UniProt functional annotation for Q9EP80



	UniProt functional annotation for Q9EP80

UniProt code: Q9EP80.

Organism: Rattus norvegicus (Rat).

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

Function: Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function. {ECO:0000269|PubMed:16138078, ECO:0000269|PubMed:18297063, ECO:0000269|PubMed:21252856, ECO:0000269|PubMed:23843614}.

Subunit: Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR (By similarity). Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition. {ECO:0000250, ECO:0000269|PubMed:10027300, ECO:0000269|PubMed:10340301, ECO:0000269|PubMed:11122333, ECO:0000269|PubMed:11237868, ECO:0000269|PubMed:11931741, ECO:0000269|PubMed:14672991, ECO:0000269|PubMed:17914463, ECO:0000269|PubMed:19109914, ECO:0000269|PubMed:23889934}.

Subcellular location: Cytoplasm, perinuclear region {ECO:0000269|PubMed:23889934}. Membrane {ECO:0000269|PubMed:23889934}; Peripheral membrane protein {ECO:0000269|PubMed:23889934}. Membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000269|PubMed:23889934}. Cell junction, synapse, synaptosome {ECO:0000269|PubMed:23889934}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:23889934}. Note=Also membrane- associated, present at excitatory synapses.

Tissue specificity: Ubiquitous.

Developmental stage: Expressed early in development (E15), and gradually increases, reaching a peak at around 2 weeks after birth.

Domain: The AH domain mediates binding to F-actin.

Domain: The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization.

Ptm: Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors. {ECO:0000250}.

Ptm: Palmitoylation on Cys-414 is essential for long-term synaptic depression (LTD). {ECO:0000250}.

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:		Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function. {ECO:0000269\|PubMed:16138078, ECO:0000269\|PubMed:18297063, ECO:0000269\|PubMed:21252856, ECO:0000269\|PubMed:23843614}.


Subunit:		Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR (By similarity). Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition. {ECO:0000250, ECO:0000269\|PubMed:10027300, ECO:0000269\|PubMed:10340301, ECO:0000269\|PubMed:11122333, ECO:0000269\|PubMed:11237868, ECO:0000269\|PubMed:11931741, ECO:0000269\|PubMed:14672991, ECO:0000269\|PubMed:17914463, ECO:0000269\|PubMed:19109914, ECO:0000269\|PubMed:23889934}.
Subcellular location:		Cytoplasm, perinuclear region {ECO:0000269\|PubMed:23889934}. Membrane {ECO:0000269\|PubMed:23889934}; Peripheral membrane protein {ECO:0000269\|PubMed:23889934}. Membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000269\|PubMed:23889934}. Cell junction, synapse, synaptosome {ECO:0000269\|PubMed:23889934}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:23889934}. Note=Also membrane- associated, present at excitatory synapses.
Tissue specificity:		Ubiquitous.
Developmental stage:		Expressed early in development (E15), and gradually increases, reaching a peak at around 2 weeks after birth.
Domain:		The AH domain mediates binding to F-actin.
Domain:		The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization.
Ptm:		Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors. {ECO:0000250}.
Ptm:		Palmitoylation on Cys-414 is essential for long-term synaptic depression (LTD). {ECO:0000250}.