Recombinant Human Homer protein homolog 2 (HOMER2)

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)

Subcellular Location

Cytoplasm; Cell membrane; Postsynaptic density; Synapse; Cell projection, stereocilium

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Forms coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is reduced by AKT activation (PubMed:18218901). Interacts with NFATC1 and NFATC4 (PubMed:18218901). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (By similarity)

• Xiao B. et al. Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. — Neuron (1998)
• Soloviev M. et al. Molecular characterisation of two structurally distinct groups of human homers, generated by extensive alternative splicing. — J. Mol. Biol. (2000)
• Yoshida M. et al. Mammalian neuralized interacts with a novel protein which has a EVH1-like domain. (JUL-)
• Zody M.C. et al. Analysis of the DNA sequence and duplication history of human chromosome 15. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Tu J.C. et al. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. — Neuron (1998)
• Huang G.N. et al. NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. — Science (2008)
• Azaiez H. et al. HOMER2, a stereociliary scaffolding protein, is essential for normal hearing in humans and mice. — PLoS Genet. (2015)