Information on EC 2.7.11.1 - non-specific serine/threonine protein kinase and Organism(s) Mus musculus

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Mus musculus


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.1
-
RECOMMENDED NAME
GeneOntology No.
non-specific serine/threonine protein kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a protein = ADP + a phosphoprotein
show the reaction diagram
catalytic mechanism and regulation of PKN
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (non-specific)
This is a heterogeneous group of serine/threonine protein kinases that do not have an activating compound and are either non-specific or their specificity has not been analysed to date.
CAS REGISTRY NUMBER
COMMENTARY hide
191808-15-8
phosphoinositide dependent protein kinase 1
340830-03-7
-
37278-10-7
-
377752-08-4
ribosomal protein S6 kinase 2
389133-24-8
ribosomal S6 kinase 3
52660-18-1
casein kinase, protein kinase CK2
9026-43-1
this CAS Reg. No. encompasses a great variety of protein kinases including the serine/threonine specific kinases
90698-26-3
ribosomal protein S6 kinase 1
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
-
the serine/threonine kinase LKB1 is the main upstream kinase of the AMP-activated protein kinase cascade that senses cellular energy state and adjusts cellular metabolism
physiological function
additional information
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 + AKAP450
ADP + phospho-AKAP450
show the reaction diagram
ATP + AMP-activated protein kinase
ADP + phosphorylated AMP-activated protein kinase
show the reaction diagram
-
-
-
-
?
ATP + apoptosis signal-regulating kinase 1
ADP + phosphorylated-apoptosis signal-regulating kinase 1
show the reaction diagram
MPK28 stimulates APK1 activity by Thr838 phosphorylation
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
-
-
-
-
?
ATP + casein
ADP + phosphorylated casein
show the reaction diagram
-
substrate of TSSK3
-
-
?
ATP + Cdc25C
ADP + phosphorylated Cdc25C
show the reaction diagram
phosphorylated Cdc25C on Ser216
-
-
?
ATP + Cre-responsive element modulator
ADP + phospho-Crem
show the reaction diagram
ATP + Crem protein
ADP + phosphorylated Crem protein
show the reaction diagram
the enzyme phosphorylates Crem protein at Ser117
-
-
?
ATP + GST-CREB2 protein
ADP + phosphorylated GST-CREB2 protein
show the reaction diagram
-
-
-
-
?
ATP + GST-NFAT3D4-261-365
ADP + phosphorylated GST-NFAT3D4-261-365
show the reaction diagram
-
-
-
-
?
ATP + histone H1
ADP + phosphorylated histone H1
show the reaction diagram
ATP + histone H2A
ADP + phosphorylated histone H2A
show the reaction diagram
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H2AX
ADP + phosphorylated histone H2AX
show the reaction diagram
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H2B
ADP + phosphorylated histone H2B
show the reaction diagram
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H3
ADP + phosphorylated histone H3
show the reaction diagram
ATP + histone H4
ADP + phosphorylated histone H4
show the reaction diagram
recombinant substrate from Xenopus laevis, substrate of SSTK
-
-
?
ATP + ICAP-1alpha protein
ADP + phosphorylated ICAP-1alpha protein
show the reaction diagram
-
phosphorylated at threonine 38
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
ATP + p53 protein
ADP + phosphorylated p53 protein
show the reaction diagram
-
at Ser15
-
-
?
ATP + PACSIN 1 protein
ADP + phospho-PACSIN 1 protein
show the reaction diagram
i.e. casein kinase 2 substrate in neurons 1 protein, casein kinase 2 phosphorylates PACSIN 1 at Ser358, no activity with PACSIN1 mutant S358A. Ser358 is located within the unstructured linker sequence connecting the N-terminal F-BAR domain with the C-terminal SH3 domain
-
-
?
ATP + PACSIN protein
ADP + phosphorylated PACSIN protein
show the reaction diagram
-
phosphorylation at Ser358
-
-
?
ATP + protein
?
show the reaction diagram
ATP + protein
ADP + a phosphoprotein
show the reaction diagram
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + protein
ADP + protein tyrosine phosphate
show the reaction diagram
-
GST-Limk1-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro
-
-
?
ATP + protein kinase C
ADP + phospho-protein kinase C
show the reaction diagram
-
-
-
?
