id: P02751
gene_symbol: FN1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:26571399
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
- term:
    id: GO:0007044
    label: cell-substrate junction assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
    - reference_id: PMID:24658351
      supporting_text: Structural basis for pure antagonism of integrin αVβ3 by 
        a high-affinity form of fibronectin
- term:
    id: GO:0007160
    label: cell-matrix adhesion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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).
    supported_by:
    - reference_id: PMID:33962943
      supporting_text: 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.
    - reference_id: file:human/FN1/FN1-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000033
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:33962943
      supporting_text: Structural insights into integrin α(5)β(1) opening by 
        fibronectin ligand
    - reference_id: PMID:11792823
      supporting_text: Fibulin-1 suppression of fibronectin-regulated cell 
        adhesion and motility
    - reference_id: PMID:19738201
      supporting_text: 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...
- term:
    id: GO:0043394
    label: proteoglycan binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Fibronectin binds proteoglycans and heparan sulfate through 
      specific heparin-binding domains. This is a well-characterized core 
      molecular function important for ECM organization.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:29030641
      supporting_text: Lubricin binds cartilage proteins, cartilage oligomeric 
        matrix protein, fibronectin and collagen II at the cartilage surface
    - reference_id: file:human/FN1/FN1-uniprot.txt
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:11209058
    - PMID:20123964
    supported_by:
    - reference_id: PMID:20123964
      supporting_text: In subconfluent ECs, LPP3 induced expression of 
        fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin
        homologue (PTEN)-dependent ma...
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    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.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:22952693
    supported_by:
    - reference_id: PMID:22952693
      supporting_text: Cleavage of nidogen-1 by cathepsin S impairs its binding 
        to basement membrane partners.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Fibronectin is secreted and localized to the extracellular space 
      and ECM. This is accurate but overly broad - more specific cellular 
      component terms exist.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
    supported_by:
    - reference_id: file:human/FN1/FN1-uniprot.txt
- term:
    id: GO:0006953
    label: acute-phase response
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Fibronectin can be upregulated during acute-phase response as part 
      of tissue repair. This represents a specific physiological context.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000043
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:1423622
      supporting_text: 'The three-dimensional structure of the tenth type III module
        of fibronectin: an insight into RGD-mediated interactions'
    - reference_id: file:human/FN1/FN1-uniprot.txt
- term:
    id: GO:0008201
    label: heparin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Heparin binding is a well-characterized core molecular function of 
      fibronectin through three distinct heparin-binding domains (Hep I, II, 
      III).
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:10075919
    supported_by:
    - reference_id: PMID:10075919
      supporting_text: Crystal structure of a heparin- and integrin-binding 
        segment of human fibronectin
- term:
    id: GO:0008360
    label: regulation of cell shape
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Fibronectin influences cell shape through integrin-mediated 
      cytoskeletal reorganization during adhesion and spreading. This is a 
      downstream consequence of cell adhesion.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin binds integrin receptors and other cell surface 
      receptors. This is accurate but somewhat general compared to the more 
      specific integrin binding term.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:34089617
    supported_by:
    - reference_id: PMID:34089617
      supporting_text: Blockade of checkpoint ILT3/LILRB4/gp49B binding to 
        fibronectin ameliorates autoimmune disease in BXSB/Yaa mice
- term:
    id: GO:0005604
    label: basement membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin is present in basement membranes but is more 
      characteristic of interstitial ECM. Plasma fibronectin is distinct from 
      cellular fibronectin in basement membranes.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Fibronectin is secreted into the extracellular space where it 
      assembles into ECM fibrils. This is a correct core localization 
      annotation.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:15292204
    supported_by:
    - reference_id: PMID:15292204
      supporting_text: BBK32, a fibronectin binding MSCRAMM from Borrelia 
        burgdorferi, contains a disordered region that undergoes a 
        conformational change on ligand binding
- term:
    id: GO:0014850
    label: response to muscle activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin expression can be modulated by mechanical forces 
      including muscle activity. This represents a regulatory context rather 
      than core function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin can be associated with apical surfaces of polarized 
      epithelia, but this is not a primary or characteristic localization.
    action: REMOVE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
- term:
    id: GO:0016504
    label: peptidase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin fragments can modulate protease activity, but this is 
      not a well-established core molecular function of intact fibronectin.
    action: REMOVE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Extracellular matrix is the primary and most characteristic 
      localization of fibronectin. This is a core cellular component annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
    - reference_id: PMID:16157329
      supporting_text: Sequential deposition of latent TGF-beta binding proteins
        (LTBPs) during formation of the extracellular matrix in human lung 
        fibroblasts
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin acts as a ligand for integrin receptors and other cell 
      surface receptors, mediating cell signaling. This is a valid molecular 
      function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
    - reference_id: PMID:11792823
      supporting_text: Fibulin-1 suppression of fibronectin-regulated cell 
        adhesion and motility
- term:
    id: GO:0150102
    label: negative regulation of monocyte activation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Fibronectin can modulate monocyte activation through receptor 
      interactions, including inhibitory checkpoint receptors.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:34089617
    supported_by:
    - reference_id: PMID:34089617
      supporting_text: Blockade of checkpoint ILT3/LILRB4/gp49B binding to 
        fibronectin ameliorates autoimmune disease in BXSB/Yaa mice
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11377428
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:11377428
      supporting_text: Binding of a peptide from a Streptococcus dysgalactiae 
        MSCRAMM to the N-terminal F1 module pair of human fibronectin involves 
        both modules
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12736686
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:12736686
      supporting_text: Pathogenic bacteria attach to human fibronectin through a
        tandem beta-zipper
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16457822
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:16457822
      supporting_text: CT domain of CCN2/CTGF directly interacts with 
        fibronectin and enhances cell adhesion of chondrocytes through integrin 
        alpha5beta1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:1747115
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:1747115
      supporting_text: Interaction of the small proteoglycan decorin with 
        fibronectin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18042364
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18042364
      supporting_text: TSG-6 binds via its CUB_C domain to the cell-binding 
        domain of fibronectin and increases fibronectin matrix assembly
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18160478
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18160478
      supporting_text: Novel adhesin from Pasteurella multocida that binds to 
        the integrin-binding fibronectin FnIII9-10 repeats
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18243143
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18243143
      supporting_text: Uteroglobin interacts with the heparin-binding site of 
        fibronectin and prevents fibronectin-IgA complex formation found in 
        IgA-nephropathy
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18323857
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18323857
      supporting_text: 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...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18411296
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18411296
      supporting_text: The surface-exposed carboxyl region of Mycoplasma 
        pneumoniae elongation factor Tu interacts with fibronectin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18713862
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:18713862
      supporting_text: Crystal structures of fibronectin-binding sites from 
        Staphylococcus aureus FnBPA in complex with fibronectin domains
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19542224
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:19542224
      supporting_text: Epub 2009 Jun 19. The first draft of the endostatin 
        interaction network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19738201
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:19738201
      supporting_text: 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...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080707
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:20080707
      supporting_text: EGF potentiated oncogenesis requires a tissue 
        transglutaminase-dependent signaling pathway leading to Src activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20541508
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:20541508
      supporting_text: Zinc induces structural reorganization of gelatin binding
        domain from human fibronectin and affects collagen binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20875085
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:20875085
      supporting_text: Functional analysis of a murine monoclonal antibody 
        against the repetitive region of the fibronectin-binding adhesins 
        fibronectin-binding protein A an...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20879998
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:20879998
      supporting_text: Repeat regions R1 and R2 in the P97 paralogue Mhp271 of 
        Mycoplasma hyopneumoniae bind heparin, fibronectin and porcine cilia
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21569203
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:21569203
      supporting_text: The A domain of fibronectin-binding protein B of 
        Staphylococcus aureus contains a novel fibronectin binding site
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22442151
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:22442151
      supporting_text: 'Transglutaminase-2 interaction with heparin: identification
        of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2
        m...'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24136289
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:24136289
      supporting_text: Identification and comparative analysis of hepatitis C 
        virus-host cell protein interactions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24388360
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:24388360
      supporting_text: SERPINA5 inhibits tumor cell migration by modulating the 
        fibronectin-integrin β1 signaling pathway in hepatocellular carcinoma
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25034023
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:25034023
      supporting_text: Epub 2014 Jul 14. Heparin/heparan sulfate controls 
        fibrillin-1, -2 and -3 self-interactions in microfibril assembly.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25290767
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:25290767
      supporting_text: Structural and functional analysis of the 
        fibronectin-binding protein FNE from Streptococcus equi spp
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25293691
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:25293691
      supporting_text: Affinity chromatography using heparin, fibronectin and 
        plasminogen as bait and peptide arrays were used to expand our knowledge
        of the adhesive capabi...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:2531657
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:2531657
      supporting_text: Lipoprotein(a) binds to fibronectin and has serine 
        proteinase activity capable of cleaving it
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26848503
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:26848503
      supporting_text: Epub 2016 Mar 9. Mapping and Exploring the Collagen-I 
        Proteostasis Network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27141819
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:27141819
      supporting_text: Furthermore, those PRMs also bound to fibronectin and 
        therefore might influence the Ag85 complex-dependent interaction of 
        Mycobacterium with the extra...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27616280
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:27616280
      supporting_text: 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)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30082873
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:30082873
      supporting_text: Lysyl oxidase (LOX) catalyzes the oxidative deamination 
        of lysine and hydroxylysine residues in collagens and elastin, which is 
        the first step of the ...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31759052
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:31759052
      supporting_text: We here provide evidence that LOXL2 also affects 
        deposition of other ECM components, including fibronectin, thus altering
        structural and mechanical pr...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
        cell-specific remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34968453
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:34968453
      supporting_text: Yeast two-hybrid screening, confirmed by affinity 
        chromatography, identified fibronectin as a stabilin-1 interacting 
        partner
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9269765
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:9269765
      supporting_text: Among 11 positive clones that emerged from the screen, 
        eight clones were identified as beta-2 glycoprotein I and one as 
        fibronectin
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17914904
  review:
    summary: Fibronectin forms homodimers through C-terminal disulfide bonds. 
