Fibronectin is a major extracellular matrix (ECM) glycoprotein and one of the most important adhesion molecules in vertebrates. This large 2477 amino acid multidomain protein exists as a dimer and contains three types of repeating modules (FN-I, FN-II, and FN-III repeats) that create distinct binding sites for cells and other ECM components. The core functions of fibronectin center on organizing the ECM architecture and mediating cell-ECM interactions. Through its RGD motif in the FN-III10 domain, fibronectin directly binds integrin receptors (particularly alpha5beta1, alpha4beta1, alphaVbeta3) to mediate cell adhesion, migration, and signaling. Fibronectin serves as a key structural organizer by binding collagen types I-V and VII, assembling into fibrillar networks, and coordinating ECM assembly. It also binds fibrin through N-terminal and C-terminal sites, playing critical roles in provisional matrix formation during wound healing and hemostasis. Additional functions include binding heparin/heparan sulfate proteoglycans and serving as a ligand for various cell surface receptors. Fibronectin is essential for embryonic development, particularly in mesoderm formation, neural crest cell migration, heart development, and vascular morphogenesis. While the protein participates in numerous biological contexts including wound healing, angiogenesis, and platelet function, its fundamental role is as an ECM structural constituent and cell adhesion scaffold that integrates mechanical and biochemical signals at the cell-matrix interface.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007399 nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Fibronectin plays important roles in neural crest cell migration and nervous system development during embryogenesis. However, this represents a developmental context rather than a core molecular function of the mature protein. Reason: While experimentally validated (PMID:26571399 demonstrates FN1 role in neural crest cell migration for enteric nervous system development), nervous system development represents a specific developmental context. The core function is ECM-mediated cell adhesion and migration; nervous system development is one of many developmental processes where these core functions are deployed. Appropriate to retain but mark as non-core. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... |
| GO:0007044 cell-substrate junction assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Fibronectin is a key component in assembling focal adhesions and cell-substrate junctions through integrin engagement. This is a core function directly related to fibronectin's role as a cell adhesion substrate. Reason: Cell-substrate junction assembly (focal adhesion formation) is a direct and core consequence of fibronectin-integrin interactions. The RGD motif in FN-III10 mediates integrin binding which triggers focal adhesion assembly. Multiple experimental studies confirm fibronectin's central role in this process. This IBA annotation is well-supported and represents core fibronectin biology. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a high-affinity form of fibronectin |
| GO:0007160 cell-matrix adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Cell-matrix adhesion is one of the most fundamental and core functions of fibronectin. Through integrin binding (RGD motif), fibronectin directly mediates cell attachment to the ECM. Deep research confirms fibronectin's primary role as a cell-adhesive ECM glycoprotein that forms fibrillar networks (FN1-deep-research-falcon.md). Reason: This annotation captures the quintessential function of fibronectin as a major cell adhesion molecule. Fibronectin serves as the primary ligand for multiple integrins (alpha5beta1, alpha4beta1, alphaVbeta3, alphaVbeta1, alphaVbeta6, alpha8beta1) mediating cell-matrix adhesion. This is extensively validated across decades of research and represents core fibronectin biology. The IBA annotation is phylogenetically sound. Cryo-EM structures show three simultaneous FN-integrin interactions at the synergy site, RGD loop, and ADMIDAS (PMID:33962943). Supporting Evidence: PMID:33962943 The complex of integrin alpha5beta1 with FN7-10 shows three simultaneous interactions critical for the stabilization of integrin opening, namely, (i) at the synergy site of FN9, (ii) at the RGD loop of FN10, and (iii) at the adjacent to MIDAS (ADMIDAS) of the integrin beta1 betaI domain. file:human/FN1/FN1-deep-research-falcon.md Fibronectin's primary role is as a cell-adhesive ECM glycoprotein that forms fibrillar networks and functions as a scaffold to organize other ECM components and associated signaling molecules. |
| GO:0007507 heart development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Fibronectin is essential for cardiac morphogenesis and heart development, particularly in cardiac cushion formation and valve development. However, like nervous system development, this represents a specific developmental context. Reason: While fibronectin is critical for heart development (particularly endocardial cushion formation and valve morphogenesis), this represents application of core adhesion/migration functions in a specific developmental context. Heart development is one of many developmental processes requiring fibronectin. The underlying core functions are ECM organization and cell adhesion/migration. Appropriate as non-core. Supporting Evidence: GO_REF:0000033 |
| GO:0005178 integrin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Integrin binding is a core molecular function of fibronectin. The RGD sequence in the FN-III10 domain directly binds integrin alpha5beta1, and other sites engage additional integrins. Reason: This is a fundamental molecular function annotation representing direct protein-protein interaction. Fibronectin contains the canonical RGD motif (Arg-Gly-Asp) in the 10th type III repeat that is the primary recognition site for integrin alpha5beta1. Additional integrin binding sites exist for alpha4beta1 (via CS-1 region), alphaVbeta3, and others. Extensively validated by structural and biochemical studies. This is core fibronectin function. Supporting Evidence: PMID:33962943 Structural insights into integrin Ξ±(5)Ξ²(1) opening by fibronectin ligand PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility PMID:19738201 Quantitative, comparative analyses of the proteomes of two receptor-ligand pairs, alpha(4)beta(1)-vascular cell adhesion molecule-1 and alpha(5)beta(1... |
| GO:0043394 proteoglycan binding | IBA GO_REF:0000033 | ACCEPT | Summary: Fibronectin binds proteoglycans and heparan sulfate through specific heparin-binding domains. This is a well-characterized core molecular function important for ECM organization. Reason: Fibronectin contains three heparin-binding sites (Hep I, Hep II, Hep III) that mediate binding to heparan sulfate proteoglycans including syndecans and perlecan. This interaction is important for fibronectin matrix assembly and ECM organization. Multiple studies validate proteoglycan binding as a core molecular function. The IBA annotation is appropriate. Supporting Evidence: PMID:29030641 Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface file:human/FN1/FN1-uniprot.txt |
| GO:0001525 angiogenesis | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Fibronectin supports angiogenesis through ECM scaffolding and integrin-mediated endothelial cell adhesion and migration. While important, this is a specific biological context rather than core function. Reason: Angiogenesis represents a specific biological process where fibronectin's core adhesion and migration functions are deployed. The anastellin fragment can inhibit angiogenesis (PMID:11209058), and fibronectin supports endothelial cell migration (PMID:20123964). However, angiogenesis is one of many processes utilizing fibronectin's core functions. This IEA annotation from keyword mapping is too general for core function. Mark as non-core. Supporting Evidence: PMID:20123964 In subconfluent ECs, LPP3 induced expression of fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin homologue (PTEN)-dependent ma... |
| GO:0002020 protease binding | IEA GO_REF:0000117 | ACCEPT | Summary: Fibronectin binds various proteases including cathepsins and MMPs. While validated, this is less specific than other molecular function terms describing fibronectin's binding activities. Reason: Experimentally validated by PMID:22952693 showing cathepsin S cleavage of nidogen-1 affecting fibronectin binding. Fibronectin is also a substrate for multiple matrix metalloproteinases (MMPs). While this annotation is somewhat general, it describes a real molecular interaction. The ARBA machine learning annotation is supported by experimental evidence. Accept but note this is less informative than specific binding partner annotations. Supporting Evidence: PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | MODIFY | Summary: Fibronectin is secreted and localized to the extracellular space and ECM. This is accurate but overly broad - more specific cellular component terms exist. Reason: While factually correct that fibronectin is in the extracellular region, this is too general. More specific and informative terms include GO:0031012 (extracellular matrix) and GO:0005615 (extracellular space). This IEA annotation should be replaced with the more specific GO:0031012 which better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: file:human/FN1/FN1-uniprot.txt |