ATP + protein kinase C
ADP + phosphorylated protein kinase C
show the reaction diagram
-
-
-
-
?
ATP + protein kinase Czeta
ADP + phosphorylated protein kinase Czeta
show the reaction diagram
phosphorylation and activation of protein kinase Czeta
-
-
?
ATP + protein p21
ADP + phosphoprotein p21
show the reaction diagram
-
threonine 57, threonine 145, serine 98, serine 130, and serine 146 are phosphorylated by JNK, JNK mediates stabilization of protein p21 via the phosphorylation of threonine 57
-
-
?
ATP + Rab8a protein
ADP + phosphorylated Rab8a protein
show the reaction diagram
-
-
-
-
?
ATP + RRSSSY
ADP + RRSS-phosphoS-Y
show the reaction diagram
-
peptide substrate of TSSK3 consisting of the consensus sequence
-
-
?
ATP + SF2/ASF
ADP + phosphorylated SF2/ASF
show the reaction diagram
-
SF2/ASF is a human SR splicing factor, phosphorylation in the RS domain
-
-
?
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + stathmin
ADP + phosphorylated stathmin
show the reaction diagram
-
phosphorylates on Ser
-
-
?
ATP + testis-specific serine-threonine kinase 3
ADP + phosphorylated testis-specific serine-threonine kinase 3
show the reaction diagram
ATP + Trx-His-S-CREB protein
ADP + phosphorylated Trx-His-S-CREB protein
show the reaction diagram
i.e. thioredoxin fusion cAMP responsive element binding protein, phosphorylation at Ser133
-
-
?
ATP + vimentin
ADP + phosphorylated vimentin
show the reaction diagram
kinase assays demonstrate that Stk33 is able to specifically phosphorylate the non-alpha-helical amino-terminal domain of vimentin in vitro
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
casein + ATP
phosphorylated casein + ADP
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
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 + AKAP450
ADP + phospho-AKAP450
show the reaction diagram
Q9DC28
-
-
-
?
ATP + AMP-activated protein kinase
ADP + phosphorylated AMP-activated protein kinase
show the reaction diagram
-
-
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
-
-
-
-
?
ATP + Cre-responsive element modulator
ADP + phospho-Crem
show the reaction diagram
-
Tssk-4 phosphorylates Cre-responsive element modulator, Crem, at Ser117
-
-
?
ATP + Crem protein
ADP + phosphorylated Crem protein
show the reaction diagram
Q9D411
the enzyme phosphorylates Crem protein at Ser117
-
-
?
ATP + histone H3
ADP + phosphorylated histone H3
show the reaction diagram
-
RSK2 is a key regulator of histone H3 phosphorylation
-
-
?
ATP + ICAP-1alpha protein
ADP + phosphorylated ICAP-1alpha protein
show the reaction diagram
-
phosphorylated at threonine 38
-
-
?
ATP + PACSIN 1 protein
ADP + phospho-PACSIN 1 protein
show the reaction diagram
O54833
i.e. casein kinase 2 substrate in neurons 1 protein, casein kinase 2 phosphorylates PACSIN 1 at Ser358, no activity with PACSIN1 mutant S358A. Ser358 is located within the unstructured linker sequence connecting the N-terminal F-BAR domain with the C-terminal SH3 domain
-
-
?
ATP + PACSIN protein
ADP + phosphorylated PACSIN protein
show the reaction diagram
-
phosphorylation at Ser358
-
-
?
ATP + protein
?
show the reaction diagram
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + protein
ADP + protein tyrosine phosphate
show the reaction diagram
-
GST-Limk1-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro
-
-
?
ATP + protein kinase C
ADP + phospho-protein kinase C
show the reaction diagram
O54833
-
-
-
?
ATP + protein kinase C
ADP + phosphorylated protein kinase C
show the reaction diagram
-
-
-
-
?
ATP + protein kinase Czeta
ADP + phosphorylated protein kinase Czeta
show the reaction diagram
Q9Z2A0
phosphorylation and activation of protein kinase Czeta
-
-
?
ATP + Rab8a protein
ADP + phosphorylated Rab8a protein
show the reaction diagram
-
-
-
-
?
