O88831 · KKCC2_RAT
- ProteinCalcium/calmodulin-dependent protein kinase kinase 2
- GeneCamkk2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids587 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1 and CAMK4. Phosphorylates CAMK1D (By similarity).
Seems to be involved in hippocampal activation of CREB1 (By similarity).
Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca2+ signals. May play a role in neurite growth. Isoform 2 may promote neurite elongation, while isoform 1 may promoter neurite branching.
Seems to be involved in hippocampal activation of CREB1 (By similarity).
Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca2+ signals. May play a role in neurite growth. Isoform 2 may promote neurite elongation, while isoform 1 may promoter neurite branching.
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Activated by Ca2+/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca2+/calmodulin. In part, activity is independent on Ca2+/calmodulin.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | neuron projection | |
Cellular Component | nucleoplasm | |
Molecular Function | ATP binding | |
Molecular Function | calcium ion binding | |
Molecular Function | calmodulin binding | |
Molecular Function | calmodulin-dependent protein kinase activity | |
Molecular Function | protein kinase activator activity | |
Molecular Function | protein kinase activity | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | CAMKK-AMPK signaling cascade | |
Biological Process | positive regulation of protein phosphorylation | |
Biological Process | protein autophosphorylation | |
Biological Process | protein phosphorylation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCalcium/calmodulin-dependent protein kinase kinase 2
- EC number
- Short namesCaM-KK 2; CaM-kinase kinase 2; CaMKK 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO88831
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly nuclear in unstimulated cells, relocalizes into cytoplasm and neurites after forskolin induction.
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Chain | PRO_0000086146 | 2-587 | Calcium/calmodulin-dependent protein kinase kinase 2 | |||
Sequence: SSCVSSQPTSDRAAPQDELGSGGVSRESQKPCEALRGLSSLSIHLGMESFIVVTECEPGRGVDLSLARDQPLEADGQELPLDASEPESRSLLSGGKMSLQERSQGGPASSSSLDMNGRCICPSLSYSPASSPQSSPRMPRRPTVESHHVSITGLQDCVQLNQYTLKDEIGKGSYGVVKLAYNENDNTYYAMKVLSKKKLIRQAGFPRRPPPRGTRPAPGGCIQPRGPIEQVYQEIAILKKLDHPNVVKLVEVLDDPNEDHLYMVFELVNQGPVMEVPTLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDIKPSNLLVGEDGHIKIADFGVSNEFKGSDALLSNTVGTPAFMAPESLSETRKIFSGKALDVWAMGVTLYCFVFGQCPFMDERIMCLHSKIKSQALEFPDQPDIAEDLKDLITRMLDKNPESRIVVPEIKLHPWVTRHGAEPLPSEDENCTLVEVTEEEVENSVKHIPSLATVILVKTMIRKRSFGNPFEGSRREERSLSAPGNLLTKKPTREWEPLSEPKEARQRRQPPGPRASPCGGGGSALVKGGPCVESCGAPAPGSPPRTPPQQPEEAMEPE | ||||||
Modified residue | 99 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 113 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 128 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 132 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 136 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 494 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 510 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 571 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by PKA (By similarity).
Each isoform may show a different pattern of phosphorylation (By similarity).
Autophosphorylated
Each isoform may show a different pattern of phosphorylation (By similarity).
Autophosphorylated
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Mainly expressed in brain, but detected in all tissues tested (at protein level). In the brain, isoform 1 may be predominant. with high levels in the cerebellum and hippocampus, although isoform 3 is detectable. Isoform 3 is also expressed in lung.
