcript product was not separately identified by the experiment. Retain the source identity and positive generic binding as non-core; this is not a natural FBN2 splice-product assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12429738 Latent transforming growth factor beta-binding protein 1 int... | KEEP AS NON CORE | Summary: FBN2 fragments bind LTBP1; the source partner is Q14766 (human LTBP1). Reason: Blot-overlay and solid-phase assays support the LTBP1 interaction. The exact B7ZLY3 transcript product was not separately identified by the experiment. Retain the source identity and positive generic binding as non-core; this is not a natural FBN2 splice-product assay. 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: Recombinant human FBN2 binds bovine MAGP1/P27424. Reason: Controlled solid-phase assays test the FBN2 N-terminal fragment. The source uses bovine MAGP partners; retain that measured interaction without inferring a separately tested human partner or a natural splice-product function. Generic binding is 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: Recombinant human FBN2 binds bovine MAGP2/Q28022. Reason: Controlled solid-phase assays test the FBN2 N-terminal fragment. The source uses bovine MAGP partners; retain that measured interaction without inferring a separately tested human partner or a natural splice-product function. Generic binding is non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Recombinant FBN2 rF86 binds the BMP10 prodomain. Reason: PMID18339631 Figure 6 and Table 3 directly measure binding of the recombinant FBN2 N-terminal fragment rF86 to the BMP10 prodomain by surface plasmon resonance (reported Kd 13 nM); the more distal rF37 fragment is negative. GO:0036122 covers binding to a BMP-family member and does not require the mature growth-factor domain. This evidence therefore supports BMP binding more precisely than generic protein binding. The assayed ligand is a prodomain: no receptor activation, mature-ligand affinity, pathway sign or natural splice-product specificity is inferred. This is a specific matrix interaction, not an additional core molecular activity. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Recombinant FBN2 rF86 binds the BMP2 prodomain. Reason: PMID18339631 Figure 6 and Table 3 directly measure binding of the recombinant FBN2 N-terminal fragment rF86 to the BMP2 prodomain by surface plasmon resonance (reported Kd 8 nM); the more distal rF37 fragment is negative. GO:0036122 covers binding to a BMP-family member and does not require the mature growth-factor domain. This evidence therefore supports BMP binding more precisely than generic protein binding. The assayed ligand is a prodomain: no receptor activation, mature-ligand affinity, pathway sign or natural splice-product specificity is inferred. This is a specific matrix interaction, not an additional core molecular activity. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Recombinant FBN2 rF86 binds the BMP4 prodomain. Reason: PMID18339631 Figure 6 and Table 3 directly measure binding of the recombinant FBN2 N-terminal fragment rF86 to the BMP4 prodomain by surface plasmon resonance (reported Kd 25 nM); the more distal rF37 fragment is negative. GO:0036122 covers binding to a BMP-family member and does not require the mature growth-factor domain. This evidence therefore supports BMP binding more precisely than generic protein binding. The assayed ligand is a prodomain: no receptor activation, mature-ligand affinity, pathway sign or natural splice-product specificity is inferred. This is a specific matrix interaction, not an additional core molecular activity. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Recombinant FBN2 rF86 binds the BMP7 prodomain. Reason: PMID18339631 Figure 6 and Table 3 directly measure binding of the recombinant FBN2 N-terminal fragment rF86 to the BMP7 prodomain by surface plasmon resonance (reported Kd 15 nM); the more distal rF37 fragment is negative. GO:0036122 covers binding to a BMP-family member and does not require the mature growth-factor domain. This evidence therefore supports BMP binding more precisely than generic protein binding. The assayed ligand is a prodomain: no receptor activation, mature-ligand affinity, pathway sign or natural splice-product specificity is inferred. This is a specific matrix interaction, not an additional core molecular activity. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18339631 Targeting of bone morphogenetic protein growth factor comple... | MODIFY | Summary: Recombinant FBN2 rF86 binds the GDF5/BMP14 prodomain. Reason: PMID18339631 Figure 6 and Table 3 directly measure binding of the recombinant FBN2 N-terminal fragment rF86 to the GDF5/BMP14 prodomain by surface plasmon resonance (reported Kd 24 nM); the more distal rF37 fragment is negative. GO:0036122 covers binding to a BMP-family member and does not require the mature growth-factor domain. This evidence therefore supports BMP binding more precisely than generic protein binding. The assayed ligand is a prodomain: no receptor activation, mature-ligand affinity, pathway sign or natural splice-product specificity is inferred. This is a specific matrix interaction, not an additional core