| GO:0006953 acute-phase response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Fibronectin can be upregulated during acute-phase response as part of tissue repair. This represents a specific physiological context. Reason: Fibronectin levels can increase during acute inflammation and tissue injury as part of provisional matrix formation and wound healing. However, this represents a regulatory context rather than core function. The acute-phase response is one of many physiological situations where fibronectin participates. The core functions are ECM organization and cell adhesion. Mark as non-core. Supporting Evidence: GO_REF:0000043 |
| GO:0007155 cell adhesion | IEA GO_REF:0000043 | ACCEPT | Summary: Cell adhesion is a core function of fibronectin, mediating attachment of cells to ECM through integrin binding. This IEA annotation correctly captures fundamental fibronectin biology. Reason: This is essentially equivalent to the more specific GO:0007160 (cell-matrix adhesion) and represents a core function. Fibronectin is one of the most important cell adhesion molecules in vertebrates. Through integrin binding, it mediates cell attachment, spreading, and migration. Extensively validated across literature. Accept this IEA annotation as accurate, though GO:0007160 (cell-matrix adhesion) is more specific. Supporting Evidence: PMID:1423622 The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions file:human/FN1/FN1-uniprot.txt |
| GO:0008201 heparin binding | IEA GO_REF:0000043 | ACCEPT | Summary: Heparin binding is a well-characterized core molecular function of fibronectin through three distinct heparin-binding domains (Hep I, II, III). Reason: Fibronectin contains three separate heparin-binding sites that mediate interactions with heparin and heparan sulfate proteoglycans. This is extensively characterized structurally and functionally. Heparin binding is important for fibronectin matrix assembly and ECM organization. NAS evidence from PMID:10075919 provides structural characterization. This IEA keyword-based annotation is accurate and represents core molecular function. Supporting Evidence: PMID:10075919 Crystal structure of a heparin- and integrin-binding segment of human fibronectin |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Fibronectin influences cell shape through integrin-mediated cytoskeletal reorganization during adhesion and spreading. This is a downstream consequence of cell adhesion. Reason: Cell shape regulation occurs as a consequence of fibronectin-integrin interactions triggering cytoskeletal reorganization. While valid, this is an indirect effect downstream of the core adhesion function rather than a direct molecular activity. Cells spread and change shape when adhering to fibronectin substrates, but this is secondary to the primary function of integrin binding and focal adhesion formation. Mark as non-core. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Fibronectin binds integrin receptors and other cell surface receptors. This is accurate but somewhat general compared to the more specific integrin binding term. Reason: Fibronectin acts as a ligand for multiple cell surface receptors including integrins (alpha5beta1, alpha4beta1, alphaVbeta3, etc.) and other receptors like ILT3/LILRB4 (PMID:34089617). While GO:0005178 (integrin binding) is more specific and informative, this broader term is also accurate. The IEA annotation from Ensembl orthology is valid. Accept as it captures fibronectin's receptor-binding function. Supporting Evidence: PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice |
| GO:0005604 basement membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fibronectin is present in basement membranes but is more characteristic of interstitial ECM. Plasma fibronectin is distinct from cellular fibronectin in basement membranes. Reason: While fibronectin can be found in basement membranes, it is not a core structural component like laminin, collagen IV, nidogen, and perlecan. Fibronectin is more abundant in interstitial ECM. The cellular fibronectin isoform (containing EIIIA and EIIIB domains) is found in some basement membrane zones, but this is a minor localization. The primary fibronectin localization is GO:0031012 (extracellular matrix). Mark as non-core. Supporting Evidence: GO_REF:0000107 |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: Fibronectin is secreted into the extracellular space where it assembles into ECM fibrils. This is a correct core localization annotation. Reason: Fibronectin is a secreted protein that localizes to the extracellular space. Both plasma fibronectin (soluble in blood/body fluids) and cellular fibronectin (assembled into ECM) occupy extracellular space. Extensively validated by experimental localization (PMID:15292204 IDA evidence). This is an appropriate and accurate cellular component annotation for a major ECM protein. Supporting Evidence: PMID:15292204 BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, contains a disordered region that undergoes a conformational change on ligand binding |
| GO:0014850 response to muscle activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fibronectin expression can be modulated by mechanical forces including muscle activity. This represents a regulatory context rather than core function. Reason: Mechanical forces and muscle activity can influence fibronectin expression and matrix remodeling in musculoskeletal tissues. However, this is a specific physiological context of fibronectin regulation rather than a core molecular function. Response to muscle activity is peripheral to the core ECM organization and cell adhesion functions. Mark as non-core. Supporting Evidence: GO_REF:0000107 |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000107 | REMOVE | Summary: Fibronectin can be associated with apical surfaces of polarized epithelia, but this is not a primary or characteristic localization. Reason: This IEA annotation from Ensembl orthology is likely incorrect or represents a very minor localization. Fibronectin is primarily an extracellular matrix and extracellular space protein. While fibronectin may interact with cells at apical surfaces in some epithelial contexts, this is not a characteristic localization and lacks strong experimental support. The primary localizations (ECM, extracellular space) are better represented by other annotations. Remove as not representative of core fibronectin biology. Supporting Evidence: GO_REF:0000107 |
| GO:0016504 peptidase activator activity | IEA GO_REF:0000107 | REMOVE | Summary: Fibronectin fragments can modulate protease activity, but this is not a well-established core molecular function of intact fibronectin. Reason: While fibronectin can be cleaved by proteases and may influence protease activity in certain contexts, peptidase activator activity is not a well-documented core molecular function. The IEA annotation from Ensembl orthology lacks strong experimental support. Fibronectin is primarily a substrate for proteases (MMPs, cathepsins) rather than an activator. No compelling evidence supports this as a core function. Remove. Supporting Evidence: GO_REF:0000107 |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Extracellular matrix is the primary and most characteristic localization of fibronectin. This is a core cellular component annotation. Reason: This is the most important cellular component annotation for fibronectin. Fibronectin is one of the major structural constituents of the ECM, assembling into fibrillar networks that organize the matrix architecture. Both cellular and plasma fibronectin ultimately localize to and organize ECM. Extensively validated across decades of research and multiple experimental approaches (IDA, HDA, ISS evidence in other annotations). This IEA annotation is accurate and represents core fibronectin localization. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... PMID:16157329 Sequential deposition of latent TGF-beta binding proteins (LTBPs) during formation of the extracellular matrix in human lung fibroblasts |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000107 | ACCEPT | Summary: Fibronectin acts as a ligand for integrin receptors and other cell surface receptors, mediating cell signaling. This is a valid molecular function. Reason: Fibronectin functions as a bona fide receptor ligand, particularly for integrin receptors (alpha5beta1, alpha4beta1, alphaVbeta3, etc.) where it triggers intracellular signaling cascades upon binding. This leads to focal adhesion kinase activation, MAPK signaling, PI3K/Akt pathway activation, and other downstream events. The term accurately describes fibronectin's role in receptor-mediated signaling. Accept as valid molecular function. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility |
| GO:0150102 negative regulation of monocyte activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Fibronectin can modulate monocyte activation through receptor interactions, including inhibitory checkpoint receptors. Reason: PMID:34089617 demonstrates that blockade of fibronectin binding to checkpoint receptor ILT3/LILRB4 ameliorates autoimmune disease by affecting monocyte activation. While experimentally validated, this represents a specific immunomodulatory function in a particular disease context rather than a core function. The fundamental role is receptor binding; monocyte regulation is a downstream consequence in specific contexts. Mark as non-core. Supporting Evidence: PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice |
| GO:0005515 protein binding | IPI PMID:11377428 Binding of a peptide from a Streptococcus dysgalactiae MSCRA... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:11377428 Binding of a peptide from a Streptococcus dysgalactiae MSCRAMM to the N-terminal F1 module pair of human fibronectin involves both modules |
