UniProt functional annotation for P11275



	UniProt functional annotation for P11275

UniProt code: P11275.

Organism: Rattus norvegicus (Rat).

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

Function: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in synaptic plasticity, neurotransmitter release and long-term potentiation. Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (PubMed:15312654). Regulates dendritic spine development. Also regulates the migration of developing neurons. Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (By similarity). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11798, ECO:0000250|UniProtKB:Q9UQM7, ECO:0000269|PubMed:15312654}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000250|UniProtKB:Q9UQM7};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000250|UniProtKB:Q9UQM7};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9UQM7};

Activity regulation: Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity. {ECO:0000269|PubMed:2842767}.

Subunit: There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity). Interacts with BAALC (PubMed:15659234). Interacts with MPDZ (PubMed:15312654). Interacts with SYN1 (PubMed:1328883). Interacts with CAMK2N2 (PubMed:9724800). Interacts with SYNGAP1 (PubMed:15312654). Interacts with SYNPO2 (PubMed:17923693). Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2. Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity). {ECO:0000250|UniProtKB:P11798, ECO:0000250|UniProtKB:Q9UQM7, ECO:0000269|PubMed:1328883, ECO:0000269|PubMed:15312654, ECO:0000269|PubMed:15659234, ECO:0000269|PubMed:17923693, ECO:0000269|PubMed:9724800}.

Subcellular location: Cell junction, synapse {ECO:0000269|PubMed:15659234}. Cell junction, synapse, postsynaptic density {ECO:0000269|PubMed:15659234}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q9UQM7}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q9UQM7}. Note=Postsynaptic lipid rafts. {ECO:0000269|PubMed:15659234}.

Ptm: Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state. {ECO:0000250|UniProtKB:Q9UQM7}.

Ptm: Palmitoylated (PubMed:23687301). Probably palmitoylated by ZDHHC3 and ZDHHC7 (PubMed:23687301). {ECO:0000269|PubMed:23687301}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {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:		Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in synaptic plasticity, neurotransmitter release and long-term potentiation. Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (PubMed:15312654). Regulates dendritic spine development. Also regulates the migration of developing neurons. Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (By similarity). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250\|UniProtKB:P11798, ECO:0000250\|UniProtKB:Q9UQM7, ECO:0000269\|PubMed:15312654}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000250\|UniProtKB:Q9UQM7};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000250\|UniProtKB:Q9UQM7};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250\|UniProtKB:Q9UQM7};
Activity regulation:		Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity. {ECO:0000269\|PubMed:2842767}.
Subunit:		There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity). Interacts with BAALC (PubMed:15659234). Interacts with MPDZ (PubMed:15312654). Interacts with SYN1 (PubMed:1328883). Interacts with CAMK2N2 (PubMed:9724800). Interacts with SYNGAP1 (PubMed:15312654). Interacts with SYNPO2 (PubMed:17923693). Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2. Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity). {ECO:0000250\|UniProtKB:P11798, ECO:0000250\|UniProtKB:Q9UQM7, ECO:0000269\|PubMed:1328883, ECO:0000269\|PubMed:15312654, ECO:0000269\|PubMed:15659234, ECO:0000269\|PubMed:17923693, ECO:0000269\|PubMed:9724800}.
Subcellular location:		Cell junction, synapse {ECO:0000269\|PubMed:15659234}. Cell junction, synapse, postsynaptic density {ECO:0000269\|PubMed:15659234}. Cell projection, dendritic spine {ECO:0000250\|UniProtKB:Q9UQM7}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q9UQM7}. Note=Postsynaptic lipid rafts. {ECO:0000269\|PubMed:15659234}.
Ptm:		Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state. {ECO:0000250\|UniProtKB:Q9UQM7}.
Ptm:		Palmitoylated (PubMed:23687301). Probably palmitoylated by ZDHHC3 and ZDHHC7 (PubMed:23687301). {ECO:0000269\|PubMed:23687301}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {ECO:0000305}.