Affinage

HOMER1

Homer protein homolog 1 · UniProt Q86YM7

Length
354 aa
Mass
40.3 kDa
Annotated
2026-06-10
90 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOMER1 encodes EVH1-domain postsynaptic scaffolding proteins that organize macromolecular signaling complexes around group I metabotropic glutamate receptors and intracellular calcium machinery (PMID:10464340, PMID:35217690). The EVH1 domain recognizes PPXXF-like proline-rich motifs in diverse partners — mGluR5, Shank2/3, ankyrin-G, RyR1/2, plasma membrane Ca2+ ATPases, and eEF2K — and its binding preference overlaps with Ena/VASP proteins, reflecting incomplete divergence from a shared ancestor (PMID:31078268, PMID:33398084, PMID:38989636). Long constitutively expressed isoforms (Homer1b/c) tetramerize through a coiled-coil tail to crosslink these partners into a complex that retains mGluR5 in the ER, directs receptor dendritic targeting, and physically couples surface channels to ER calcium stores (PMID:10464340, PMID:11102477, PMID:41267651). Through these complexes Homer1b/c controls ER calcium release via IP3R, RyR, and TRPC channels and tunes excitation-contraction-like Ca2+ signaling (PMID:17355963, PMID:21518270), while the activity-induced short isoform Homer1a — generated by an alternative poly(A) site switch — acts as a dominant-negative that disassembles the complex, uncouples channels, and remodels AMPAR composition during homeostatic plasticity (PMID:16407107, PMID:23133416, PMID:17196693). In neurons the Homer1c–mGluR5 interaction is required for late-phase LTP and spatial learning, and dynamic regulation of the Shank3/Homer1/mGluR5 axis governs synaptic scaling (PMID:21945599, PMID:41043992). Excess ER Ca2+ release through Homer1-organized complexes drives oxidative and ER-stress-mediated cell death in multiple injury models, and Homer1 also participates in calcium-sensing receptor signaling in osteoblasts and astrocyte glutamate signaling (PMID:27396622, PMID:31527082, PMID:27075036). Homer1 abundance is set epigenetically by SIN3A-mediated repression, and its developmental level shapes inhibitory tone and attentional performance (PMID:32069266, PMID:41430469).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1999 High

    Established the founding mechanism — that Homer1 directly binds mGluR5 and controls its subcellular trafficking — resolving how a scaffold dictates receptor surface availability.

    Evidence Co-IP, point mutagenesis, and EM in heterologous cells showing Homer1b retains mGluR5 in the ER while Homer1a permits surface trafficking

    PMID:10464340

    Open questions at the time
    • Did not resolve the structural basis of EVH1 motif recognition
    • Trafficking shown in heterologous cells, not yet endogenous neurons
  2. 2000 High

    Showed isoform-specific control of receptor targeting in neurons and that activity transiently induces Homer1a, linking neuronal stimulation to scaffold remodeling.

    Evidence Transfection and live imaging in cerebellar granule cells with pharmacological depolarization

    PMID:11102477

    Open questions at the time
    • Functional consequence for synaptic transmission not measured
    • Mechanism of persistent axonal localization after Homer1a degradation unexplained
  3. 2002 Medium

    Identified an additional isoform (Homer1d) whose N-terminus permits ER-to-plasma-membrane trafficking, showing isoform identity tunes receptor localization beyond the simple long/short dichotomy.

    Evidence HEK293T transfection, immunofluorescence, in vitro binding

    PMID:12176012

    Open questions at the time
    • Single lab, heterologous system only
    • Endogenous expression and neuronal relevance of Homer1d not established
  4. 2006 High

    Defined Homer1a's role in vivo as a dominant-negative disruptor of the long-isoform mGluR–IP3R complex with behavioral consequences, connecting molecular antagonism to circuit-level output.

    Evidence Transgenic Homer1a overexpression in striatal neurons with behavioral and amphetamine-challenge readouts

    PMID:16407107

    Open questions at the time
    • Direct in vivo measurement of complex disassembly not shown
    • Behavioral effects not mapped to specific synaptic mechanisms
  5. 2006 Medium

    Broadened the Homer1 interactome to plasma membrane Ca2+ ATPases, establishing Homer1 as a hub coupling extrusion pumps into the calcium signaling complex.

    Evidence Reciprocal co-IP and co-localization in MDCK cells and hippocampal neurons

    PMID:16554037

    Open questions at the time
    • Functional consequence of PMCA–Homer coupling for Ca2+ extrusion not tested
    • Single lab
  6. 2006 High

    Identified alternative poly(A) site selection as the activity-dependent switch generating Homer1a, explaining how stimulation rapidly converts long to short isoform.

    Evidence Mini-gene reporter, poly(A) site mapping, and transcriptional/translational inhibitor experiments

    PMID:17196693

    Open questions at the time
    • 3'-end processing factors mediating the switch not identified
    • Promoter-independence shown but upstream signaling to the poly(A) machinery unknown
  7. 2007 High

    Demonstrated that Homer1 physically couples surface Cav1.2 to RyR2 and that isoform identity tunes Ca2+-induced Ca2+ release, generalizing the scaffold's channel-coupling role beyond neurons.