| GO:0005515 protein binding | IPI PMID:12736686 Pathogenic bacteria attach to human fibronectin through a ta... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:12736686 Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper |
| GO:0005515 protein binding | IPI PMID:16457822 CT domain of CCN2/CTGF directly interacts with fibronectin a... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:16457822 CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin alpha5beta1 |
| GO:0005515 protein binding | IPI PMID:1747115 Interaction of the small proteoglycan decorin with fibronect... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:1747115 Interaction of the small proteoglycan decorin with fibronectin |
| GO:0005515 protein binding | IPI PMID:18042364 TSG-6 binds via its CUB_C domain to the cell-binding domain ... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18042364 TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly |
| GO:0005515 protein binding | IPI PMID:18160478 Novel adhesin from Pasteurella multocida that binds to the i... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18160478 Novel adhesin from Pasteurella multocida that binds to the integrin-binding fibronectin FnIII9-10 repeats |
| GO:0005515 protein binding | IPI PMID:18243143 Uteroglobin interacts with the heparin-binding site of fibro... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18243143 Uteroglobin interacts with the heparin-binding site of fibronectin and prevents fibronectin-IgA complex formation found in IgA-nephropathy |
| GO:0005515 protein binding | IPI PMID:18323857 NEDD8 acts as a 'molecular switch' defining the functional s... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18323857 The von Hippel-Lindau (VHL) tumour suppressor protein is important in the E3 ubiquitin ligase ECV (Elongin B/C-CUL2-VHL)-mediated destruction of hypox... |
| GO:0005515 protein binding | IPI PMID:18411296 The surface-exposed carboxyl region of Mycoplasma pneumoniae... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18411296 The surface-exposed carboxyl region of Mycoplasma pneumoniae elongation factor Tu interacts with fibronectin |
| GO:0005515 protein binding | IPI PMID:18713862 Crystal structures of fibronectin-binding sites from Staphyl... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:18713862 Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains |
| GO:0005515 protein binding | IPI PMID:19542224 The first draft of the endostatin interaction network. | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:19542224 Epub 2009 Jun 19. The first draft of the endostatin interaction network. |
| GO:0005515 protein binding | IPI PMID:19738201 Proteomic analysis of integrin-associated complexes identifi... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:19738201 Quantitative, comparative analyses of the proteomes of two receptor-ligand pairs, alpha(4)beta(1)-vascular cell adhesion molecule-1 and alpha(5)beta(1... |
| GO:0005515 protein binding | IPI PMID:20080707 EGF potentiated oncogenesis requires a tissue transglutamina... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:20080707 EGF potentiated oncogenesis requires a tissue transglutaminase-dependent signaling pathway leading to Src activation. |
| GO:0005515 protein binding | IPI PMID:20541508 Zinc induces structural reorganization of gelatin binding do... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:20541508 Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding |
| GO:0005515 protein binding | IPI PMID:20875085 Functional analysis of a murine monoclonal antibody against ... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:20875085 Functional analysis of a murine monoclonal antibody against the repetitive region of the fibronectin-binding adhesins fibronectin-binding protein A an... |
| GO:0005515 protein binding | IPI PMID:20879998 Repeat regions R1 and R2 in the P97 paralogue Mhp271 of Myco... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:20879998 Repeat regions R1 and R2 in the P97 paralogue Mhp271 of Mycoplasma hyopneumoniae bind heparin, fibronectin and porcine cilia |
| GO:0005515 protein binding | IPI PMID:21569203 The A domain of fibronectin-binding protein B of Staphylococ... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:21569203 The A domain of fibronectin-binding protein B of Staphylococcus aureus contains a novel fibronectin binding site |
| GO:0005515 protein binding | IPI PMID:22442151 Transglutaminase-2 interaction with heparin: identification ... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:22442151 Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 m... |
| GO:0005515 protein binding | IPI PMID:24136289 Identification and comparative analysis of hepatitis C virus... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:24136289 Identification and comparative analysis of hepatitis C virus-host cell protein interactions. |
| GO:0005515 protein binding | IPI PMID:24388360 SERPINA5 inhibits tumor cell migration by modulating the fib... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:24388360 SERPINA5 inhibits tumor cell migration by modulating the fibronectin-integrin Ξ²1 signaling pathway in hepatocellular carcinoma |
| GO:0005515 protein binding | IPI PMID:25034023 Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:25034023 Epub 2014 Jul 14. Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self-interactions in microfibril assembly. |
| GO:0005515 protein binding | IPI PMID:25290767 Structural and functional analysis of the fibronectin-bindin... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:25290767 Structural and functional analysis of the fibronectin-binding protein FNE from Streptococcus equi spp |
| GO:0005515 protein binding | IPI PMID:25293691 Proteolytic processing of the cilium adhesin MHJ_0194 (P123J... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:25293691 Affinity chromatography using heparin, fibronectin and plasminogen as bait and peptide arrays were used to expand our knowledge of the adhesive capabi... |
| GO:0005515 protein binding | IPI PMID:2531657 Lipoprotein(a) binds to fibronectin and has serine proteinas... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:2531657 Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:26848503 Mapping and Exploring the Collagen-I Proteostasis Network. | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:26848503 Epub 2016 Mar 9. Mapping and Exploring the Collagen-I Proteostasis Network. |
| GO:0005515 protein binding | IPI PMID:27141819 Mycobacterial antigen 85 complex (Ag85) as a target for fico... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:27141819 Furthermore, those PRMs also bound to fibronectin and therefore might influence the Ag85 complex-dependent interaction of Mycobacterium with the extra... |
| GO:0005515 protein binding | IPI PMID:27616280 Interactions of surface-displayed glycolytic enzymes of Myco... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:27616280 interactions of the previously confirmed surface-located glycolytic enzymes...to the human extracellular matrix (ECM) proteins fibrinogen (Fn), fibronectin (Fc), lactoferrin (Lf), laminin (Ln) and vitronectin (Vc) |
| GO:0005515 protein binding | IPI PMID:30082873 Insights into the structure and dynamics of lysyl oxidase pr... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:30082873 Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagens and elastin, which is the first step of the ... |
| GO:0005515 protein binding | IPI PMID:31759052 Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Li... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:31759052 We here provide evidence that LOXL2 also affects deposition of other ECM components, including fibronectin, thus altering structural and mechanical pr... |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:34968453 Stabilin-1 mediates beneficial monocyte recruitment and tole... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:34968453 Yeast two-hybrid screening, confirmed by affinity chromatography, identified fibronectin as a stabilin-1 interacting partner |
| GO:0005515 protein binding | IPI PMID:9269765 Novel interaction of apolipoprotein(a) with beta-2 glycoprot... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:9269765 Among 11 positive clones that emerged from the screen, eight clones were identified as beta-2 glycoprotein I and one as fibronectin |
| GO:0042802 identical protein binding | IPI PMID:17914904 Force-induced unfolding of fibronectin in the extracellular ... | ACCEPT | Summary: Fibronectin forms homodimers through C-terminal disulfide bonds. This is a core molecular function. Reason: Fibronectin exists as a disulfide-bonded dimer. Two monomers link via C-terminal disulfide bonds, essential for function and matrix assembly. This is a core molecular property validated by structural studies. IPI annotations correctly capture this fundamental aspect of fibronectin biology. Supporting Evidence: PMID:17914904 Force-induced unfolding of fibronectin in the extracellular matrix of living cells |
| GO:0042802 identical protein binding | IPI PMID:18042364 TSG-6 binds via its CUB_C domain to the cell-binding domain ... | ACCEPT | Summary: Fibronectin forms homodimers through C-terminal disulfide bonds. This is a core molecular function. Reason: Fibronectin exists as a disulfide-bonded dimer. Two monomers link via C-terminal disulfide bonds, essential for function and matrix assembly. This is a core molecular property validated by structural studies. IPI annotations correctly capture this fundamental aspect of fibronectin biology. Supporting Evidence: PMID:18042364 TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly |
| GO:0042802 identical protein binding | IPI PMID:19826086 Fibronectin forms the most extensible biological fibers disp... | ACCEPT | Summary: Fibronectin forms homodimers through C-terminal disulfide bonds. This is a core molecular function. Reason: Fibronectin exists as a disulfide-bonded dimer. Two monomers link via C-terminal disulfide bonds, essential for function and matrix assembly. This is a core molecular property validated by structural studies. IPI annotations correctly capture this fundamental aspect of fibronectin biology. Supporting Evidence: PMID:19826086 Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites |
| GO:0042802 identical protein binding | IPI PMID:19931242 The interaction of angiocidin with tissue transglutaminase. | ACCEPT | Summary: Fibronectin forms homodimers through C-terminal disulfide bonds. This is a core molecular function. Reason: Fibronectin exists as a disulfide-bonded dimer. Two monomers link via C-terminal disulfide bonds, essential for function and matrix assembly. This is a core molecular property validated by structural studies. IPI annotations correctly capture this fundamental aspect of fibronectin biology. Supporting Evidence: PMID:19931242 Cross-linked angiocidin inhibited cell migration in contrast to monomeric angiocidin and inhibited localization of fibronectin (FN), a pro-tumorigenic... |
| GO:0042802 identical protein binding | IPI PMID:20541508 Zinc induces structural reorganization of gelatin binding do... | ACCEPT | Summary: Fibronectin forms homodimers through C-terminal disulfide bonds. This is a core molecular function. Reason: Fibronectin exists as a disulfide-bonded dimer. Two monomers link via C-terminal disulfide bonds, essential for function and matrix assembly. This is a core molecular property validated by structural studies. IPI annotations correctly capture this fundamental aspect of fibronectin biology. Supporting Evidence: PMID:20541508 Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3788061 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-3788061 |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | ACCEPT | Summary: Fibronectin is synthesized and modified in the ER during secretion. Minor localization annotation. Reason: As a secreted glycoprotein, fibronectin is synthesized in the ER. This represents the secretory pathway rather than functional localization. Accurate but represents trafficking. Accept as valid but note this is transient, not functional localization. Supporting Evidence: Reactome:R-HSA-8952289 |
| GO:0005577 fibrinogen complex | IPI PMID:20541508 Zinc induces structural reorganization of gelatin binding do... | ACCEPT | Summary: Fibronectin binds fibrin/fibrinogen forming complexes important for provisional matrix and wound healing. Reason: Fibronectin contains fibrin-binding sites at N-terminal and C-terminal regions. Interaction with fibrin(ogen) is critical for provisional matrix formation during hemostasis and wound healing. Experimentally validated. Core molecular interaction. Accept. Supporting Evidence: PMID:20541508 Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding |
| GO:0005615 extracellular space | IDA PMID:15292204 BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorfe... | ACCEPT | Summary: Fibronectin is secreted into extracellular space. Core localization annotation. Reason: Fibronectin is a secreted protein localizing to extracellular space. Both plasma fibronectin (soluble in body fluids) and cellular fibronectin (assembled into ECM) occupy extracellular space. Appropriate cellular component annotation. Supporting Evidence: PMID:15292204 BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, contains a disordered region that undergoes a conformational change on ligand binding |
| GO:0072378 blood coagulation, fibrin clot formation | IDA PMID:3997886 Incorporation of thrombospondin into fibrin clots. | KEEP AS NON CORE | Summary: Fibronectin participates in fibrin clot formation through fibrin binding, but this is a specific physiological context. Reason: Fibronectin-fibrin interaction contributes to clot formation and provisional matrix assembly (PMID:3997886). However, blood coagulation represents one specific biological context where fibronectin's core binding functions are deployed. The fundamental activities are fibrin binding and ECM organization. Mark as non-core. Supporting Evidence: PMID:3997886 In contrast, incorporation of 125I-fibronectin into clots was dependent upon cross-linking |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:23658023 We show that identified candidate molecules can support attachment and self-renewal of hESCs alone (fibrillin-1) or in combination with fibronectin (p... |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1566981 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-1566981 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-202723 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-202723 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-216050 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-216050 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327733 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2327733 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2327746 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2327746 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396337 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2396337 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2533950 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2533950 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2537665 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2537665 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2545196 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2545196 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2681681 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2681681 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2731141 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-2731141 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-349593 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-349593 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354066 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354066 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354073 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354073 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354087 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354087 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354124 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354124 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354149 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354149 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-354165 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-354165 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372693 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-372693 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372697 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-372697 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-372705 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-372705 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377640 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-377640 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377641 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-377641 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377643 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-377643 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-377644 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-377644 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3785684 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-3785684 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-429415 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-429415 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-429441 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-429441 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-481007 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6785895 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-6785895 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9624017 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-9624017 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9638552 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-9638552 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9865226 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-9865226 |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9932034 | MODIFY | Summary: Extracellular region annotation - too general, should use extracellular matrix. Reason: While fibronectin is in the extracellular region, this term is too general. The more specific GO:0031012 (extracellular matrix) better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: Reactome:R-HSA-9932034 |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: Plasma fibronectin is stored in platelet alpha granules and released upon activation. Reason: Fibronectin is a known component of platelet alpha granules, released during platelet activation for hemostasis and provisional matrix formation. Well-documented localization for plasma fibronectin pool. Accept as valid cellular component annotation. Supporting Evidence: Reactome:R-HSA-481007 |