      This is a core molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17914904
      supporting_text: Force-induced unfolding of fibronectin in the 
        extracellular matrix of living cells
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18042364
  review:
    summary: Fibronectin forms homodimers through C-terminal disulfide bonds. 
      This is a core molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:18042364
      supporting_text: TSG-6 binds via its CUB_C domain to the cell-binding 
        domain of fibronectin and increases fibronectin matrix assembly
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:19826086
  review:
    summary: Fibronectin forms homodimers through C-terminal disulfide bonds. 
      This is a core molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19826086
      supporting_text: Fibronectin forms the most extensible biological fibers 
        displaying switchable force-exposed cryptic binding sites
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:19931242
  review:
    summary: Fibronectin forms homodimers through C-terminal disulfide bonds. 
      This is a core molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19931242
      supporting_text: Cross-linked angiocidin inhibited cell migration in 
        contrast to monomeric angiocidin and inhibited localization of 
        fibronectin (FN), a pro-tumorigenic...
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:20541508
  review:
    summary: Fibronectin forms homodimers through C-terminal disulfide bonds. 
      This is a core molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20541508
      supporting_text: Zinc induces structural reorganization of gelatin binding
        domain from human fibronectin and affects collagen binding
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3788061
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-3788061
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8952289
  review:
    summary: Fibronectin is synthesized and modified in the ER during secretion.
      Minor localization annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-8952289
- term:
    id: GO:0005577
    label: fibrinogen complex
  evidence_type: IPI
  original_reference_id: PMID:20541508
  review:
    summary: Fibronectin binds fibrin/fibrinogen forming complexes important for
      provisional matrix and wound healing.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20541508
      supporting_text: Zinc induces structural reorganization of gelatin binding
        domain from human fibronectin and affects collagen binding
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:15292204
  review:
    summary: Fibronectin is secreted into extracellular space. Core localization
      annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:15292204
      supporting_text: BBK32, a fibronectin binding MSCRAMM from Borrelia 
        burgdorferi, contains a disordered region that undergoes a 
        conformational change on ligand binding
- term:
    id: GO:0072378
    label: blood coagulation, fibrin clot formation
  evidence_type: IDA
  original_reference_id: PMID:3997886
  review:
    summary: Fibronectin participates in fibrin clot formation through fibrin 
      binding, but this is a specific physiological context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:3997886
    supported_by:
    - reference_id: PMID:3997886
      supporting_text: In contrast, incorporation of 125I-fibronectin into clots
        was dependent upon cross-linking
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:23658023
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23658023
      supporting_text: We show that identified candidate molecules can support 
        attachment and self-renewal of hESCs alone (fibrillin-1) or in 
        combination with fibronectin (p...
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1566981
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-1566981
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202723
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-202723
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-216050
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-216050
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2327733
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2327733
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2327746
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2327746
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2396337
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2396337
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2533950
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2533950
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2537665
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2537665
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2545196
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2545196
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2681681
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2681681
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2731141
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2731141
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-349593
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-349593
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354066
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354066
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354073
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354073
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354087
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354087
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354124
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354124
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354149
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354149
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-354165
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-354165
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-372693
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-372693
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-372697
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-372697
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-372705
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-372705
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-377640
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-377640
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-377641
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-377641
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-377643
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-377643
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-377644
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-377644
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3785684
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-3785684
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-429415
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-429415
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-429441
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-429441
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-481007
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-481007
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6785895
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-6785895
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9624017
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9624017
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9638552
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9638552
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865226
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9865226
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9932034
  review:
    summary: Extracellular region annotation - too general, should use 
      extracellular matrix.
    action: MODIFY
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9932034
    proposed_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
- term:
    id: GO:0031093
    label: platelet alpha granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-481007
  review:
    summary: Plasma fibronectin is stored in platelet alpha granules and 
      released upon activation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-481007
- term:
    id: GO:0043542
    label: endothelial cell migration
  evidence_type: IDA
  original_reference_id: PMID:20123964
  review:
    summary: Fibronectin supports endothelial cell migration, but this is a 
      cell-type-specific process.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:20123964
    supported_by:
    - reference_id: PMID:20123964
      supporting_text: In subconfluent ECs, LPP3 induced expression of 
        fibronectin via beta-catenin/LEF-1 signaling in a phosphatase and tensin
        homologue (PTEN)-dependent ma...
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700181
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9700181
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700190
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9700190
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700193
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9700193
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712078
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9712078
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712079
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9712079
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712083
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9712083
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712084
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9712084
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712085
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9712085
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9724099
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9724099
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9850958
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9850958
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IDA
  original_reference_id: PMID:33962943
  review:
    summary: Integrin binding is a core molecular function mediated by RGD motif
      and other sites.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:33962943
      supporting_text: Structural insights into integrin α(5)β(1) opening by 
        fibronectin ligand
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33962943
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:33962943
      supporting_text: Structural insights into integrin α(5)β(1) opening by 
        fibronectin ligand
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12167537
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:12167537
      supporting_text: Several regions of the repeat domain of the 
        Staphylococcus caprae autolysin, AtlC, are involved in fibronectin 
        binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12421310
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:12421310
      supporting_text: Elongation factor Tu and E1 beta subunit of pyruvate 
        dehydrogenase complex act as fibronectin binding proteins in Mycoplasma 
        pneumoniae
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15292204
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:15292204
      supporting_text: BBK32, a fibronectin binding MSCRAMM from Borrelia 
        burgdorferi, contains a disordered region that undergoes a 
        conformational change on ligand binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17849409
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:17849409
      supporting_text: Interestingly, GlnA1 was able to bind the extracellular 
        matrix (ECM) protein fibronectin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19429745
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:19429745
      supporting_text: 'Enolase from Paracoccidioides brasiliensis: isolation and
        identification as a fibronectin-binding protein'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IDA
  original_reference_id: PMID:26571399
  review:
    summary: Extracellular matrix is the primary localization of fibronectin. 
