UniProt functional annotation for Q96RR4



	UniProt functional annotation for Q96RR4

UniProt code: Q96RR4.

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 belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}.

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;

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;

Activity regulation: Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity). {ECO:0000250}.

Subunit: Interacts with calmodulin. {ECO:0000250}.

Subcellular location: Nucleus {ECO:0000269|PubMed:21957496}. Cytoplasm {ECO:0000269|PubMed:21957496}. Cell projection, neuron projection {ECO:0000269|PubMed:21957496}. Note=Predominantly nuclear in unstimulated cells, relocalizes into cytoplasm and neurites after forskolin induction. {ECO:0000269|PubMed:21957496}.

Tissue specificity: Ubiquitously expressed with higher levels in the brain. Intermediate levels are detected in spleen, prostate, thyroid and leukocytes. The lowest level is in lung. {ECO:0000269|PubMed:9662074}.

Induction: [Isoform 1]: Up-regulated by PKA pathway. {ECO:0000269|PubMed:21957496}.

Domain: The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.

Domain: The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates. {ECO:0000250}.

Ptm: Autophosphorylated and phosphorylated by PKA. Each isoform may show a different pattern of phosphorylation. {ECO:0000269|PubMed:21957496}.

Miscellaneous: [Isoform 1]: Major isoform.

Miscellaneous: [Isoform 2]: Major isoform. {ECO:0000305}.

Miscellaneous: [Isoform 5]: Inactive. Does not activate CAMK1 and CAMK4. {ECO:0000305}.

Miscellaneous: [Isoform 6]: Inactive. Does not activate CAMK1 and CAMK4. {ECO:0000305}.

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Sequence caution: Sequence=AAC72943.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA34507.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD38990.1; Type=Miscellaneous discrepancy; Note=Intron retention.; 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 belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269\|PubMed:11395482, ECO:0000269\|PubMed:12935886, ECO:0000269\|PubMed:21957496, ECO:0000269\|PubMed:9662074}.


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;
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;
Activity regulation:		Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity). {ECO:0000250}.
Subunit:		Interacts with calmodulin. {ECO:0000250}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:21957496}. Cytoplasm {ECO:0000269\|PubMed:21957496}. Cell projection, neuron projection {ECO:0000269\|PubMed:21957496}. Note=Predominantly nuclear in unstimulated cells, relocalizes into cytoplasm and neurites after forskolin induction. {ECO:0000269\|PubMed:21957496}.
Tissue specificity:		Ubiquitously expressed with higher levels in the brain. Intermediate levels are detected in spleen, prostate, thyroid and leukocytes. The lowest level is in lung. {ECO:0000269\|PubMed:9662074}.
Induction:		[Isoform 1]: Up-regulated by PKA pathway. {ECO:0000269\|PubMed:21957496}.
Domain:		The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.
Domain:		The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates. {ECO:0000250}.
Ptm:		Autophosphorylated and phosphorylated by PKA. Each isoform may show a different pattern of phosphorylation. {ECO:0000269\|PubMed:21957496}.
Miscellaneous:		[Isoform 1]: Major isoform.
Miscellaneous:		[Isoform 2]: Major isoform. {ECO:0000305}.
Miscellaneous:		[Isoform 5]: Inactive. Does not activate CAMK1 and CAMK4. {ECO:0000305}.
Miscellaneous:		[Isoform 6]: Inactive. Does not activate CAMK1 and CAMK4. {ECO:0000305}.
Similarity:		Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Sequence caution:		Sequence=AAC72943.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA34507.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAD38990.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};