Names & Taxonomy

Uniprot ID:
O00468
Entry Name:
AGRIN_HUMAN
Status:
reviewed
Protein Names:
Agrin [Cleaved into: Agrin N-terminal 110 kDa subunit; Agrin C-terminal 110 kDa subunit; Agrin C-terminal 90 kDa fragment (C90); Agrin C-terminal 22 kDa fragment (C22)]
Gene Names:
AGRN AGRIN
Gene Names Primary:
AGRN
Organism:
Homo sapiens (Human)

Structure

Length:
2067
Sequence:
MAGRSHPGPLRPLLPLLVVAACVLPGAGGTCPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTGDTRIFFVNPAPPYLWPAHKNELMLNSSLMRITLRNLEEVEFCVEDKPGTHFTPVPPTPPDACRGMLCGFGAVCEPNAEGPGRASCVCKKSPCPSVVAPVCGSDASTYSNECELQRAQCSQQRRIRLLSRGPCGSRDPCSNVTCSFGSTCARSADGLTASCLCPATCRGAPEGTVCGSDGADYPGECQLLRRACARQENVFKKFDGPCDPCQGALPDPSRSCRVNPRTRRPEMLLRPESCPARQAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQCQGRDQCPEPCRFNAVCLSRRGRPRCSCDRVTCDGAYRPVCAQDGRTYDSDCWRQQAECRQQRAIPSKHQGPCDQAPSPCLGVQCAFGATCAVKNGQAACECLQACSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPCDRCGQCRFGALCEAETGRCVCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASAGPCETCGDAVCAFGAVCSAGQCVCPRCEHPPPGPVCGSDGVTYGSACELREAACLQQTQIEEARAGPCEQAECGSGGSGSGEDGDCEQELCRQRGGIWDEDSEDGPCVCDFSCQSVPGSPVCGSDGVTYSTECELKKARCESQRGLYVAAQGACRGPTFAPLPPVAPLHCAQTPYGCCQDNITAARGVGLAGCPSACQCNPHGSYGGTCDPATGQCSCRPGVGGLRCDRCEPGFWNFRGIVTDGRSGCTPCSCDPQGAVRDDCEQMTGLCSCKPGVAGPKCGQCPDGRALGPAGCEADASAPATCAEMRCEFGARCVEESGSAHCVCPMLTCPEANATKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPCQEAVAPSTHPTSASVTVTTPGLLLSQALPAPPGALPLAPSSTAHSQTTPPPSSRPRTTASVPRTTVWPVLTVPPTAPSPAPSLVASAFGESGSTDGSSDEELSGDQEASGGGSGGLEPLEGSSVATPGPPVERASCYNSALGCCSDGKTPSLDAEGSNCPATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFDPTTAFRAPDVARALLRQIQVSRRRSLGVRRPLQEHVRFMDFDWFPAFITGATSGAIAAGATARATTASRLPSSAVTPRAPHPSHTSQPVAKTTAAPTTRRPPTTAPSRVPGRRPPAPQQPPKPCDSQPCFHGGTCQDWALGGGFTCSCPAGRGGAVCEKVLGAPVPAFEGRSFLAFPTLRAYHTLRLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGQWHRLELSRHWRRGTLSVDGETPVLGESPSGTDGLNLDTDLFVGGVPEDQAAVALERTFVGAGLRGCIRLLDVNNQRLELGIGPGAATRGSGVGECGDHPCLPNPCHGGAPCQNLEAGRFHCQCPPGRVGPTCADEKSPCQPNPCHGAAPCRVLPEGGAQCECPLGREGTFCQTASGQDGSGPFLADFNGFSHLELRGLHTFARDLGEKMALEVVFLARGPSGLLLYNGQKTDGKGDFVSLALRDRRLEFRYDLGKGAAVIRSREPVTLGAWTRVSLERNGRKGALRVGDGPRVLGESPKSRKVPHTVLNLKEPLYVGGAPDFSKLARAAAVSSGFDGAIQLVSLGGRQLLTPEHVLRQVDVTSFAGHPCTRASGHPCLNGASCVPREAAYVCLCPGGFSGPHCEKGLVEKSAGDVDTLAFDGRTFVEYLNAVTESELANEIPVPETLDSGALHEKALQSNHFELSLRTEATQGLVLWSGKATERADYVALAIVDGHLQLSYNLGSQPVVLRSTVPVNTNRWLRVVAHREQREGSLQVGNEAPVTGSSPLGATQLDTDGALWLGGLPELPVGPALPKAYGTGFVGCLRDVVVGRHPLHLLEDAVTKPELRPCPTP
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Secreted, extracellular space, extracellular matrix