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + testis-specific serine-threonine kinase 3
ADP + phosphorylated testis-specific serine-threonine kinase 3
show the reaction diagram
-
substrate of phosphoinositide-dependent kinase-1 leading to activation
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
activity in organisms with mutated APP and tau, not in wild-type, overview
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-phosphoinositide
enzyme is dependent on
Calmodulin
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
dependent on
Mn2+
-
preferred cation, optimal at 10 mM
additional information
-
divalent cations are required for activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-oleoyl-2-acetylglycerol
-
inhibits phorbol ester binding
kaempferol
-
an inhibitor of RSK2 invitro and in vivo, and suppresses proliferation and EGF-induced transformation in JB6 Cl41 cells, overview
luteolin
-
i.e. 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone, directly inhibits TPL2 activity, luteolin binds to TPL2 in an ATP-competitive manner, binding mode of luteolin, molecular modeling and docking study, overview. Luteolin easily docks to the ATP binding site of TPL2, which is located between the N-lobe and C-lobe of the kinase domain. In a cellular system, phosphorylation of TPL2 is increased by luteolin treatment, and luteolin suppresses TNF-alpha-induced TPL2 activity in JB6 P+ cells
PF670462
a CK1delta/epsilon kinase inhibitor
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arachidonic acid
-
activates in vitro, binds at the autoinhibitory site at the C-terminus
brain-derived neurotrophic factor
BDNF
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inositol 6-phosphate
specifically induces PACSIN 1 phosphorylation
-
lysophosphatidic acid
-
activates isozyme PKNalpha
RhoA
-
small GTPase, binds to the ACC domain and activates isozymes PKNalpha and PRK2/PKNgamma/PAK-2
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.145
myelin basic protein
-
pH 7.4, 30°C, recombinant TSSK3
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Cardiac Pak1 activity is markedly increased by transverse aortic constriction in both C57BL/6 and FVBN mice
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
7.4
-
TSSK3
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 8.2
-
TSSK3 shows a broad range pH-optimum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.1
amino acid sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
isozyme PKNalpha
Manually annotated by BRENDA team
-
rat BUB1 mRNA accumulation correlates with the proliferation status of cells in culture
Manually annotated by BRENDA team
MAST3 shows selective expression in striatum and cortex as determined by in situ hybridization
Manually annotated by BRENDA team
MAST3 shows selective expression in striatum and cortex as determined by in situ hybridization
Manually annotated by BRENDA team
-
tumour-promotion-sensitive P+
Manually annotated by BRENDA team
-
isozyme PRK2/PKNgamma/PAK-2
Manually annotated by BRENDA team
expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
primary hippocampal neurons
Manually annotated by BRENDA team
MAST4 shows selective expression in oligodendrozytes
Manually annotated by BRENDA team
sertoli cell culture SerW3 is used
Manually annotated by BRENDA team
expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR; expression detected by RT-PCR
Manually annotated by BRENDA team
-
giant cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
low activity
Manually annotated by BRENDA team
-
kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
x * 35000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 35000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione-immobilized bead chromatography, and gel filtration
-
protein A-coupled Sepharose bead chromatography
-
recombinant GST-tagged wild-type Tssk4 and Myc-Tssk4T197A mutant from HEK-293T cells by glutathione affinity and immunoaffinity chromatography, respectively. Native Tssk4 from testis gland by immunoaffinity precipitation
recombinant wild-type and mutant GST-fusion TSSK3s by glutathione affinity chromatography, recombinant Myc-tagged catalytic subunit of phosphoinositide-dependent kinase-1 from human 293T cells
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
alpha'-subunit
-
bacterially expressed catalytic domain of PKD
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ectopic overexpression of RSK2 in MEF cells induces anchorage-independent cell transformation
-
expressed in Escherichia coli
expressed in Escherichia coli BL21 cells
-
expression in COS7 cells
-
expression of wild-type and mutant GST-fusion TSSK3s in Escherichia coli strain BL21, expression of Myc-tagged catalytic subunit of phosphoinositide-dependent kinase-1 in human 293T cells
