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The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. The major isoform of this gene plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4. Protein products of this gene also phosphorylate AMP-activated protein kinase (AMPK). This gene has its strongest expression in the brain and influences signalling cascades involved with learning and memory, neuronal differentiation and migration, neurite outgrowth, and synapse formation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. The identified isoforms differ in their ability to undergo autophosphorylation and to phosphorylate downstream kinases. [provided by RefSeq, Jul 2012]
CAMKK2 (Calcium/Calmodulin Dependent Protein Kinase Kinase 2) is a Protein Coding gene. Diseases associated with CAMKK2 include Parkinson Disease, Late-Onset. Among its related pathways are Dopamine-DARPP32 Feedback onto cAMP Pathway and Immune response Function of MEF2 in T lymphocytes. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein kinase activity. An important paralog of this gene is CAMKK1.
Calmodulin-dependent kinases (CaMK) are a family of serine/threonine kinases that mediate many of the second messenger effects of Ca2+. At basal Ca2+ levels, CaMKs are maintained in a dormant state through autoinhibition, which can be relieved by increases in Ca2+ levels.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004674 | protein serine/threonine kinase activity | IEA | -- |
GO:0004683 | calmodulin-dependent protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | TAS | 11395482 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA | -- |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005829 | cytosol | IDA,TAS | -- |
GO:0042995 | cell projection | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | AMP-activated Protein Kinase (AMPK) Signaling | ||
2 | Immune response Function of MEF2 in T lymphocytes |
Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
.36
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Immune response Function of MEF2 in T lymphocytes
.36
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3 | Glucose / Energy Metabolism | ||
4 | Neuroscience | ||
5 | Adipocytokine signaling pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | 11395482 |
GO:0001934 | positive regulation of protein phosphorylation | IMP | 26103054 |
GO:0006468 | protein phosphorylation | IDA | 11395482 |
GO:0016310 | phosphorylation | IEA | -- |
GO:0018108 | peptidyl-tyrosine phosphorylation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
ATP | Investigational | Nutra | 0 | |||
Calcium | Nutra | 6876 | ||||
A 484954 | Pharma | EEF2K Inhibitor, CaM kinase III (eEF-2 kinase) inhibitor | 0 | |||
NH125 | Pharma | Selective eEF-2 kinase inhibitor, CaM kinase III (eEF-2 kinase) inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
|||
Autocamtide-2-related inhibitory peptide, myristoylated |
|
201422-04-0 |
|
|
||
KN 93 |
|
139298-40-1 |
|
|
Compound | Action | Cas Number |
---|---|---|
A 484954 | CaM kinase III (eEF-2 kinase) inhibitor | 142557-61-7 |
Autocamtide-2-related inhibitory peptide, myristoylated | CaM kinase II inhibitor; enhanced cell permeable derivative of Autocamtide-2-related inhibitory peptide | 201422-04-0 |
KN 93 | CaM kinase II inhibitor; also K+ channel blocker (KV) | 139298-40-1 |
NH 125 | CaM kinase III (eEF-2 kinase) inhibitor | 278603-08-0 |
ExUns: | 1a | · | 1b | · | 1c | ^ | 2 | ^ | 3a | · | 3b | ^ | 4 | ^ | 5 | ^ | 6a | · | 6b | ^ | 7a | · | 7b | · | 7c | · | 7d | · | 7e | ^ | 8a | · | 8b | ^ | 9 | ^ | 10 | ^ | 11a | · | 11b | ^ | 12 | ^ | 13a | · | 13b | · | 13c | · | 13d | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP12: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP13: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP14: | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP15: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP16: | - | - | - | - |
ExUns: | 14 | ^ | 15 | ^ | 16a | · | 16b | · | 16c | ^ | 17 | ^ | 18 | ^ | 19 | ^ | 20 | ^ | 21 | ^ | 22 | ^ | 23 | ^ | 24a | · | 24b | ^ | 25 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | ||||||||||||||||||||||||||
SP2: | |||||||||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||||||||
SP4: | - | - | |||||||||||||||||||||||||||
SP5: | |||||||||||||||||||||||||||||
SP6: | |||||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||||
SP8: | |||||||||||||||||||||||||||||
SP9: | |||||||||||||||||||||||||||||
SP10: | - | - | |||||||||||||||||||||||||||
SP11: | |||||||||||||||||||||||||||||
SP12: | |||||||||||||||||||||||||||||
SP13: | |||||||||||||||||||||||||||||
SP14: | |||||||||||||||||||||||||||||
SP15: | |||||||||||||||||||||||||||||
SP16: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CAMKK2 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CAMKK2 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CAMKK2 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CAMKK2 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Camkk2 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Camkk2 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | CAMKK2 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | CAMKK2 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
ManyToMany | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | camkk2 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | CAMKK2 31 |
|
OneToOne | |
zgc:194737 30 |
|
||||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP002250 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | CG17698 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | ckk-1 30 31 32 |
|
OneToMany | |
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | TOS3 31 33 |
|
ManyToMany | |
SAK1 31 |
|
ManyToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
871740 | Uncertain Significance: not provided | 121,240,713(-) |
T/TGGCCTCCTCC NM_001270485.2(CAMKK2):c.1743_1752dup (p.Met585fs) |
FRAMESHIFT_VARIANT,THREE_PRIME_UTR_VARIANT,INTRON | |
rs115336463 | Benign: not provided | 121,274,173(-) |
G/A NM_001270485.2(CAMKK2):c.354C>T (p.Asn118=) |
SYNONYMOUS | |
rs1207121718 | A colorectal adenocarcinoma sample |
p.Ala182Thr |
|||
rs139606987 | Benign: not provided | 121,255,566(-) |
G/A NM_001270485.2(CAMKK2):c.891C>T (p.Ile297=) |
SYNONYMOUS | |
rs35407516 | Benign: not provided | 121,274,077(-) |
G/A NM_001270485.2(CAMKK2):c.450C>T (p.His150=) |
SYNONYMOUS |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv1008629 | CNV | insertion | 20482838 |
esv2660506 | CNV | deletion | 23128226 |
esv2746484 | CNV | deletion | 23290073 |
esv2746485 | CNV | deletion | 23290073 |
esv3336861 | CNV | duplication | 20981092 |
esv3630945 | CNV | loss | 21293372 |
nsv1048801 | CNV | gain | 25217958 |
nsv1054878 | CNV | gain | 25217958 |
nsv455731 | CNV | loss | 19166990 |
nsv513372 | CNV | insertion | 21212237 |
nsv521928 | CNV | gain | 19592680 |
nsv560454 | CNV | loss | 21841781 |
nsv560455 | CNV | gain | 21841781 |
nsv560456 | CNV | loss | 21841781 |
nsv952494 | CNV | deletion | 24416366 |
nsv983372 | CNV | duplication | 23825009 |
Disorder | Aliases | PubMed IDs |
---|---|---|
parkinson disease, late-onset |
|
|