molecular activity. The verified human P43026 record identifies GDF5 as BMP14; the human SW1353-derived prodomain is distinct from the mouse mature growth factor used elsewhere in the paper. Proposed replacements: BMP binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20855508 Fibrillin-1 and -2 differentially modulate endogenous TGF-Ξ² ... | KEEP AS NON CORE | Summary: FBN2 rF86 binds the C-terminal region of LTBP1. Reason: The original SPR experiment directly tests this pair. Retain generic binding as non-core; the accompanying mouse osteoblast phenotypes support contextual matrix signaling without assigning a natural splice-product-specific interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20855508 Fibrillin-1 and -2 differentially modulate endogenous TGF-Ξ² ... | KEEP AS NON CORE | Summary: FBN2 rF86 binds the C-terminal region of LTBP4. Reason: The original SPR experiment directly tests this pair. Retain generic binding as non-core; the accompanying mouse osteoblast phenotypes support contextual matrix signaling without assigning a natural splice-product-specific interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25034023 Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self... | MODIFY | Summary: Recombinant human FBN2 N- and C-terminal fragments bind fibronectin. Reason: PMID25034023 Results 3.3 and Figure 3B test recombinant human FBN2 N- and C-terminal fragments against immobilized human plasma fibronectin in solid-phase binding assays. Binding persists in the tested heparin concentrations. GO:0001968 fibronectin binding captures the measured partner specificity, rather than leaving a generic protein-binding label. The separate FBN1 interaction in Figure 3A retains its own source context. No fibronectin receptor activity, natural FBN2 splice-product specificity or new core molecular activity is inferred. 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: FBN2 and FBN1 fragments interact heterotypically. Reason: Figure 3A directly tests N-to-C-terminal fibrillin interactions and heparin inhibition. The positive fragment interaction is retained as non-core generic binding; it does not specify native stoichiometry or a natural splice product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26601954 Characterization of Microfibrillar-associated Protein 4 (MFA... | KEEP AS NON CORE | Summary: Human MFAP4 binds two experimentally tested FBN2 regions. Reason: SPR and solid-phase assays support binding to rF86 and cbEGF23β33. Retain generic binding as non-core. The separate mouse-skin co-localization experiment concerns FBN1 and is not treated as FBN2 tissue evidence. Supporting Evidence: |
| GO:0005576 extracellular region | EXP PMID:32329225 Placensin is a glucogenic hormone secreted by human placenta... | ACCEPT | Summary: The FBN2-derived placensin product is secreted into extracellular fluid. Reason: Human trophoblast-conditioned medium and serum contain FBN2-derived placensin immunoreactivity and IP-MS peptides. This supports the broad extracellular location while preserving the source parent accession. Exact endogenous cleavage termini and furin dependence were not measured; the truncated 1,473-aa splice product lacks this C-terminal sequence. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: The gene produces extracellular matrix fibrillin-2 and a secreted C-terminal product. Reason: The combined orthology and UniProt subcellular-location mapping supports extracellular residence. Unlike a mature-microfibril-only assertion, this broad location remains useful for the secreted placensin product and precursor as well as deposited matrix protein. PMID:32329225 directly examines endogenous human trophoblast conditioned medium and serum, while PMID:8120105 supports extracellular matrix deposition. It is not restricted to any one matrix compartment or asserted for every splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Mouse Fbn2 is the literal ortholog source; its donor record is independently captured. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. UniProtKB-SubCell:SL-0243 Β· Secreted SUPPORTS TRANSFER The target official UniProt record supplies secreted/extracellular localization; the combined source is not a new target-specific localization experiment. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1592387 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-1592387 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-1592387 Β· Fibulin binds elastic fibres SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129353 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2129353 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129353 Β· Tropoelastin associates with microfibrils SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129357 | ACCEPT | Summary: The Reactome source places multiple FBN2 processing states extracellularly. Reason: R-HSA-2129357 contains precursor FBN2(29β2912), matrix-side FBN2(29β2779), and C-terminal FBN2(2780β2912) output entities, all linked to P35556 and extracellular region. The broad compartment captures both matrix and released C-terminal products and is retained. The source models furin-mediated processing; it does not make FBN2 a protease, prove endogenous cleavage chemistry, or establish processing of truncated splice isoform 2. Reactome start 29 differs from the official mature-chain start 78 and is recorded as the database entity boundary, not adopted as a new natural product. