The ARC gene, located on chromosome 15 in the mouse, chromosome 7 in the rat, and chromosome 8 in the human, is conserved across vertebrate species and has low sequence homology to spectrin, a cytoskeletal protein involved in forming the actin cellular cortex. A number of promoter and enhancer regions have been identified that mediate activity-dependent Arc transcription: a serum response element (SRE; see serum response factor) at ~1.5 kb upstream of the initiation site. a second SRE at ~6.5 kb; and a synaptic activity response element (SARE) sequence at ~7 kb upstream that contains binding sites for cyclic AMP response element-binding protein (CREB), myocyte enhancer factor 2 (MEF2), and SRF.
The 3' UTR of the mRNA contains a cis-acting element required for the localization of Arc to neuronal dendrites, as well as sites for two exon junction complexes (EJCs) that make Arc a natural target for nonsense mediated decay (NMD). Also important for translocation of cytoplasmic Arc mRNA to activated synapses is an 11 nucleotide binding site for heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2).
It is suspected that the ARC gene originated from the gag gene of a Ty3/gypsy retrotransposon and was repurposed for mediating neuron-neuron communication.