UniProt functional annotation for O62305



	UniProt functional annotation for O62305

UniProt code: O62305.

Organism: Caenorhabditis elegans.

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.

Function: Acts in the signaling of a variety of pathways and processes. Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such as heat, starvation and oxidation, which plays a role in prolonging lifespan. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Has roles in locomotion, oocyte maturation, brood size, egg laying, defecation, meiotic maturation and neuronal cell fate specification. Required for the regulation of synaptic density and neuromuscular junction morphology. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. Involved in activation of ADF neurons and increased tph-1 transcription following exposure to pathogenic bacteria which leads to learned olfactory aversion to the bacteria (PubMed:23325232, PubMed:23505381). Implicated in the muscle regulation of spicule protraction. In conjunction with egl-2 has a role in the suppression of mating behavior under food deprivation to encourage foraging. Involved in restricting str-2 expression to only one of the two AWC neurons. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor. {ECO:0000269|PubMed:10571181, ECO:0000269|PubMed:12221132, ECO:0000269|PubMed:15166144, ECO:0000269|PubMed:16079277, ECO:0000269|PubMed:16267094, ECO:0000269|PubMed:17898212, ECO:0000269|PubMed:17941711, ECO:0000269|PubMed:17942636, ECO:0000269|PubMed:21145946, ECO:0000269|PubMed:21771813, ECO:0000269|PubMed:22629462, ECO:0000269|PubMed:23325232, ECO:0000269|PubMed:23505381, ECO:0000269|PubMed:23663262, ECO:0000269|PubMed:23805378}.

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:16079277};

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:16079277};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:16079277};

Activity regulation: Ca2(+)/calmodulin binding removes an autoinhibitory regulatory segment located C-terminal to the kinase domain. This releases the catalytic activity of the enzyme and makes accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by another kinase domain within the oligomeric holoenzyme keeps CaMKII active in the absence of Ca(2+)/calmodulin by preventing the rebinding of the regulatory segment to the kinase domain and by increasing the affinity of calmodulin for the enzyme. Can respond to high-frequency Ca(2+) pulses to become Ca(2+) independent. {ECO:0000269|PubMed:16325579, ECO:0000269|PubMed:20139983}.

Subunit: Dodecamer. Subunits are tightly packed around a central ring- shaped scaffold with extensive contacts between the regulatory segment of one kinase and the catalytic domain of another enabling cooperative activation of a subunit by the adjacent molecule (PubMed:16441656, PubMed:20139983). Interacts with and phosphorylates daf-16; the interaction promotes daf-16 nuclear localization. Interacts with egl-2 and tir-1 (PubMed:15625192, PubMed:21145946). Interacts with nsy-1 (PubMed:11336672). {ECO:0000269|PubMed:11336672, ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16441656, ECO:0000269|PubMed:20139983, ECO:0000269|PubMed:21145946}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:16079277}. Cell projection, axon {ECO:0000269|PubMed:15625192}. Perikaryon {ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16079277}. Note=Localizes at or near the Golgi apparatus (PubMed:16079277). Localizes to post-synaptic regions and is enriched in punctate structures in axons of AWC neurons where it co-localizes with tir-1. Localization is regulated by tir-1 (PubMed:15625192). {ECO:0000269|PubMed:15625192, ECO:0000269|PubMed:16079277}.

Tissue specificity: Expressed in the nervous system. Observed in the ADF and AWC neurons. Position in AWC neurons is regulated by microtubules. Localized to clusters in ventral cord neurites which appear to be required for glr-1 trafficking. Also present in oocytes. {ECO:0000269|PubMed:10647014, ECO:0000269|PubMed:16079277, ECO:0000269|PubMed:16267094, ECO:0000269|PubMed:23325232}.

Disruption phenotype: Increased frequency of defecation, typified by a weaker repetition of the defecation motor program, an echo, 10 s after the primary motor program. Abnormal spicule protraction. Lack of tph-1 transcriptional up-regulation during learned olfactory aversion to bacteria. Reduced brood size, body length and width. Lethargic movement. A gain-of function mutation reduces locomotory activity, alters excitation of three muscle types and lengthens the period of the motor output of a behavioral clock. Both classes of mutation inhibit neurotransmitter release. {ECO:0000269|PubMed:10647014, ECO:0000269|PubMed:12221132, ECO:0000269|PubMed:17898212, ECO:0000269|PubMed:17941711, ECO:0000269|PubMed:17942636, ECO:0000269|PubMed:23325232}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {ECO:0000255}.

Annotations taken from UniProtKB at the EBI.


Organism:		Caenorhabditis elegans.
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.