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129357 Β· Fibrillin C-terminal processing SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129362 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2129362 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129362 Β· Fibrillin microfibril assembly SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129375 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2129375 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129375 Β· Elastin cross-linking by lysyl oxidase SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2129385 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2129385 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2129385 Β· MFAP2, MFAP5 bind microfibrils SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2161282 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2161282 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2161282 Β· Elastic fibres bind associated proteins SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396399 | ACCEPT | Summary: Fibrillin-2 is extracellular in this verified Reactome matrix context. Reason: Reactome:R-HSA-2396399 genuinely contains P35556 through the inspected nested entity path to FBN2(29β2779) in extracellular region. Retain this positive compartment claim consistently with the other GO:0005576 records: extracellular region remains informative for this gene's matrix, precursor and released-product biology, even though microfibril is a more specific location. This source's evidence concerns the matrix chain and is not extended to placensin or splice isoform 2. Product scope belongs in the evidence assessment and functional-product model, not an invented imported-row isoform field. Event chemistry and activities of other participants are not transferred to FBN2; Reactome start 29 is not adopted as the official mature N terminus. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2396399 Β· Fibrillins bind BMPs SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2485148 | ACCEPT | Summary: The Reactome source places multiple FBN2 processing states extracellularly. Reason: R-HSA-2485148 contains the P35556 microfibrillar input and modeled cleavage products, including FBN2(29β?) with an explicitly unknown end. All inspected FBN2 entities are extracellular. This broad location retains the released-fragment scope beyond intact microfibrils; it does not assign MMP protease activity to FBN2 or convert a modeled degradation fragment into a curated natural product. The literal database coordinates are preserved without extension to splice isoform 2. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-2485148 Β· Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13 SUPPORTS TRANSFER Actual input/output and recursively nested hasComponent/hasMember/repeatedUnit paths reach P35556 entities in GO:0005576. Target routes are preserved in the source guide; unrelated event branches were not exhaustively audited. |
| GO:0006006 glucose metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Placensin positively regulates hepatocyte gluconeogenesis. Reason: The actual PAINT node includes FBN2; the correction concerns the extracellular hormone role rather than target descent. In PMID:32329225, human recombinant placensin increases glucose output in mouse primary hepatocytes and AML12 cells assayed in glucose-free medium supplied with lactate and pyruvate, accompanied by PEPCK/G6Pase transcript induction (Glucogenic actions of placensin, Figure 3AβB; Methods, Stimulation of hepatocyte functions). These observations support positive regulation of gluconeogenesis (GO:0045722), a more precise child of GO:0010907. The recipient hepatocyte machinery performs the chemistry; placensin regulates it. This is a lateral role correction from imported GO:0006006, not a strict descendant refinement of that original term. The assay is not claimed to resolve all glucose output by isotope tracing or to demonstrate a human in-vivo metabolic intervention. The role belongs to C-terminal placensin, not mature fibrillin-2 or truncated splice isoform 2. The FBN1 comparator is acknowledged: its raw GOA has glucose metabolism by IDA, but the current reviewed asprosin record also corrects that role to positive regulation of glucose metabolism; the narrower placensin choice follows its own accessible assay scope. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002778720 Β· PTN002778720 SUPPORTS TRANSFER The actual PANTHER v19 tree places human FBN2 leaf PTN002513885 below this node; its ungapped 2,912-residue alignment exactly matches official P35556. Current InterPro/PANTHER source files use PTHR47333, whereas the live v19 geneinfo/tree use PTHR24039; these releases are kept distinct. The selected GO:0006006 IBD is seeded by P35555. The target path is confirmed and human FBN2-derived placensin supplies independent positive regulatory evidence; the propagated metabolic-participant wording needs correction. Proposed replacements: positive regulation of gluconeogenesis |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | TOO GENERAL | Summary: The generic signaling inference is already entailed by retained hormone activity. Reason: GO_REF:0000108 derives this row from GO:0005179 using an inter-ontology link. The official typed path is hormone activity is_a receptor agonist activity (GO:0048018), part_of signal transduction (GO:0007165). Retained hormone row 3 therefore provides the more informative assertion. This is a positive but uninformative inference, not evidence that placensin lacks signaling effects, nor a claim that a particular receptor or complete intracellular pathway was identified in PMID:32329225. The cAMP/PKA response in PMID:32329225 is a downstream readout and does not by itself establish a G-protein-coupled receptor or the adenylate-cyclase-activating GPCR pathway. FBN1/asprosin has a separate source-specific GO:0007189 annotation supported by pharmacological observations; that assertion is not transferred to placensin by paralogy or a shared second messenger. No new signaling-pathway assertion is proposed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO:0005179 Β· hormone activity SUPPORTS TRANSFER Actual GO_REF method and the two-edge typed GO path explain the inference. The target hormone evidence is retained. |
| GO:0030023 extracellular matrix constituent conferring elasticity | IC PMID:8120105 Structure and expression of fibrillin-2, a novel microfibril... | KEEP AS NON CORE | Summary: FBN2 contributes to elastic matrices through its microfibrillar scaffold. Reason: The IC inference from microfibril localization is biologically sound: matrix recoil need not be intrinsic recoil of an isolated fibrillin molecule. Preserve this positive context as non-core relative to the broader scaffold function, which also covers nonelastic tissues. The source presents localization and structural inference, not a direct recoil assay. Supporting Evidence: |
| GO:0030023 extracellular matrix constituent conferring elasticity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Elastic-matrix contribution is a defensible contextual function of fibrillin-2. Reason: The actual ARBA00086221 consequence is GO:0030023, with two FunFam conditions plus primate scope; the complete FunFam match was not independently reconstructed. PMID:8120105 provides FBN2-specific microfibrillar association and preferential localization in elastic matrices, supporting the same contextual inference as the direct IC row. The GO definition concerns a matrix component enabling recoil and does not demand that isolated FBN2 itself be an elastomer. Retain this role without replacing the broader, useful structural MF or claiming direct mechanical measurement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00086221 Β· ARBA00086221 SUPPORTS TRANSFER Actual rule conditions and consequence read. Independent target tissue/microfibril evidence supports the bounded matrix-role inference; no fresh FunFam assignment was fabricated. |
| GO:0030501 positive regulation of bone mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved positive regulation of bone mineralization annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0030501 from PMID:20855508. Fbn2-null mouse osteoblasts and marrow stromal cells form fewer mineralized nodules, and reduced bone formation is observed in vivo. Rescue by suppressing excessive TGF-Ξ² signaling supports an extracellular regulatory role. The same study explicitly argues against fibrillin microfibrils being the obligatory structural substrate of mineralization. The Ensembl Compara electronic transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0030501, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse osteoblasts and marrow stromal cells form fewer mineralized nodules, and reduced bone formation is observed in vivo. Rescue by suppressing excessive TGF-Ξ² signaling supports an extracellular regulatory role. The same study explicitly argues against fibrillin microfibrils being the obligatory structural substrate of mineralization. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. |
| GO:0030501 positive regulation of bone mineralization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved positive regulation of bone mineralization annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0030501 from PMID:20855508. Fbn2-null mouse osteoblasts and marrow stromal cells form fewer mineralized nodules, and reduced bone formation is observed in vivo. Rescue by suppressing excessive TGF-Ξ² signaling supports an extracellular regulatory role. The same study explicitly argues against fibrillin microfibrils being the obligatory structural substrate of mineralization. The curator-reviewed ISS transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0030501, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse osteoblasts and marrow stromal cells form fewer mineralized nodules, and reduced bone formation is observed in vivo. Rescue by suppressing excessive TGF-Ξ² signaling supports an extracellular regulatory role. The same study explicitly argues against fibrillin microfibrils being the obligatory structural substrate of mineralization. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse Fbn2 evidence supports the conserved negative regulation of transforming growth factor beta receptor signaling pathway annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0030512 from PMID:20855508. Fbn2-null mouse osteoblasts show increased pSmad2/3, TGF-Ξ² reporter activity and active TGF-Ξ² with reduced matrix LTBP1/TGF-Ξ² sequestration. Blocking TGF-Ξ² signaling improves maturation. This supports matrix-mediated limitation of signaling in this context, not universal antagonism across every tissue or direct receptor enzymology. The Ensembl Compara electronic transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0030512, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse osteoblasts show increased pSmad2/3, TGF-Ξ² reporter activity and active TGF-Ξ² with reduced matrix LTBP1/TGF-Ξ² sequestration. Blocking TGF-Ξ² signaling improves maturation. This supports matrix-mediated limitation of signaling in this context, not universal antagonism across every tissue or direct receptor enzymology. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse Fbn2 evidence supports the conserved negative regulation of transforming growth factor beta receptor signaling pathway annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0030512 from PMID:20855508. Fbn2-null mouse osteoblasts show increased pSmad2/3, TGF-Ξ² reporter activity and active TGF-Ξ² with reduced matrix LTBP1/TGF-Ξ² sequestration. Blocking TGF-Ξ² signaling improves maturation. This supports matrix-mediated limitation of signaling in this context, not universal antagonism across every tissue or direct receptor enzymology. The curator-reviewed ISS transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0030512, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse osteoblasts show increased pSmad2/3, TGF-Ξ² reporter activity and active TGF-Ξ² with reduced matrix LTBP1/TGF-Ξ² sequestration. Blocking TGF-Ξ² signaling improves maturation. This supports matrix-mediated limitation of signaling in this context, not universal antagonism across every tissue or direct receptor enzymology. |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | KEEP AS NON CORE | Summary: FBN2 is detected in human HUES1-derived extracellular matrix. Reason: Table 1 reports the FBN2 target separately from mouse feeder samples. Retain the positive HDA compartment as non-core; bottom-up proteomics of extracted ECM does not resolve intact microfibril assembly or establish a role in stem-cell self-renewal. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | UNDECIDED | Summary: The source-specific FBN2 proteomic identification remains unresolved. Reason: The actual main table inverts FBN1/2 and FBLN1/2 protein names, and the exact supplemental accession join was not recovered. Preserve uncertainty about this HDA target detection without claiming misattribution. Independent FBN2 matrix biology resolves the generic structural function, but cannot reconstruct the particular screen identification. Supporting Evidence: |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | KEEP AS NON CORE | Summary: Sole-FBN2/P35556 records support extracellular-matrix detection. Reason: The original workbook contains four such records in adjacent breast and normal omentum preparations; each has one reported unique peptide. Mixed fibrillin groups are kept separate. Retain positive HDA localization as non-core without inferring which intact splice or processed product generated the peptides. Supporting Evidence: |
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Fibrillin-2 has a supported extracellular-matrix location. Reason: The actual structural IBD clade includes FBN2, and target localization independently supports extracellular matrix. Retain this broad, biologically informative positive compartment consistently with the other verified matrix detections; the term is not discarded because microfibril and basement-membrane components are more specific. The PAINT statement concerns matrix fibrillin-2 and does not assign the soluble hormone to matrix. Current GOA and selected IBD extant-source lists differ; that source-version difference is retained and is not circularity or evidence of target loss. The separate PMID:28327460 HDA row remains UNDECIDED because its exact target identification was not recovered; independent matrix evidence cannot reconstruct that source-specific assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000620536 Β· PTN000620536 SUPPORTS TRANSFER The actual PANTHER v19 tree places human FBN2 leaf PTN002513885 below this node; its ungapped 2,912-residue alignment exactly matches official P35556. Current InterPro/PANTHER source files use PTHR47333, whereas the live v19 geneinfo/tree use PTHR24039; these releases are kept distinct. Actual positive IBD GO:0031012 and target ancestry verified. The target is a legitimate seed. The current GOA seed list includes WB:WBGene00001403 and omits selected IBD seeds P98095/Q75N90; both original lists remain unchanged. |