    Evidence Homer1 KO mice, split-GFP complementation, electrophysiology, and Ca2+ imaging in smooth muscle

    PMID:17355963

    Open questions at the time
    • Stoichiometry of the Cav1.2–Homer–RyR2 complex not resolved
    • Whether the same coupling operates at neuronal ER-PM junctions not tested here
  8. 2009 High

    Showed Homer1b directly and biphasically modulates RyR2 channel gating through ligand binding rather than multimerization, refining the mechanism of ER calcium control.

    Evidence Single-channel electrophysiology and [3H]ryanodine binding with domain-dissection in vitro reconstitution

    PMID:19296124

    Open questions at the time
    • Physiological concentration regime in vivo unclear
    • Single lab in vitro system
  9. 2011 Medium

    Articulated the mechanism by which Homer1 keeps TRPC channels closed and STIM1 opens them upon complex dissociation, placing Homer1 at the store-operated Ca2+ entry switch.

    Evidence Mechanistic synthesis of mutational/binding data with functional Ca2+ influx assays

    PMID:21518270

    Open questions at the time
    • Model built partly on prior data rather than single new experiment
    • Dynamics of STIM1 competition with Homer not directly visualized
  10. 2011 High

    Established that Homer1c–mGluR5 interaction is necessary for late-phase LTP and spatial learning, tying the scaffold to a defined plasticity mechanism via pharmacological epistasis.

    Evidence Homer1 KO mice with AAV-Homer1c rescue, LTP recordings, mGluR antagonists, and water-maze testing

    PMID:21945599

    Open questions at the time
    • Downstream effectors linking mGluR5 to late-LTP not defined
    • Whether other partners contribute to rescue not excluded
  11. 2012 High

    Showed Homer1 controls synaptic AMPAR composition and that Homer1a acts through long isoforms, linking scaffold dynamics to receptor subunit identity in plasticity.

    Evidence Homer1 KO and Homer1a transgenic mice with patch-clamp, polyamine sensitivity, and immunohistochemistry

    PMID:23133416

    Open questions at the time
    • Molecular intermediary connecting Homer to GluA2 trafficking unidentified
    • Temporal dynamics of the Homer1a–long-isoform interaction not resolved
  12. 2013 High

    Connected Homer1b/c–mGluR5 signaling to acute stress-induced cognitive impairment, demonstrating physiological regulation of the complex by environmental challenge.

    Evidence Social defeat stress model with co-IP, AAV overexpression rescue, and pharmacological epistasis

    PMID:23447597

    Open questions at the time
    • Signaling pathway reducing Homer1b/c levels after stress not defined
    • Cell-type specificity within hippocampus not resolved
  13. 2014 High

    Revealed that PKC phosphorylation of mGluR1 uncouples it from Homer1, providing a kinase-driven mechanism for disassembling the complex pathologically.

    Evidence Co-IP, phosphoinositide hydrolysis assays, and phosphatase/PKC treatment of rat synaptic membranes

    PMID:24626340

    Open questions at the time
    • Specific PKC isoform not identified
    • Whether the same phospho-switch operates physiologically beyond cocaine exposure untested
  14. 2019 High

    Extended Homer1's calcium-signaling role outside the synapse by showing it partners with CaSR and mTORC2 to confer Ca2+-sensitivity to AKT signaling in osteoblasts.

    Evidence Co-IP, siRNA knockdown, and HEK-293 reconstitution with Western blot

    PMID:31527082

    Open questions at the time
    • Direct EVH1 motif on CaSR not mapped
    • In vivo skeletal relevance not tested
  15. 2019 Medium

    Multiple injury models established Homer1 as a driver of pathological ER Ca2+ release leading to oxidative/ER stress and apoptosis, defining a maladaptive arm of its calcium function.

    Evidence siRNA knockdown with Ca2+ imaging, ROS/mitochondrial readouts, and pharmacological dissection in endothelial, dopaminergic, and cortical neuron models

    PMID:24036210 PMID:27396622 PMID:31369778

    Open questions at the time
    • Isoform responsible (long vs short) not always resolved
    • Single-lab siRNA studies without rescue
  16. 2019 High

    Mapped the precise PPXXF-like motifs (PPHHF, FLPPP) in RyR1 bound by the Homer1 EVH1 domain, quantifying a high-affinity, Ca2+-sensitive interaction in skeletal muscle.

    Evidence Co-IP, sucrose-gradient centrifugation, and bio-layer interferometry

    PMID:31078268

    Open questions at the time
    • Functional effect on RyR1 channel gating not measured here
    • Physiological role in skeletal EC coupling not established
  17. 2020 High

    Placed Homer1 under SIN3A epigenetic control, showing its abundance gates the mGluR-dependence of LTP and learning-induced ERK signaling.

    Evidence Conditional Sin3a KO mice with Western blot, LTP recordings, ERK immunoblot, and behavior

    PMID:32069266

    Open questions at the time
    • Direct SIN3A occupancy at the Homer1 promoter not shown
    • Whether Homer1 fully accounts for the Sin3a-KO phenotype not isolated
  18. 2020 Medium

    Linked Homer1b/c to local translation by scaffolding eEF2K under mTORC1 control, connecting the complex to activity-dependent synaptic protein synthesis.