| GO:0043542 endothelial cell migration | IDA PMID:20123964 Lipid phosphate phosphatase 3 stabilization of beta-catenin ... | KEEP AS NON CORE | Summary: Fibronectin supports endothelial cell migration, but this is a cell-type-specific process. Reason: PMID:20123964 demonstrates fibronectin-mediated endothelial cell migration. However, this represents application of core cell adhesion/migration functions in a specific cell type (angiogenesis context). Fibronectin mediates migration of many cell types. Mark as non-core. Supporting Evidence: PMID:20123964 In subconfluent ECs, LPP3 induced expression of fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin homologue (PTEN)-dependent ma... |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700181 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9700181 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700190 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9700190 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700193 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9700193 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712078 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9712078 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712079 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9712079 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712083 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9712083 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712084 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9712084 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9712085 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9712085 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9724099 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9724099 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9850958 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9850958 |
| GO:0005178 integrin binding | IDA PMID:33962943 Structural insights into integrin Ξ±(5)Ξ²(1) opening by fibron... | ACCEPT | Summary: Integrin binding is a core molecular function mediated by RGD motif and other sites. Reason: Fibronectin's RGD motif in FN-III10 binds integrin alpha5beta1. Additional sites engage alpha4beta1, alphaVbeta3, and others. Extensively validated by structural and biochemical studies. Core function. Accept. Supporting Evidence: PMID:33962943 Structural insights into integrin Ξ±(5)Ξ²(1) opening by fibronectin ligand |
| GO:0005515 protein binding | IPI PMID:33962943 Structural insights into integrin Ξ±(5)Ξ²(1) opening by fibron... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:33962943 Structural insights into integrin Ξ±(5)Ξ²(1) opening by fibronectin ligand |
| GO:0005515 protein binding | IPI PMID:12167537 Several regions of the repeat domain of the Staphylococcus c... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:12167537 Several regions of the repeat domain of the Staphylococcus caprae autolysin, AtlC, are involved in fibronectin binding |
| GO:0005515 protein binding | IPI PMID:12421310 Elongation factor Tu and E1 beta subunit of pyruvate dehydro... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:12421310 Elongation factor Tu and E1 beta subunit of pyruvate dehydrogenase complex act as fibronectin binding proteins in Mycoplasma pneumoniae |
| GO:0005515 protein binding | IPI PMID:15292204 BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorfe... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:15292204 BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, contains a disordered region that undergoes a conformational change on ligand binding |
| GO:0005515 protein binding | IPI PMID:17849409 Identification of novel bacterial plasminogen-binding protei... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:17849409 Interestingly, GlnA1 was able to bind the extracellular matrix (ECM) protein fibronectin |
| GO:0005515 protein binding | IPI PMID:19429745 Enolase from Paracoccidioides brasiliensis: isolation and id... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:19429745 Enolase from Paracoccidioides brasiliensis: isolation and identification as a fibronectin-binding protein |
| GO:0031012 extracellular matrix | IDA PMID:26571399 A collagen VI-dependent pathogenic mechanism for Hirschsprun... | ACCEPT | Summary: Extracellular matrix is the primary localization of fibronectin. Core cellular component annotation. Reason: This is the most important cellular component annotation for fibronectin. Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks. Extensively validated across decades of research. This annotation is accurate and represents core fibronectin localization. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... |
| GO:1901166 neural crest cell migration involved in autonomic nervous system development | IDA PMID:26571399 A collagen VI-dependent pathogenic mechanism for Hirschsprun... | KEEP AS NON CORE | Summary: Fibronectin mediates neural crest migration for autonomic nervous system development. Specific developmental context. Reason: This is essentially the same as GO:0048484 but more specific to autonomic nervous system. Experimentally validated (PMID:26571399). Represents specific developmental application of core migration functions. Mark as non-core. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:25834989 Fibulin1C peptide induces cell attachment and extracellular ... | KEEP AS NON CORE | Summary: Fibronectin can promote cell proliferation through integrin signaling. Regulatory function in specific contexts. Reason: Experimental validation (PMID:25834989) shows fibulin1C peptide induces proliferation via fibronectin interactions. While valid, proliferation regulation is a downstream consequence and context-dependent. Core functions are adhesion and signaling. Mark as non-core. Supporting Evidence: PMID:25834989 In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups |
| GO:0005102 signaling receptor binding | IDA PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronec... | ACCEPT | Summary: Fibronectin binds signaling receptors including integrins and checkpoint receptors. Reason: Experimental validation (PMID:34089617) shows fibronectin binds ILT3/LILRB4 checkpoint receptor. Combined with integrin binding, this term accurately captures receptor-binding function. While GO:0005178 (integrin binding) is more specific, this broader term is also valid. Accept. Supporting Evidence: PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice |
| GO:0150102 negative regulation of monocyte activation | IDA PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronec... | KEEP AS NON CORE | Summary: Fibronectin modulates monocyte activation through checkpoint receptor interactions. Reason: Experimental validation (PMID:34089617) in autoimmune disease model. Fibronectin-ILT3 interactions regulate monocyte function. While valid, this represents a specific immunomodulatory function in particular disease contexts. Core function is receptor binding. Mark as non-core. Supporting Evidence: PMID:34089617 Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700131 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9700131 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9700179 | KEEP AS NON CORE | Summary: Fibronectin interacts with integrins at the plasma membrane, but fibronectin itself is extracellular. Reason: These Reactome annotations refer to fibronectin-integrin complexes at cell surfaces. However, fibronectin is an extracellular protein; plasma membrane localization refers to its binding partners (integrins). This is indirect. Additionally, 12 separate annotations for the same term represent over-annotation. Mark as non-core. Supporting Evidence: Reactome:R-HSA-9700179 |
| GO:0007229 integrin-mediated signaling pathway | IDA PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics dri... | ACCEPT | Summary: Fibronectin-integrin binding triggers signaling cascades. This is a direct consequence of integrin engagement. Reason: Fibronectin binding to integrins triggers intracellular signaling (FAK, PI3K, MAPK pathways). Experimental validation (PMID:19126672). While downstream of integrin binding, signaling initiation is a direct and important consequence of fibronectin-integrin interactions. Accept. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts |
| GO:0034446 substrate adhesion-dependent cell spreading | IDA PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics dri... | ACCEPT | Summary: Fibronectin substrates promote cell spreading through integrin engagement. Direct functional consequence. Reason: Cell spreading on fibronectin substrates is a direct and measurable consequence of integrin-mediated adhesion. Well-validated experimentally (PMID:19126672, PMID:24658351, PMID:16236823). This represents a core adhesive function of fibronectin. Accept. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics dri... | ACCEPT | Summary: Fibronectin-integrin engagement activates PI3K/Akt signaling. Direct signaling consequence. Reason: Fibronectin binding to integrins triggers PI3K/Akt pathway activation, promoting cell survival and migration. Experimental validation (PMID:19126672). This is a well-established signaling consequence of fibronectin-integrin interactions. Accept. Supporting Evidence: PMID:19126672 Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts |
| GO:0005201 extracellular matrix structural constituent | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:28344315 Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:28327460 In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribu... |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:28327460 In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribu... |
| GO:0031012 extracellular matrix | IDA PMID:16157329 Sequential deposition of latent TGF-beta binding proteins (L... | ACCEPT | Summary: Extracellular matrix is the primary localization of fibronectin. Core cellular component annotation. Reason: This is the most important cellular component annotation for fibronectin. Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks. Extensively validated across decades of research. This annotation is accurate and represents core fibronectin localization. Supporting Evidence: PMID:16157329 Sequential deposition of latent TGF-beta binding proteins (LTBPs) during formation of the extracellular matrix in human lung fibroblasts |
| GO:0043394 proteoglycan binding | IDA PMID:29030641 Lubricin binds cartilage proteins, cartilage oligomeric matr... | ACCEPT | Summary: Proteoglycan binding through heparin-binding domains. Core molecular function. Reason: Fibronectin contains three heparin-binding sites that mediate binding to heparan sulfate proteoglycans. Important for fibronectin matrix assembly and ECM organization. Experimentally validated. Core molecular function. Accept. Supporting Evidence: PMID:29030641 Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:28344315 Proteomic characterization of human multiple myeloma bone marrow extracellular matrix |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:28675934 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:28675934 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:23979707 By comparing proteomic changes in primary human endothelial cells morphogenesis on matrigel to general adhesion mechanisms in cells spreading on cultu... |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:27559042 We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM) |
| GO:0005201 extracellular matrix structural constituent | ISS GO_REF:0000024 | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: GO_REF:0000024 |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:20551380 For instance, we were able to detect matrix metalloproteinase-9 by mass spectrometry and relate its presence to degradation of fibronectin in a clinic... |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks that organize matrix architecture. Reason: This is a core molecular function annotation. Fibronectin provides structural integrity to the ECM through its fibrillar assembly and interactions with other matrix components. This term captures fibronectin's fundamental role as an ECM scaffold protein. Multiple experimental validations (HDA, RCA, ISS evidence codes) support this annotation. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | MODIFY | Summary: Fibronectin is extracellular, but more specific terms (ECM, extracellular space) are preferable. Reason: While factually correct, GO:0005576 is too general. Replace with GO:0031012 (extracellular matrix) which better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: PMID:27068509 Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:27559042 We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM) |
| GO:0005615 extracellular space | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Fibronectin is secreted into extracellular space. Core localization annotation. Reason: Fibronectin is a secreted protein localizing to extracellular space. Both plasma fibronectin (soluble in body fluids) and cellular fibronectin (assembled into ECM) occupy extracellular space. Appropriate cellular component annotation. Supporting Evidence: PMID:20551380 For instance, we were able to detect matrix metalloproteinase-9 by mass spectrometry and relate its presence to degradation of fibronectin in a clinic... |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:20551380 For instance, we were able to detect matrix metalloproteinase-9 by mass spectrometry and relate its presence to degradation of fibronectin in a clinic... |
| GO:0031012 extracellular matrix | ISS PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeli... | ACCEPT | Summary: Extracellular matrix is the primary localization of fibronectin. Core cellular component annotation. Reason: This is the most important cellular component annotation for fibronectin. Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks. Extensively validated across decades of research. This annotation is accurate and represents core fibronectin localization. Supporting Evidence: PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury |
| GO:0031012 extracellular matrix | HDA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: Extracellular matrix is fibronectin's primary localization. Accurate HDA annotation. Reason: High-throughput detection assays confirm fibronectin as an ECM component. While multiple HDA annotations exist, they come from different studies/contexts. ECM is the core localization. Accept but note some redundancy across annotations. Supporting Evidence: PMID:23979707 By comparing proteomic changes in primary human endothelial cells morphogenesis on matrigel to general adhesion mechanisms in cells spreading on cultu... |
| GO:1904237 positive regulation of substrate-dependent cell migration, cell attachment to substrate | IDA PMID:25834989 Fibulin1C peptide induces cell attachment and extracellular ... | ACCEPT | Summary: Fibronectin promotes cell migration and attachment. Direct functional consequence. Reason: Experimental validation (PMID:25834989). Fibronectin directly mediates cell attachment and promotes migration. While this term is somewhat redundant with 'cell adhesion' and 'cell-matrix adhesion', it accurately captures a direct functional consequence. Accept. Supporting Evidence: PMID:25834989 In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups |
| GO:0005515 protein binding | IPI PMID:10788510 The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aure... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:10788510 The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen |
| GO:0051702 biological process involved in interaction with symbiont | IDA PMID:12167537 Several regions of the repeat domain of the Staphylococcus c... | KEEP AS NON CORE | Summary: Fibronectin serves as an adhesion target for bacterial pathogens. Host-pathogen interaction context. Reason: Multiple experimental validations (PMID:12167537, PMID:19429745, PMID:12421310) show bacterial pathogens bind fibronectin. While biologically important, this represents pathogen exploitation of fibronectin's adhesive properties. Not a core host function but rather pathogen binding to ECM. Mark as non-core. Supporting Evidence: PMID:12167537 Several regions of the repeat domain of the Staphylococcus caprae autolysin, AtlC, are involved in fibronectin binding |
| GO:0005515 protein binding | IPI PMID:16677310 Mycobacterium tuberculosis malate synthase is a laminin-bind... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:16677310 tb malate synthase (MS) has adapted to function as an adhesin which binds to laminin and fibronectin |
| GO:0051702 biological process involved in interaction with symbiont | IDA PMID:19429745 Enolase from Paracoccidioides brasiliensis: isolation and id... | KEEP AS NON CORE | Summary: Fibronectin serves as an adhesion target for bacterial pathogens. Host-pathogen interaction context. Reason: Multiple experimental validations (PMID:12167537, PMID:19429745, PMID:12421310) show bacterial pathogens bind fibronectin. While biologically important, this represents pathogen exploitation of fibronectin's adhesive properties. Not a core host function but rather pathogen binding to ECM. Mark as non-core. Supporting Evidence: PMID:19429745 Enolase from Paracoccidioides brasiliensis: isolation and identification as a fibronectin-binding protein |
| GO:0005515 protein binding | IPI PMID:19220903 Surface displaced alfa-enolase of Lactobacillus plantarum is... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:19220903 Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein |
| GO:0051702 biological process involved in interaction with symbiont | IDA PMID:12421310 Elongation factor Tu and E1 beta subunit of pyruvate dehydro... | KEEP AS NON CORE | Summary: Fibronectin serves as an adhesion target for bacterial pathogens. Host-pathogen interaction context. Reason: Multiple experimental validations (PMID:12167537, PMID:19429745, PMID:12421310) show bacterial pathogens bind fibronectin. While biologically important, this represents pathogen exploitation of fibronectin's adhesive properties. Not a core host function but rather pathogen binding to ECM. Mark as non-core. Supporting Evidence: PMID:12421310 Elongation factor Tu and E1 beta subunit of pyruvate dehydrogenase complex act as fibronectin binding proteins in Mycoplasma pneumoniae |
| GO:0001755 neural crest cell migration | IDA PMID:26571399 A collagen VI-dependent pathogenic mechanism for Hirschsprun... | KEEP AS NON CORE | Summary: Fibronectin mediates neural crest cell migration during development. Specific developmental context. Reason: Experimentally validated (PMID:26571399) - neural crest cells migrate along fibronectin-rich pathways. However, this represents a specific developmental context. The core function is ECM-mediated cell adhesion and migration. Mark as non-core. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... |