      Core cellular component annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
- term:
    id: GO:1901166
    label: neural crest cell migration involved in autonomic nervous system 
      development
  evidence_type: IDA
  original_reference_id: PMID:26571399
  review:
    summary: Fibronectin mediates neural crest migration for autonomic nervous 
      system development. Specific developmental context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:26571399
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:25834989
  review:
    summary: Fibronectin can promote cell proliferation through integrin 
      signaling. Regulatory function in specific contexts.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:25834989
    supported_by:
    - reference_id: PMID:25834989
      supporting_text: In addition, FBLN1C1 stimulated fibulin1 deposition in PF
        and COPD fibroblasts, and augmented fibronectin and perlecan deposition 
        in all three groups
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IDA
  original_reference_id: PMID:34089617
  review:
    summary: Fibronectin binds signaling receptors including integrins and 
      checkpoint receptors.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:34089617
    supported_by:
    - reference_id: PMID:34089617
      supporting_text: Blockade of checkpoint ILT3/LILRB4/gp49B binding to 
        fibronectin ameliorates autoimmune disease in BXSB/Yaa mice
- term:
    id: GO:0150102
    label: negative regulation of monocyte activation
  evidence_type: IDA
  original_reference_id: PMID:34089617
  review:
    summary: Fibronectin modulates monocyte activation through checkpoint 
      receptor interactions.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:34089617
    supported_by:
    - reference_id: PMID:34089617
      supporting_text: Blockade of checkpoint ILT3/LILRB4/gp49B binding to 
        fibronectin ameliorates autoimmune disease in BXSB/Yaa mice
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700131
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9700131
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700179
  review:
    summary: Fibronectin interacts with integrins at the plasma membrane, but 
      fibronectin itself is extracellular.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-9700179
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:19126672
  review:
    summary: Fibronectin-integrin binding triggers signaling cascades. This is a
      direct consequence of integrin engagement.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:19126672
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IDA
  original_reference_id: PMID:19126672
  review:
    summary: Fibronectin substrates promote cell spreading through integrin 
      engagement. Direct functional consequence.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B
      signal transduction
  evidence_type: IDA
  original_reference_id: PMID:19126672
  review:
    summary: Fibronectin-integrin engagement activates PI3K/Akt signaling. 
      Direct signaling consequence.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:19126672
    supported_by:
    - reference_id: PMID:19126672
      supporting_text: Spontaneous phosphoinositide 3-kinase signaling dynamics 
        drive spreading and random migration of fibroblasts
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: HDA
  original_reference_id: PMID:28344315
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28344315
      supporting_text: Proteomic characterization of human multiple myeloma bone
        marrow extracellular matrix
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:28327460
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28327460
      supporting_text: In the stem-cell niche, the extracellular matrix (ECM) 
        serves as a structural support that additionally provides stem cells 
        with signals that contribu...
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:28327460
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28327460
      supporting_text: In the stem-cell niche, the extracellular matrix (ECM) 
        serves as a structural support that additionally provides stem cells 
        with signals that contribu...
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IDA
  original_reference_id: PMID:16157329
  review:
    summary: Extracellular matrix is the primary localization of fibronectin. 
      Core cellular component annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16157329
      supporting_text: Sequential deposition of latent TGF-beta binding proteins
        (LTBPs) during formation of the extracellular matrix in human lung 
        fibroblasts
- term:
    id: GO:0043394
    label: proteoglycan binding
  evidence_type: IDA
  original_reference_id: PMID:29030641
  review:
    summary: Proteoglycan binding through heparin-binding domains. Core 
      molecular function.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:29030641
      supporting_text: Lubricin binds cartilage proteins, cartilage oligomeric 
        matrix protein, fibronectin and collagen II at the cartilage surface
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:28344315
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28344315
      supporting_text: Proteomic characterization of human multiple myeloma bone
        marrow extracellular matrix
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:28675934
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28675934
      supporting_text: Characterization of the Extracellular Matrix of Normal 
        and Diseased Tissues Using Proteomics
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:28675934
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28675934
      supporting_text: Characterization of the Extracellular Matrix of Normal 
        and Diseased Tissues Using Proteomics
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:23979707
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23979707
      supporting_text: By comparing proteomic changes in primary human 
        endothelial cells morphogenesis on matrigel to general adhesion 
        mechanisms in cells spreading on cultu...
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:27559042
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:27559042
      supporting_text: We used proteomics to profile glycoproteins in the human 
        cardiac extracellular matrix (ECM)
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: GO_REF:0000024
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:20551380
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20551380
      supporting_text: For instance, we were able to detect matrix 
        metalloproteinase-9 by mass spectrometry and relate its presence to 
        degradation of fibronectin in a clinic...
- term:
    id: GO:0005201
    label: extracellular matrix structural constituent
  evidence_type: RCA
  original_reference_id: PMID:25037231
  review:
    summary: Fibronectin is a major structural constituent of the ECM, 
      assembling into fibrillar networks that organize matrix architecture.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:25037231
      supporting_text: Extracellular matrix signatures of human primary 
        metastatic colon cancers and their metastases to liver
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:25037231
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:25037231
      supporting_text: Extracellular matrix signatures of human primary 
        metastatic colon cancers and their metastases to liver
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: HDA
  original_reference_id: PMID:27068509
  review:
    summary: Fibronectin is extracellular, but more specific terms (ECM, 
      extracellular space) are preferable.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
    supported_by:
    - reference_id: PMID:27068509
      supporting_text: 'Extracellular matrix remodelling in response to venous hypertension:
        proteomics of human varicose veins'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:27559042
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:27559042
      supporting_text: We used proteomics to profile glycoproteins in the human 
        cardiac extracellular matrix (ECM)
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: HDA
  original_reference_id: PMID:20551380
  review:
    summary: Fibronectin is secreted into extracellular space. Core localization
      annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20551380
      supporting_text: For instance, we were able to detect matrix 
        metalloproteinase-9 by mass spectrometry and relate its presence to 
        degradation of fibronectin in a clinic...
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:20551380
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20551380
      supporting_text: For instance, we were able to detect matrix 
        metalloproteinase-9 by mass spectrometry and relate its presence to 
        degradation of fibronectin in a clinic...
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: ISS
  original_reference_id: PMID:22261194
  review:
    summary: Extracellular matrix is the primary localization of fibronectin. 
      Core cellular component annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:22261194
      supporting_text: Proteomics analysis of cardiac extracellular matrix 
        remodeling in a porcine model of ischemia/reperfusion injury
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:23979707
  review:
    summary: Extracellular matrix is fibronectin's primary localization. 
      Accurate HDA annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23979707
      supporting_text: By comparing proteomic changes in primary human 
        endothelial cells morphogenesis on matrigel to general adhesion 
        mechanisms in cells spreading on cultu...
- term:
    id: GO:1904237
    label: positive regulation of substrate-dependent cell migration, cell 
      attachment to substrate
  evidence_type: IDA
  original_reference_id: PMID:25834989
  review:
    summary: Fibronectin promotes cell migration and attachment. Direct 
      functional consequence.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:25834989
    supported_by:
    - reference_id: PMID:25834989
      supporting_text: In addition, FBLN1C1 stimulated fibulin1 deposition in PF
        and COPD fibroblasts, and augmented fibronectin and perlecan deposition 
        in all three groups
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10788510
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:10788510
      supporting_text: The fibronectin-binding MSCRAMM FnbpA of Staphylococcus 
        aureus is a bifunctional protein that also binds to fibrinogen
- term:
    id: GO:0051702
    label: biological process involved in interaction with symbiont
  evidence_type: IDA
  original_reference_id: PMID:12167537
  review:
    summary: Fibronectin serves as an adhesion target for bacterial pathogens. 