    Evidence Co-IP, genetic/pharmacological perturbation, and protein-synthesis assays in SH-SY5Y and cortical neurons

    PMID:32892352

    Open questions at the time
    • EVH1 motif on eEF2K not mapped
    • Single lab; in vivo relevance untested
  19. 2021 High

    Identified ankyrin-G as an EVH1 partner localized to spine-head nanodomains and showed Homer1 globally shapes the postsynaptic proteome, expanding its structural-organizational role.

    Evidence Proximity ligation, STORM super-resolution, proteomics, and Homer1 KO mice

    PMID:33398084

    Open questions at the time
    • Causal chain from ankyrin-G binding to spine enlargement not fully resolved
    • Mechanism of proteome reshaping beyond direct partners unclear
  20. 2022 High

    Defined the activity-dependent core interaction network and showed depolarization selectively dissociates mGlu5 and Shank3 from Homer1, refining which partners are dynamically regulated.

    Evidence Co-IP with label-free quantitative mass spectrometry in WT and Homer1 KO mice

    PMID:35217690

    Open questions at the time
    • Temporal resolution of dissociation limited
    • Signaling triggering selective dissociation not identified
  21. 2022 Medium

    Showed Homer1 suppresses MAPK signaling and shifts astrocyte phenotype after hemorrhage, indicating a neuroinflammatory regulatory role.

    Evidence AAV overexpression/knockdown in vivo with cytokine array, immunofluorescence, and Western blot

    PMID:35287697

    Open questions at the time
    • Direct mechanism linking Homer1 to MAPK proteins not defined
    • Isoform responsible not specified
  22. 2024 High

    Defined the expanded EVH1 binding motif across the human proteome and revealed its evolutionary and structural kinship to Ena/VASP, framing Homer1 ligand recognition mechanistically.

    Evidence High-throughput proteome peptide screening, NMR, and phylogenetic analysis

    PMID:38989636

    Open questions at the time
    • Functional validation of newly identified binders not performed
    • Biological relevance of Ena/VASP overlap untested
  23. 2024 Medium

    Showed Preso stabilizes the mGluR1–Homer1 complex via CDK5/CaMKII phospho-regulation to drive excitotoxic ER stress after TBI, identifying a druggable phospho-switch.

    Evidence Co-IP, CDK5/CaMKII kinase assays, blocking peptides, and post-TBI behavior

    PMID:38531909

    Open questions at the time
    • Single lab
    • Quantitative contribution of each phospho-site to complex stability not separated
  24. 2025 High

    Provided the NMR solution structure of the EVH1 domain and MD of the coiled-coil tetramer, revealing ligand-induced conformational flexibility relevant to dynamic complex rearrangement.

    Evidence NMR spectroscopy, molecular dynamics simulations, and structural modeling

    PMID:41267651

    Open questions at the time
    • Conformational transitions not yet linked to specific functional outputs
    • Full-length structure with bound partners not determined
  25. 2025 High

    Demonstrated that developmental Homer1 level sets prefrontal inhibitory tone and attentional performance, identifying Homer1 as a quantitative trait locus for pre-attentive processing.

    Evidence Forward genetics and mapping in genetically diverse mice with AAV knockdown, electrophysiology, and behavior

    PMID:41430469

    Open questions at the time
    • Molecular link between Homer1 and GABA receptor upscaling unresolved
    • Developmental window of action not precisely defined
  26. 2025 High

    Showed activity-dependent Shank3 dephosphorylation gates its binding to long Homer1 and that resulting agonist-dependent mGluR5 signaling is required for synaptic upscaling, integrating phospho-regulation with homeostatic plasticity.

    Evidence Phosphomimetic mutagenesis, co-IP, competitive/non-competitive mGluR5 inhibitors, and scaling electrophysiology in cultured neurons

