HOMER2

This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The encoded protein is a postsynaptic density scaffolding protein. Alternative splicing results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 14.

Full Name

Homer Scaffolding Protein 2

Function

Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses (PubMed:9808459).

Required for normal hearing (PubMed:25816005).

Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (PubMed:18218901).

Biological Process

Behavioral response to cocaine Source: Ensembl
Calcium-mediated signaling using intracellular calcium source Source: Ensembl
Chemical homeostasis within a tissue Source: Ensembl
G protein-coupled glutamate receptor signaling pathway Source: GO_Central
Negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
Negative regulation of interleukin-2 production Source: UniProtKB
Regulation of G protein-coupled receptor signaling pathway Source: Ensembl
Regulation of store-operated calcium entry Source: GO_Central
Sensory perception of sound Source: UniProtKB

Cellular Location

Cytoplasm; Cell membrane; Postsynaptic density; Synapse; Stereocilium. Postsynaptic density of neuronal cells. The stabilization and clustering of the metabotropic glutamate receptors appears to be mediated by isoform 1 and isoform 2 at the cell surface.

Involvement in disease

Deafness, autosomal dominant, 68 (DFNA68):
A form of non-syndromic sensorineural hearing loss with postlingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.