Function:		Acts in the signaling of a variety of pathways and processes. Phosphorylates 'Ser-319' of daf-16 in response to stress signals, such as heat, starvation and oxidation, which plays a role in prolonging lifespan. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Has roles in locomotion, oocyte maturation, brood size, egg laying, defecation, meiotic maturation and neuronal cell fate specification. Required for the regulation of synaptic density and neuromuscular junction morphology. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. Involved in activation of ADF neurons and increased tph-1 transcription following exposure to pathogenic bacteria which leads to learned olfactory aversion to the bacteria (PubMed:23325232, PubMed:23505381). Implicated in the muscle regulation of spicule protraction. In conjunction with egl-2 has a role in the suppression of mating behavior under food deprivation to encourage foraging. Involved in restricting str-2 expression to only one of the two AWC neurons. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor. {ECO:0000269\|PubMed:10571181, ECO:0000269\|PubMed:12221132, ECO:0000269\|PubMed:15166144, ECO:0000269\|PubMed:16079277, ECO:0000269\|PubMed:16267094, ECO:0000269\|PubMed:17898212, ECO:0000269\|PubMed:17941711, ECO:0000269\|PubMed:17942636, ECO:0000269\|PubMed:21145946, ECO:0000269\|PubMed:21771813, ECO:0000269\|PubMed:22629462, ECO:0000269\|PubMed:23325232, ECO:0000269\|PubMed:23505381, ECO:0000269\|PubMed:23663262, ECO:0000269\|PubMed:23805378}.


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:16079277};
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:16079277};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:16079277};
Activity regulation:		Ca2(+)/calmodulin binding removes an autoinhibitory regulatory segment located C-terminal to the kinase domain. This releases the catalytic activity of the enzyme and makes accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by another kinase domain within the oligomeric holoenzyme keeps CaMKII active in the absence of Ca(2+)/calmodulin by preventing the rebinding of the regulatory segment to the kinase domain and by increasing the affinity of calmodulin for the enzyme. Can respond to high-frequency Ca(2+) pulses to become Ca(2+) independent. {ECO:0000269\|PubMed:16325579, ECO:0000269\|PubMed:20139983}.
Subunit:		Dodecamer. Subunits are tightly packed around a central ring- shaped scaffold with extensive contacts between the regulatory segment of one kinase and the catalytic domain of another enabling cooperative activation of a subunit by the adjacent molecule (PubMed:16441656, PubMed:20139983). Interacts with and phosphorylates daf-16; the interaction promotes daf-16 nuclear localization. Interacts with egl-2 and tir-1 (PubMed:15625192, PubMed:21145946). Interacts with nsy-1 (PubMed:11336672). {ECO:0000269\|PubMed:11336672, ECO:0000269\|PubMed:15625192, ECO:0000269\|PubMed:16441656, ECO:0000269\|PubMed:20139983, ECO:0000269\|PubMed:21145946}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:16079277}. Cell projection, axon {ECO:0000269\|PubMed:15625192}. Perikaryon {ECO:0000269\|PubMed:15625192, ECO:0000269\|PubMed:16079277}. Note=Localizes at or near the Golgi apparatus (PubMed:16079277). Localizes to post-synaptic regions and is enriched in punctate structures in axons of AWC neurons where it co-localizes with tir-1. Localization is regulated by tir-1 (PubMed:15625192). {ECO:0000269\|PubMed:15625192, ECO:0000269\|PubMed:16079277}.
Tissue specificity:		Expressed in the nervous system. Observed in the ADF and AWC neurons. Position in AWC neurons is regulated by microtubules. Localized to clusters in ventral cord neurites which appear to be required for glr-1 trafficking. Also present in oocytes. {ECO:0000269\|PubMed:10647014, ECO:0000269\|PubMed:16079277, ECO:0000269\|PubMed:16267094, ECO:0000269\|PubMed:23325232}.
Disruption phenotype:		Increased frequency of defecation, typified by a weaker repetition of the defecation motor program, an echo, 10 s after the primary motor program. Abnormal spicule protraction. Lack of tph-1 transcriptional up-regulation during learned olfactory aversion to bacteria. Reduced brood size, body length and width. Lethargic movement. A gain-of function mutation reduces locomotory activity, alters excitation of three muscle types and lengthens the period of the motor output of a behavioral clock. Both classes of mutation inhibit neurotransmitter release. {ECO:0000269\|PubMed:10647014, ECO:0000269\|PubMed:12221132, ECO:0000269\|PubMed:17898212, ECO:0000269\|PubMed:17941711, ECO:0000269\|PubMed:17942636, ECO:0000269\|PubMed:23325232}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. {ECO:0000255}.