      Host-pathogen interaction context.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:12167537
      supporting_text: Several regions of the repeat domain of the 
        Staphylococcus caprae autolysin, AtlC, are involved in fibronectin 
        binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16677310
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:16677310
      supporting_text: tb malate synthase (MS) has adapted to function as an 
        adhesin which binds to laminin and fibronectin
- term:
    id: GO:0051702
    label: biological process involved in interaction with symbiont
  evidence_type: IDA
  original_reference_id: PMID:19429745
  review:
    summary: Fibronectin serves as an adhesion target for bacterial pathogens. 
      Host-pathogen interaction context.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:19429745
      supporting_text: 'Enolase from Paracoccidioides brasiliensis: isolation and
        identification as a fibronectin-binding protein'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19220903
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:19220903
      supporting_text: Surface displaced alfa-enolase of Lactobacillus plantarum
        is a fibronectin binding protein
- term:
    id: GO:0051702
    label: biological process involved in interaction with symbiont
  evidence_type: IDA
  original_reference_id: PMID:12421310
  review:
    summary: Fibronectin serves as an adhesion target for bacterial pathogens. 
      Host-pathogen interaction context.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:12421310
      supporting_text: Elongation factor Tu and E1 beta subunit of pyruvate 
        dehydrogenase complex act as fibronectin binding proteins in Mycoplasma 
        pneumoniae
- term:
    id: GO:0001755
    label: neural crest cell migration
  evidence_type: IDA
  original_reference_id: PMID:26571399
  review:
    summary: Fibronectin mediates neural crest cell migration during 
      development. Specific developmental context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:26571399
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
- term:
    id: GO:0048484
    label: enteric nervous system development
  evidence_type: IDA
  original_reference_id: PMID:26571399
  review:
    summary: Fibronectin supports enteric nervous system development through 
      neural crest cell migration. Specific developmental context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:26571399
    supported_by:
    - reference_id: PMID:26571399
      supporting_text: 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...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26627825
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:26627825
      supporting_text: 2015 Dec 1. Extracellular Fibrinogen-binding Protein 
        (Efb) from Staphylococcus aureus Inhibits the Formation of 
        Platelet-Leukocyte Complexes.
- term:
    id: GO:0001932
    label: regulation of protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:11792823
  review:
    summary: Fibronectin-integrin interactions regulate protein phosphorylation 
      through FAK and other kinases.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:11792823
    supported_by:
    - reference_id: PMID:11792823
      supporting_text: Fibulin-1 suppression of fibronectin-regulated cell 
        adhesion and motility
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:25834989
  review:
    summary: Fibronectin-integrin signaling can regulate gene expression. 
      Indirect regulatory function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:25834989
    supported_by:
    - reference_id: PMID:25834989
      supporting_text: In addition, FBLN1C1 stimulated fibulin1 deposition in PF
        and COPD fibroblasts, and augmented fibronectin and perlecan deposition 
        in all three groups
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: IDA
  original_reference_id: PMID:25834989
  review:
    summary: Fibronectin promotes fibroblast proliferation. Cell-type-specific 
      regulatory function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:25834989
    supported_by:
    - reference_id: PMID:25834989
      supporting_text: In addition, FBLN1C1 stimulated fibulin1 deposition in PF
        and COPD fibroblasts, and augmented fibronectin and perlecan deposition 
        in all three groups
- term:
    id: GO:0071635
    label: negative regulation of transforming growth factor beta production
  evidence_type: IDA
  original_reference_id: PMID:25834989
  review:
    summary: Fibronectin can modulate TGF-beta production. Context-specific 
      regulatory function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:25834989
    supported_by:
    - reference_id: PMID:25834989
      supporting_text: In addition, FBLN1C1 stimulated fibulin1 deposition in PF
        and COPD fibroblasts, and augmented fibronectin and perlecan deposition 
        in all three groups
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IPI
  original_reference_id: PMID:11792823
  review:
    summary: Integrin binding is a core molecular function mediated by RGD motif
      and other sites.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11792823
      supporting_text: Fibulin-1 suppression of fibronectin-regulated cell 
        adhesion and motility
- term:
    id: GO:0070372
    label: regulation of ERK1 and ERK2 cascade
  evidence_type: IDA
  original_reference_id: PMID:11792823
  review:
    summary: Fibronectin-integrin interactions regulate ERK signaling. Direct 
      signaling consequence.
    action: ACCEPT
    reason: Fibronectin engagement regulates ERK1/2 MAPK cascade through 
      integrin-FAK-MAPK pathway. Experimental validation (PMID:11792823). 
      Well-established signaling consequence. Accept.
    additional_reference_ids:
    - PMID:11792823
    supported_by:
    - reference_id: PMID:11792823
      supporting_text: Fibulin-1 suppression of fibronectin-regulated cell 
        adhesion and motility
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9278415
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:9278415
      supporting_text: The self-association and fibronectin-binding sites of 
        fibulin-1 map to calcium-binding epidermal growth factor-like domains
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:1400330
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:1400330
      supporting_text: Fibulin binds to itself and to the carboxyl-terminal 
        heparin-binding region of fibronectin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10627046
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:10627046
      supporting_text: 'The PE-PGRS glycine-rich proteins of Mycobacterium tuberculosis:
        a new family of fibronectin-binding proteins'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:3141278
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:3141278
      supporting_text: Characterization of fibronectin-binding antigens released
        by Mycobacterium tuberculosis and Mycobacterium bovis BCG
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IDA
  original_reference_id: PMID:1632457
  review:
    summary: Extracellular matrix is the primary localization of fibronectin. 
      Core cellular component annotation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:1632457
      supporting_text: Plasminogen activator inhibitor-1 deposition in the 
        extracellular matrix of cultured human mesangial cells
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IMP
  original_reference_id: PMID:24658351
  review:
    summary: Integrin binding is a core molecular function mediated by RGD motif
      and other sites.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:24658351
      supporting_text: Structural basis for pure antagonism of integrin αVβ3 by 
        a high-affinity form of fibronectin
- term:
    id: GO:0033622
    label: integrin activation
  evidence_type: IMP
  original_reference_id: PMID:24658351
  review:
    summary: Fibronectin binding can induce integrin activation (inside-out 
      signaling). Well-validated function.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:24658351
    supported_by:
    - reference_id: PMID:24658351
      supporting_text: Structural basis for pure antagonism of integrin αVβ3 by 
        a high-affinity form of fibronectin
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IMP
  original_reference_id: PMID:24658351
  review:
    summary: Fibronectin substrates promote cell spreading through integrin 
      engagement. Direct functional consequence.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:24658351
      supporting_text: Structural basis for pure antagonism of integrin αVβ3 by 
        a high-affinity form of fibronectin
- term:
    id: GO:0035987
    label: endodermal cell differentiation
  evidence_type: IDA
  original_reference_id: PMID:23154389
  review:
    summary: Fibronectin-integrin interactions regulate endodermal 
      differentiation in ES cells. Specific developmental context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:23154389
    supported_by:
    - reference_id: PMID:23154389
      supporting_text: From this screen we identified fibronectin (FN) and 
        vitronectin (VTN) as ECMP components that promoted DE differentiation
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: Fibronectin is found in extracellular exosomes. Minor localization 
      annotation.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes 
        isolated from expressed prostatic secretions in urine.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:21276792
  review:
    summary: Fibronectin is found in extracellular exosomes. Minor localization 
      annotation.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21276792
      supporting_text: Epub 2011 Jan 26. Morphologic and proteomic 
        characterization of exosomes released by cultured extravillous 
        trophoblast cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11773026
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:11773026
      supporting_text: In vitro localization of TIGR/MYOC in trabecular meshwork
        extracellular matrix and binding to fibronectin
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IPI
  original_reference_id: PMID:22952693
  review:
    summary: Fibronectin binds and is cleaved by proteases. Valid molecular 
      interaction.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:22952693
    supported_by:
    - reference_id: PMID:22952693
      supporting_text: Cleavage of nidogen-1 by cathepsin S impairs its binding 
        to basement membrane partners.
