HOMER1
Encyclopedia
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.
has with an N-terminal EVH1 domain
, involved in protein interaction, and 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 in to 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.
as well as peripheral tissue including heart
, kidney
, ovary
, testis, and skeletal muscle
. Subcellularly in neurons, Homer1 is concentrated in postsynaptic structure and consist major part of postsynaptic density.
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 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the HOMER1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Other names are Vesl and PSD-Zip45.
Domain structure
Homer1 proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
has with an N-terminal EVH1 domain
EVH1 domain
The EVH1 domain is an evolutionary conserved protein domain.The EVH1 domain is found in multi-domain proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals...
, involved in protein interaction, and 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 in to 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
HOMER2
Homer protein homolog 2 is a protein that in humans is encoded by the HOMER2 gene.-Further reading:...
and Homer3
HOMER3
Homer protein homolog 3 is a protein that in humans is encoded by the HOMER3 gene.-Interactions:HOMER3 has been shown to interact with TRPC1 and RYR1....
, in addition to Homer1, which have similar domain structure. They also have similar alternatively spliced forms.
Distribution
Homer1 is expressed widely in central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
as well as peripheral tissue including heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, testis, and skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
. Subcellularly in neurons, Homer1 is concentrated in postsynaptic structure and consist major part of postsynaptic density.
Functions
EVH1 domain interactsProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PPXXF motif. This sequence motif exists in group 1 metabotrophic glutamate receptor (mGluR1 and mGluR5), IP3 receptors (IP3R), Shank
Shank
Shank is the lower part of the leg; shin.It may also refer to:* Shank , a cut of meat * Shank , an action game* Shank , An LGBT based film* Shank , a thriller set in futuristic London...
, transient receptor potential canonical (TRPC) family channels
TRPC
TRPC is a family of transient receptor potential cation channels in animals.TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics...
, drebrin, oligophrenin, dynamin3
Dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface as well as at the...
, CENTG1
CENTG1
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 is an enzyme that in humans is encoded by the AGAP2 gene.-Interactions:CENTG1 has been shown to interact with PIK3R1, HOMER1 and EPB41L1.-Further reading:...
, and ryanodin receptor
RYR1
Ryanodine receptor 1 also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is a protein primarily found in skeletal muscle...
. 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
Postsynaptic density
The postsynaptic density is a protein dense specialization attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron...
.
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
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...
. 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
Dendritic spine
A dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single synapse of an axon. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body...
structure. Therefore, the short form of Homer is considered to be a part of a mechanism of homeostatic plasticity
Homeostatic plasticity
In Neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity, a compensatory adjustment that occurs over the timescale of days....
that dampens the neuronal responsiveness when input activity is too high.
The coiled-coil domain is reported to interact with syntaxin13 and activated Cdc42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
. The interaction with Cdc42 inhibit the activity of Cdc42 to remodel dendritic spine structure.