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FLASH GENE
Symbol FST contributors: mct - updated : 20-09-2017
HGNC name follistatin
HGNC id 3971
Location 5q11.2      Physical location : 52.776.594 - 52.781.902
Synonym name
  • activin-binding protein
  • follistatin isoform FST317
  • Synonym symbol(s) FS, FSA
    DNA
    TYPE functioning gene
    STRUCTURE 5.33 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1122 344 38 - 2008 18184649
  • also called FST 344
  • truncated
  • has a 10-fold lower affinity to activin compared to FS288
  • 6 - 1386 - 315 - 2008 18184649
    also called FST 315, FST315 isoform is the predominant form
    - - - - - - 2016 27807065
  • less than 5p100 of the encoded mRNA
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Digestiveliver   highly
     pharynx   highly
    Endocrineadrenal glandcortex   
    endocrinebraindiencephalonpituitary  
    Endocrinepancreas    
    Hearing/Equilibriumear   highly
    Reproductivefemale systemovary  highly
     male systemprostate  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES globular Hydrophobic
    STRUCTURE
    motifs/domains
  • N terminal hydrophobic domain (for activin binding), critical for MSTN blockade, mediating the increase in muscle mass, and less pivotal for activin binding, which accounts for the decrease in the fat tissue
  • four contiguous domains
  • three of them highly similar to each other as well as to EGF and pancreatic secretory trypsin inhibitor (PI14)
  • three follistatin-like domains
  • three kazal-like domains
  • conjugated GlycoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to murine Fst
    Homologene
    FAMILY
  • members of the TGF-beta superfamily
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • neutralizing the biological activity of activin (at least in pituitary)
  • inhibiting FSH in ovarian follicular fluid
  • potent tissue regulator in the gonad,pituitary glands, pregnancy membranes, vasculature and liver
  • exert critical autocrine or paracrine control in many tissues by binding and bio-neutralizing activin and several other transforming growth factor-beta ligands
  • mesenchymal factor that controls size, patterning and gustatory cell differentiation in developing taste papillae
  • normally acts to inhibit other TGFB family members in addition to myostatin to regulate muscle size
  • antagonist of activin and related TGFB superfamily members that has important reproductive actions as well as critical regulatory functions in other tissues and systems
  • regulates germ cell nest breakdown and primordial follicle formation
  • mediates muscle growth and bone mineralization
  • GDF11, ACTB and FST are crucial components of a circuit that controls both total cell number and the ratio of neuronal versus glial cells in in this system
  • possible involvement of a mechanism including follistatin in the uremic wasting process
  • is essential for skeletal muscle development and growth
  • is an autocrine protein with a heparin-binding motif that serves to regulate the cell proliferative activity of the paracrine hormone
  • single-chain glycosylated protein whose primary function consists in binding and neutralizing some members of the TGFB superfamily such as activin and bone morphogenic proteins
  • novel role of FST in the induction of brown adipocyte character and regulation of energy metabolism
  • important role of FST, a soluble glycoprotein that is known to bind and antagonize MSTN actions, during brown fat differentiation and the regulation of cellular metabolism
  • physiological inhibitor of MSTN, inducing a dramatic increase in skeletal muscle mass, requiring the type 1 IGFI receptor/AKT1/MTOR pathway
  • anabolic effects of FST are influenced by the interaction between muscle fibres and motor nerves
  • FST levels are associated with circulating leptin levels and display a day-night rhythm and a menstrual cycle
  • plays a role in tumourigenesis, metastasis and angiogenesis of solid tumours through its interaction with activin and BMPs, thus resulting in pathophysiological function
  • can induce ovarian arrest during pregnancy
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FSH participating in a negative feedback loop which regulates the activin function
  • activin (activin antagonist)
  • binding to ANG
  • all of the follistatin antagonists possess an N-terminal domain followed by two or three follistatin domains (FSD)
  • interactions between mesenchyme-derived FST and epithelial BMP7 play a central role in the morphogenesis, innervation and maintenance of taste buds and their stem/progenitor cells
  • myostatin-binding protein that can inhibit myostatin (MSTN) activity and promote muscle growth
  • GDF9 decreases basal and activin A-induced FST and FSTL3 expression
  • SMAD3 is the critical intracellular link that mediates the effects of FST on MTOR signaling
  • FST-mediated skeletal muscle hypertrophy is regulated by SMAD3 and MTOR independently of MSTN
  • FST interacts with NOG in the development of the axial skeleton
  • up-regulation of FST in chondrocytes by skeletal dysplasia-inducing TRPV4 mutations contributes to disease pathogenesis
  • HNRNPD is a negative regulator of FST expression and participates in the regulation of cell survival under glucose deprivation
  • FST-induced muscle hypertrophy requires the activation of the insulin/IGF1 pathway by either insulin or IGF1
  • is an inhibitor of TGFB1 superfamily ligands that repress skeletal muscle growth and promote muscle wasting
  • ubiquitous secretory propeptide that functions as a potent inhibitor of the MSTN pathway, resulting in an increase in skeletal muscle mass
  • is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues
  • cell & other
    REGULATION
    activated by activin A (critical role of intron 1 of FST in mediating Smad-dependent effects of activin and regulating the expression level of this gene in some cell types, such as pituitary cells of gonadotrope lineage)
    GLI2 (key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    while both activin subunits were downregulated in the majority of liver tumours
    tumoral     --low  
    in breast cancers compared with normal tissue and low FST expression predicts increased metastasis and reduced overall survival
    constitutional     --low  
    in recurrent miscarriage and women with recurrent miscarriage have lower endometrial expression of FST during the luteal phase
    constitutional     --over  
    of ACVR2A, ACVR2B, and FST in the endometrium may play a role in adenomyosis-related infertility
    constitutional     --low  
    FST levels were lower in late pregnancy in preeclamptic women compared to normal pregnant women
    Susceptibility
    Variant & Polymorphism
    Candidate gene candidate gene for polycystic ovary syndrome PCOS (minor role)
    Marker
  • activin A or FST could be considered promising biomarkers for the discrimination between an intrauterine pregnancies (IUP) and a failed pregnancy (ectopic pregnancies (EP) or missed abortions (MA))
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    activin/follistatin system as promising target for therapeutic intervention in hepatocarcinogenesis
    neuromuscularmyopathy 
    follistatin gene therapy for mild to moderately affected, ambulatory sporadic inclusion body myositis patients
    neuromuscularmyopathy 
    using the FS344 isoform of FST in Becker muscular dystrophy is the future directions for clinical gene therapy trials using follistatin.
    cancerreproductiveprostate
    potential therapeutic target in prostate cancer
    respiratorylung 
    potential of follistatin as a therapeutic for prevention of airway remodelling in asthma and other inflammatory lung diseases
    ANIMAL & CELL MODELS
  • Fst(-/-) mice exhibit dramatically decreased neurogenesis, a phenotype that can only be partially explained by increased GDF11