UniProt functional annotation for Q9Z214



	UniProt functional annotation for Q9Z214

UniProt code: Q9Z214.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Postsynaptic density scaffolding protein. Binds and cross- links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER- associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 3 counteracts the effects by competing for binding sites. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, and isoform 2 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development. Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (By similarity). {ECO:0000250|UniProtKB:Q86YM7, ECO:0000269|PubMed:14528310, ECO:0000269|PubMed:19345194}.

Subunit: Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194). Interacts with GRM1, GRM5, ITPR1, DYN3, RYR1, RYR2 and SHANK3 (PubMed:10433269, PubMed:10798399, PubMed:12810060, PubMed:12887973, PubMed:9069287, PubMed:9808458, PubMed:9808459, PubMed:9727012). Interacts with IFT57 and OPHN1 (PubMed:15034583). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with SHANK1; forms high- order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent (PubMed:10433269, PubMed:19345194). Interacts with NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (PubMed:17584991). {ECO:0000250|UniProtKB:Q86YM7, ECO:0000269|PubMed:10433269, ECO:0000269|PubMed:10798399, ECO:0000269|PubMed:12810060, ECO:0000269|PubMed:12887973, ECO:0000269|PubMed:14528310, ECO:0000269|PubMed:15034583, ECO:0000269|PubMed:17584991, ECO:0000269|PubMed:19345194, ECO:0000269|PubMed:9069287, ECO:0000269|PubMed:9727012, ECO:0000269|PubMed:9808458, ECO:0000269|PubMed:9808459}.

Subcellular location: Cytoplasm {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Cell junction, synapse {ECO:0000269|PubMed:10433269}. Cell projection, dendritic spine {ECO:0000269|PubMed:19345194, ECO:0000269|PubMed:30021165}. Note=Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum. {ECO:0000250}.

Tissue specificity: Highly expressed in cortex, Purkinje cells of the cerebellum, hippocampus, striatum and olfactory bulb. Isoform 1 and isoform 3 are expressed in skeletal and cardiac muscle. {ECO:0000269|PubMed:11118290}.

Developmental stage: In the developing hippocampus, the expression of isoform 1 is high at P8, then decreased with progression of hippocampal development. Isoform 3 expression was constitutively low, and not regulated during hippocampal development.

Induction: [Isoform 3]: Induced in the hippocampus, by seizure and synaptic mechanisms in association with long-term potentiation (LTP). It is also induced in the striatum by drugs that alter dopamine signaling.

Domain: The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (PubMed:19345194). {ECO:0000269|PubMed:19345194}.

Similarity: Belongs to the Homer family. {ECO:0000305}.

Sequence caution: Sequence=AAC53113.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Postsynaptic density scaffolding protein. Binds and cross- links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER- associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 3 counteracts the effects by competing for binding sites. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, and isoform 2 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development. Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (By similarity). {ECO:0000250\|UniProtKB:Q86YM7, ECO:0000269\|PubMed:14528310, ECO:0000269\|PubMed:19345194}.


Subunit:		Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194). Interacts with GRM1, GRM5, ITPR1, DYN3, RYR1, RYR2 and SHANK3 (PubMed:10433269, PubMed:10798399, PubMed:12810060, PubMed:12887973, PubMed:9069287, PubMed:9808458, PubMed:9808459, PubMed:9727012). Interacts with IFT57 and OPHN1 (PubMed:15034583). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with SHANK1; forms high- order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent (PubMed:10433269, PubMed:19345194). Interacts with NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (PubMed:17584991). {ECO:0000250\|UniProtKB:Q86YM7, ECO:0000269\|PubMed:10433269, ECO:0000269\|PubMed:10798399, ECO:0000269\|PubMed:12810060, ECO:0000269\|PubMed:12887973, ECO:0000269\|PubMed:14528310, ECO:0000269\|PubMed:15034583, ECO:0000269\|PubMed:17584991, ECO:0000269\|PubMed:19345194, ECO:0000269\|PubMed:9069287, ECO:0000269\|PubMed:9727012, ECO:0000269\|PubMed:9808458, ECO:0000269\|PubMed:9808459}.
Subcellular location:		Cytoplasm {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Cell junction, synapse {ECO:0000269\|PubMed:10433269}. Cell projection, dendritic spine {ECO:0000269\|PubMed:19345194, ECO:0000269\|PubMed:30021165}. Note=Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum. {ECO:0000250}.
Tissue specificity:		Highly expressed in cortex, Purkinje cells of the cerebellum, hippocampus, striatum and olfactory bulb. Isoform 1 and isoform 3 are expressed in skeletal and cardiac muscle. {ECO:0000269\|PubMed:11118290}.
Developmental stage:		In the developing hippocampus, the expression of isoform 1 is high at P8, then decreased with progression of hippocampal development. Isoform 3 expression was constitutively low, and not regulated during hippocampal development.
Induction:		[Isoform 3]: Induced in the hippocampus, by seizure and synaptic mechanisms in association with long-term potentiation (LTP). It is also induced in the striatum by drugs that alter dopamine signaling.
Domain:		The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (PubMed:19345194). {ECO:0000269\|PubMed:19345194}.
Similarity:		Belongs to the Homer family. {ECO:0000305}.
Sequence caution:		Sequence=AAC53113.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};