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expression of wild-type and mutant GST-tagged MPK38 in human in MCF-7, HEK-293, H-1299, and HCT-116 cells, coexpression with FLAG-tagged p53
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gene tssk4, localization on chromosome 14qC3, DNA and amino acid sequence determination and analysis of splicing variant beta, expression of wild-type Myc-tagged TSSKbeta in HEK-293T cells; gene tssk4, localization on chromosome 14qC3, DNA and amino acid sequence determination and analysis of splicing variant gamma, expression of wild-type Myc-tagged TSSKdelta in HEK-293T cells; gene tssk4, localization on chromosome 14qC3, DNA and amino acid sequence determination and analysis of splicing variant gamma, expression of wild-type Myc-tagged TSSKgamma in HEK-293T cells; gene tssk4, localization on chromosome 14qC3, DNA and amino acid sequence determination and analysis of splicing variant TSSKalpha, expression of wild-type and mutant Myc-tagged TSSKalpha in HEK-293T cells
gene Tssk4, recombinant expression of GST-tagged Tssk4 in Escherichia coli strain BL21
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in COS cells transfected with Kiz-1 complementary DNA Kiz-1 is found mainly in the cytoplasm
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isolation and characterization of cDNA
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isolation of cDNA
-
isozymes Tssk1, Tssk2, and Tssk3, DNA and amino acid sequence determination and analysis, recombinant expression of the isozymes in HEK-293T cells; isozyme Tssk4, DNA and amino acid sequence determination and analysis, recombinant expression of GST-tagged wild-type isozyme Tssk4 and of Myc-Tssk4T197A mutant in HEK-293T cells
located at the distal end of mouse chromosome 5
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PKNalpha gene mapps to 19p12-p13.1 of chromosome 8 situated at the prostanoid receptor gene locus
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SSTK gene, DNA and amino acid sequence determination and analysis, transient expression of Myc-tagged SSTK in 293T cells
Tssk1 and Tssk2 genes are tandemly located on chromosome 16 separated by an intergenic region of only 3.06 kb
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Pim1 mRNA is upregulated by interleukin-3, interleukin-6 and TPO. In contrast, Pim2 and Pim3 mRNA expression is not changed with these cytokines
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K39R
-
site-directed mutagenesis, inactive mutant
K40R
kinase-dead MPK38 mutant shows no complex formation with ASK1 since MPK38-ASK1 complex formation is dependent on the activities of both kinases
K54M
site-directed mutagenesis of splicing variant TSSKalpha
S166A
-
site-directed mutagenesis, mutation of a T-loop residue, highly reduced kinase activity compared to the wild-type TSSK3, no autophosphorylation
S166D
-
site-directed mutagenesis, mutation of a T-loop residue, reduced kinase activity compared to the wild-type TSSK3, no autophosphorylation
S166G
-
site-directed mutagenesis, mutation of a T-loop residue, highly reduced kinase activity compared to the wild-type TSSK3, no autophosphorylation
S370A
-
site-directed mutagenesis, S6K2 mutant is inactive
S370D
-
site-directed mutagenesis, S6K2 mutant is inactive
T168A
-
site-directed mutagenesis, mutation of a T-loop residue, inactive TSSK3 mutant, no autophosphorylation
T168D
-
site-directed mutagenesis, mutation of a T-loop residue, unaltered kinase activity and reduced autophosphorylation compared to the wild-type TSSK3
T197A
site-directed mutagenesis of the autophosphorylation site Thr residue of isozyme Tssk4
T228A
-
site-directed mutagenesis, S6K2 mutant shows reduced activation compared to the wild-type enzyme
T228A/T338E
-
site-directed mutagenesis, S6K2 mutant is inactive
T228E
-
site-directed mutagenesis, S6K2 mutant shows highly reduced activation compared to the wild-type enzyme
T256A
the conditional IPTG inducible expression of wild type Sgk, but not of the kinase dead mutant T256A Sgk, protects Con8 mammary epithelial tumor cells from serum starvation-induced apoptosis
T256A/S422A
unlike the wild-type enzyme the phosphorylation site mutant has no effect on cell survival
T338E
-
site-directed mutagenesis, S6K2 mutant is fully active and rapamycin-resistant, while the S6K1 mutant is inactive
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
high-tidal-volume ventilation induced microvascular permeability, lung fibrosis, and chemokine production are dependent, in part, on activation of the Akt and ERK1/2 pathways
molecular biology
results demonstrate that MPK38 physically interacts with ASK1 in vivo and acts as a positive upstream regulator of ASK1