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FLASH GENE

Symbol

MSTN

contributors: mct/pgu - updated : 18-01-2015

HGNC name	myostatin
HGNC id	4223

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Nervous brain forebrain cerebral cortex     Homo sapiens Olfactory (smell) olfactory bulb         Homo sapiens Skin/Tegument skin         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining epidermis     Homo sapiens Muscular striatum skeletal   predominantly Homo sapiens

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
	is capable of inhibiting myoblast proliferation by arresting cell cycles in the G1 phase and blocking myoblast differentiation by inhibiting MYOD1 activity
	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
	WFIKKN1 and WFIKKN2 proteins are antagonists of MSTN and GDF11, but in the case of TGFB1, BMP2 and BMP4 they function as growth factor binding proteins
	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
	MSTN positively regulates slow isoform MYH7 but negatively regulates fast isoforms MYH1, MYH4
	TDGF1 modulates myogenic cell determination and promotes proliferation by antagonizing the TGFB1 ligand myostatin (MSTN)
	SMYD3 modulates MSTN and MET transcription in primary skeletal muscle cells
	WFIKKN1 and WFIKKN2 are important modulators of GDF11 and MSTN activity
	IGF1 regulates MSTN expression via CREB1 transcription factor during muscle cell differentiation
	FST is a physiological inhibitor of MSTN, inducing a dramatic increase in skeletal muscle mass, requiring the type 1 IGFI receptor/AKT1/MTOR pathway

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed neuromuscular myopathy   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 cardiovascular aquired   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