- term:
    id: GO:0072562
    label: blood microparticle
  evidence_type: HDA
  original_reference_id: PMID:22516433
  review:
    summary: Fibronectin detected in blood microparticles. Minor localization 
      annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:22516433
    supported_by:
    - reference_id: PMID:22516433
      supporting_text: Epub 2012 Apr 10. Proteomic analysis of microvesicles 
        from plasma of healthy donors reveals high individual variability.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  review:
    summary: Fibronectin is found in extracellular exosomes. Minor localization 
      annotation.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: 2008 Dec 3. Large-scale proteomics and phosphoproteomics 
        of urinary exosomes.
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IDA
  original_reference_id: PMID:19738201
  review:
    summary: Integrin binding is a core molecular function mediated by RGD motif
      and other sites.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19738201
      supporting_text: 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...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16336961
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:16336961
      supporting_text: A novel role for fibronectin type I domain in the 
        regulation of human hematopoietic cell adhesiveness through binding to 
        follistatin domains of FLRG a...
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12225811
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:12225811
      supporting_text: Matrix-matrix interaction of cartilage oligomeric matrix 
        protein and fibronectin
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IDA
  original_reference_id: PMID:16236823
  review:
    summary: Fibronectin substrates promote cell spreading through integrin 
      engagement. Direct functional consequence.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16236823
      supporting_text: Field emission scanning electron microscopy and 
        immunohistochemistry showed that the endothelial cells spread on 
        laminin-10 and formed fibronectin-pos...
- term:
    id: GO:0005577
    label: fibrinogen complex
  evidence_type: IDA
  original_reference_id: PMID:3997886
  review:
    summary: Fibronectin binds fibrin/fibrinogen forming complexes important for
      provisional matrix and wound healing.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:3997886
      supporting_text: In contrast, incorporation of 125I-fibronectin into clots
        was dependent upon cross-linking
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11956183
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:11956183
      supporting_text: The type XIII collagen ectodomain is a 150-nm rod and 
        capable of binding to fibronectin, nidogen-2, perlecan, and heparin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15165854
  review:
    summary: This annotation documents a protein-protein interaction but uses 
      the uninformative term 'protein binding'.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:15165854
      supporting_text: Recombinant collagen XVI interacts with fibrillin-1 and 
        with fibronectin indicating multiple molecular interactions in which 
        this ubiquitously express...
- term:
    id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  evidence_type: IDA
  original_reference_id: PMID:15308636
  review:
    summary: Fibronectin transits through ERGIC during secretion. Minor but 
      accurate localization.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:15308636
    supported_by:
    - reference_id: PMID:15308636
      supporting_text: 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.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: NAS
  original_reference_id: PMID:14718574
  review:
    summary: Fibronectin is extracellular, but more specific terms (ECM, 
      extracellular space) are preferable.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0031012
      label: extracellular matrix
    supported_by:
    - reference_id: PMID:14718574
      supporting_text: 'Epub 2004 Jan 12. The human plasma proteome: a nonredundant
        list developed by combination of four separate sources.'
- term:
    id: GO:0005518
    label: collagen binding
  evidence_type: NAS
  original_reference_id: PMID:3024962
  review:
    summary: Collagen binding is a core molecular function of fibronectin 
      mediated by gelatin-binding domains.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:3024962
    - Reactome:R-HSA-2327733
    supported_by:
    - reference_id: PMID:3024962
      supporting_text: Mapping the collagen-binding site of human fibronectin by
        expression in Escherichia coli
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: NAS
  original_reference_id: PMID:1423622
  review:
    summary: Cell adhesion is a core function of fibronectin mediating 
      attachment to ECM.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:1423622
    supported_by:
    - reference_id: PMID:1423622
      supporting_text: 'The three-dimensional structure of the tenth type III module
        of fibronectin: an insight into RGD-mediated interactions'
- term:
    id: GO:0008201
    label: heparin binding
  evidence_type: NAS
  original_reference_id: PMID:10075919
  review:
    summary: Heparin binding through three distinct heparin-binding domains. 
      Core molecular function.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:10075919
    supported_by:
    - reference_id: PMID:10075919
      supporting_text: Crystal structure of a heparin- and integrin-binding 
        segment of human fibronectin
- term:
    id: GO:0009611
    label: response to wounding
  evidence_type: NAS
  original_reference_id: PMID:7989369
  review:
    summary: Fibronectin participates in wound healing through provisional 
      matrix formation. Specific physiological context.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids:
    - PMID:7989369
    supported_by:
    - reference_id: PMID:7989369
      supporting_text: Further characterization of the NH2-terminal 
        fibrin-binding site on fibronectin
- term:
    id: GO:0030198
    label: extracellular matrix organization
  evidence_type: NAS
  review:
    summary: Added to align core_functions with existing annotations.
    action: NEW
    reason: Core function term not present in existing_annotations.
    supported_by:
    - reference_id: file:human/FN1/FN1-uniprot.txt
      supporting_text: Fibronectin binds collagen types I-V and VII, assembling 
        into fibrillar networks
- term:
    id: GO:0070051
    label: fibrinogen binding
  evidence_type: NAS
  review:
    summary: Added to align core_functions with existing annotations.
    action: NEW
    reason: Core function term not present in existing_annotations.
    supported_by:
    - reference_id: PMID:7989369
      supporting_text: Characterization of the NH2-terminal fibrin-binding site 
        on fibronectin
- term:
    id: GO:0007596
    label: blood coagulation
  evidence_type: NAS
  review:
    summary: Added to align core_functions with existing annotations.
    action: NEW
    reason: Core function term not present in existing_annotations.
    supported_by:
    - reference_id: PMID:7989369
      supporting_text: Characterization of the NH2-terminal fibrin-binding site 
        on fibronectin
core_functions:
- molecular_function:
    id: GO:0005178
    label: integrin binding
  description: Fibronectin binds integrins (alpha5beta1, alpha4beta1, 
    alphaVbeta3, alphaVbeta1, alphaVbeta6, alpha8beta1) via the RGD motif in 
    FN-III10 domain, mediating cell adhesion, migration, and signaling at the 
    cell-matrix interface. This is the primary molecular function enabling 
    fibronectin's role as a major cell adhesion molecule.
  locations:
  - id: GO:0031012
    label: extracellular matrix
  directly_involved_in:
  - id: GO:0007160
    label: cell-matrix adhesion
  - id: GO:0007044
    label: cell-substrate junction assembly
  supported_by:
  - reference_id: PMID:33962943
    supporting_text: Structural insights into integrin alpha5beta1 opening by 
      fibronectin ligand
  - reference_id: PMID:24658351
    supporting_text: Structural basis for pure antagonism of integrin 
      alphaVbeta3 by fibronectin
- molecular_function:
    id: GO:0005518
    label: collagen binding
  description: Fibronectin binds collagen types I-V and VII through FN-I 
    modules, organizing the ECM architecture and coordinating fibrillar network 
    assembly. This interaction is essential for ECM structural integrity.
  locations:
  - id: GO:0031012
    label: extracellular matrix
  directly_involved_in:
  - id: GO:0030198
    label: extracellular matrix organization
  supported_by:
  - reference_id: file:human/FN1/FN1-uniprot.txt
    supporting_text: Fibronectin binds collagen types I-V and VII, assembling 
      into fibrillar networks
- molecular_function:
    id: GO:0070051
    label: fibrinogen binding
  description: Fibronectin binds fibrinogen through N-terminal and C-terminal 
    sites (FN-I modules), playing critical roles in provisional matrix formation
    during wound healing and hemostasis. This allows rapid assembly of a 
    temporary scaffold supporting cell migration and tissue repair.
  locations:
  - id: GO:0031012
    label: extracellular matrix
  directly_involved_in:
  - id: GO:0007596
    label: blood coagulation
  supported_by:
  - reference_id: PMID:7989369
    supporting_text: Characterization of the NH2-terminal fibrin-binding site on
      fibronectin
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity.