    PMID:41043992

    Open questions at the time
    • Phosphatase mediating Shank3 dephosphorylation not identified
    • In vivo relevance of the scaling mechanism not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the conformational dynamics of the EVH1 domain and coiled-coil tetramer are coupled to the kinase/phosphatase signals that selectively assemble or disassemble specific partner complexes in vivo remains unresolved.
  • No structure of full-length Homer1 bound to partners
  • Quantitative rules governing which partners dissociate upon activity not established
  • Isoform-resolved contributions in non-neuronal tissues incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Partners
ANK3EEF2KGRM1GRM5RYR1RYR2SHANK2SHANK3
Complex memberships
CaSR-Homer1-mTORC2 complexCav1.2-Homer1-RyR2 complexmGluR1/5-IP3R signaling complexmGluR5-Homer1-Shank postsynaptic complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Homer1b (constitutively expressed splice form) directly binds mGluR5 via its EVH1 domain and retains mGluR5 in the endoplasmic reticulum, inhibiting surface expression; point mutations disrupting this binding eliminate ER retention, demonstrating direct protein-protein interaction underlies ER retention. In contrast, Homer1a co-expression allows mGluR5 to traffic to the plasma membrane. Heterologous cell expression, co-immunoprecipitation, point mutagenesis, electron microscopy The Journal of biological chemistry High 10464340
2000 Homer1b/c promotes dendritic targeting of mGluR5 and formation of synaptic clusters colocalizing with synaptophysin in neurons, whereas Homer1a promotes both dendritic and axonal targeting. Neuronal depolarization induces transient endogenous Homer1a expression, causing persistent axonal mGluR5 localization even after Homer1a degradation. Transfection in cultured cerebellar granule cells, live confocal imaging, pharmacological depolarization The Journal of neuroscience High 11102477
2002 A novel Homer1 isoform, Homer1d, contains a unique 18 amino acid N-terminal sequence that, unlike Homer1b, allows the Homer1d–mGluR5b complex to traffic from the ER to the plasma membrane when co-expressed in HEK293T cells; both isoforms bind mGluR5b in vitro. HEK293T transfection, immunofluorescence localization, in vitro binding assay Biochemical and biophysical research communications Medium 12176012
2006 Homer1a, the short activity-dependent splice variant, acts as an endogenous dominant-negative modulator of the mGluR1/5–IP3R signaling complex assembled by long Homer1b/c isoforms, disrupting the macromolecular complex. Transgenic overexpression of Homer1a in striatal medium spiny neurons alters motor performance and striatal responses to amphetamine. Transgenic mouse generation, behavioral testing, pharmacological challenge Proceedings of the National Academy of Sciences of the United States of America High 16407107
2006 Homer1 (Ania-3 isoform) directly interacts via its EVH1 domain with the PDZ domain-binding C-terminal tail of the b-splice forms of all plasma membrane Ca2+ ATPases (PMCA1b, 2b, 3b, 4b); endogenous Homer/Ania-3 and PMCA2 co-localize in soma and dendrites of hippocampal neurons. Co-immunoprecipitation, co-localization in MDCK cells and primary neurons, in vitro binding Biochemical and biophysical research communications Medium 16554037
2007 Homer1 mediates a dynamic physical interaction between the L-type Ca2+ channel Cav1.2 and the ryanodine receptor RyR2 in smooth muscle. Homer1b/c coupling reduces responsiveness to membrane depolarization, whereas Homer1a uncouples Cav1.2 and RyR2 to enhance depolarization-induced Ca2+-induced Ca2+ release. Deletion of Homer1 (but not Homer2 or Homer3) in mice impairs urinary bladder excitation-contraction coupling. Homer1 knockout mice, split-GFP complementation assay, electrophysiology, calcium imaging The Journal of biological chemistry High 17355963
2009 Homer1b modulates ryanodine receptor 2 (RyR2) activity in vitro: low concentrations (~50–100 nM) activate RyR2 single-channel activity and reduce its Ca2+ EC50, while higher concentrations (>200 nM) reduce activity. The short Homer1 (lacking the coiled-coil domain) mimics the effect of Homer1b, indicating action through direct ligand binding rather than multimerization. Single-channel electrophysiology, [3H]ryanodine binding assay, in vitro reconstitution Pflugers Archiv : European journal of physiology High 19296124
2011 Homer1 keeps TRPC channels closed by coupling them to IP3 receptors via a Homer-binding ligand on TRPC; dissociation of the TRPC–Homer–IP3R complex allows STIM1 access to TRPC channel negative charges to gate them open. The Homer- and STIM1-binding sites on TRPC are separated by only four amino acid residues. Molecular mechanism analysis based on mutational and binding data from prior experiments; functional Ca2+ influx assays Acta physiologica (Oxford, England) Medium 21518270
2011 Homer1 knockout in mice impairs late-phase LTP in hippocampal CA1 (both HFS- and TBS-induced). AAV-mediated re-expression of Homer1c rescues both LTP and spatial learning deficits in Homer1 KO mice. The rescue of late-LTP by Homer1c is blocked by an mGluR5 antagonist but not an mGluR1 antagonist, placing Homer1c–mGluR5 interaction as necessary for plasticity. Homer1 KO mice, AAV gene delivery, electrophysiology (LTP), pharmacological blockade, radial arm water maze Neurobiology of learning and memory High 21945599
