HOMER1

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; OMA:HOMER1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q14.1 Start 79,372,636 bp End 79,514,134 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13|13 C3 Start 93,436,143 bp End 93,541,637 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle temporal gyrus orbitofrontal cortex Skeletal muscle tissue of biceps brachii endothelial cell Epithelium of choroid plexus right ventricle frontal pole vastus lateralis muscle superior frontal gyrus Top expressed in dorsal striatum triceps brachii muscle temporal muscle olfactory tubercle superior frontal gyrus nucleus accumbens sternocleidomastoid muscle prefrontal cortex muscle of thigh dentate gyrus of hippocampal formation granule cell 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 discdkac 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
Wikidata
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Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the HOMER1 gene. Other names are Vesl and PSD-Zip45.

Structure

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. 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. Mammals have Homer2 and Homer3, in addition to Homer1, which have similar domain structure. They also have similar alternatively spliced forms.

Dimeric-tetrameric coiled-coil domain of Homer1b. PDB rendering based on 3CVE.

Tissue distribution

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.

Function

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. 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. Also, through crosslinking another multimeric protein Shank, it is proposed to comprise a core of the postsynaptic density.

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. 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.

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.

Rapid antidepressant effects

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

See also

• HOMER2
• HOMER3

Further reading

• Xiao B, Tu JC, Worley PF (June 2000). "Homer: a link between neural activity and glutamate receptor function". Current Opinion in Neurobiology. 10 (3): 370–374. doi:10.1016/S0959-4388(00)00087-8. PMID 10851183. S2CID 8699597.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
• Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF (March 1997). "Homer: a protein that selectively binds metabotropic glutamate receptors". Nature. 386 (6622): 284–288. Bibcode:1997Natur.386..284B. doi:10.1038/386284a0. PMID 9069287. S2CID 4346579.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, et al. (July 1999). "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins". Neuron. 23 (3): 583–592. doi:10.1016/S0896-6273(00)80810-7. PMID 10433269. S2CID 16429070.
• Roche KW, Tu JC, Petralia RS, Xiao B, Wenthold RJ, Worley PF (September 1999). "Homer 1b regulates the trafficking of group I metabotropic glutamate receptors". The Journal of Biological Chemistry. 274 (36): 25953–25957. doi:10.1074/jbc.274.36.25953. PMID 10464340.
• Minakami R, Kato A, Sugiyama H (June 2000). "Interaction of Vesl-1L/Homer 1c with syntaxin 13". Biochemical and Biophysical Research Communications. 272 (2): 466–471. doi:10.1006/bbrc.2000.2777. PMID 10833436.
• Ango F, Prézeau L, Muller T, Tu JC, Xiao B, Worley PF, et al. (June 2001). "Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer". Nature. 411 (6840): 962–965. doi:10.1038/35082096. PMID 11418862. S2CID 4417727.
• Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, et al. (June 2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Molecular Vision. 8: 205–220. PMID 12107410.
• Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF, Pessah IN (November 2002). "Homer regulates gain of ryanodine receptor type 1 channel complex". The Journal of Biological Chemistry. 277 (47): 44722–44730. doi:10.1074/jbc.M207675200. PMID 12223488.
• Hwang SY, Wei J, Westhoff JH, Duncan RS, Ozawa F, Volpe P, et al. (August 2003). "Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling". Cell Calcium. 34 (2): 177–184. doi:10.1016/S0143-4160(03)00082-4. PMID 12810060.
• Norton N, Williams HJ, Williams NM, Spurlock G, Zammit S, Jones G, et al. (July 2003). "Mutation screening of the Homer gene family and association analysis in schizophrenia". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 120B (1): 18–21. doi:10.1002/ajmg.b.20032. PMID 12815733. S2CID 25053099.
• Westhoff JH, Hwang SY, Duncan RS, Ozawa F, Volpe P, Inokuchi K, Koulen P (September 2003). "Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling". Cell Calcium. 34 (3): 261–269. doi:10.1016/S0143-4160(03)00112-X. PMID 12887973.
• Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, et al. (September 2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell. 114 (6): 777–789. doi:10.1016/S0092-8674(03)00716-5. PMID 14505576. S2CID 10552676.
• Rong R, Ahn JY, Huang H, Nagata E, Kalman D, Kapp JA, et al. (November 2003). "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis". Nature Neuroscience. 6 (11): 1153–1161. doi:10.1038/nn1134. PMID 14528310. S2CID 807407.