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FLASH GENE
Symbol FN1 contributors: mct/npt - updated : 09-01-2018
HGNC name fibronectin 1
HGNC id 3778
Corresponding disease
EDS10 Ehlers-Danlos syndrome, type X
GFND2 glomerulopathy with fibronectin deposits 2
SMDCF1 spondylometaphyseal dysplasia, corner fracture type 1
Location 2q35      Physical location : 216.225.180 - 216.300.791
Synonym name
  • cold inducible globulin
  • migration stimulating factor
    • Synonym symbol(s) FN, CIG, FINC, LETS, MSF, GFND2, DKFZp686F10164, DKFZp686H0342, DKFZp686I1370, DKFZp686O13149
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 75.13 kb     46 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    text
  • alternative splicing of FN1 gene results in the generation of protein variants containing an additional EIIIA domain that sustains cell proliferation or differentiation during physiological or pathological tissue remodeling (PMID: 27090359)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    46 - 8815 - 2477 - 2005 16322219
    47 - 8647 - 2421 - 2005 16322219
    46 - 8449 - 2355 - 2005 16322219
    46 - 8374 - 2330 - 2005 16322219
    44 - 8272 - 2296 - 2005 16322219
    13 - 2402 - 657 - 2005 16322219
    44 - 7912 - 2176 - 2005 16322219
    45 - 8205 - 2267 - 2005 16322219
    45 - 8124 - 2240 - 2005 16322219
    45 - 8199 - 2265 - 2005 16322219
    47 - 8742 - 2446 - 2005 16322219
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     liver    
     mouthtongue  highly
    Reproductivefemale systemplacenta  highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
     digestive
    cell lineage
    cell lines
    fluid/secretion plasma (soluble dimeric form)
    at STAGE
    physiological period embryo, fetal
    Text liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • P2 adhesive glycoprotein
  • 12 fibronectin type-I domains
  • two fibronectin type-II domains
  • 16 fibronectin type-III domains, and he third type III domain (3FN3) interacts with other parts of fibronectin and with anastellin, a protein fragment that causes fibronectin aggregation
  • a gelatin-binding domain (GBD)
    • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text extracellular matrix
    basic FUNCTION
  • involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape
  • it might be a critical molecule produced by T(H)1 cells involved in pathogen eradication
  • upregulates osteoclast activity despite inhibiting osteoclast formation and these effects involve nitric oxide and IL1B signaling
  • laminin and fibronectin may play crucial roles in the control of trophoblast adhesion and invasion, in placentation and angiogenesis
  • glycoprotein involved in cellular adhesion and migration processes
  • O-glycosylated oncofetal fibronectin has a synergistic effect with transforming growth factor (TGFB1) in EMT induction
  • FN1 and WNT7A together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis
  • is a key factor in serum to recruit mesenchymal progenitor cells and might be involved in subchondral mesenchymal progenitor cell migration into cartilage defects after microfracture
  • is essential for endogenous cardiac progenitor cells (CPCs) expansion and repair required for stabilization of cardiac function after myocardial infarction (MI)
  • FN1 and ITGA5 play requisite roles in cardiac morphogenesis
  • EPPIN and FN1 bind to each other in human semen and on human ejaculated spermatozoa
  • opposing effects of collagen I and VTN on FN1 fibril structure and function
  • FN1 matrix plays a crucial role in the regulation of angiogenesis during development, tissue repair and pathogene
  • is an ECM glycoprotein substantially expressed during tissue repair
  • indispensable role for FN1 in chronic liver fibrosis/cirrhosis in negatively regulating TGFB1 bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions
  • Dental Bud Stem Cells (DBSCs) differentiation toward osteoblastic lineage was enhanced when cells were grown on fibronectin (FN1), vitronectin (VTN), and osteopontin (SPP1)
  • is a modular extracellular matrix protein that is essential for vertebrate development
  • is a major extracellular matrix protein implicated in cell adhesion and differentiation in the bone marrow (BM) environment
  • is a fundamental component of the hematopoietic tissue and the EIIIA exon may play a key role in modulating hematopiesis in conditions of BM stress or diseases
  • FN1 expression is an early and progressive event that occurs during liver fibrogenesis
  • plays a critical role in inflammasome-activated cells by amplifying caspase-1 activation and inducing inflammatory cell death
  • play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells
  • likely a reduced amount of secreted fibronectin from chondrocytes could result in a deficient matrix network in cartilage
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , development , immunity/defense
    text adhesion, migration
    PATHWAY
    metabolism
    signaling
  • SOX2-FN1 axis is a key pathway in mediating the migration and invasion of ovarian cancer cells
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
  • heparin
    • protein
  • collagen, actin
  • binds BMP1-like proteinases and FN1 is an important determinant of the activity levels of BMP1-like proteinases
  • HAND2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of FN1 levels
  • interaction between the NC4 domain of COL9A1 and FN1 may represent an interaction in cartilage that could contribute to the matrix integrity of the tissue
  • is potentially a critical mediator for TGFB-specific production balance of 2 major proteoglycans, aggrecan and versican, during chondrogenesis
  • synthesis of FN1 is mediated by a transcriptional complex consisting of NFATC1, SP7 and FOS
  • association between EPO and FN1 expression in glomerular mesangial cells
  • RHOA stimulates the production of FN1 by podocytes, specifically testing the role of nuclear factor of activated T cells (NFATC1)
  • NFATC1 mediates RHOA-induced FN1 upregulation in glomerular podocytes
  • interaction between fibronectin (FN1) and collagen
  • FN1 and its major receptor, ITGB1/ITGA5 are required for embryogenesis
  • BST1 binds FN1 with high affinity within its heparin-binding domains 1 and 2
  • fibronectin-derived homophilic binding peptide, anastellin, as an effective inhibitor of angiogenesis
  • a binding site in DPT for FN1 was identified as the DPT-4 (PHGQVVVAVRS) peptide, and the major binding site in FN1 for DPT was the 14th type III repeat (III14) domain
  • NME1/fibronectin axis represents a barrier to melanoma progression
  • TGM2 is involved in cell-matrix interactions through association with the extracellular matrix protein, fibronectin (FN1)
  • binding of TGM2 to the ECM of small intestinal tissue sections is the sum of binding to FN1 via its N-terminal domain and binding to an abundant, novel extracellular matrix (ECM) interaction partner via its second C-terminal beta-barrel domain
  • thyroid hormone regulates FN1 expression through the activation of the HIF1A
    • cell & other
  • bind cell surfaces and various compounds including fibrin, DNA
    • REGULATION
    induced by decreased DICER1 expression that induces FN1 expression via an EGR1-dependent manner
    Other degradation by LRP
    ASSOCIATED DISORDERS
    corresponding disease(s) EDS10 , GFND2 , SMDCF1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer cells
    tumoral       gain of function
    up-regulated in germ cells yolk sac tumors
    tumoral     --over  
    in renal cancer
    Susceptibility susceptibility to lung fibrosing alveolitis in systemic sclerosis
    Variant & Polymorphism
    Candidate gene
  • EPPIN-FN1 complex may involve in semen coagulation, liquefaction and the survival and preparation of spermatozoa for fertility in the female reproductive tract
    • Marker
  • FN1 mRNA expression might serve as a marker for renal cell cancer (RCC) aggressiveness, indicating early systemic progression particularly for patients with papillary RCC
  • serum- and CSF-FN1 levels constitute a potential clinical diagnostic biomarker for epilepsy and could also be used for differential diagnosis
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    offers crucial molecular insights and promises to develop putative candidate therapeutic interventions in women with ovarian cancer
    ANIMAL & CELL MODELS