2012 Homer1 KO causes redistribution of GluA2 AMPAR subunit from dendrites to soma and increases the AMPA/NMDA current ratio at Schaffer collateral synapses. Conversely, sustained overexpression of Homer1a reduces AMPA/NMDA ratios and GluA2-lacking (Ca2+-permeable) AMPARs, abolishes LTP maintenance, and its effect requires GluA2-containing AMPARs and long Homer1 isoforms, indicating activity-dependent interaction between Homer1a and long Homer1 isoforms in regulating synaptic AMPAR composition. Homer1 KO and Homer1a transgenic mice, patch-clamp electrophysiology, polyamine sensitivity assay, immunohistochemistry Frontiers in synaptic neuroscience High 23133416
2013 Homer1b/c levels and mGluR5/Homer1b/c interaction in the dorsal hippocampus are reduced up to 8 h after acute social defeat stress. Overexpression of Homer1b/c in dorsal hippocampus reverses the stress-induced cognitive deficit, and mGluR5 blockade during stress also rescues cognition, placing Homer1b/c–mGluR5 signaling as mediating acute stress-induced cognitive impairment. Mouse social defeat stress model, co-immunoprecipitation, AAV-mediated overexpression, pharmacological blockade, behavioral testing The Journal of neuroscience High 23447597
2014 Prenatal cocaine exposure causes PKC-mediated hyperphosphorylation of mGluR1 on serine residues, uncoupling mGluR1 from Homer1 and Gq/11 proteins, and reducing mGluR1-mediated phosphoinositide hydrolysis. Phosphatase treatment restores mGluR1 coupling; PKC-mediated phosphorylation of control synaptic membranes mimics the prenatal cocaine effect. Co-immunoprecipitation, phosphoinositide hydrolysis assay, phosphatase and PKC treatment of synaptic membranes from P21 rat brains PloS one High 24626340
2019 Homer1 forms a complex with the calcium-sensing receptor (CaSR) in human osteoblasts, confirmed by co-immunoprecipitation. The CaSR–Homer1 complex formation increases in response to extracellular Ca2+ and is bound to mTORC2. Both CaSR and Homer1 are required for extracellular Ca2+-stimulated AKT Ser473 phosphorylation, which inhibits apoptosis and promotes β-catenin stabilization. Co-transfection of Homer1c and CaSR in HEK-293 cells is necessary and sufficient to confer Ca2+-sensitivity to AKT phosphorylation. Co-immunoprecipitation, siRNA knockdown, HEK-293 co-transfection, Western blot The Journal of biological chemistry High 31527082
2019 Homer1 knockdown using siRNA attenuates ER Ca2+ release (via IP3R and RyR pathways) and reduces intracellular calcium overload in brain endothelial cells subjected to oxidative stress (t-BHP), thereby decreasing ROS generation, mitochondrial dysfunction, and apoptosis. siRNA knockdown, Ca2+ imaging (Fura-2), cell viability assays, mitochondrial membrane potential measurement Biochemical and biophysical research communications Medium 27396622
2019 Homer1 knockdown in dopamine neurons attenuates ER Ca2+ release following MPP+ injury and reduces intracellular calcium overload and ROS generation. The protective effect is partially dependent on NMDA receptors and L-type calcium channels but not TRPC channels, as shown by pharmacological antagonists in Homer1-knockdown cells. siRNA knockdown, Ca2+ imaging, pharmacological dissection, cell viability/death assays Cellular signalling Medium 24036210
2019 Homer1/mGluR1-mediated ER stress contributes to LPA-induced neurotoxicity in cortical neurons. Homer1 siRNA knockdown reduces ER Ca2+ release and prevents LPA-induced ER stress and apoptosis; increased mGluR1 expression by LPA enhances the Homer1–mGluR1 pathway to release ER Ca2+. siRNA knockdown, Ca2+ imaging, Western blot for ER stress markers, cell viability assays Neurochemistry international Medium 31369778
2019 Homer1 directly interacts with skeletal muscle ryanodine receptor RyR1 via its EVH1 domain, with high affinity particularly at 1 mM Ca2+. Two consensus PPXXF-like proline-rich sequences (PPHHF and FLPPP) in RyR1 serve as the binding sites, identified by co-immunoprecipitation, sucrose-gradient centrifugation, and bio-layer interferometry. Co-immunoprecipitation, sucrose density-gradient centrifugation, bio-layer interferometry Biochemical and biophysical research communications High 31078268
2020 SIN3A corepressor negatively regulates Homer1 expression; postnatal neuronal deletion of Sin3a increases Homer1 expression, enhances hippocampal LTP, alters the mGluR1α and mGluR5 dependence of LTP, and increases ERK activation after learning. This places Homer1 downstream of SIN3A-mediated epigenetic control in plasticity pathways. Conditional KO mice (Sin3a), Western blot, electrophysiology (LTP), ERK immunoblotting, behavioral testing JCI insight High 32069266
2020 Homer1b/c scaffolding protein interacts with eEF2K (eukaryotic elongation factor kinase 2), controlling eEF2K localization and local synaptic protein synthesis. This interaction is regulated by mTORC1-dependent phosphorylation of eEF2K at S396, and the interaction modulates rates of synaptic protein synthesis. Co-immunoprecipitation, pharmacological and genetic approaches in SH-SY5Y and mouse cortical neurons, protein synthesis assays Journal of neurochemistry Medium 32892352
