Mus musculus Protein: Agrn
Summary
InnateDB Protein IDBP-208367.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Agrn
Protein Name agrin
Synonyms Agrin; nmf380;
Species Mus musculus
Ensembl Protein ENSMUSP00000071229
InnateDB Gene IDBG-208363 (Agrn)
Protein Structure
UniProt Annotation
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. This neuron-specific (z+) isoform is a 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 homestasis 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 transmembrane agrin (TM-agrin) isoform, 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 2 and isoform 3: these isoforms lacking the 'z' insert (z0) are muscle-specific, have no AChR clustering ability and may be involved in nervous system endothelial cell differentiation.Agrin N-terminal 110 kDa subunit: 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). {ECO:0000250}.Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase in the number of filopodia.
Subcellular Localization Cell junction, synapse. Cell membrane; Single-pass type II membrane protein.
Disease Associations
Tissue Specificity Expressed in central nervous system (CNS) synapses such as in the cerebral cortex and hippocampus. Localizes to basal lamina of hippocampal blood vessels. Both (z+) and (z-) isoforms found in kidney, heart and cerebral vasculature. {ECO:0000269PubMed:10402191, ECO:0000269PubMed:11018052, ECO:0000269PubMed:17611272, ECO:0000269PubMed:18230682}.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
Experimentally validated
Total 6 [view]
Protein-Protein 1 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 5 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 7 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
Biological Process
Cellular Component
Protein Structure and Domains
PDB ID MGI:87961
InterPro IPR000082 SEA domain
IPR002049 EGF-like, laminin
IPR002350 Kazal domain
IPR003645 Follistatin-like, N-terminal
IPR003884 Factor I / membrane attack complex
PFAM PF01390
PF00053
PF00050
PF07648
PRINTS
PIRSF
SMART SM00200
SM00180
SM00280
SM00274
SM00057
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt
PhosphoSite PhosphoSite-A2ASQ1
TrEMBL Z4YJS5
UniProt Splice Variant
Entrez Gene 11603
UniGene Mm.431676
RefSeq
MGI ID
MGI Symbol Agrn
OMIM
CCDS
HPRD
IMGT
EMBL AF294811 AL928667 CT998563
GenPept AAG02119