| Post Translational Modifications | Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer. Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses. Ubiquitinated by RNF216 at Lys-268 and Lys-269 limiting ARC protein levels induced by synaptic activity and thus regulating ARC-dependent forms of synaptic plasticity. Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization. Phosphorylation by CaMK2 inhibits synaptic activity. |
| Function | Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system. ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation. ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons. Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory. Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis. Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses. Accumulates at weaker synapses, probably to prevent their undesired enhancement. This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material. Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory. Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1. In addition to its role in synapses, also involved in the regulation of the immune system: specifically expressed in skin-migratory dendritic cells and regulates fast dendritic cell migration, thereby regulating T-cell activation. |
| Protein Name | Activity-Regulated Cytoskeleton-Associated ProteinHarcActivity-Regulated Gene 3.1 Protein HomologArc/Arg3.1Arg3.1 |
| Database Links | Reactome: R-HSA-9031628 |
| Cellular Localisation | Extracellular Vesicle MembraneLipid-AnchorPostsynaptic Cell MembraneSynapsePostsynaptic DensityEarly Endosome MembraneCell ProjectionDendriteCytoplasmCytoskeletonCell CortexDendritic SpineCytoplasmic VesicleSecretory VesicleAcrosomeClathrin-Coated Vesicle MembraneForms Virion-Like Extracellular Vesicles That Are Released From NeuronsEnriched In Postsynaptic Density Of Dendritic SpinesTargeted To Inactive Synapses Following Interaction With Camk2b In The Kinase Inactive StateAccumulation At Weaker Synapses May Be Required To Prevent Their Undesired EnhancementAssociated With The Cell Cortex Of Neuronal Soma And DendritesAssociated With The Sperm Tail |
| Alternative Protein Names | Activity-Regulated Cytoskeleton-Associated Protein proteinHarc proteinActivity-Regulated Gene 3.1 Protein Homolog proteinArc/Arg3.1 proteinArg3.1 proteinARC proteinKIAA0278 protein |
Information sourced from Uniprot.org