2021 Homer1 interacts with ankyrin-G 190 kDa isoform via the PPXXF motif in ankyrin-G recognized by the Homer1 EVH1 domain. This interaction localizes to distinct nanodomains in the spine head (shown by proximity ligation + super-resolution microscopy) and is critical for ankyrin-G 190's ability to increase spine head size. Homer1 KO upregulates ankyrin-G but downregulates Shank3 in cortical fractions, and causes global reshaping of the postsynaptic proteome. Proximity ligation assay, super-resolution microscopy (STORM), proteomic analysis, Homer1 KO mice, Western blot Molecular psychiatry High 33398084
2022 Activity-dependent depolarization in cortex dissociates Homer1 from mGlu5 (mGluR5) and from Shank3, as quantified by co-immunoprecipitation and label-free quantitative mass spectrometry in wildtype versus Homer1 KO mice. The high-confidence Homer1 interaction network consists of mGlu5, Shank2, Shank3, and Homer1-3; only mGlu5 and Shank3 significantly reduce co-association following depolarization. Co-immunoprecipitation, label-free quantitative mass spectrometry, Homer1 KO mice Scientific reports High 35217690
2022 Homer1 inhibits MAPK signaling; overexpression of Homer1 suppresses MAPK pathway-related proteins, while Homer1 knockdown increases them. Homer1 overexpression promotes conversion of A1 (neurotoxic) to A2 (neuroprotective) astrocyte phenotypes after intracerebral hemorrhage, and reduces inflammatory cytokine TNFSF10 while increasing anti-inflammatory factors activin A, persephin, and TWEAK. AAV-mediated overexpression/knockdown in vivo, mouse cytokine array, immunofluorescence, Western blot Journal of neuroinflammation Medium 35287697
2024 High-throughput screening of the human proteome identified sequences binding the Homer1 EVH1 domain and defined an expanded binding motif. The Homer1 EVH1 domain shares overlapping binding preference with Ena/VASP actin polymerases; phylogenetic analysis shows this overlap reflects incomplete divergence from a common Ena/VASP ancestor. The EVH1 domain shows ligand-induced conformational transitions in its partner-binding region as shown by NMR. High-throughput peptide/proteome screening, NMR, structural bioinformatics, phylogenetic analysis Protein science High 38989636
2024 Preso directly associates with the mGluR1–Homer1 complex and promotes CDK5-mediated phosphorylation of the Homer1-binding site on mGluR1, enhancing mGluR1–Homer1 interaction and excitotoxic ER stress after traumatic brain injury. Preso also inhibits CaMKIIα-mediated phosphorylation of the Homer1 hinge region, further stabilizing the complex. Blocking peptides targeting Preso–mGluR1–Homer1 interaction improved motor recovery after TBI. Co-immunoprecipitation, phosphorylation assays (CDK5, CaMKIIα), blocking peptides, behavioral assay post-TBI Cell death discovery Medium 38531909
2025 NMR solution structure of the Homer1 EVH1 domain reveals subtle differences in and around the partner-binding region compared to prior crystal structures, suggesting ligand-induced conformational transitions. Molecular dynamics simulations of the full-length Homer1 coiled-coil tetramer reveal that the N-terminal coiled-coil region is the most flexible, and this highly conserved segment likely has functional relevance for dynamic postsynaptic rearrangements. NMR spectroscopy, molecular dynamics simulations, structural modeling Proteins High 41267651
2025 Developmental reduction of Homer1 expression in the prefrontal cortex leads to upscaling of GABA receptors and enhanced inhibitory tone, improving prefrontal signal-to-noise ratio and attentional performance in adult mice. Genetic mapping identified Homer1 within a locus explaining ~19% of variance in pre-attentive processing. Forward genetics, genetic mapping in 200 genetically diverse mice, AAV knockdown, electrophysiology, behavioral testing Nature neuroscience High 41430469
2025 Activity-dependent dephosphorylation of Shank3 at S1586/S1615 enhances its binding to long-form Homer1; a phosphomimetic Shank3 mutant shows reduced Homer1 binding. Downstream agonist-dependent mGluR5 signaling (enabled by the Shank3/Homer1 interaction) is necessary for synaptic upscaling, as only competitive (not non-competitive) mGluR5 inhibition impairs upscaling; mGluR5 activation rescues upscaling in the presence of phosphomimetic Shank3. Phosphomimetic mutagenesis, co-immunoprecipitation, competitive/non-competitive pharmacological inhibitors, synaptic scaling electrophysiology in cultured rat neurons The Journal of neuroscience High 41043992
2017 In astrocytes, long Homer1b/c isoforms cluster with mGlu5 in processes and relocalize endoplasmic reticulum to the proximity of the plasma membrane, optimizing Ca2+ signaling and glutamate release. Homer1a is upregulated in reactive astrocytes and, by disrupting the mGlu5–ER interaction, decreases Ca2+ signaling intensity and limits glutamate release duration. In vivo siRNA knockdown of Homer1a restores mGlu5-mediated Ca2+ signaling and sensitizes astrocytes to apoptosis. Immunostaining, Ca2+ imaging, ER proximity assay, in vivo siRNA, glutamate release assay Cerebral cortex High 27075036
2006 Alternative poly(A) site selection regulates vesl-1/Homer1 alternative splicing: neural activity enhances 3'-end processing at the proximal poly(A) site (vesl-1M), switching transcription from the long (Homer1b/c) to the short (Homer1a/Homer1M) isoform. This switch is independent of de novo protein synthesis and not coupled to the vesl-1 promoter. RT-PCR, poly(A) site mapping, mini-gene reporter assay, pharmacological stimulation, transcriptional inhibitors Neuroscience research High 17196693