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara.
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
- id: PMID:10075919
  title: Crystal structure of a heparin- and integrin-binding segment of human 
    fibronectin.
  findings: []
- id: PMID:10627046
  title: 'The PE-PGRS glycine-rich proteins of Mycobacterium tuberculosis: a new family
    of fibronectin-binding proteins?'
  findings: []
- id: PMID:10788510
  title: The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a 
    bifunctional protein that also binds to fibrinogen.
  findings: []
- id: PMID:11377428
  title: Binding of a peptide from a Streptococcus dysgalactiae MSCRAMM to the 
    N-terminal F1 module pair of human fibronectin involves both modules.
  findings: []
- id: PMID:11773026
  title: In vitro localization of TIGR/MYOC in trabecular meshwork extracellular
    matrix and binding to fibronectin.
  findings: []
- id: PMID:11792823
  title: Fibulin-1 suppression of fibronectin-regulated cell adhesion and 
    motility.
  findings: []
- id: PMID:11956183
  title: The type XIII collagen ectodomain is a 150-nm rod and capable of 
    binding to fibronectin, nidogen-2, perlecan, and heparin.
  findings: []
- id: PMID:12167537
  title: Several regions of the repeat domain of the Staphylococcus caprae 
    autolysin, AtlC, are involved in fibronectin binding.
  findings: []
- id: PMID:12225811
  title: Matrix-matrix interaction of cartilage oligomeric matrix protein and 
    fibronectin.
  findings: []
- id: PMID:12421310
  title: Elongation factor Tu and E1 beta subunit of pyruvate dehydrogenase 
    complex act as fibronectin binding proteins in Mycoplasma pneumoniae.
  findings: []
- id: PMID:12736686
  title: Pathogenic bacteria attach to human fibronectin through a tandem 
    beta-zipper.
  findings: []
- id: PMID:1400330
  title: Fibulin binds to itself and to the carboxyl-terminal heparin-binding 
    region of fibronectin.
  findings: []
- id: PMID:1423622
  title: 'The three-dimensional structure of the tenth type III module of fibronectin:
    an insight into RGD-mediated interactions.'
  findings: []
- id: PMID:14718574
  title: 'The human plasma proteome: a nonredundant list developed by combination
    of four separate sources.'
  findings: []
- id: PMID:15165854
  title: Molecular structure and interaction of recombinant human type XVI 
    collagen.
  findings: []
- id: PMID:15292204
  title: BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, 
    contains a disordered region that undergoes a conformational change on 
    ligand binding.
  findings: []
- id: PMID:15308636
  title: 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.
  findings: []
- id: PMID:16157329
  title: Sequential deposition of latent TGF-beta binding proteins (LTBPs) 
    during formation of the extracellular matrix in human lung fibroblasts.
  findings: []
- id: PMID:16236823
  title: Laminin-10 and Lutheran blood group glycoproteins in adhesion of human 
    endothelial cells.
  findings: []
- id: PMID:1632457
  title: Plasminogen activator inhibitor-1 deposition in the extracellular 
    matrix of cultured human mesangial cells.
  findings: []
- id: PMID:16336961
  title: A novel role for fibronectin type I domain in the regulation of human 
    hematopoietic cell adhesiveness through binding to follistatin domains of 
    FLRG and follistatin.
  findings: []
- id: PMID:16457822
  title: CT domain of CCN2/CTGF directly interacts with fibronectin and enhances
    cell adhesion of chondrocytes through integrin alpha5beta1.
  findings: []
- id: PMID:16677310
  title: Mycobacterium tuberculosis malate synthase is a laminin-binding 
    adhesin.
  findings: []
- id: PMID:1747115
  title: Interaction of the small proteoglycan decorin with fibronectin. 
    Involvement of the sequence NKISK of the core protein.
  findings: []
- id: PMID:17849409
  title: Identification of novel bacterial plasminogen-binding proteins in the 
    human pathogen Mycobacterium tuberculosis.
  findings: []
- id: PMID:17914904
  title: Force-induced unfolding of fibronectin in the extracellular matrix of 
    living cells.
  findings: []
- id: PMID:18042364
  title: TSG-6 binds via its CUB_C domain to the cell-binding domain of 
    fibronectin and increases fibronectin matrix assembly.
  findings: []
- id: PMID:18160478
  title: Novel adhesin from Pasteurella multocida that binds to the 
    integrin-binding fibronectin FnIII9-10 repeats.
  findings: []
- id: PMID:18243143
  title: Uteroglobin interacts with the heparin-binding site of fibronectin and 
    prevents fibronectin-IgA complex formation found in IgA-nephropathy.
  findings: []
- id: PMID:18323857
  title: NEDD8 acts as a 'molecular switch' defining the functional selectivity 
    of VHL.
  findings: []
- id: PMID:18411296
  title: The surface-exposed carboxyl region of Mycoplasma pneumoniae elongation
    factor Tu interacts with fibronectin.
  findings: []
- id: PMID:18713862
  title: Crystal structures of fibronectin-binding sites from Staphylococcus 
    aureus FnBPA in complex with fibronectin domains.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19126672
  title: Spontaneous phosphoinositide 3-kinase signaling dynamics drive 
    spreading and random migration of fibroblasts.
  findings: []
- id: PMID:19220903
  title: Surface displaced alfa-enolase of Lactobacillus plantarum is a 
    fibronectin binding protein.
  findings: []
- id: PMID:19429745
  title: 'Enolase from Paracoccidioides brasiliensis: isolation and identification
    as a fibronectin-binding protein.'
  findings: []
- id: PMID:19542224
  title: The first draft of the endostatin interaction network.
  findings: []
- id: PMID:19738201
  title: Proteomic analysis of integrin-associated complexes identifies RCC2 as 
    a dual regulator of Rac1 and Arf6.
  findings: []
- id: PMID:19826086
  title: Fibronectin forms the most extensible biological fibers displaying 
    switchable force-exposed cryptic binding sites.
  findings: []
- id: PMID:19931242
  title: The interaction of angiocidin with tissue transglutaminase.
  findings: []
- id: PMID:20080707
  title: EGF potentiated oncogenesis requires a tissue 
    transglutaminase-dependent signaling pathway leading to Src activation.
  findings: []
- id: PMID:20123964
  title: Lipid phosphate phosphatase 3 stabilization of beta-catenin induces 
    endothelial cell migration and formation of branching point structures.
  findings: []
- id: PMID:20541508
  title: Zinc induces structural reorganization of gelatin binding domain from 
    human fibronectin and affects collagen binding.
  findings: []
- id: PMID:20551380
  title: Proteomics characterization of extracellular space components in the 
    human aorta.
  findings: []
- id: PMID:20875085
  title: Functional analysis of a murine monoclonal antibody against the 
    repetitive region of the fibronectin-binding adhesins fibronectin-binding 
    protein A and fibronectin-binding protein B from Staphylococcus aureus.
  findings: []
- id: PMID:20879998
  title: Repeat regions R1 and R2 in the P97 paralogue Mhp271 of Mycoplasma 
    hyopneumoniae bind heparin, fibronectin and porcine cilia.
  findings: []
- id: PMID:21276792
  title: Morphologic and proteomic characterization of exosomes released by 
    cultured extravillous trophoblast cells.
  findings: []
- id: PMID:21569203
  title: The A domain of fibronectin-binding protein B of Staphylococcus aureus 
    contains a novel fibronectin binding site.
  findings: []
- id: PMID:22261194
  title: Proteomics analysis of cardiac extracellular matrix remodeling in a 
    porcine model of ischemia/reperfusion injury.
  findings: []
- id: PMID:22442151
  title: 'Transglutaminase-2 interaction with heparin: identification of a heparin
    binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix.'
  findings: []
- id: PMID:22516433
  title: Proteomic analysis of microvesicles from plasma of healthy donors 
    reveals high individual variability.
