HOMER1

The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (By similarity).

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. Isoform 1 regulates the trafficking and surface expression of GRM5. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 5 counteracts the effects by competing for binding sites. Isoform 3 regulates the trafficking and surface expression of GRM5. Isoform 5 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, isoform 2 and isoform 3 to regulate synaptic metabotropic glutamate function. Isoform 5, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development (By similarity). Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). 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 (By similarity).

Belongs to the Homer family.

Isoform 1

Expressed in skeletal muscle at the level of the Z line, in the forebrain and cerebellum.

Isoform 2

Expressed in cardiac and skeletal muscle.

Isoform 3

Expressed in skeletal muscle at the level of the Z line, in the forebrain and cerebellum.

Isoform 4

Expressed in the hippocampus.

Isoform 5

Expressed in skeletal muscle at the level of the Z line, in the heart, forebrain and cerebellum.

• Cytoplasm
• Postsynaptic density
• Synapse
• Cell projection
• Dendritic spine
• Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum. The N-terminal of isoform 2 may facilitate trafficking of the complex with GRM5 from the endoplasmic reticulum (ER) to the plasma membrane (PM).

Vesl1, Homer1, Homer protein homolog 1, Homer-1, VASP/Ena-related gene up-regulated during seizure and LTP 1, Vesl-1

• entrezGene:26556
• swissprot:Q9Z2Y3

Proteins

Neuroscience

41413Da