UniProt functional annotation for O35274



	UniProt functional annotation for O35274

UniProt code: O35274.

Organism: Rattus norvegicus (Rat).

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

Function: Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross- linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G- protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity). {ECO:0000250, ECO:0000269|PubMed:15743906, ECO:0000269|PubMed:15793568}.

Subunit: Interacts with DCLK2 (By similarity). Possibly exists as a homodimer, homotrimer or a homotetramer. Interacts with F-actin, PPP1CA, neurabin-1, TGN38 and D(2) dopamine receptor. Interacts with RGS1, RGS2, RGS4, RGS19 and ADRA1B, ADRA2A, ADRA2B, ADRA2C, CDKN2A, PPP1R2, RASGFR1 and TIAM1. Interacts (via C-terminus) with SPATA13 (via C-terminal tail) (By similarity). Interacts with ADRA2B (By similarity). {ECO:0000250|UniProtKB:Q6R891, ECO:0000250|UniProtKB:Q96SB3}.

Subcellular location: Cytoplasm, cytoskeleton. Nucleus {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000269|PubMed:15514983}. Cell junction, adherens junction. Cell projection, dendritic spine {ECO:0000269|PubMed:15514983}. Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell projection, ruffle membrane {ECO:0000250}. Note=Enriched at synapse and cadherin-based cell-cell adhesion sites. In neurons, both cytosolic and membrane-associated, and highly enriched in the postsynaptic density apposed to exitatory synapses (PubMed:15514983). Colocalizes with PPP1R2 at actin-rich adherens junctions in epithelial cells and in dendritic spines. Accumulates in the lamellipodium, filopodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment (By similarity). {ECO:0000250, ECO:0000269|PubMed:15514983}.

Tissue specificity: Ubiquitous. Abundantly expressed in the brain. Expressed at highest levels in hippocampus and at lower levels in the cortex, cerebellum and brainstem. Localizes to the dendritic spines of neurons. Also localizes to aspiny neurons, such as GABAergic interneurons.

Developmental stage: Expression is low during embryogenesis and increases around postnatal day 21.

Domain: The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates.

Ptm: Stimulation of D1 (but not D2) dopamine receptors induces Ser-94 and Ser-177 phosphorylation. Dephosphorylation of these residues is mediated by PP1 and possibly PP2A. Spinophilin unphosphorylated or phosphorylated at Ser-94 is concentrated in the postsynaptic density, whereas spinophilin phosphorylated at Ser-177 is absent from the postsynaptic density and enriched in the cytosol. Phosphorylation of spinophilin disrupts its association with F-actin, but does not affect its binding to PP1. {ECO:0000269|PubMed:12417592, ECO:0000269|PubMed:15228588}.

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:		Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross- linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G- protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity). {ECO:0000250, ECO:0000269\|PubMed:15743906, ECO:0000269\|PubMed:15793568}.


Subunit:		Interacts with DCLK2 (By similarity). Possibly exists as a homodimer, homotrimer or a homotetramer. Interacts with F-actin, PPP1CA, neurabin-1, TGN38 and D(2) dopamine receptor. Interacts with RGS1, RGS2, RGS4, RGS19 and ADRA1B, ADRA2A, ADRA2B, ADRA2C, CDKN2A, PPP1R2, RASGFR1 and TIAM1. Interacts (via C-terminus) with SPATA13 (via C-terminal tail) (By similarity). Interacts with ADRA2B (By similarity). {ECO:0000250\|UniProtKB:Q6R891, ECO:0000250\|UniProtKB:Q96SB3}.
Subcellular location:		Cytoplasm, cytoskeleton. Nucleus {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000269\|PubMed:15514983}. Cell junction, adherens junction. Cell projection, dendritic spine {ECO:0000269\|PubMed:15514983}. Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell projection, ruffle membrane {ECO:0000250}. Note=Enriched at synapse and cadherin-based cell-cell adhesion sites. In neurons, both cytosolic and membrane-associated, and highly enriched in the postsynaptic density apposed to exitatory synapses (PubMed:15514983). Colocalizes with PPP1R2 at actin-rich adherens junctions in epithelial cells and in dendritic spines. Accumulates in the lamellipodium, filopodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment (By similarity). {ECO:0000250, ECO:0000269\|PubMed:15514983}.
Tissue specificity:		Ubiquitous. Abundantly expressed in the brain. Expressed at highest levels in hippocampus and at lower levels in the cortex, cerebellum and brainstem. Localizes to the dendritic spines of neurons. Also localizes to aspiny neurons, such as GABAergic interneurons.
Developmental stage:		Expression is low during embryogenesis and increases around postnatal day 21.
Domain:		The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates.
Ptm:		Stimulation of D1 (but not D2) dopamine receptors induces Ser-94 and Ser-177 phosphorylation. Dephosphorylation of these residues is mediated by PP1 and possibly PP2A. Spinophilin unphosphorylated or phosphorylated at Ser-94 is concentrated in the postsynaptic density, whereas spinophilin phosphorylated at Ser-177 is absent from the postsynaptic density and enriched in the cytosol. Phosphorylation of spinophilin disrupts its association with F-actin, but does not affect its binding to PP1. {ECO:0000269\|PubMed:12417592, ECO:0000269\|PubMed:15228588}.