Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system (PubMed:29328916). 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 (PubMed:29328916). ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons (PubMed:29328916). 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 (PubMed:10818134, PubMed:17088211, PubMed:17088212, PubMed:17088213). 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 (PubMed:17088211, PubMed:17088212). Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses (PubMed:23791196). Accumulates at weaker synapses, probably to prevent their undesired enhancement (PubMed:22579289). This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material (PubMed:29328916). Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory (PubMed:10818134). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (By similarity). 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 (By similarity). Homooligomer; homooligomerizes into virion-like capsids (PubMed:29328916, PubMed:30028513, PubMed:31080121). Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2 (PubMed:17088211). Interacts with CAMK2B (in the kinase inactive state); leading to target ARC to inactive synapses (PubMed:22579289). Interacts with PSEN1 (By similarity). Interacts with GRIN2A and GRIN2B; inhibiting homooligomerization (PubMed:31080121). Forms virion-like extracellular vesicles that are released from neurons (PubMed:29328916). Enriched in postsynaptic density of dendritic spines (PubMed:17088211). Targeted to inactive synapses following interaction with CAMK2B in the kinase inactive state (PubMed:22579289). Accumulation at weaker synapses may be required to prevent their undesired enhancement (PubMed:22579289). Associated with the cell cortex of neuronal soma and dendrites (PubMed:7857651). Associated with the sperm tail (By similarity). Expressed exclusively in certain parts of the brain including cortex and molecular layer of the hippocampus. Typically expressed at high level in a minority of neurons. Basal expression higher in cortex than in hippocampus, highest in visual cortex. Expressed during postnatal development from day 8 (PubMed:7857651). Highest expression around day 23 with moderate levels expressed to adulthood (PubMed:7857651). Arc expression is regulated at transcription, post-transcription and translation levels (PubMed:9808461, PubMed:10570490, PubMed:11226315, PubMed:18614031). Transcription is tightly coupled to encoding of information in neuronal circuits (PubMed:10570490). Expression is induced by neuronal and synaptic activity (PubMed:7777577, PubMed:7857651, PubMed:10570490). Induced at highest level in hippocampus within 30 minutes, dropping to basal levels within 24 hours (PubMed:7777577, PubMed:7857651). Arc transcripts are transported to dendrites and become enriched at sites of local synaptic activity where they are locally translated into protein (PubMed:9808461, PubMed:18614031). Arc transcripts resemble some viral RNAs and contain an internal ribosomal entry site (IRES) that allows cap-independent translation (PubMed:11226315). The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein (PubMed:29328916, PubMed:25864631). It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells (PubMed:29328916). Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons (PubMed:29328916). 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. 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. Transcripts enriched in dendrites may be translated locally. Belongs to the ARC/ARG3.1 family.