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Information on EC 2.7.11.17 - Ca2+/calmodulin-dependent protein kinase

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EC Tree
IUBMB Comments
Requires calmodulin and Ca2+ for activity. A wide range of proteins can act as acceptor, including vimentin, synapsin, glycogen synthase, myosin light chains and the microtubule-associated tau protein. Not identical with EC 2.7.11.18 (myosin-light-chain kinase) or EC 2.7.11.26 (tau-protein kinase).
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This record set is specific for:
UNIPROT: Q16566
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Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
caldesmon, cam kinase ii, camkiv, cam kinase, calcium/calmodulin-dependent protein kinase ii, calmodulin-dependent protein kinase, camkk2, calcium/calmodulin-dependent protein kinase, ca2+/calmodulin-dependent protein kinase, camk ii, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
calcium-calmodulin-dependent protein kinase IV
-
calcium/calmodulin-dependent protein kinase IV
-
calcium/calmodulin-dependent protein kinase type IV catalytic chain
-
CaM-KIV
multifunctional enzyme
CaMKIV
CAKI
-
-
-
-
caldesmon
-
-
-
-
Calspermin
-
-
-
-
CAM kinase-GR
-
-
-
-
CMPK
-
-
-
-
kinase, caldesmon (phosphorylating)
-
-
-
-
kinase, microtubule-associated protein 2 (phosphorylating)
-
-
-
-
MAP kinase
-
-
-
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MAP-2 kinase
-
-
-
-
MAP-2 protein serine kinase
-
-
-
-
microtubule associated protein kinase
-
-
-
-
microtubule-associated protein 2 kinase
-
-
-
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peripheral plasma membrane protein CaMGUK
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (Ca2+/calmodulin-dependent)
Requires calmodulin and Ca2+ for activity. A wide range of proteins can act as acceptor, including vimentin, synapsin, glycogen synthase, myosin light chains and the microtubule-associated tau protein. Not identical with EC 2.7.11.18 (myosin-light-chain kinase) or EC 2.7.11.26 (tau-protein kinase).
CAS REGISTRY NUMBER
COMMENTARY hide
141467-21-2
-
93229-57-3
-
97350-82-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-
-
?
ATP + CREB1 protein
ADP + phosphorylated CREB1 protein
show the reaction diagram
-
-
-
?
ATP + synapsin I
ADP + phosphosynapsin I
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
-
-
?
ATP + CREB1 protein
ADP + phosphorylated CREB1 protein
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-methyl-7-([6-[(quinolin-8-yl)oxy]pyrimidin-4-yl]oxy)-2H-1-benzopyran-2-one
-
6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]-N-(4-methoxyphenyl)pyrimidin-4-amine
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7-([6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]pyrimidin-4-yl]oxy)-4-methyl-2H-1-benzopyran-2-one
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7-[(6-chloropyrimidin-4-yl)oxy]-4-methyl-2H-1-benzopyran-2-one
-
8-([6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]pyrimidin-4-yl]oxy)quinoline
-
8-([6-[(naphthalen-2-yl)oxy]pyrimidin-4-yl]oxy)-1,4-dihydroquinoline
-
8-[(6-chloropyrimidin-4-yl)oxy]quinoline
-
CaMK phosphatase
specifically dephosphorylates and regulates activity
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CaMKP phosphatase-N
specifically dephosphorylates and regulates activity
-
curcumin
curcumin strongly interacts with isoform CAMK4
KN-62
specific CaMK inhibitor
KN-93
specific CaMK inhibitor
protein phosphatase 1
negative CaMK regulation by dephosphorylation
-
Protein phosphatase 2A
negative CaMK regulation by dephosphorylation
-
protein phosphatase 2B
calcineurin, negative CaMK regulation by dephosphorylation
-
protein phosphatase 2C
negative CaMK regulation by dephosphorylation
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protein phosphatase M
negative CaMK regulation by dephosphorylation
-
STO-609
selective inhibitor
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ca2+/calmodulin-dependent protein kinase kinase
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.072 - 0.35
4-methyl-7-([6-[(quinolin-8-yl)oxy]pyrimidin-4-yl]oxy)-2H-1-benzopyran-2-one
0.06
6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]-N-(4-methoxyphenyl)pyrimidin-4-amine
Homo sapiens
pH and temperature not specified in the publication, for HuH7 cells: 0.06 mM
0.054
7-([6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]pyrimidin-4-yl]oxy)-4-methyl-2H-1-benzopyran-2-one
Homo sapiens
pH and temperature not specified in the publication, for HuH7 cells
0.124 - 0.33
7-[(6-chloropyrimidin-4-yl)oxy]-4-methyl-2H-1-benzopyran-2-one
0.04
8-([6-[(5-methoxy-1H-benzimidazol-2-yl)sulfanyl]pyrimidin-4-yl]oxy)quinoline
Homo sapiens
pH and temperature not specified in the publication, for HuH7 cells: 0.04 mM
0.055 - 0.38