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by homer1 proteins and neuronal excitation. The Journal of neuroscience : the official journal of the Society for Neuroscience 190 11102477
1999 Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. The Journal of biological chemistry 178 10464340
2005 Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Genes, brain, and behavior 164 16011574
2010 Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biological psychiatry 150 20673876
2005 Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function. The Journal of neuroscience : the official journal of the Society for Neuroscience 110 16354916
2009 Extended daily access to cocaine results in distinct alterations in Homer 1b/c and NMDA receptor subunit expression within the medial prefrontal cortex. Synapse (New York, N.Y.) 87 19306440
2022 Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage. Journal of neuroinflammation 83 35287697
2003 Homer1 proteins and AMPA receptors modulate cocaine-induced behavioural plasticity. The European journal of neuroscience 78 14511343
2007 Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes, brain, and behavior 73 16734773
2013 Homer1 knockdown protects dopamine neurons through regulating calcium homeostasis in an in vitro model of Parkinson's disease. Cellular signalling 62 24036210
2015 Homer1/mGluR5 activity moderates vulnerability to chronic social stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 61 25409593
2019 Increased Homer1-mGluR5 mediates chronic stress-induced depressive-like behaviors and glutamatergic dysregulation via activation of PERK-eIF2α. Progress in neuro-psychopharmacology & biological psychiatry 55 31265863
2013 Homer1 mediates acute stress-induced cognitive deficits in the dorsal hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 23447597
2021 Homer1 promotes dendritic spine growth through ankyrin-G and its loss reshapes the synaptic proteome. Molecular psychiatry 54 33398084
2010 Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients. Journal of psychiatric research 53 20598711
2011 The closing and opening of TRPC channels by Homer1 and STIM1. Acta physiologica (Oxford, England) 50 21518270
2006 Regulation of motor performance and striatal function by synaptic scaffolding proteins of the Homer1 family. Proceedings of the National Academy of Sciences of the United States of America 50 16407107
2013 Protective effects of SKF-96365, a non-specific inhibitor of SOCE, against MPP+-induced cytotoxicity in PC12 cells: potential role of Homer1. PloS one 47 23383239
2006 The Homer-1 protein Ania-3 interacts with the plasma membrane calcium pump. Biochemical and biophysical research communications 44 16554037
2007 Ca2+ signaling in microdomains: Homer1 mediates the interaction between RyR2 and Cav1.2 to regulate excitation-contraction coupling. The Journal of biological chemistry 43 17355963
2013 Imbalances in prefrontal cortex CC-Homer1 versus CC-Homer2 expression promote cocaine preference. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 23658151
2017 Homer1 Scaffold Proteins Govern Ca2+ Dynamics in Normal and Reactive Astrocytes. Cerebral cortex (New York, N.Y. : 1991) 39 27075036
2020 Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells. Journal of cellular biochemistry 38 32037619
2004 The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses. The Journal of comparative neurology 38 15236236
2011 Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of Homer1 knockout mice by recombinant Adeno-associated viral gene delivery of Homer1c. Neurobiology of learning and memory 36 21945599
2009 Cocaine activates Homer1 immediate early gene transcription in the mesocorticolimbic circuit: differential regulation by dopamine and glutamate signaling. Synapse (New York, N.Y.) 35 18932227
2021 Gender-Dependent Deregulation of Linear and Circular RNA Variants of HOMER1 in the Entorhinal Cortex of Alzheimer's Disease. International journal of molecular sciences 33 34502114
2012 Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression. Frontiers in synaptic neuroscience 32 23133416
2022 The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight. Neuroscience and biobehavioral reviews 30 35248676
2017 Hippocampal Regulation of Postsynaptic Density Homer1 by Associative Learning. Neural plasticity 30 29238619
2022 Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress. Chinese medicine 27 35610650
2005 Association of a polymorphism in the Homer1 gene with cocaine dependence in an African American population. Psychiatric genetics 26 16314758
2014 Diagnostic potential of differentially expressed Homer1, IL-1β, and TNF-α in coronary artery disease. International journal of molecular sciences 25 25551602
2009 HOMER1 promoter analysis in Parkinson's disease: association study with psychotic symptoms. Neuropsychobiology 24 19648775
2019 Homer1 mediates CaSR-dependent activation of mTOR complex 2 and initiates a novel pathway for AKT-dependent β-catenin stabilization in osteoblasts. The Journal of biological chemistry 22 31527082
2013 Cocaine-elicited imbalances in ventromedial prefrontal cortex Homer1 versus Homer2 expression: implications for relapse. Addiction biology 22 24118426
2013 Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients. The pharmacogenomics journal 22 24126708
2006 Alternative poly(A) site-selection regulates the production of alternatively spliced vesl-1/homer1 isoforms that encode postsynaptic scaffolding proteins. Neuroscience research 21 17196693
2002 An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells. Biochemical and biophysical research communications 21 12176012
2020 Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling. JCI insight 19 32069266
2020 Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression. Journal of affective disorders 19 33128940
2013 MicroRNA-3906 regulates fast muscle differentiation through modulating the target gene homer-1b in zebrafish embryos. PloS one 19 23936160
2002 Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm. Brain research. Molecular brain research 18 12399110
2015 Potential roles for Homer1 and Spinophilin in the preventive effect of electroconvulsive seizures on stress-induced CA3c dendritic retraction in the hippocampus. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 16 25935093
2013 Spinal synaptic scaffolding protein Homer 1b/c regulates CREB phosphorylation and c-fos activation induced by inflammatory pain in rats. Neuroscience letters 15 24316406