  findings: []
- id: PMID:22952693
  title: Cleavage of nidogen-1 by cathepsin S impairs its binding to basement 
    membrane partners.
  findings: []
- id: PMID:23154389
  title: Regulation of endodermal differentiation of human embryonic stem cells 
    through integrin-ECM interactions.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed 
    prostatic secretions in urine.
  findings: []
- id: PMID:23658023
  title: Comparative proteomic analysis of supportive and unsupportive 
    extracellular matrix substrates for human embryonic stem cell maintenance.
  findings: []
- id: PMID:23979707
  title: SILAC-based proteomics of human primary endothelial cell morphogenesis 
    unveils tumor angiogenic markers.
  findings: []
- id: PMID:24136289
  title: Identification and comparative analysis of hepatitis C virus-host cell 
    protein interactions.
  findings: []
- id: PMID:24388360
  title: SERPINA5 inhibits tumor cell migration by modulating the 
    fibronectin-integrin β1 signaling pathway in hepatocellular carcinoma.
  findings: []
- id: PMID:24658351
  title: Structural basis for pure antagonism of integrin αVβ3 by a 
    high-affinity form of fibronectin.
  findings: []
- id: PMID:25034023
  title: Heparin/heparan sulfate controls fibrillin-1, -2 and -3 
    self-interactions in microfibril assembly.
  findings: []
- id: PMID:25037231
  title: Extracellular matrix signatures of human primary metastatic colon 
    cancers and their metastases to liver.
  findings: []
- id: PMID:25290767
  title: Structural and functional analysis of the fibronectin-binding protein 
    FNE from Streptococcus equi spp. equi.
  findings: []
- id: PMID:25293691
  title: Proteolytic processing of the cilium adhesin MHJ_0194 (P123J ) in 
    Mycoplasma hyopneumoniae generates a functionally diverse array of cleavage 
    fragments that bind multiple host molecules.
  findings: []
- id: PMID:2531657
  title: Lipoprotein(a) binds to fibronectin and has serine proteinase activity 
    capable of cleaving it.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25834989
  title: Fibulin1C peptide induces cell attachment and extracellular matrix 
    deposition in lung fibroblasts.
  findings: []
- id: PMID:26571399
  title: A collagen VI-dependent pathogenic mechanism for Hirschsprung's 
    disease.
  findings: []
- id: PMID:26627825
  title: Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus 
    aureus Inhibits the Formation of Platelet-Leukocyte Complexes.
  findings: []
- id: PMID:26848503
  title: Mapping and Exploring the Collagen-I Proteostasis Network.
  findings: []
- id: PMID:27068509
  title: 'Extracellular matrix remodelling in response to venous hypertension: proteomics
    of human varicose veins.'
  findings: []
- id: PMID:27141819
  title: Mycobacterial antigen 85 complex (Ag85) as a target for ficolins and 
    mannose-binding lectin.
  findings: []
- id: PMID:27559042
  title: Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity 
    in Human Atrial Fibrillation.
  findings: []
- id: PMID:27616280
  title: Interactions of surface-displayed glycolytic enzymes of Mycoplasma 
    pneumoniae with components of the human extracellular matrix.
  findings: []
- id: PMID:28327460
  title: Comprehensive proteomic characterization of stem cell-derived 
    extracellular matrices.
  findings: []
- id: PMID:28344315
  title: Proteomic characterization of human multiple myeloma bone marrow 
    extracellular matrix.
  findings: []
- id: PMID:28675934
  title: Characterization of the Extracellular Matrix of Normal and Diseased 
    Tissues Using Proteomics.
  findings: []
- id: PMID:29030641
  title: Lubricin binds cartilage proteins, cartilage oligomeric matrix protein,
    fibronectin and collagen II at the cartilage surface.
  findings: []
- id: PMID:30082873
  title: Insights into the structure and dynamics of lysyl oxidase propeptide, a
    flexible protein with numerous partners.
  findings: []
- id: PMID:3024962
  title: Mapping the collagen-binding site of human fibronectin by expression in
    Escherichia coli.
  findings: []
- id: PMID:3141278
  title: Characterization of fibronectin-binding antigens released by 
    Mycobacterium tuberculosis and Mycobacterium bovis BCG.
  findings: []
- id: PMID:31759052
  title: Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 
    regulate endothelial ECM and angiogenesis through non-catalytic scaffolding 
    mechanisms.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the 
    human interactome.
  findings: []
- id: PMID:33962943
  title: Structural insights into integrin α(5)β(1) opening by fibronectin 
    ligand.
  findings: []
- id: PMID:34089617
  title: Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin 
    ameliorates autoimmune disease in BXSB/Yaa mice.
  findings: []
- id: PMID:34968453
  title: Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic 
    macrophage programming during CVB3-induced viral myocarditis.
  findings: []
- id: PMID:3997886
  title: Incorporation of thrombospondin into fibrin clots.
  findings: []
- id: PMID:7989369
  title: Further characterization of the NH2-terminal fibrin-binding site on 
    fibronectin.
  findings: []
- id: PMID:9269765
  title: Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I 
    mediated by the kringle IV domain.
  findings: []
- id: PMID:9278415
  title: The self-association and fibronectin-binding sites of fibulin-1 map to 
    calcium-binding epidermal growth factor-like domains.
  findings: []
- id: Reactome:R-HSA-1566981
  title: Fibronectin degradation by MMP1, 3, 7, 12, 13, 19, CTSS
  findings: []
- id: Reactome:R-HSA-202723
  title: Integrin alpha5beta1 binds FN1 dimer
  findings: []
- id: Reactome:R-HSA-216050
  title: Integrins alpha4beta1, alpha8beta1, alphaVbeta1, alphaVbeta3, 
    alphaVbeta6 bind Fibronectin matrix
  findings: []
- id: Reactome:R-HSA-2327733
  title: FN1 binds Collagen types I-V, VII
  findings: []
- id: Reactome:R-HSA-2327746
  title: FN1 aggregation
  findings: []
- id: Reactome:R-HSA-2396337
  title: HSPG2 binds FGF2(10-155), Fibronectn matrix, Transthyretin tetramer, 
    PDGFA homodimer, PDGFB homodimer
  findings: []
- id: Reactome:R-HSA-2533950
  title: Fibronectin degradation by MMP14
  findings: []
- id: Reactome:R-HSA-2537665
  title: Fibulin-1 and -2 bind fibronectin
  findings: []
- id: Reactome:R-HSA-2545196
  title: FN1 dimerizes
  findings: []
- id: Reactome:R-HSA-2681681
  title: Tenascins C, R, (X, N) bind fibronectin matrix
  findings: []
- id: Reactome:R-HSA-2731141
  title: Syndecan-1 binds fibronectin
  findings: []
- id: Reactome:R-HSA-349593
  title: Interaction of integrin alphaIIbbeta3 with Fibronectin
  findings: []
- id: Reactome:R-HSA-354066
  title: Translocation of PTK2 to Focal complexes
  findings: []
- id: Reactome:R-HSA-354073
  title: Autophosphorylation of PTK2 at Y397
  findings: []
- id: Reactome:R-HSA-354087
  title: Recruitment of GRB2 to p-PTK2
  findings: []
- id: Reactome:R-HSA-354124
  title: Phosphorylation of pPTK2 by SRC
  findings: []
- id: Reactome:R-HSA-354149
  title: Interaction of integrin alphaIIb beta3 with Fibrinogen
  findings: []
- id: Reactome:R-HSA-354165
  title: Interaction of SOS with GRB2 bound to FADK1
  findings: []
- id: Reactome:R-HSA-372693
