Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the HOMER1 gene.^[5][6][7] Other names are Vesl and PSD-Zip45.

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HOMER1
Identifiers
Aliases	HOMER1, HOMER, HOMER1A, HOMER1B, HOMER1C, SYN47, Ves-1, homer scaffolding protein 1, homer scaffold protein 1
External IDs	OMIM: 604798 MGI: 1347345 HomoloGene: 3155 GeneCards: HOMER1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q14.1 Start 79,372,636 bp[1] End 79,514,134 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 C3 Start 93,436,143 bp[2] End 93,541,637 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle temporal gyrus orbitofrontal cortex endothelial cell right ventricle frontal pole vastus lateralis muscle superior frontal gyrus parietal lobe postcentral gyrus Top expressed in triceps brachii muscle temporal muscle olfactory tubercle superior frontal gyrus nucleus accumbens sternocleidomastoid muscle prefrontal cortex digastric muscle temporal lobe atrioventricular valve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transmembrane transporter binding signaling adaptor activity protein binding G protein-coupled glutamate receptor binding Cellular component cytoplasm postsynaptic membrane membrane postsynaptic density plasma membrane apical part of cell synapse axon cell junction Z disc neuron projection costamere postsynapse cytosol neuron spine cell projection dendritic spine dendrite glutamatergic synapse postsynaptic cytosol Biological process phospholipase C-activating G protein-coupled glutamate receptor signaling pathway positive regulation of signal transduction behavioral response to cocaine skeletal muscle contraction regulation of calcium ion import response to calcium ion chemical homeostasis within a tissue skeletal muscle fiber development positive regulation of calcium ion transport chemical synaptic transmission regulation of cation channel activity regulation of store-operated calcium entry protein tetramerization regulation of synaptic transmission, glutamatergic regulation of dendritic spine maintenance G protein-coupled glutamate receptor signaling pathway regulation of postsynaptic neurotransmitter receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9456 26556 Ensembl ENSG00000152413 ENSMUSG00000007617 UniProt Q86YM7 Q9Z2Y3 RefSeq (mRNA) NM_004272 NM_001277077 NM_001277078 NM_001284189 NM_011982 NM_147176 NM_152134 NM_001347598 RefSeq (protein) NP_001264006 NP_001264007 NP_004263 NP_001271118 NP_001334527 NP_036112 NP_671705 NP_687036 Location (UCSC) Chr 5: 79.37 – 79.51 Mb Chr 13: 93.44 – 93.54 Mb PubMed search [3] [4]
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Homer1 protein has an N-terminal EVH1 domain, involved in protein interaction, and a C-terminal coiled-coil domain involved in self association. It consists of two major splice variants, short-form (Homer1a) and long-form (Homer1b and c). Homer1a has only EVH1 domain and is monomeric while Homer1b and 1c have both EVH1 and coiled-coil domains and are tetrameric.^[8][9] The coiled-coil can be further separated into N-terminal half and C-terminal half. The N-terminal half of the coiled-coil domain is predicted to be a parallel dimer while the C-terminus half is a hybrid of dimeric and anti-parallel tetrameric coiled-coil. As a whole, long Homer is predicted to have a dumbbell-like structure where two pairs of EVH1 domains are located on two sides of long (~50 nm) coiled-coil domain.^[9] Mammals have Homer2 and Homer3, in addition to Homer1, which have similar domain structure. They also have similar alternatively spliced forms.

Homer1 is expressed widely in the central nervous system as well as peripheral tissue including heart, kidney, ovary, testis, and skeletal muscle. Subcellularly in neurons, Homer1 is concentrated in postsynaptic structures and constitutes a major part of the postsynaptic density.

EVH1 domain interacts with PPXXF motif. This sequence motif exists in group 1 metabotrophic glutamate receptor (mGluR1 and mGluR5), IP₃ receptors (IP₃R), Shank, transient receptor potential canonical (TRPC) family channels, drebrin, oligophrenin, dynamin3, CENTG1, and ryanodin receptor.^{[5][7][10][11][12][13]} Through its tetrameric structure, long forms of Homer (such as Homer1b and Homer1c) are proposed to cross link different proteins. For example, group 1 mGluR is crossed linked with its signaling downstream, IP₃ receptor.^[10] Also, through crosslinking another multimeric protein Shank, it is proposed to comprise a core of the postsynaptic density.^[9]

Notably, the expression of Homer1a is induced by neuronal activity while that of Homer1b and 1c are constitutive. Thus Homer1a is classified as an immediate early gene. Homer1a, acts as a natural dominant negative form that blocks interaction between long-forms and their ligand proteins by competing with the EVH1 binding site on the ligand proteins. In this way, the short form of Homer uncouples mGluR signaling and also shrinks dendritic spine structure.^[6][14] Therefore, the short form of Homer is considered to be a part of a mechanism of homeostatic plasticity that dampens the neuronal responsiveness when input activity is too high. The long form Homer1c plays a role in synaptic plasticity and the stabilization of synaptic changes during long-term potentiation.^[15]

The coiled-coil domain is reported to interact with syntaxin13 and activated Cdc42. The interaction with Cdc42 inhibit the activity of Cdc42 to remodel dendritic spine structure.

Homer1a switches mGluR5 signaling to increase AMPA receptor activity for the rapid antidepressant actions of sleep deprivation.^[16]

• HOMER2
• HOMER3