Recombinant Human HOMER1 protein

HOMER1 is a scaffolding protein encoded by the *HOMER1* gene, belonging to the HOMER family of postsynaptic density proteins. It plays a critical role in organizing synaptic signaling complexes by interacting with metabotropic glutamate receptors (mGluRs), inositol triphosphate receptors (IP3Rs), and other cytoskeletal elements. Structurally, HOMER1 contains an N-terminal Enabled/VASP homology 1 (EVH1) domain for binding proline-rich motifs in target proteins and a C-terminal coiled-coil domain enabling self-oligomerization. These features allow HOMER1 to form multivalent scaffolds that regulate calcium signaling, synaptic plasticity, and receptor trafficking.

Alternative splicing generates two major isoforms: the short, activity-inducible Homer1a and the long, constitutively expressed Homer1b/c. Homer1a lacks the coiled-coil domain, acting as a dominant-negative regulator that disrupts HOMER1-mediated complexes during neuronal activation. This dynamic regulation is crucial for adapting synaptic strength in learning and memory processes. Dysregulation of HOMER1 has been linked to neuropsychiatric disorders, including schizophrenia, addiction, and epilepsy, highlighting its therapeutic relevance.

Recombinant HOMER1 proteins are engineered for functional studies, typically expressed in bacterial or mammalian systems with tags (e.g., His, GST) for purification. These tools enable researchers to dissect protein-protein interactions, map binding domains, or screen small molecules targeting HOMER1-associated pathways. For instance, recombinant Homer1a is used to study mGluR5 signaling modulation in addiction models, while full-length isoforms help reconstitute synaptic complexes *in vitro*. Additionally, HOMER1 variants with mutations in EVH1 or coiled-coil domains are employed to explore structural determinants of scaffolding activity. Such studies advance our understanding of synaptic pathology and guide drug discovery for neurological diseases.