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FLASH GENE

Symbol

HOMER1

contributors: mct/npt - updated : 23-12-2014

HGNC name	homer homolog 1 (Drosophila)
HGNC id	17512

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	5q14.1      Physical location : 78.669.786 - 78.809.700
Synonym name	homer 1, neuralized binding protein
	homer, neuronal immediate early gene, 1
Synonym symbol(s)	SYN47, HOMER1A, HOMER1B, HOMER1C, Vesl-1, HOMER

DNA

TYPE	functioning gene
STRUCTURE	140.01 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

Map	pter - D5S1977 - D5S1962 - ARSB - HOMER1 - THBS4 - D5S620 - D5S2029 - D5S627 - D5S626 - HAPLN1 - D5S459 - D5S428 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004272 9 - 4228 NP_004263 39 354 in the brain 2012 22749857 also called HOMER1A or Vesl1s exons 1-5, regulating trafficking and surface expression at metabotropic Glu receptors a long 3-prime UTR with multiple destabilizing repeat sequences typical of immediate early genes, whereas the subsequently identified Homer family members have a short 3-prime UTR without the repeats associated with global GRM5 distribution activity-induced protein believed to participate in synaptic remodeling/plasticity responses to temporal lobe seizure and learning variant B 10 - 1166 isoform B 39 354 constitutive,low expression in dentritic spines, expressed at high levels in cortex, hippocampus, and cerebellum, with moderate expression in heart and kidney and weaker expression in liver 2012 22749857 also called HOMER1B exons 1-10, inhibiting surface expression of metabotropic Glu receptors coexpression with HOMER1C induced dendritic expression of GRM5 HOMER1B/C might promote neuronal apoptosis via the BAX/BCL2 dependent pathway during neuroinflammation in CNS long form, that reduced cell surface expression by retaining GRM in the endoplasmic reticulum variant C - - - isoform C - 366 expressed at high levels in hippocampus, striatum, and cortex 2012 22749857 also called HOMER1C an insertion of 12 amino acids between the conserved N terminus and the CC domain coexpression with HOMER1B induced dendritic expression of GRM5 may play an important role in the mechanisms of neuronal death in the striatum HOMER1B/C might promote neuronal apoptosis via the BAX/BCL2 dependent pathway during neuroinflammation in CNS NM_001277077 6 - 3922 NP_001264006 - 224 - 2012 22749857 also called HOMER1E variant F - - 641 isoform F - 180 - 2012 22749857 also called HOMER1F short HOMER isoforms lacking the coiled-coil domain and thus acting in a dominant negative manner by binding to HOMER ligands displacing them from the HOMER scaffold NM_001277078 6 - 3923 NP_001264007 - 177 - 2012 22749857 also called HOMER1H short HOMER isoforms lacking the coiled-coil domain and thus acting in a dominant negative manner by binding to HOMER ligands displacing them from the HOMER scaffold short HOMER proteins act in a dominant negative manner to prevent retention in subcellular compartments

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine thyroid       highly Nervous brain diencephalon hypothalamus       brain basal nuclei striatum       brain limbic system hippocampus   highly   brain forebrain     highly Homo sapiens Reproductive female system placenta     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminus Ena/vasodilator-stimulated phosphoprotein homology 1 (EVH-1) domain that contains a PDZ domain capable of binding to HOMER ligands such as cell surface receptors, other scaffolding proteins and enzymes involved in cell signaling cascades
	a WAS homology domain (WH1),variant EVASP
	a C terminal coiled-coil region,mediating self-multimerization

mono polymer

monomer , oligo

HOMOLOGY

interspecies

homolog to murine Ania3

Homologene

FAMILY

Homer protein family

CATEGORY

adaptor , receptor

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
text	HOMER1B in ER and Golgi

basic FUNCTION	clustering and linking metabotropic glutamate receptors group I with the inositol triphosphate receptors regulator of GRMs signaling
	"adapter" that also modifies signaling properties of its target protein and modulating the function of its target protein RyR1 and excitation-contraction coupling in skeletal myotubes
	synaptic scaffolding protein having a function crucially involved in pain plasticity and protecting against chronic inflammatory pain
	can reduce GRM5 coupling to postsynaptic effectors without relying on large changes in the subcellular distribution of the receptor
	may have a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness (Maret 2007)
	regulates the activity-induced biphasic changes of post- and pre-synaptic sites (Inoue 2007)
	brain-coping marker against stressors, and might represent the molecular link between sleep, cognition, and neuropsychiatric disorder
	activation of HOMER 1 suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness
	plays a critical role in determining the apoptotic susceptibility to TNFSF10 (Shin 2009)
	important role of GRM1 in pain-related amygdala plasticity and evidence for the involvement of HOMER1 proteins in the forebrain in the modulation of pain hypersensitivity
	accelerate ATP2B1 mediated Ca2+ clearance in hippocampal neurons
	stress induces a cognitive deficit that is likely mediated by GRM5/HOMER1 signaling in the hippocampus
	may play an important role in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD)
	postsynaptic density scaffold protein, playing a vital role in maintaining synaptic integrity, regulating intracellular calcium mobilization, and being critical for the regulation of cellular apoptosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

PATHWAY

metabolism

signaling

neurotransmission

a component

INTERACTION

DNA

RNA

small molecule

protein	HOMER3
	binding of SHANK3 C terminus to HOMER1 is critical for its expression at synapses, and HOMER1 stabilizes SHANK3 protein
	ATP2B1 mediated Ca2+ clearance from hippocampal neurons was accelerated in the presence of HOMER proteins
	regulation of HOMER1 splicing by GNRH1 contributes to gonadotropin gene control
	role for OPHN1 as an interaction partner of HOMER1B/C in spine endocytic zone (EZ) positioning

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in spinal cord neurons after peripheral inflammation in an NMDA receptor-dependent manner constitutional     --over   after sleep deprivation and after inflammation, seizure, and psychostimulant or antipsychotic drug use, playing a major role in neuroprotection tumoral     --over   in intrahepatic cholangiocarcinoma, with a worse prognosis

Susceptibility

to psychotic symptoms in Parkinson disease (PD)

Variant & Polymorphism other	allele A of the rs4704559 marker associated to psychotic symptoms in PD (De Luca 2009)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   promising therapeutic target for the treatment of chronic inflammatory pain neurology acquired   suppression of HOMER1B/C expression potentially protects neurons from glutamate excitotoxicity after injury and might be an effective intervention target in traumatic brain injury

ANIMAL & CELL MODELS