Function

Function:
Isoform 1: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homeostasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain.; Isoform 2: transmembrane form that is the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases.; Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.; Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation.; Agrin N-terminal 110 kDa subunit: is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity).
Gene Ontology Go:
basal lamina
cell junction
cytoplasm
extracellular exosome
extracellular matrix
extracellular region
Golgi lumen
integral component of membrane
lysosomal lumen
plasma membrane
synapse
calcium ion binding
chondroitin sulfate binding
dystroglycan binding
heparan sulfate proteoglycan binding
laminin binding
sialic acid binding
structural constituent of cytoskeleton
axon guidance
carbohydrate metabolic process
chondroitin sulfate metabolic process
clustering of voltage-gated sodium channels
extracellular matrix organization
fat-soluble vitamin metabolic process
G-protein coupled acetylcholine receptor signaling pathway
glycosaminoglycan biosynthetic process
glycosaminoglycan catabolic process
glycosaminoglycan metabolic process
phototransduction, visible light
positive regulation of filopodium assembly
positive regulation of GTPase activity
positive regulation of synaptic growth at neuromuscular junction
positive regulation of transcription from RNA polymerase II promoter
receptor clustering
retinoid metabolic process
signal transduction
small molecule metabolic process
synapse organization
vitamin metabolic process
Gene Ontology Biological Process:
axon guidance
carbohydrate metabolic process
chondroitin sulfate metabolic process
clustering of voltage-gated sodium channels
extracellular matrix organization
fat-soluble vitamin metabolic process
glycosaminoglycan biosynthetic process
glycosaminoglycan catabolic process
glycosaminoglycan metabolic process
G-protein coupled acetylcholine receptor signaling pathway
phototransduction, visible light
positive regulation of filopodium assembly
positive regulation of GTPase activity
positive regulation of synaptic growth at neuromuscular junction
positive regulation of transcription from RNA polymerase II promoter
receptor clustering
retinoid metabolic process
signal transduction
small molecule metabolic process
synapse organization
vitamin metabolic process
Gene Ontology Molecular Function:
calcium ion binding
chondroitin sulfate binding
dystroglycan binding
heparan sulfate proteoglycan binding
laminin binding
sialic acid binding
structural constituent of cytoskeleton
Gene Ontology Cellular Component:
basal lamina
cell junction
cytoplasm
extracellular exosome
extracellular matrix
extracellular region
Golgi lumen
integral component of membrane
lysosomal lumen
plasma membrane
synapse
Keywords:
Alternative splicing
Calcium
Cell junction
Cell membrane
Complete proteome
Congenital myasthenic syndrome
Developmental protein
Differentiation
Disease mutation
Disulfide bond
EGF-like domain
Extracellular matrix
Glycoprotein
Heparan sulfate
Laminin EGF-like domain
Membrane
Phosphoprotein
Polymorphism
Proteoglycan
Reference proteome
Repeat
Secreted
Signal
Synapse
Transmembrane
Transmembrane helix
Interacts With:
O15265

Publication

PubMed ID:
9652404 16710414 9151673 15489334 11161480 16487930 19159218 20551380 21969364 22683512 19631309 22205389 24951643