  title: Phosphorylation of BCAR1 by SRC-PTK2 complex
  findings: []
- id: Reactome:R-HSA-372697
  title: Crk binding to p130cas
  findings: []
- id: Reactome:R-HSA-372705
  title: Recruitment of BCAR1 to PTK2 complex
  findings: []
- id: Reactome:R-HSA-377640
  title: Autophosphorylation of SRC
  findings: []
- id: Reactome:R-HSA-377641
  title: Clustering of Integrin alphaIIb beta3 complexes
  findings: []
- id: Reactome:R-HSA-377643
  title: Dephosphorylation of inactive SRC by PTPB1
  findings: []
- id: Reactome:R-HSA-377644
  title: Release of CSK from SRC
  findings: []
- id: Reactome:R-HSA-3785684
  title: Fibronectin degradation by CTSG
  findings: []
- id: Reactome:R-HSA-3788061
  title: Fibronectin degradation by ADAM8
  findings: []
- id: Reactome:R-HSA-429415
  title: SYK binds to integrin alphaIIb beta3
  findings: []
- id: Reactome:R-HSA-429441
  title: SYK activation by SRC
  findings: []
- id: Reactome:R-HSA-481007
  title: Exocytosis of platelet alpha granule contents
  findings: []
- id: Reactome:R-HSA-6785895
  title: Expression of IL4, IL13-upregulated extracellular proteins
  findings: []
- id: Reactome:R-HSA-8952289
  title: FAM20C phosphorylates FAM20C substrates
  findings: []
- id: Reactome:R-HSA-9624017
  title: p-SHC1 binds integrin alpha5beta1:fibronectin
  findings: []
- id: Reactome:R-HSA-9638552
  title: SfaS binds the fibronectin matrix
  findings: []
- id: Reactome:R-HSA-9700131
  title: ALK mutants bind type I TKIs
  findings: []
- id: Reactome:R-HSA-9700179
  title: Ligand-independent dimerization of ALK fusions
  findings: []
- id: Reactome:R-HSA-9700181
  title: Autophosphorylation of ALK fusions
  findings: []
- id: Reactome:R-HSA-9700190
  title: ALK mutants bind SHC
  findings: []
- id: Reactome:R-HSA-9700193
  title: ALK mutants phosphorylate SHC1
  findings: []
- id: Reactome:R-HSA-9712078
  title: ALK mutants bind PI3KR1
  findings: []
- id: Reactome:R-HSA-9712079
  title: ALK mutants bind STAT3
  findings: []
- id: Reactome:R-HSA-9712083
  title: ALK mutants bind PI3KCA
  findings: []
- id: Reactome:R-HSA-9712084
  title: PI3K synthesizes PIP3 downstream of ALK mutants
  findings: []
- id: Reactome:R-HSA-9712085
  title: ALK mutants phosphorylate STAT3
  findings: []
- id: Reactome:R-HSA-9724099
  title: ALK mutants:p-3Y SHC binds GRB2
  findings: []
- id: Reactome:R-HSA-9850958
  title: pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants
  findings: []
- id: Reactome:R-HSA-9865226
  title: PP2A dephosphorylates serine-127 of YAP1
  findings: []
- id: Reactome:R-HSA-9932034
  title: CsgA binds the fibronectin matrix
  findings: []
- id: file:human/FN1/FN1-deep-research-falcon.md
  title: Deep research report for FN1
  findings: []
- id: file:human/FN1/FN1-uniprot.txt
  title: UniProt record for FN1 (P02751)
  findings: []
alternative_products:
- name: '15'
  id: P02751-15
  description: >-
    The canonical plasma fibronectin isoform. Secreted by hepatocytes into blood.
    LACKS both
    EDA (EIIIA) and EDB (EIIIB) alternatively spliced domains. Soluble dimer that
    circulates
    in plasma. Most abundant form in adults. GO annotations for "blood microparticle"
    and
    "extracellular matrix organization" typically refer to this form.
- name: '1'
  id: P02751-1
  sequence_note: VSP_060347
  description: >-
    A cellular fibronectin isoform. Contains V region variation. Cellular FN isoforms
    are
    produced by fibroblasts and deposited in tissue extracellular matrix.
- name: 2 (MSF-FN70, Migration stimulation factor FN70)
  id: P02751-2
  sequence_note: VSP_060343, VSP_060344, VSP_060345
  description: >-
    A truncated 70 kDa form called Migration Stimulation Factor (MSF-FN70). Secreted
    by
    fetal and tumor fibroblasts. Has distinct bioactivity promoting cell migration.
    Important
    in tumor microenvironment.
- name: 3 (V89)
  id: P02751-3
  sequence_note: VSP_060347, VSP_060353
  description: >-
    An isoform containing EDB domain and V89 variant. Cellular fibronectin with
    embryonic/
    wound healing expression pattern.
- name: 4 (Fibronectin III-15X)
  id: P02751-4
  sequence_note: VSP_060347, VSP_060351, VSP_060354,
  description: >-
    An isoform with variation in type III domain 15. Less well characterized.
- name: 5 (Fibronectin (V+I-10)-)
  id: P02751-5
  sequence_note: VSP_060347, VSP_060351, VSP_060356
  description: >-
    An isoform lacking type I domain 10 but containing V region. Domain deletion
    isoform.
- name: 6 (Fibronectin (V+III-15)-)
  id: P02751-6
  sequence_note: VSP_060347, VSP_060350
  description: >-
    An isoform lacking type III domain 15 but containing V region. Domain deletion
    isoform.
- name: 7 (Fibronectin containing EDB domain)
  id: P02751-7
  sequence_note: VSP_060353
  description: >-
    CELLULAR FIBRONECTIN containing the EDB (EIIIB) alternatively spliced domain.
    EDB+ FN is
    an ONCOFETAL ANTIGEN - expressed during embryogenesis and wound healing but
    absent in
    normal adult tissues. Re-expressed in tumors and used as cancer biomarker and
    target for
    antibody-drug conjugates. Distinct from plasma FN which lacks EDB.
- name: 8 (Fibronectin not containing EDA domain)
  id: P02751-8
  sequence_note: VSP_060347, VSP_060349
  description: >-
    An isoform lacking the EDA (EIIIA) domain. May contain other variations. Intermediate
    between full cellular FN and plasma FN.
- name: 9 (Fibronectin not containing EDA and EDB domains and)
  id: P02751-9
  sequence_note: VSP_060347, VSP_060349, VSP_060352,
  description: >-
    An isoform lacking both EDA and EDB domains, similar to plasma FN pattern but
    with other
    sequence variations. Represents the EDA-/EDB- cellular FN form.
- name: '10'
  id: P02751-10
  sequence_note: VSP_060347, VSP_060349, VSP_060351
  description: >-
    A less characterized isoform lacking EDA domain with additional variations.
- name: 11 (Fibronectin containing EDB domain, exon x+2)
  id: P02751-11
  sequence_note: VSP_060348
  description: >-
    CELLULAR FIBRONECTIN containing EDB domain with additional exon variation. Oncofetal
    antigen expressed in embryogenesis, wound healing, and tumors.
- name: '12'
  id: P02751-12
  sequence_note: VSP_060346, VSP_060349, VSP_060352,
  description: >-
    A less characterized isoform. Functional role not well established.
- name: '13'
  id: P02751-13
  sequence_note: VSP_060349, VSP_060351
  description: >-
    A less characterized isoform lacking EDA domain. Functional role not well established.
- name: '14'
  id: P02751-14
  sequence_note: VSP_060347, VSP_060349, VSP_060353
  description: >-
    An isoform containing EDB domain but lacking EDA. Oncofetal antigen pattern.
- name: 16 (Migration stimulation factor, MSF)
  id: P02751-16
  sequence_note: VSP_060344, VSP_060345
  description: >-
    Migration Stimulation Factor (MSF). A truncated bioactive form that promotes
    cell
    migration. Produced by fetal fibroblasts and some tumors. Has distinct functions
    from
    full-length fibronectin in promoting motility.
- name: '17'
  id: P02751-17
  sequence_note: VSP_060347, VSP_060352, VSP_060353
  description: >-
    An isoform containing EDB domain. Likely has oncofetal expression pattern similar
    to
    other EDB+ isoforms.