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Polar residues | ||||
Sequence: MSSCVSSQPTSDRAA | ||||||
Region | 1-32 | Disordered | ||||
Sequence: MSSCVSSQPTSDRAAPQDELGSGGVSRESQKP | ||||||
Region | 74-115 | Disordered | ||||
Sequence: EADGQELPLDASEPESRSLLSGGKMSLQERSQGGPASSSSLD | ||||||
Compositional bias | 92-115 | Polar residues | ||||
Sequence: LLSGGKMSLQERSQGGPASSSSLD | ||||||
Domain | 164-445 | Protein kinase | ||||
Sequence: YTLKDEIGKGSYGVVKLAYNENDNTYYAMKVLSKKKLIRQAGFPRRPPPRGTRPAPGGCIQPRGPIEQVYQEIAILKKLDHPNVVKLVEVLDDPNEDHLYMVFELVNQGPVMEVPTLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDIKPSNLLVGEDGHIKIADFGVSNEFKGSDALLSNTVGTPAFMAPESLSETRKIFSGKALDVWAMGVTLYCFVFGQCPFMDERIMCLHSKIKSQALEFPDQPDIAEDLKDLITRMLDKNPESRIVVPEIKLHPWV | ||||||
Region | 203-225 | RP domain | ||||
Sequence: QAGFPRRPPPRGTRPAPGGCIQP | ||||||
Region | 204-224 | Disordered | ||||
Sequence: AGFPRRPPPRGTRPAPGGCIQ | ||||||
Region | 471-476 | Autoinhibitory domain | ||||
Sequence: ENSVKH | ||||||
Region | 474-499 | Calmodulin-binding | ||||
Sequence: VKHIPSLATVILVKTMIRKRSFGNPF | ||||||
Region | 496-587 | Disordered | ||||
Sequence: GNPFEGSRREERSLSAPGNLLTKKPTREWEPLSEPKEARQRRQPPGPRASPCGGGGSALVKGGPCVESCGAPAPGSPPRTPPQQPEEAMEPE | ||||||
Compositional bias | 522-538 | Basic and acidic residues | ||||
Sequence: REWEPLSEPKEARQRRQ | ||||||
Compositional bias | 569-587 | Pro residues | ||||
Sequence: PGSPPRTPPQQPEEAMEPE |
Domain
The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.
The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates.
Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O88831-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsCAMKK2+E16
- Length587
- Mass (Da)64,446
- Last updated1998-11-01 v1
- ChecksumC9E49B72578F3971
O88831-2
- Name2
- SynonymsCAMKK2-E16
- Differences from canonical
- 519-587: KPTREWEPLSEPKEARQRRQPPGPRASPCGGGGSALVKGGPCVESCGAPAPGSPPRTPPQQPEEAMEPE → QGSEDSLRGPEPAPVGEEEVLL
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F1LPT4 | F1LPT4_RAT | Camkk2 | 544 | ||
A0A8I6GKR3 | A0A8I6GKR3_RAT | Camkk2 | 543 | ||
A0A8I6GBY8 | A0A8I6GBY8_RAT | Camkk2 | 575 | ||
A0A8I5ZSP8 | A0A8I5ZSP8_RAT | Camkk2 | 540 |
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Polar residues | ||||
Sequence: MSSCVSSQPTSDRAA | ||||||
Compositional bias | 92-115 | Polar residues | ||||
Sequence: LLSGGKMSLQERSQGGPASSSSLD | ||||||
Sequence conflict | 180 | in Ref. 2; AA sequence | ||||
Sequence: L → S | ||||||
Sequence conflict | 245 | in Ref. 2; AA sequence | ||||
Sequence: P → V | ||||||
Sequence conflict | 300 | in Ref. 2; AA sequence | ||||
Sequence: Missing | ||||||
Sequence conflict | 465 | in Ref. 2; AA sequence | ||||
Sequence: V → S | ||||||
Sequence conflict | 468 | in Ref. 2; AA sequence | ||||
Sequence: E → T | ||||||
Alternative sequence | VSP_046047 | 519-587 | in isoform 2 | |||
Sequence: KPTREWEPLSEPKEARQRRQPPGPRASPCGGGGSALVKGGPCVESCGAPAPGSPPRTPPQQPEEAMEPE → QGSEDSLRGPEPAPVGEEEVLL | ||||||
Compositional bias | 522-538 | Basic and acidic residues | ||||
Sequence: REWEPLSEPKEARQRRQ | ||||||
Compositional bias | 569-587 | Pro residues | ||||
Sequence: PGSPPRTPPQQPEEAMEPE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB018081 EMBL· GenBank· DDBJ | BAA33524.1 EMBL· GenBank· DDBJ | mRNA |