UniProt functional annotation for Q9UQM7



	UniProt functional annotation for Q9UQM7

UniProt code: Q9UQM7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Acts as a negative regulator of 2- arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}.

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:0000269|PubMed:23805378};

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:0000269|PubMed:23805378};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:23805378};

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:14722083}.

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 (PubMed:14722083, PubMed:29784083). Interacts with BAALC. Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2. Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity). Interacts with SHANK3 (PubMed:28130356). Interacts with GRIN2B (PubMed:28130356). Interacts with CACNB2 (PubMed:28130356). Interacts with LRRC7 (PubMed:28130356). Interacts with GRM5 (PubMed:28130356). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:14722083, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29784083}.

Subcellular location: Cell junction, synapse {ECO:0000250|UniProtKB:P11275}. Cell junction, synapse, postsynaptic density {ECO:0000250|UniProtKB:P11275}. Cell projection, dendritic spine {ECO:0000269|PubMed:28130356}. Cell projection, dendrite {ECO:0000269|PubMed:28130356}. Note=Postsynaptic lipid rafts. {ECO:0000250|UniProtKB:P11275}.

Ptm: Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state. {ECO:0000269|PubMed:14722083}.

Ptm: Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7. {ECO:0000250|UniProtKB:P11275}.

Disease: Mental retardation, autosomal dominant 53 (MRD53) [MIM:617798]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:29560374}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Mental retardation, autosomal recessive 63 (MRT63) [MIM:618095]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT63 patients manifest global developmental delay, severe intellectual disability, and seizures. {ECO:0000269|PubMed:29784083}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {ECO:0000305}.

Sequence caution: Sequence=BAA76812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Acts as a negative regulator of 2- arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250\|UniProtKB:P11275, ECO:0000250\|UniProtKB:P11798, ECO:0000269\|PubMed:23805378, ECO:0000269\|PubMed:28130356, ECO:0000269\|PubMed:29100089}.


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:0000269\|PubMed:23805378};
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:0000269\|PubMed:23805378};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:23805378};
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:14722083}.
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 (PubMed:14722083, PubMed:29784083). Interacts with BAALC. Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2. Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity). Interacts with SHANK3 (PubMed:28130356). Interacts with GRIN2B (PubMed:28130356). Interacts with CACNB2 (PubMed:28130356). Interacts with LRRC7 (PubMed:28130356). Interacts with GRM5 (PubMed:28130356). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity). {ECO:0000250\|UniProtKB:P11275, ECO:0000250\|UniProtKB:P11798, ECO:0000269\|PubMed:14722083, ECO:0000269\|PubMed:28130356, ECO:0000269\|PubMed:29784083}.
Subcellular location:		Cell junction, synapse {ECO:0000250\|UniProtKB:P11275}. Cell junction, synapse, postsynaptic density {ECO:0000250\|UniProtKB:P11275}. Cell projection, dendritic spine {ECO:0000269\|PubMed:28130356}. Cell projection, dendrite {ECO:0000269\|PubMed:28130356}. Note=Postsynaptic lipid rafts. {ECO:0000250\|UniProtKB:P11275}.
Ptm:		Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state. {ECO:0000269\|PubMed:14722083}.
Ptm:		Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7. {ECO:0000250\|UniProtKB:P11275}.
Disease:		Mental retardation, autosomal dominant 53 (MRD53) [MIM:617798]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269\|PubMed:25533962, ECO:0000269\|PubMed:28130356, ECO:0000269\|PubMed:29100089, ECO:0000269\|PubMed:29560374}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Mental retardation, autosomal recessive 63 (MRT63) [MIM:618095]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT63 patients manifest global developmental delay, severe intellectual disability, and seizures. {ECO:0000269\|PubMed:29784083}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {ECO:0000305}.
Sequence caution:		Sequence=BAA76812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};