| GO:0048484 enteric nervous system development | IDA PMID:26571399 A collagen VI-dependent pathogenic mechanism for Hirschsprun... | KEEP AS NON CORE | Summary: Fibronectin supports enteric nervous system development through neural crest cell migration. Specific developmental context. Reason: Experimentally validated (PMID:26571399) in Hirschsprung's disease model. Fibronectin provides migration substrate for enteric neural crest cells. However, this is a specific developmental context. Core function is ECM organization and cell migration support. Mark as non-core. Supporting Evidence: PMID:26571399 This appears to be due to the fact that collagen VI is a poor substratum for supporting eNCC migration and can even interfere with the migration-promo... |
| GO:0005515 protein binding | IPI PMID:26627825 Extracellular Fibrinogen-binding Protein (Efb) from Staphylo... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:26627825 2015 Dec 1. Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus aureus Inhibits the Formation of Platelet-Leukocyte Complexes. |
| GO:0001932 regulation of protein phosphorylation | IDA PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion... | ACCEPT | Summary: Fibronectin-integrin interactions regulate protein phosphorylation through FAK and other kinases. Reason: Fibronectin binding triggers phosphorylation cascades via FAK, Src, and downstream kinases. Experimental validation (PMID:11792823). This is a direct consequence of integrin engagement. Accept. Supporting Evidence: PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility |
| GO:0010628 positive regulation of gene expression | IDA PMID:25834989 Fibulin1C peptide induces cell attachment and extracellular ... | KEEP AS NON CORE | Summary: Fibronectin-integrin signaling can regulate gene expression. Indirect regulatory function. Reason: Experimental validation (PMID:25834989). Fibronectin signaling influences gene expression through downstream pathways. However, this is an indirect effect. Core functions are receptor binding and signaling initiation. Mark as non-core. Supporting Evidence: PMID:25834989 In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups |
| GO:0048146 positive regulation of fibroblast proliferation | IDA PMID:25834989 Fibulin1C peptide induces cell attachment and extracellular ... | KEEP AS NON CORE | Summary: Fibronectin promotes fibroblast proliferation. Cell-type-specific regulatory function. Reason: Experimental validation (PMID:25834989). Fibronectin supports fibroblast proliferation through integrin signaling. However, this is a cell-type-specific regulatory function. Core functions are adhesion and receptor engagement. Mark as non-core. Supporting Evidence: PMID:25834989 In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups |
| GO:0071635 negative regulation of transforming growth factor beta production | IDA PMID:25834989 Fibulin1C peptide induces cell attachment and extracellular ... | KEEP AS NON CORE | Summary: Fibronectin can modulate TGF-beta production. Context-specific regulatory function. Reason: Experimental validation (PMID:25834989). Fibronectin interactions negatively regulate TGF-beta production in fibrosis context. However, this is a specific regulatory function in particular disease contexts. Core functions are ECM organization and receptor binding. Mark as non-core. Supporting Evidence: PMID:25834989 In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups |
| GO:0005178 integrin binding | IPI PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion... | ACCEPT | Summary: Integrin binding is a core molecular function mediated by RGD motif and other sites. Reason: Fibronectin's RGD motif in FN-III10 binds integrin alpha5beta1. Additional sites engage alpha4beta1, alphaVbeta3, and others. Extensively validated by structural and biochemical studies. Core function. Accept. Supporting Evidence: PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility |
| GO:0070372 regulation of ERK1 and ERK2 cascade | IDA PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion... | ACCEPT | Summary: Fibronectin-integrin interactions regulate ERK signaling. Direct signaling consequence. Reason: Fibronectin engagement regulates ERK1/2 MAPK cascade through integrin-FAK-MAPK pathway. Experimental validation (PMID:11792823). Well-established signaling consequence. Accept. Supporting Evidence: PMID:11792823 Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility |
| GO:0005515 protein binding | IPI PMID:9278415 The self-association and fibronectin-binding sites of fibuli... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:9278415 The self-association and fibronectin-binding sites of fibulin-1 map to calcium-binding epidermal growth factor-like domains |
| GO:0005515 protein binding | IPI PMID:1400330 Fibulin binds to itself and to the carboxyl-terminal heparin... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:1400330 Fibulin binds to itself and to the carboxyl-terminal heparin-binding region of fibronectin |
| GO:0005515 protein binding | IPI PMID:10627046 The PE-PGRS glycine-rich proteins of Mycobacterium tuberculo... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:10627046 The PE-PGRS glycine-rich proteins of Mycobacterium tuberculosis: a new family of fibronectin-binding proteins |
| GO:0005515 protein binding | IPI PMID:3141278 Characterization of fibronectin-binding antigens released by... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:3141278 Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG |
| GO:0031012 extracellular matrix | IDA PMID:1632457 Plasminogen activator inhibitor-1 deposition in the extracel... | ACCEPT | Summary: Extracellular matrix is the primary localization of fibronectin. Core cellular component annotation. Reason: This is the most important cellular component annotation for fibronectin. Fibronectin is a major structural constituent of the ECM, assembling into fibrillar networks. Extensively validated across decades of research. This annotation is accurate and represents core fibronectin localization. Supporting Evidence: PMID:1632457 Plasminogen activator inhibitor-1 deposition in the extracellular matrix of cultured human mesangial cells |
| GO:0005178 integrin binding | IMP PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a h... | ACCEPT | Summary: Integrin binding is a core molecular function mediated by RGD motif and other sites. Reason: Fibronectin's RGD motif in FN-III10 binds integrin alpha5beta1. Additional sites engage alpha4beta1, alphaVbeta3, and others. Extensively validated by structural and biochemical studies. Core function. Accept. Supporting Evidence: PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a high-affinity form of fibronectin |
| GO:0033622 integrin activation | IMP PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a h... | ACCEPT | Summary: Fibronectin binding can induce integrin activation (inside-out signaling). Well-validated function. Reason: Fibronectin engagement can promote integrin activation and conformational changes that enhance ligand binding. Experimental validation (PMID:24658351). This is a well-characterized aspect of integrin-fibronectin interactions. Accept. Supporting Evidence: PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a high-affinity form of fibronectin |
| GO:0034446 substrate adhesion-dependent cell spreading | IMP PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a h... | ACCEPT | Summary: Fibronectin substrates promote cell spreading through integrin engagement. Direct functional consequence. Reason: Cell spreading on fibronectin substrates is a direct and measurable consequence of integrin-mediated adhesion. Well-validated experimentally (PMID:19126672, PMID:24658351, PMID:16236823). This represents a core adhesive function of fibronectin. Accept. Supporting Evidence: PMID:24658351 Structural basis for pure antagonism of integrin Ξ±VΞ²3 by a high-affinity form of fibronectin |
| GO:0035987 endodermal cell differentiation | IDA PMID:23154389 Regulation of endodermal differentiation of human embryonic ... | KEEP AS NON CORE | Summary: Fibronectin-integrin interactions regulate endodermal differentiation in ES cells. Specific developmental context. Reason: Experimental validation (PMID:23154389) in human embryonic stem cells. Fibronectin-ECM interactions regulate differentiation. However, this represents a specific developmental context. Core functions are ECM organization and integrin binding. Mark as non-core. Supporting Evidence: PMID:23154389 From this screen we identified fibronectin (FN) and vitronectin (VTN) as ECMP components that promoted DE differentiation |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Fibronectin is found in extracellular exosomes. Minor localization annotation. Reason: Multiple proteomic studies (PMID:23533145, PMID:21276792, PMID:19056867) detect fibronectin in exosomes. While valid, exosomes represent a minor and specialized localization compared to ECM and extracellular space. This is peripheral to core fibronectin biology. Mark as non-core. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0070062 extracellular exosome | IDA PMID:21276792 Morphologic and proteomic characterization of exosomes relea... | KEEP AS NON CORE | Summary: Fibronectin is found in extracellular exosomes. Minor localization annotation. Reason: Multiple proteomic studies (PMID:23533145, PMID:21276792, PMID:19056867) detect fibronectin in exosomes. While valid, exosomes represent a minor and specialized localization compared to ECM and extracellular space. This is peripheral to core fibronectin biology. Mark as non-core. Supporting Evidence: PMID:21276792 Epub 2011 Jan 26. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells. |
| GO:0005515 protein binding | IPI PMID:11773026 In vitro localization of TIGR/MYOC in trabecular meshwork ex... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:11773026 In vitro localization of TIGR/MYOC in trabecular meshwork extracellular matrix and binding to fibronectin |
| GO:0002020 protease binding | IPI PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: Fibronectin binds and is cleaved by proteases. Valid molecular interaction. Reason: Experimental validation (PMID:22952693). Fibronectin binds various proteases including cathepsins and MMPs, and is a substrate for proteolytic remodeling. While somewhat general, this represents real molecular interactions important for ECM remodeling. Accept. Supporting Evidence: PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners. |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | KEEP AS NON CORE | Summary: Fibronectin detected in blood microparticles. Minor localization annotation. Reason: Proteomic analysis (PMID:22516433) detects fibronectin in blood microparticles. While valid, this represents a minor and specialized localization. Plasma fibronectin is the relevant pool, microparticles are peripheral. Mark as non-core. Supporting Evidence: PMID:22516433 Epub 2012 Apr 10. Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Fibronectin is found in extracellular exosomes. Minor localization annotation. Reason: Multiple proteomic studies (PMID:23533145, PMID:21276792, PMID:19056867) detect fibronectin in exosomes. While valid, exosomes represent a minor and specialized localization compared to ECM and extracellular space. This is peripheral to core fibronectin biology. Mark as non-core. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0005178 integrin binding | IDA PMID:19738201 Proteomic analysis of integrin-associated complexes identifi... | ACCEPT | Summary: Integrin binding is a core molecular function mediated by RGD motif and other sites. Reason: Fibronectin's RGD motif in FN-III10 binds integrin alpha5beta1. Additional sites engage alpha4beta1, alphaVbeta3, and others. Extensively validated by structural and biochemical studies. Core function. Accept. Supporting Evidence: PMID:19738201 Quantitative, comparative analyses of the proteomes of two receptor-ligand pairs, alpha(4)beta(1)-vascular cell adhesion molecule-1 and alpha(5)beta(1... |
| GO:0005515 protein binding | IPI PMID:16336961 A novel role for fibronectin type I domain in the regulation... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:16336961 A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG a... |
| GO:0005515 protein binding | IPI PMID:12225811 Matrix-matrix interaction of cartilage oligomeric matrix pro... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:12225811 Matrix-matrix interaction of cartilage oligomeric matrix protein and fibronectin |
| GO:0034446 substrate adhesion-dependent cell spreading | IDA PMID:16236823 Laminin-10 and Lutheran blood group glycoproteins in adhesio... | ACCEPT | Summary: Fibronectin substrates promote cell spreading through integrin engagement. Direct functional consequence. Reason: Cell spreading on fibronectin substrates is a direct and measurable consequence of integrin-mediated adhesion. Well-validated experimentally (PMID:19126672, PMID:24658351, PMID:16236823). This represents a core adhesive function of fibronectin. Accept. Supporting Evidence: PMID:16236823 Field emission scanning electron microscopy and immunohistochemistry showed that the endothelial cells spread on laminin-10 and formed fibronectin-pos... |
| GO:0005577 fibrinogen complex | IDA PMID:3997886 Incorporation of thrombospondin into fibrin clots. | ACCEPT | Summary: Fibronectin binds fibrin/fibrinogen forming complexes important for provisional matrix and wound healing. Reason: Fibronectin contains fibrin-binding sites at N-terminal and C-terminal regions. Interaction with fibrin(ogen) is critical for provisional matrix formation during hemostasis and wound healing. Experimentally validated. Core molecular interaction. Accept. Supporting Evidence: PMID:3997886 In contrast, incorporation of 125I-fibronectin into clots was dependent upon cross-linking |
| GO:0005515 protein binding | IPI PMID:11956183 The type XIII collagen ectodomain is a 150-nm rod and capabl... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:11956183 The type XIII collagen ectodomain is a 150-nm rod and capable of binding to fibronectin, nidogen-2, perlecan, and heparin |
| GO:0005515 protein binding | IPI PMID:15165854 Molecular structure and interaction of recombinant human typ... | REMOVE | Summary: This annotation documents a protein-protein interaction but uses the uninformative term 'protein binding'. Reason: Per GO curation guidelines, 'protein binding' (GO:0005515) is too vague. While fibronectin binds many proteins (collagens, integrins, bacterial adhesins, ECM components), these should use more specific terms like 'integrin binding' (GO:0005178), 'collagen binding' (GO:0005518), or 'proteoglycan binding' (GO:0043394). Remove in favor of specific molecular function annotations. Supporting Evidence: PMID:15165854 Recombinant collagen XVI interacts with fibrillin-1 and with fibronectin indicating multiple molecular interactions in which this ubiquitously express... |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IDA PMID:15308636 Proteomics of endoplasmic reticulum-Golgi intermediate compa... | ACCEPT | Summary: Fibronectin transits through ERGIC during secretion. Minor but accurate localization. Reason: As a secreted glycoprotein, fibronectin traffics through ERGIC during secretion. Experimental evidence (PMID:15308636). While transient rather than functional location, it is accurate for the secretory pathway. Accept. Supporting Evidence: PMID:15308636 2004 Aug 11. Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46. |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | MODIFY | Summary: Fibronectin is extracellular, but more specific terms (ECM, extracellular space) are preferable. Reason: While factually correct, GO:0005576 is too general. Replace with GO:0031012 (extracellular matrix) which better captures fibronectin's structural role as an ECM component. Proposed replacements: extracellular matrix Supporting Evidence: PMID:14718574 Epub 2004 Jan 12. The human plasma proteome: a nonredundant list developed by combination of four separate sources. |
| GO:0005518 collagen binding | NAS PMID:3024962 Mapping the collagen-binding site of human fibronectin by ex... | ACCEPT | Summary: Collagen binding is a core molecular function of fibronectin mediated by gelatin-binding domains. Reason: Fibronectin binds collagen types I-V and VII through gelatin-binding domains (FN-II repeats). This interaction organizes collagen fibrils and is essential for ECM architecture. Extensively validated (PMID:3024962 NAS and multiple other studies). Core molecular function. Supporting Evidence: PMID:3024962 Mapping the collagen-binding site of human fibronectin by expression in Escherichia coli |
| GO:0007155 cell adhesion | NAS PMID:1423622 The three-dimensional structure of the tenth type III module... | ACCEPT | Summary: Cell adhesion is a core function of fibronectin mediating attachment to ECM. Reason: Cell adhesion is a quintessential fibronectin function. Through integrin binding, fibronectin mediates cell attachment, spreading, and migration. NAS evidence from PMID:1423622 (structural study of RGD domain). Core function. Accept. Supporting Evidence: PMID:1423622 The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions |
| GO:0008201 heparin binding | NAS PMID:10075919 Crystal structure of a heparin- and integrin-binding segment... | ACCEPT | Summary: Heparin binding through three distinct heparin-binding domains. Core molecular function. Reason: Fibronectin contains three heparin-binding sites (Hep I, II, III). Extensively characterized structurally and functionally (PMID:10075919 NAS). Important for matrix assembly and ECM organization. Core molecular function. Accept. Supporting Evidence: PMID:10075919 Crystal structure of a heparin- and integrin-binding segment of human fibronectin |
| GO:0009611 response to wounding | NAS PMID:7989369 Further characterization of the NH2-terminal fibrin-binding ... | KEEP AS NON CORE | Summary: Fibronectin participates in wound healing through provisional matrix formation. Specific physiological context. Reason: Fibronectin is essential for wound healing, forming provisional matrix and supporting cell migration. NAS evidence (PMID:7989369) characterizing fibrin-binding sites. However, wound healing represents a specific physiological context. Core functions are fibrin binding and ECM organization. Mark as non-core. Supporting Evidence: PMID:7989369 Further characterization of the NH2-terminal fibrin-binding site on fibronectin |
| GO:0030198 extracellular matrix organization | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: file:human/FN1/FN1-uniprot.txt Fibronectin binds collagen types I-V and VII, assembling into fibrillar networks |
| GO:0070051 fibrinogen binding | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: PMID:7989369 Characterization of the NH2-terminal fibrin-binding site on fibronectin |
| GO:0007596 blood coagulation | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: PMID:7989369 Characterization of the NH2-terminal fibrin-binding site on fibronectin |
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