2011 Knockdown of synaptic scaffolding protein Homer 1b/c attenuates secondary hyperalgesia induced by complete Freund's adjuvant in rats. Anesthesia and analgesia 15 22003220
2009 In vitro modulation of the cardiac ryanodine receptor activity by Homer1. Pflugers Archiv : European journal of physiology 15 19296124
2023 Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 14 38091015
2007 Cocaine induces the expression of homer 1b/c, homer 3a/b, and hsp 27 proteins in rat cerebellum. Synapse (New York, N.Y.) 14 17455232
2023 Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia. International journal of molecular sciences 13 38069134
2021 The Role of Stress-Induced Changes of Homer1 Expression in Stress Susceptibility. Biochemistry. Biokhimiia 13 34225586
2021 Liraglutide preconditioning attenuates myocardial ischemia/ reperfusion injury via homer1 activation. Aging 12 33535171
2016 Association of HOMER1 rs2290639 with suicide attempts in Hong Kong Chinese and the potentially functional role of this polymorphism. SpringerPlus 12 27386253
2009 Early changes in Homer1 proteins in the spinal dorsal horn are associated with loose ligation of the rat sciatic nerve. Anesthesia and analgesia 12 19923532
2010 Delayed appearance of the scaffolding proteins PSD-95 and Homer-1 at the developing rat calyx of Held synapse. The Journal of comparative neurology 11 20886623
2022 Activity dependent dissociation of the Homer1 interactome. Scientific reports 10 35217690
2014 Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq Proteins. PloS one 10 24626340
2018 Clinical and Diagnostic Significance of Homer1 in hepatitis B virus-induced Hepatocellular Carcinoma. Journal of Cancer 9 29556326
2016 Down-regulation of Homer1 attenuates t-BHP-induced oxidative stress through regulating calcium homeostasis and ER stress in brain endothelial cells. Biochemical and biophysical research communications 9 27396622
2023 Ndufa4 Regulates the Proliferation and Apoptosis of Neurons via miR-145a-5p/Homer1/Ccnd2. Molecular neurobiology 7 36763283
2023 hsa_circ_0006916 Exerts Effect on Amyloid Beta-Induced Neuron Injury by Targeting miR-217/HOMER1. Annals of clinical and laboratory science 7 37094855
2022 Arc and Homer1 are involved in comorbid epilepsy and depression: A microarray data analysis. Epilepsy & behavior : E&B 7 35665606
2021 The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells. International journal of molecular sciences 7 34204449
2019 Pb exposure reduces the expression of SNX6 and Homer1 in offspring rats and PC12 cells. Toxicology 7 30738087
2019 Homer1/mGluR1-mediated ER stress contributes to lysophosphatidic acid-induced neurotoxicity in cortical neurons. Neurochemistry international 7 31369778
2018 Polymorphisms of HOMER1 gene are associated with piglet splay leg syndrome and one significant SNP can affect its intronic promoter activity in vitro. BMC genetics 7 30526478
2009 Homer1 regulates the susceptibility to TRAIL. Experimental cell research 7 19376111
2020 Bicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1-dependent phosphorylation. Journal of neurochemistry 6 32892352
2019 Interaction of the Homer1 EVH1 domain and skeletal muscle ryanodine receptor. Biochemical and biophysical research communications 6 31078268
2017 Cocaine alters Homer1 natural antisense transcript in the nucleus accumbens. Molecular and cellular neurosciences 6 29055697
2016 Diagnostic Potential of Differentially Expressed Homer1 and Homer2 in Ischemic Stroke. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 6 27832625
2024 Elaboration of the Homer1 recognition landscape reveals incomplete divergence of paralogous EVH1 domains. Protein science : a publication of the Protein Society 5 38989636
2005 Homer 1b/c expression correlates with zebrafish olfactory system development. Journal of neurocytology 5 16217622
2024 Preso enhances mGluR1-mediated excitotoxicity by modulating the phosphorylation of mGluR1-Homer1 complex and facilitating an ER stress after traumatic brain injury. Cell death discovery 4 38531909
2024 Serum Homer1 is a Novel Biomarker for Predicting the Clinical Outcomes of Acute Ischemic Stroke Patients. Journal of inflammation research 3 38434583
2020 A single nucleotide polymorphism in the HOMER1 gene is associated with sleep latency and theta power in sleep electroencephalogram. PloS one 3 32645048
2017 Homer1 (VesL-1) in the rat esophagus: focus on myenteric plexus and neuromuscular junction. Histochemistry and cell biology 3 28337539
2025 Activity Deprivation Modulates the Shank3/Homer1/mGluR5 Signaling Pathway to Enable Synaptic Upscaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 2 41043992
2015 Inhibition of Attention for Affective Material: Contributions by HOMER1 Gene Variation. Psychology & neuroscience 2 26779324
2025 DST-3, a novel cryptotanshinone derivate, attenuates glutamate excitotoxicity after ischemic stroke via CREB-Homer1 axis activation. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 40929882
2025 Structural Modeling and Dynamics of the Full-Length Homer1 Multimer. Proteins 1 41267651
2024 Elaboration of the Homer1 Recognition Landscape Reveals Incomplete Divergence of Paralogous EVH1 Domains. bioRxiv : the preprint server for biology 1 38645240
2026 Cerebrospinal fluid HOMER1 and NPTX2 as candidate signatures in early-stage multiple system atrophy-parkinsonism. Journal of the neurological sciences 0 41780424
2026 Modulation of Homer1 EVH1 domain internal dynamics by putative autism-associated mutations. FEBS letters 0 42206738
2025 Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells. Open life sciences 0 40059879
2025 Inhba, Homer1 and Bdnf are major targets of transcriptomic dysregulation by neurodegenerative disease-associated excitotoxic NMDA receptor signaling. Communications biology 0 41339520
2025 Genetic mapping identifies Homer1 as a developmental modifier of attention. Nature neuroscience 0 41430469
2024 Genetic mapping identifies Homer1 as a developmental modifier of attention. bioRxiv : the preprint server for biology 0 36993710
2024 HOMER1 Polymorphism and Parkinson's Disease-Psychosis: Is there an Association? Annals of Indian Academy of Neurology 0 38751916
2015 The Impact of Small RNA Interference Against Homer1 on Rats with Type 2 Diabetes and ERK Phosphorylation. Cell biochemistry and biophysics 0 27259299

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