| GO:0042593 glucose homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: Placensin contributes to glucose homeostasis as an extracellular regulatory product. Reason: The target descends from the actual positive IBD node. PMID:32329225 independently shows that a human FBN2-derived C-terminal construct increases glucose output in mouse hepatocytes and liver and raises circulating glucose in mice. This supports the conserved glucogenic regulatory role while retaining the limits: no human intervention or endogenous FBN2-loss test of systemic glucose homeostasis was reported in the inspected study, and pregnancy serum associations alone do not prove causality. The role belongs to placensin rather than matrix fibrillin-2 or truncated splice isoform 2. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002778720 Β· PTN002778720 SUPPORTS TRANSFER The actual PANTHER v19 tree places human FBN2 leaf PTN002513885 below this node; its ungapped 2,912-residue alignment exactly matches official P35556. Current InterPro/PANTHER source files use PTHR47333, whereas the live v19 geneinfo/tree use PTHR24039; these releases are kept distinct. Selected GO:0042593 IBD is seeded by P35555; current GOA additionally lists MGI:95490. Target ancestry and independent human-ligand experiments support retention without using donor counts. |
| GO:0043010 camera-type eye development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-2 has a contextual structural role in the developing eye. Reason: The actual ARBA00084629 rule predicts camera-type eye development. Human tissue observations in PMID:25406291 identify FBN2-containing ECM around the developing lens, ciliary margins, corneal stroma, choroid and sclera, with stage-dependent distribution. This supports a bounded, non-core developmental structural inference, not proof from a human functional perturbation or a resolved mechanism of morphogenesis. The proposed early vascular scaffold for the future zonule remains a hypothesis. PMID:24899048 provides fetal ocular localization but its disease associations do not independently establish embryonic causality. The actual typed GO query does not place GO:0048048 below GO:0043010, so these rows are not collapsed by label similarity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084629 Β· ARBA00084629 SUPPORTS TRANSFER Actual rule conditions and consequence read; the primate/FunFam condition pair is documented, but all rule training examples and exact current FunFam matches were not independently recovered. Human FBN2 protein localization, not a FBN1-only title, grounds the contextual assessment. |
| GO:0043010 camera-type eye development | IEP PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: FBN2 is deposited in extracellular structures of the developing human camera-type eye. Reason: Retain the curatorβs IEP-based developmental inference as a contextual non-core role: FBN2 forms part of developing ocular ECM rather than being supported solely by disease association. Localization does not demonstrate a specific causal morphogenetic mechanism. No verified strict ancestor path to the separate embryonic-eye term warrants automatic redundancy rejection. Supporting Evidence: |
| GO:0045669 positive regulation of osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved positive regulation of osteoblast differentiation annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0045669 from PMID:20855508. Fbn2-null mouse cultures and bone show impaired osteoblast maturation, reduced osterix/collagen expression and fewer maturation-marker-positive cells; TGF-Ξ² antagonism improves maturation. Fibrillin-2 acts through extracellular matrix regulation rather than being a differentiation transcription factor. The Ensembl Compara electronic transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0045669, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse cultures and bone show impaired osteoblast maturation, reduced osterix/collagen expression and fewer maturation-marker-positive cells; TGF-Ξ² antagonism improves maturation. Fibrillin-2 acts through extracellular matrix regulation rather than being a differentiation transcription factor. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. |
| GO:0045669 positive regulation of osteoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved positive regulation of osteoblast differentiation annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0045669 from PMID:20855508. Fbn2-null mouse cultures and bone show impaired osteoblast maturation, reduced osterix/collagen expression and fewer maturation-marker-positive cells; TGF-Ξ² antagonism improves maturation. Fibrillin-2 acts through extracellular matrix regulation rather than being a differentiation transcription factor. The curator-reviewed ISS transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0045669, PMID:20855508, and the operative mouse study were read. Fbn2-null mouse cultures and bone show impaired osteoblast maturation, reduced osterix/collagen expression and fewer maturation-marker-positive cells; TGF-Ξ² antagonism improves maturation. Fibrillin-2 acts through extracellular matrix regulation rather than being a differentiation transcription factor. |
| GO:0048048 embryonic eye morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-2 has a contextual structural role in the developing eye. Reason: The actual ARBA00090262 rule predicts embryonic eye morphogenesis. Human tissue observations in PMID:25406291 identify FBN2-containing ECM around the developing lens, ciliary margins, corneal stroma, choroid and sclera, with stage-dependent distribution. This supports a bounded, non-core developmental structural inference, not proof from a human functional perturbation or a resolved mechanism of morphogenesis. The proposed early vascular scaffold for the future zonule remains a hypothesis. PMID:24899048 provides fetal ocular localization but its disease associations do not independently establish embryonic causality. The actual typed GO query does not place GO:0048048 below GO:0043010, so these rows are not collapsed by label similarity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00090262 Β· ARBA00090262 SUPPORTS TRANSFER Actual rule conditions and consequence read; the primate/FunFam condition pair is documented, but all rule training examples and exact current FunFam matches were not independently recovered. Human FBN2 protein localization, not a FBN1-only title, grounds the contextual assessment. |
| GO:0048048 embryonic eye morphogenesis | IEP PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: FBN2-containing matrix is present during human embryonic eye morphogenesis. Reason: The primary immunostaining documents stage-specific structural deposition in developing ocular tissues. Keep the IEP-based positive matrix-role inference non-core, with curator deference; the proposed nascent-zonule scaffold mechanism remains a hypothesis rather than a demonstrated perturbation result. Supporting Evidence: |
| GO:0060346 bone trabecula formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved bone trabecula formation annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0060346 from PMID:20855508. Actual mouse Fbn2-null vertebral microCT and histomorphometry show fewer trabeculae, lower bone mass and decreased bone formation. This provides donor grounding for a contextual skeletal role through matrix regulation; it does not imply that fibrillin-2 is a bone-specific protein or an osteoblast enzyme. The Ensembl Compara electronic transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0060346, PMID:20855508, and the operative mouse study were read. Actual mouse Fbn2-null vertebral microCT and histomorphometry show fewer trabeculae, lower bone mass and decreased bone formation. This provides donor grounding for a contextual skeletal role through matrix regulation; it does not imply that fibrillin-2 is a bone-specific protein or an osteoblast enzyme. Ensembl:ENSMUSP00000025497 Β· Mouse Fbn2 protein model SUPPORTS TRANSFER The current mouse UniProt record cross-references ENSMUSP00000025497.6 to Fbn2. The direct Ensembl lookup returned HTTP 503; an independent current Ensembl gene-tree replay was not obtained. The literal GOA source identifier is preserved. |
| GO:0060346 bone trabecula formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Fbn2 evidence supports the conserved bone trabecula formation annotation. Reason: The literal source is Q61555 (mouse Fbn2), not a fibrillin-1 paralog. Its current QuickGO record carries an IMP annotation to GO:0060346 from PMID:20855508. Actual mouse Fbn2-null vertebral microCT and histomorphometry show fewer trabeculae, lower bone mass and decreased bone formation. This provides donor grounding for a contextual skeletal role through matrix regulation; it does not imply that fibrillin-2 is a bone-specific protein or an osteoblast enzyme. The curator-reviewed ISS transfer is retained as an inference to human FBN2; the mouse experiments are not relabeled as direct human perturbation evidence. No inference is made for soluble placensin or the truncated splice product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q61555 Β· Mouse Fbn2 SUPPORTS TRANSFER Actual donor IMP GO:0060346, PMID:20855508, and the operative mouse study were read. Actual mouse Fbn2-null vertebral microCT and histomorphometry show fewer trabeculae, lower bone mass and decreased bone formation. This provides donor grounding for a contextual skeletal role through matrix regulation; it does not imply that fibrillin-2 is a bone-specific protein or an osteoblast enzyme. |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:12429739 Fibrillins can co-assemble in fibrils, but fibrillin fibril ... | KEEP AS NON CORE | Summary: Human FBN2 has a supported basement-membrane-associated matrix context. Reason: This source establishes human dermal microfibrils and dermal-epidermal junction staining, without resolving uniform lamina-densa incorporation. Independent human GBM and Descemet/anterior lens-capsule localization supports the same generic noncollagenous basement-membrane claim. Preserve the source-specific localization limit and retain the contextual location as non-core. |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:15277214 Regulation of fibrillin-1 by biglycan and decorin is importa... | KEEP AS NON CORE | Summary: The original paper directly localizes human FBN2 to renal basement-membrane regions. Reason: Results and Figure 3B identify FBN2 in GBM, with only trace Bowman capsule and tubular-basement-membrane signal. The FBN1-focused title does not negate these actual FBN2 assays. Retain this tissue-specific location as non-core; mouse injury