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FLASH GENE
Symbol AGRN contributors: mct/npt/pgu - updated : 22-08-2014
HGNC name agrin
HGNC id 329
Location 1p36.33      Physical location : 955.502 - 991.492
Synonym name agrin proteoglycan
Synonym symbol(s) FLJ45064
DNA
TYPE functioning gene
STRUCTURE 36.02 kb     36 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
text four forms generated by alternative splicing
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
36 - 7319 - 2045 - 2006 17012237
38 - 7395 - 2068 - -
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon  
Nervousbrain   highly Homo sapiens
 spinal cordanterior horn    Homo sapiens
Reproductivemale systemprostate   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal   Homo sapiens
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunelymphocyte
cell lineage
cell lines
fluid/secretion sperm
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal part of agrins contains several follistatin-domains, a domain type that is frequently implicated in binding TGFbetas four EGF-like domains, and that may have a role in the developing central nervous system (
  • nine Kazal-like domains
  • two laminin EGf-like domains
  • three laminin G-like domains
  • one SEA domain
  • C-terminal end containing three laminin G-like (LG) domains, two of which are required for binding to alpha-dystroglycan
  • C-terminal 95 kDa fragment is sufficient to induce clustering of acetylcholine receptors (
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Agrn (82.5pc)
    Homologene
    FAMILY
    CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text
  • large extracellular matrix protein
  • synaptic basal lamina on the surface of muscle fibers, colocalizing with clustered T cell receptors at the surface of activated T cells
  • isoform SN localized in the posterior post-acrosomal, neck, and flagellar mid-piece regions in sperm
  • transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain
  • induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane
  • basic FUNCTION
  • motor neuron-derived ligand that stimulates MUSK phosphorylation, play critical roles in synaptic differentiation, as synapses do not form in their absence
  • activating the muscle specific receptor tyrosine kinase (MUSK) which phosphorylates AChRs
  • neuronal aggregating factor inducing the aggregation of acetylcholine receptors and other postsynaptic proteins on muscle fibers
  • playing an organizing role in the formation and/or differentiation of interneuronal, cholinergic synapses
  • playing a key role in the formation and maintenance of the neuromuscular junction
  • inducing the aggregation of signaling proteins and the creation of signaling domains not only in nervous systems but also in immune systems
  • may play an important role in the formation of both senile plaques and neurofibrillary tangles
  • accelerating the formation of protofibrils by alpha-synuclein and decreases the half-time of fibril formation
  • stimulates synaptic differentiation by activating MUSK
  • inducing acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways
  • possible role as a receptor or coreceptor on neurons (
  • possible modulation of ATP1A3 that is important in regulating heart function
  • physiological role for Tm-agrin in the maturation of hippocampal neurons involving positive regulation of dendritic filopodia and consequent promotion of synaptogenesis, but also possible role for axonal agrin in synaptogenesis
  • having a critical role for synaptic differentiation (
  • released by motor neurons, and promotes neuromuscular synapse formation by stimulating MUSK, a receptor tyrosine kinase expressed in skeletal muscle (
  • major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction
  • ACHE is a cholinergic and agrin a synaptogenetic component of the neuromuscular junction
  • common features of ACHE and agrin extend to their capacity to play multiple roles in muscle development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ATP1A3 (that might be its neuronal receptor)
  • interaction with MUSK
  • LRP4 serves as a coreceptor of agrin (
  • NOVA1 and NOVA2, neuron-specific splicing factors identified as targets in autoimmune motor disease, are essential regulators of Z(+) AGRN, involved in synapse formation at the neuromuscular junction (NMJ)
  • binding of the TGFbeta family members to agrin that may have a dual function: agrin may serve as a reservoir for these growth factors and may also inhibit their growth promoting activity (
  • binds LRP4 and stimulates further MUSK phosphorylation, stabilizing nascent synapses
  • LRP4 is a cis-acting ligand for MUSK, whereas AGRN functions as an allosteric and paracrine regulator to promote association between LRP4 and MUSK
  • the cascade linking AGRN to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype
  • LRP4 acts bi-directionally and coordinates synapse formation by binding AGRN, activating MUSK and stimulating postsynaptic differentiation
  • AGRN induces association of CHRNA1 mRNA and nicotinic acetylcholine receptor in C2C12 myotubes
  • activator of MUSK playing a role essential for the postnatal maintenance, but not for embryonic formation, of NMJs and also for the postnatal, but not prenatal, midmuscle localization of postsynaptic specializations
  • transport system, organized by AGRN through PI3 kinase, GSK3B, CLASP2, and PHLDB2, for precise delivery of CHRNA1 vesicles from the subsynaptic nuclei to the overlying synaptic membrane
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    formation of senile plaques and neurofibrillary tangles in dementia of Alzheimer type
    constitutional        
    accelerating the formation of insoluble protein fibrils in Parkinson's disease
    constitutional     --low  
    induced by nerve injury contributes to neuropathic pain
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    acetaminophen analog, promoted agrin upregulation, and may open new approaches for treating not only neuropathic pain, but also epilepsy, tremors, and spasticity
    ANIMAL & CELL MODELS