8-([6-[(naphthalen-2-yl)oxy]pyrimidin-4-yl]oxy)-1,4-dihydroquinoline
0.039
8-[(6-chloropyrimidin-4-yl)oxy]quinoline
Homo sapiens
pH and temperature not specified in the publication, for HuH7 cells
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 11.5
within the pH range, CAMKIV maintains both its secondary and tertiary structures, along with its function, whereas significant aggregation is observed at acidic pH 2.0-4.5
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the enzyme is absent from primary human B lymphocytes but is expressed in Epstein-Barr virus-transformed B-lymphoblastoid cell lines, suggesting that expression of the kinase can be upregulated by an EBV gene products
Manually annotated by BRENDA team
Jurkat cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr protein kinase family
malfunction
overexpression and mutation in CAMKIV as well as change in Ca2+ concentration is associated with numerous neurodegenerative diseases and cancers
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KCC4_HUMAN
473
0
51926
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
51925
x * 51925, calculation from nucleotide sequence
60000
isozyme CaMKIV
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 51925, calculation from nucleotide sequence
monomer
1 * 60000, isozyme CaMKIV
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
the enzyme has seven glycosylation sites at Thr57, Ser58, Ser137, Ser189, Ser344, Ser345 and Ser356
phosphoprotein
the enzyme has five potential phosphorylation sites at Ser12, Ser13, Thr200, Ser336 and Ser360
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, NiNTA resin column chromatography, Ni-HF affinity gel filtration, and Sephacryl S-200 gel filtration
recombinant functionally active CAMKIV kinase domain
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning and recombinant expression of functionally active CAMKIV kinase domain
expressed in Escherichia coli
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
isolation and sequencing of cDNA
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
Ca2+/calmodulin-dependent protein kinases may be involved in cancer, cardiac hypertrophy, heart failure, arrhythmia, cardiomyocyte apoptosis, the regulation of higher order neuronal functions such as memory, learning disorder, Angelman's syndrome, Parkinson's disease, Alzheimer's disease, delayed neuronal death, diabetes, and osteoporosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bland, M.M.; Monroe, R.S.; Ohmstede, C.A.
The cDNA sequence and characterization of the Ca2+/calmodulin-dependent protein kinase-Gr from human brain and thymus
Gene
142
191-197
1994
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Kitani, T.; Okuno, S.; Fujisawa, H.
cDNA cloning and expression of human calmodulin-dependent protein kinase IV
J. Biochem.
115
637-640
1994
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Mosialos, G.; Hanissian, S.H.; Jawahar, S.; Vara, L.; Kieff, E.; Chatila, T.A.
A Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, expressed after transformation of primary human B lymphocytes by Epstein-Barr virus (EBV) is induced by the EBV oncogene LMP1
J. Virol.
68
1697-1705
1994
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Ishida, A.; Sueyoshi, N.; Shigeri, Y.; Kameshita, I.
Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases
Br. J. Pharmacol.
154
729-740
2008
Homo sapiens, Homo sapiens (Q14012), Homo sapiens (Q16566)
Manually annotated by BRENDA team
Matsumoto, K.; Murao, K.; Imachi, H.; Nishiuchi, T.; Cao, W.; Yu, X.; Li, J.; Ahmed, R.A.; Iwama, H.; Kobayashi, R.; Tokumitsu, H.; Ishida, T.
The role of calcium/calmodulin-dependent protein kinase cascade on MIP-1alpha gene expression of ATL cells
Exp. Hematol.
36
390-400
2008
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Naz, H.; Shahbaaz, M.; Bisetty, K.; Islam, A.; Ahmad, F.; Hassan, M.I.
Effect of pH on the structure, function, and stability of human calcium/calmodulin-dependent protein kinase IV: combined spectroscopic and MD simulation studies
Biochem. Cell Biol.
94
221-228
2016
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Jameel, E.; Naz, H.; Khan, P.; Tarique, M.; Kumar, J.; Mumtazuddin, S.; Ahamad, S.; Islam, A.; Ahmad, F.; Hoda, N.; Hassan, M.
Design, synthesis, and biological evaluation of pyrimidine derivatives as potential inhibitors of human calcium/calmodulin-dependent protein kinase IV
Chem. Biol. Drug Des.
89
741-754
2017
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team
Hoda, N.; Naz, H.; Jameel, E.; Shandilya, A.; Dey, S.; Hassan, M.; Ahmad, F.; Jayaram, B.
Curcumin specifically binds to the human calcium-calmodulin-dependent protein kinase IV Fluorescence and molecular dynamics simulation studies
J. Biomol. Struct. Dyn.
34
572-584
2016
Homo sapiens (Q16566), Homo sapiens
Manually annotated by BRENDA team