and rat-cell induction results are separate. Supporting Evidence: |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:24899048 Rare and common variants in extracellular matrix gene Fibril... | KEEP AS NON CORE | Summary: Independent human localization supports the generic basement-membrane claim, with the Bruch-layer limitation retained. Reason: The original fetal-eye co-labeling places FBN2 particularly in the central elastic layer of Bruch membrane, which does not itself establish incorporation into the RPE or choriocapillaris basal lamina. This source row has no tissue extension. Retain the same generic noncollagenous basement-membrane claim as non-core on independent human renal GBM and Descemet/anterior lens-capsule evidence; do not reinterpret the original layer measurement. |
| GO:0140144 non-collagenous component of basement membrane | IDA PMID:25406291 Human eye development is characterized by coordinated expres... | KEEP AS NON CORE | Summary: FBN2 is directly detected in defined human ocular basement membranes. Reason: The paper identifies FBN2 in Descemet membrane and anterior lens capsule at specified developmental or juvenile stages, with antibody and negative controls. Retain the contextual location as non-core; it is not uniform throughout all corneal layers or the juvenile zonule. Supporting Evidence: |
| GO:0140144 non-collagenous component of basement membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Fibrillin-2 is present in defined non-collagenous basement-membrane compartments. Reason: ARBA00096893 predicts the cellular-component term GO:0140144. Actual human evidence includes FBN2 in glomerular basement membrane and mesangial matrix in PMID:15277214, with only trace Bowman capsule/tubular-basement-membrane staining, and FBN2 in Descemet membrane and anterior lens-capsule basal lamina in PMID:25406291. PMID:24899048 places FBN2 in the central elastin layer of fetal Bruch membrane; that observation alone would not justify a uniform RPE basal-lamina claim. Retain a bounded secondary location rather than assigning all basement membranes or making a molecular-function assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00096893 Β· ARBA00096893 SUPPORTS TRANSFER Actual rule read. Independent human kidney and ocular protein localization supports the compartment claim; no universal basement-membrane distribution or complete rule-training audit is asserted. |
| 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: FBN2-containing microfibrils occupy interstitial connective-tissue matrix. Reason: The MatrisomeDB target page was not accessible, so its exact FBN2 dataset join remains unverified. Independent human fetal dermal/periappendiceal localization and human dermal microfibril imaging support the same generic interstitial-matrix claim. Retain positive TAS biology as non-core with curator deference, without claiming a recovered database record. |
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Download this section (compressed HTML)Experiment: Test the curated furin-processing model in human trophoblast cultures by enriching the native secreted C-terminal product and mapping its intact mass and N terminus, without inferring the terminus from digested internal peptides. Compare furin depletion with rescue by wild-type and catalytically inactive furin, measuring long-precursor expression, matrix-chain secretion, general secretion and viability in parallel. Test isolated products at matched concentrations in the established recipient-cell assays; distinguish reduced cleavage from a global loss of precursor secretion.
Hypothesis: Furin-dependent processing generates a defined endogenous placensin species from the long FBN2 precursor.
Type: Intact-protein mass spectrometry and controlled protease perturbation
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The exact intact endogenous placensin N terminus and the quantitative dependence of its release on furin in human trophoblasts remain unresolved in the primary experiments assessed here.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: UniProt P35556 explicitly annotates secretion of linked fibrillin-2/placensin followed by furin separation with ECO:0000269 citing PMID32329225, and the article adopts this processing model. Its Results identify the site by PiTou prediction and show furin colocalization, secreted C-terminal immunoreactivity and IP-MS peptides after proteolytic digestion. Those observations support release of the product but do not map an intact endogenous N terminus or isolate furin necessity. The recombinant Methods specify 2780β2912, while Figure 2 gives 2779β2912. This is a bounded processing-resolution question, not a denial of the curated processing model or of placensin secretion.
Significance: Defining endogenous processing would distinguish the naturally released hormone from an active recombinant fragment and test how its production is separated from matrix-chain secretion.
What would resolve it: Map intact secreted placensin termini and test furin perturbation with rescue while controlling precursor abundance, cell viability and general secretion.
Provenance (the field's own admissions):
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