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FLASH GENE
Symbol MSTN contributors: mct/pgu - updated : 18-01-2014
HGNC name myostatin
HGNC id 4223
Location 2q32.2      Physical location : 190.920.426 - 190.927.455
Synonym name growth differentiation factor 8
Synonym symbol(s) GDF8
DNA
TYPE functioning gene
STRUCTURE 7.03 kb     3 Exon(s)
MAPPING cloned Y linked N status provisional
Map cen - COL3A1 - GDF8 - INPP1 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2823 42.7 375 - 2006 17186467
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Nervousbrainforebraincerebral cortex   Homo sapiens
Olfactory (smell)olfactory bulb     Homo sapiens
Skin/Tegumentskin     Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningepidermis   Homo sapiens
Muscularstriatumskeletal highly
cell lineage
cell lines
fluid/secretion secreted into the plasma
at STAGE
physiological period fetal, pregnancy
Text developing skeletal muscle
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal signal peptide of myostatin is essential for association with SGTA
  • TGF beta-like domain
  • a consensus MYOD response element (transcriptional regulator of developmental gene)
  • three putative transcription initiation sites
  • conjugated GlycoP
    mono polymer homomer , dimer
    isoforms Precursor cleaved at a consensus Arg-X-X-Arg to yield a C terminus mature dimer
    HOMOLOGY
    Homologene
    FAMILY
  • transforming growth factor beta (TGFB) superfamily
  • BMP family
  • CATEGORY regulatory , transcription factor , signaling
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    text secreted
    basic FUNCTION
  • putative attenuator of skeletal muscle growth, correlating inversely with muscle mass index
  • negative regulator of skeletal-muscle growth, playing an important role in regulating muscle mass
  • modulating adipogenesis to generate adipocytes with favorable metabolic effects
  • not only regulates the growth of myocytes but also directly regulates muscle fibroblasts
  • GRB14, GPD1, and MSTN are potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle
  • stimulates the canonical Smad signaling pathway common to TGFB family members, as well as delayed activation of the p38 MAPK and the PI3K/Akt/mTOR signaling pathways
  • regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of CDKN1A and MYOD1
  • regulates muscle growth at least in part through regulation of AKT1
  • in muscle tissue functions to suppress myoblast proliferation and myofiber hypertrophy
  • cytokine of the transforming growth factor-beta superfamily that is known to control muscle wasting
  • acts within the human placenta to modulate glucose uptake and therefore homeostasis
  • through the disruption of maternal nutrient supply to the fetus, may thus be a potential mediator of offspring phenotype
  • dispensable for the initial atrophy occurring in response to food deprivation (FD)but attenuates the decrease in fast-twitch muscle mass during prolonged FD
  • role in the specification of myofiber types during myogenic differentiation
  • functions as a negative regulator of skeletal muscle mass
  • important regulator of muscle mass that contributes to the loss of muscle mass in a number of chronic diseases
  • myostatin and TGFB1 increase autophagy in skeletal muscle cells
  • negative regulator of skeletal muscle growth during development and in the adult
  • a procachectic TGFbeta superfamily member, abundantly secreted by cancer cells
  • is key regulator that contributes to placentation and the regulation of placental function throughout pregnancy
  • plays an important role in regulation of myoblast differentiation from induced pluripotent stem (iPS) cells of human origin
  • plays an important role as a negative regulator of skeletal muscle growth and differentiation
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SGTA (N-terminal signal peptide of myostatin is essential for its association with SGTA and the C-terminal region of SGTA containing the third TPR motif was indispensable for its interaction with myostatin)
  • myostatin interacts with its inhibitor, follistatin-like-3 (FSTL3)
  • FST is a myostatin-binding protein that can inhibit myostatin (MSTN) activity and promote muscle growth
  • potent negative regulator of myogenesis and its elevated levels in circulation results in the up-regulation of the muscle-specific E3 ligases, FBXO32 and muscle ring finger protein 1 (TRIM63)
  • induces skeletal muscle wasting through targeting sarcomeric proteins via SMAD3-mediated up-regulation of FBXO32 and FOXO1
  • increased in the expression of ATG4B, ULK2, with a trend to an increase in GABARAPL1 in cells treated with myostatin compared to control treated cells
  • is tightly controlled by Fst-like 3 (FSTL3), which is the only FST-type molecule that has been identified in the serum bound to myostatin
  • UTS2 and UCN stimulate the expression of MSTN (
  • DES and VIM, two components of the intermediate filament in muscle, directly interacted with and were degraded by FBXO32 in response to MSTN
  • SMYD3 modulates MSTN and MET transcription in primary skeletal muscle cells
  • IGF1 regulates MSTN expression via CREB1 transcription factor during muscle cell differentiation
  • cell & other
    REGULATION
    activated by cleaved by subtilisin-like convertases
    glucocorticoids that stimulate MSTN which inhibits AKIRIN1 expression and the reparative functions of satellite cells
    induced by by dexamethasone under those differentiation conditions
    inhibited by activin A receptor, type IIB(ACVR2B)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in gross muscle hypertrophy
    constitutional       loss of function
    results in increased muscle mass
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    myostatin inhibitors have entered clinical trials in patients with muscle wasting and degenerative diseases; inhibitors have the potential of increasing muscle regeneration through the effects of myostatin on myoblasts and also of inhibiting fibrosis th
    cardiovascularaquired 
    targeted inhibition of myostatin in cardiac cachexia might be a therapeutic option in the future
    obesity  
    . increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes
    diabete  
    . increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes
    diabete  
    altering the final stages of adipogenesis through targeted GDF8 exposure, may have therapeutic benefit in metabolic disaeses such as diabetes
    cancer  
    MSTN inhibition is a potential therapy for muscle wasting diseases, some of which are associated with a depletion of satellite cells
    ANIMAL & CELL MODELS
  • myostatin knockout in mice increases myogenesis and decreases adipogenesis
  • Mstn(-/-) mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity
  • Mstn-deficient animals result in an increase of skeletal muscle mass with both hyperplasia and hypertrophy
  • Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction